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10.1101/2021.02.01.21250957 | Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of 'real-world' vaccination outcomes from Israel. | A distinctive feature of the roll out of vaccination against SARS-CoV-2 virus in the UK was the decision to delay the timing of the second injection till 12 weeks after the first. The logic behind this is to protect more people sooner and so reduce the total number of severe infections, hospitalisations, and deaths. This decision caused criticism from some quarters due in part to a belief that a single injection may not give adequate immunity. A recent paper based on Israels experience of vaccination suggested that a single dose may not provide adequate protection. Here we extract the primary data from the Israeli paper and then estimate the incidence per day for each day after the first injection and also estimate vaccine effectiveness for each day from day 13 to day 24. We used a pooled estimate of the daily incidence rate during days 1 to 12 as the counterfactual estimate of incidence without disease and estimated confidence intervals using Monte Carlo modelling. After initial injection case numbers increased to day 8 before declining to low levels by day 21. Estimated vaccine effectiveness was pretty much 0 at day 14 but then rose to about 90% at day 21 before levelling off. The cause of the initial surge in infection risk is unknown but may be related to people being less cautious about maintaining protective behaviours as soon as they have the injection. What our analysis shows is that a single dose of vaccine is highly protective, although it can take up to 21 days to achieve this. The early results coming from Israel support the UK policy of extending the gap between doses by showing that a single dose can give a high level of protection. | infectious diseases |
10.1101/2021.02.01.21250905 | COVID-19 among bartenders and waiters before and after pub lockdown | AimTo study how different bans on serving alcohol in Norwegian bars and restaurants were related to the detection of SARS-CoV-2 in bartenders and waiters.
MethodsIn 24,276 bartenders and waiters and 1,287,970 persons with other occupations (mean [SD] age 41.7 [12.8] years and 51.7% men), we examined the weekly rates of workers tested and detected with SARS-CoV-2, one to five weeks before and one to five weeks after implementation of different degrees of bans on serving alcohol in pubs and restaurants, across 56 Norwegian municipalities with: 1) full blanket ban, 2) partial ban with hourly restrictions (e.g. from 10 pm), or 3) no ban, adjusted for age, sex and testing behavior.
ResultsIn municipalities introducing full ban, COVID-19 among bartenders and waiters had been reduced by 65% by three weeks (from 3.4 [95%CI=2.5-4.3] to 1.2 [95%CI=0.7-1.7] per 1000), i.e. to the same levels as that for persons with other occupations (1.8 [95%CI=1.7-1.9] vs 1.2 [95%CI=1.1-1.3] per 1000). Similarly, in municipalities introducing partial ban, COVID-19 among bartenders and waiters had been reduced by 68% by three weeks (from 2.5 [95%CI=1.4-3.6] to 0.8 [95%CI=0.0-1.5] per 1000). However, there was more uncertainty to the estimated reduction for partial bans.
ConclusionMunicipalities with higher levels of confirmed COVID-19 among bartenders and waiters implemented stricter bans on serving of alcohol than other municipalities. Contraction of COVID-19 among bartenders and waiters declined similarly in municipalities with full and partial bans. | infectious diseases |
10.1101/2021.02.01.21250769 | Sarilumab treatment of hospitalised patients with severe or critical COVID-19: a multinational, randomised, adaptive, phase 3, double-blind, placebo-controlled trial | BackgroundElevated proinflammatory cytokines have been associated with 2019 coronavirus disease (COVID-19) severity. We assessed efficacy and safety of sarilumab, an interleukin-6 receptor inhibitor, in severe (requiring supplemental oxygen by nasal canula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19.
MethodsThis was a 60-day, randomised, double-blind, placebo-controlled, multinational trial in patients hospitalised with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomised 2:2:1 to intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. The primary endpoint was time to [≥]2-point clinical improvement (7-point scale; range: 1 [death] to 7 [not hospitalised]). The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This trial is registered with ClinicalTrials.gov (NCT04327388).
FindingsBetween March 28 and July 3, 2020, 420 patients were randomised; 416 received treatment (placebo, n=84; sarilumab 200 mg, n=159; sarilumab 400 mg, n=173). At day 29, there were no significant differences in median (95% CI) time to [≥]2-point improvement between placebo (12{middle dot}0 [9{middle dot}0-15{middle dot}0] days) and sarilumab groups (200 mg: 10{middle dot}0 [9{middle dot}0-12{middle dot}0] days, p=0.96, log-rank test; 400 mg: 10{middle dot}0 [9{middle dot}0-13{middle dot}0] days, p=0.34) or in proportions of patients alive (placebo, 91{middle dot}7%; sarilumab 200 mg, 89{middle dot}9%, p=0{middle dot}63; sarilumab 400 mg, 91{middle dot}9%, p=0{middle dot}85). At day 29, there were numerical, nonsignificant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +9%, 95% CI -7{middle dot}7 to 25{middle dot}5, p=0{middle dot}25) for critical patients. There were no unexpected safety signals.
InterpretationThis trial did not demonstrate efficacy of sarilumab in patients hospitalised with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19.
FundingSanofi and Regeneron Pharmaceuticals, Inc. | infectious diseases |
10.1101/2021.02.01.21250923 | A cautionary note on recall vaccination in ex-COVID-19 subjects | Currently approved COVID-19 vaccines based on mRNA or adenovirus require a first jab followed by recall immunization. There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses. Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID). Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naive subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine. We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR. Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects. This poses caution for ExCOVID subjects to receive a second jab both because they may have a overreaction of the inflammatory response and also in light of the current vaccine shortage. | allergy and immunology |
10.1101/2021.02.01.21250923 | A cautionary note on recall vaccination in ex-COVID-19 subjects | Currently approved COVID-19 vaccines based on mRNA or adenovirus require a first jab followed by recall immunization. There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses. Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID). Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naive subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine. We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR. Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects. This poses caution for ExCOVID subjects to receive a second jab both because they may have a overreaction of the inflammatory response and also in light of the current vaccine shortage. | allergy and immunology |
10.1101/2021.02.01.21250493 | Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals | The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.
SignificanceIn this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2. | allergy and immunology |
10.1101/2021.02.02.21250979 | Vaccinating Australia: How long will it take? | The Australian Governments COVID-19 vaccine rollout strategy is scheduled to commence in late February 2021 and aims to vaccinate the Australian adult population by the end of October 2021. The task of vaccinating some 20 million people within this timeframe presents considerable logistical challenges. Key to meeting this target is the rate of vaccine delivery: the number of vaccine doses that can be administered per day. In the opening phase, high priority groups will receive the Pfizer/BioNTech vaccine through hospital hubs at an initial rate of 80,000 doses per week. However, pending regulatory approval, the currently announced plan appears to be to distribute the AstraZeneca vaccine to the bulk of the popluation through a combination of general practices and community pharmacies. Here, we run a series of projections to estimate how long it will take to vaccinate the Australian population under different assumptions about the rate of vaccine administration as well as the schedule for second doses and prevalence of vaccine hesitancy. Our analysis highlights the ambitious rate of vaccine administration that will be neccessary to meet the Australian Government completion target of October 2021. A rate of 200,000 doses per day would comfortably meet that target; 80,000 doses a day would see roll-out extended until mid-2022. Speed is of the essence when it comes to vaccine rollout: protecting the population quickly will minimise the risk of sporadic and costly lockdowns lockdowns and the potential for small, local clusters getting out of control and sparking new epidemic waves. The government should gather all its resources to maximise the daily vaccination rate, ideally aiming to ramp up administration to at least 200,000 doses per day as quickly as possible. Quickly achieving and maintaining this pace will likely require dedicated large-scale vaccination sites that are capable of delivering thousands of doses a week in addition to the enthusiastic participation of GP practices and community pharmacies around the country. Lessons on the neccessary logistical planning, including coordination of delivery, ultra-cold-chain storage and staffing, can potentially be learned from Israel, where between 7,000 and 20,000 vaccinations per million population have been delivered daily throughout January. | epidemiology |
10.1101/2021.02.02.21250979 | Vaccinating Australia: How long will it take? | The Australian Governments COVID-19 vaccine rollout strategy is scheduled to commence in late February 2021 and aims to vaccinate the Australian adult population by the end of October 2021. The task of vaccinating some 20 million people within this timeframe presents considerable logistical challenges. Key to meeting this target is the rate of vaccine delivery: the number of vaccine doses that can be administered per day. In the opening phase, high priority groups will receive the Pfizer/BioNTech vaccine through hospital hubs at an initial rate of 80,000 doses per week. However, pending regulatory approval, the currently announced plan appears to be to distribute the AstraZeneca vaccine to the bulk of the popluation through a combination of general practices and community pharmacies. Here, we run a series of projections to estimate how long it will take to vaccinate the Australian population under different assumptions about the rate of vaccine administration as well as the schedule for second doses and prevalence of vaccine hesitancy. Our analysis highlights the ambitious rate of vaccine administration that will be neccessary to meet the Australian Government completion target of October 2021. A rate of 200,000 doses per day would comfortably meet that target; 80,000 doses a day would see roll-out extended until mid-2022. Speed is of the essence when it comes to vaccine rollout: protecting the population quickly will minimise the risk of sporadic and costly lockdowns lockdowns and the potential for small, local clusters getting out of control and sparking new epidemic waves. The government should gather all its resources to maximise the daily vaccination rate, ideally aiming to ramp up administration to at least 200,000 doses per day as quickly as possible. Quickly achieving and maintaining this pace will likely require dedicated large-scale vaccination sites that are capable of delivering thousands of doses a week in addition to the enthusiastic participation of GP practices and community pharmacies around the country. Lessons on the neccessary logistical planning, including coordination of delivery, ultra-cold-chain storage and staffing, can potentially be learned from Israel, where between 7,000 and 20,000 vaccinations per million population have been delivered daily throughout January. | epidemiology |
10.1101/2021.02.01.21250959 | Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01 | SARS-CoV-2 lineage B.1.1.7, a variant first detected in the United Kingdom in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than preexisting variants, but have not identified whether it leads to any change in disease severity2. We analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39-72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8-1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42-82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness. | epidemiology |
10.1101/2021.02.01.21250959 | Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01 | SARS-CoV-2 lineage B.1.1.7, a variant first detected in the United Kingdom in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than preexisting variants, but have not identified whether it leads to any change in disease severity2. We analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39-72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8-1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42-82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness. | epidemiology |
10.1101/2021.02.01.21250959 | Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7 | SARS-CoV-2 lineage B.1.1.7, a variant first detected in the United Kingdom in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than preexisting variants, but have not identified whether it leads to any change in disease severity2. We analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39-72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8-1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42-82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness. | epidemiology |
10.1101/2021.02.01.21250893 | Metabolic subgroups and cardiometabolic multimorbidity in the UK Biobank | Background
Ischemic heart disease (IHD), diabetes, cancer and dementia share features of age-associated metabolic dysfunction. We hypothesized that metabolic diversity explains the diversity of morbidity later in life.
MethodsWe analyzed data from the UK Biobank (N = 329,908). A self-organizing map (SOM, an artificial neural network) was trained with 51 metabolic traits adjusted for age and sex. The SOM analyses produced six subgroups that summarized the multi-variable metabolic diversity. The subgroup with the lowest adiposity and disease burden was chosen as the reference. Hazard ratios (HR) were modeled by Cox regression (P < 0.0001 unless otherwise indicated). Enrichment of multi-morbidity over random expectation was tested by permutation analysis.
ResultsThe subgroup with the highest sex hormones was not associated with IHD (HR = 1.04, P = 0.14). The subgroup with high urinary excretion without kidney stress (HR = 1.24) and the subgroup with the highest apolipoprotein B and blood pressure (HR = 1.52) were associated with IHD. The subgroup with high adiposity, inflammation and kidney stress was associated with IHD (HR = 2.11), cancer (HR= 1.29), dementia (HR = 1.70) and mortality (HR = 2.12). The subgroup with high triglycerides and liver enzymes was at risk of diabetes (HR = 15.6). Paradoxical enrichment of multimorbidity in young individuals and in favorable subgroups was observed.
ConclusionsThese results support metabolic diversity as an explanation to diverging morbidity and demonstrate the potential value of population-based metabolic subgroups as public health targets for reducing aggregate burden of chronic diseases in ageing populations.
Key messagesO_LIWe introduced six data-driven subgroups of the UK Biobank as a high-dimensional model of metabolic diversity and disease risk within a human population.
C_LIO_LIThree subgroups captured features of the classical cardiometabolic spectrum with stratification along cholesterol and blood pressure, kidney or liver dysfunction and systemic inflammation.
C_LIO_LITwo novel subgroups of high sex hormones and high urinary excretion were observed.
C_LIO_LIWe defined a new concept of multimorbidity enrichment.
C_LIO_LInexpected patterns of multimorbidity indicated that metabolically "healthy" individuals with one cardiometabolic disease may be at a disproportional synergistic risk of co-morbidity.
C_LI | epidemiology |
10.1101/2021.02.01.21250944 | Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes | As the threat of Covid-19 continues and in the face of vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels. How timing of delivery of the second dose affects infection burden but also prospects for the evolution of viral immune escape are critical questions. Both hinge on the strength and duration (i.e. robustness) of the immune response elicited by a single dose, compared to natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short-term, focusing on one dose generally decreases infections, but longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection, evaluating how different second dose delays might drive immune escape via a build-up of partially immune individuals. Under certain scenarios, we find that a one-dose policy may increase the potential for antigenic evolution. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose, and to ramp up vaccination efforts throughout the world. | epidemiology |
10.1101/2021.02.01.21250781 | Changes in Characteristics of Opioid Overdose Death Trends during the COVID-19 Pandemic | BackgroundReports analyzing drug overdose (OD) mortality data during the COVID-19 pandemic are limited. Outcomes across states are heterogenous, necessitating assessments of associations between COVID-19 and OD deaths on a state-by-state level. This report aims to analyze trends in OD deaths in Massachusetts during COVID-19.
MethodsAnalyzing 3,924 death records, we characterize opioid-, cocaine-, and amphetamine-involved OD mortality and substance co-presence trends from March 24-November 8 in 2020 as compared to 2018 and 2019.
ResultsOD deaths involving amphetamines increased by 85% from 2019 to 2020 (61 vs. 113; P<0.001) but were steady from 2018 to 2019. Heroins presence continued to decrease (341 in 2018, 247 in 2019, 157 in 2020; P<0.001); however, fentanyl was present in more than 85% of all OD deaths across all periods. Among OD deaths, alcohol involvement consistently increased, present in 250 deaths in 2018, 299 in 2019 (P=0.02), and 350 in 2020 (P=0.04). In 2019, 78% of OD decedents were White and 7% were Black, versus 73% and 10% in 2020 (P=0.02).
ConclusionIncreased deaths involving stimulants, alcohol, and fentanyl reflect concerning trends in the era of COVID-19. Rising OD death rates among Black residents underscore that interventions focused on racial equity are necessary. | epidemiology |
10.1101/2021.02.01.21250781 | Changes in Characteristics of Drug Overdose Death Trends during the COVID-19 Pandemic | BackgroundReports analyzing drug overdose (OD) mortality data during the COVID-19 pandemic are limited. Outcomes across states are heterogenous, necessitating assessments of associations between COVID-19 and OD deaths on a state-by-state level. This report aims to analyze trends in OD deaths in Massachusetts during COVID-19.
MethodsAnalyzing 3,924 death records, we characterize opioid-, cocaine-, and amphetamine-involved OD mortality and substance co-presence trends from March 24-November 8 in 2020 as compared to 2018 and 2019.
ResultsOD deaths involving amphetamines increased by 85% from 2019 to 2020 (61 vs. 113; P<0.001) but were steady from 2018 to 2019. Heroins presence continued to decrease (341 in 2018, 247 in 2019, 157 in 2020; P<0.001); however, fentanyl was present in more than 85% of all OD deaths across all periods. Among OD deaths, alcohol involvement consistently increased, present in 250 deaths in 2018, 299 in 2019 (P=0.02), and 350 in 2020 (P=0.04). In 2019, 78% of OD decedents were White and 7% were Black, versus 73% and 10% in 2020 (P=0.02).
ConclusionIncreased deaths involving stimulants, alcohol, and fentanyl reflect concerning trends in the era of COVID-19. Rising OD death rates among Black residents underscore that interventions focused on racial equity are necessary. | epidemiology |
10.1101/2021.02.01.21250926 | Microscopic dynamics modeling unravels the role of asymptomatic virus carriers in SARS-CoV-2 epidemics at the interplay between biological and social factors | The recent experience of SARS-CoV-2 epidemics spreading revealed the importance of passive forms of infection transmissions. Apart from the virus survival outside the host, the latent infection transmissions caused by asymptomatic and presymptomatic hosts represent major challenges for controlling the epidemics. In this regard, social mixing and various biological factors play their subtle, but often critical, role. For example, a life-threatening condition may result in the infection contracted from an asymptomatic virus carrier. Here, we use a new recently developed microscopic agent-based modelling framework to shed light on the role of asymptomatic hosts and to unravel the interplay between the biological and social factors of these nonlinear stochastic processes. The model accounts for each human actors susceptibility and the virus survival time, as well as traceability along the infection path. These properties enable an efficient dissection of the infection events caused by asymptomatic carriers from those which involve symptomatic hosts before they develop symptoms and become removed to a controlled environment. Consequently, we assess how their relative proportions in the overall infection curve vary with changing model parameters. Our results reveal that these proportions largely depend on biological factors in the process, specifically, the virus transmissibility and the critical threshold for developing symptoms, which can be affected by the virus pathogenicity. Meanwhile, social participation activity is crucial for the overall infection level, further modulated by the virus transmissibility. | epidemiology |
10.1101/2021.02.02.21250934 | Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions | IntroductionFaecal transplantation is an evidence based treatment for Clostridiodes difficile. Patients infected with SARS-CoV-2 have been shown to shed the virus in stool for up to 33 days, well beyond the average clearance time for upper respiratory tract shedding. We carried out an analytical and clinical validation of reverse-transcriptase quantitative (RT-qPCR) as well as LAMP, LamPORE and droplet digital PCR in the detection of SARS-CoV-2 RNA in stool from donated samples for FMT, spiked samples and asymptomatic inpatients in an acute surgical unit.
MethodsKilled SARS-CoV-2 viral lysate and extracted RNA was spiked into donor stool & FMT and a linear dilution series from 10-1 to 10-5 and tested via RT-qPCR, LAMP, LamPORE and ddPCR against SARS-CoV-2. Patients admitted to the critical care unit with symptomatic SARS-CoV-2 and sequential asymptomatic patients from acute presentation to an acute surgical unit were also tested.
ResultsIn a linear dilution series, detection of the lowest dilution series was found to be 8 copies per microlitre of sample. Spiked lysate samples down to 10-2 dilution were detected in FMT samples using RTQPCR, LamPORE and ddPCR and down to 10-1 with LAMP. In symptomatic patients 5/12 had detectable SARS-CoV-2 in stool via RT-qPCR and 6/12 via LamPORE, and in 1/97 asymptomatic patients via RT-qPCR.
ConclusionsRT-qPCR can be detected in FMT donor samples using RT-qPCR, LamPORE and ddPCR to low levels using validated pathways. As previously demonstrated, nearly half of symptomatic and less than one percent of asymptomatic patients had detectable SARS-CoV-2 in stool. | gastroenterology |
10.1101/2021.02.01.21250894 | Clozapine metabolism is associated with Absolute Neutrophil Count in individuals with treatment-resistant schizophrenia | AIMTo investigate the relationship between clozapine concentration and neutrophils in a European cohort of long-term clozapine users.
METHODSPearsons Correlation and Linear Regression analyses were applied to a subset of the CLOZUK2 dataset (N = 208) to assess the association between Absolute Neutrophil Count (ANC) and plasma clozapine concentration. Norclozapine and the metabolic ratio between clozapine and norclozapine were also investigated, along with SNPs associated with clozapine metabolism
RESULTSAssociation between ANC and plasma clozapine concentration was found to be significant in a linear regression model ({beta} = -1.41, p = 0.009), with a decrease in ANC of approximately 141 cells/mm3 for every 0.1 mg/litre increase in clozapine concentration. This association was attenuated by the addition of the metabolic ratio, which was significantly negatively correlated with ANC ({beta}=-0.69, p=0.021). In a further regression model, three SNPs previously associated with norclozapine plasma concentrations and clozapine/norclozapine ratio were also found to be significantly associated with ANC: rs61750900 ({beta}=-0.410, p=0.048), rs2011425 ({beta}=0.450, p=0.026) and rs1126545 ({beta}=0.330, p=0.039)
CONCLUSIONANC was found to be significantly negatively associated with plasma clozapine concentration. Further investigation has suggested that the relationship is mediated by the clozapine/norclozapine ratio, and potentially moderated by genetic variants with effects on clozapine metabolism | pharmacology and therapeutics |
10.1101/2021.02.02.20248239 | Investigating the validity of the Strengths and Difficulties Questionnaire to assess ADHD in young adulthood | Attention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early in development and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) has been widely used to measure ADHD symptoms in children, but little is known about its utility to measure ADHD in adulthood. We used Receiver Operating Characteristic (ROC) curve analyses to examine the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD classified using the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) at age 25 years in a UK population cohort (N=4121). Analyses suggested that the SDQ ADHD subscale had high accuracy in distinguishing ADHD cases from non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87-0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages.Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood.
HighlightsO_LIThe SDQ is widely used to measure ADHD symptoms in children
C_LIO_LIWe investigated the validity of the SDQ to assess ADHD at age 25 years
C_LIO_LIThe SDQ ADHD subscale had high accuracy in distinguishing DSM-5 ADHD cases from non-cases
C_LIO_LIA lower cut-point is needed to identify ADHD diagnosis in young adulthood compared to younger ages
C_LIO_LIThe SDQ is appropriate for ADHD research across different development periods
C_LI | psychiatry and clinical psychology |
10.1101/2021.02.02.21250541 | Microbial Sharing between Pediatric Patients and Therapy Animals during Hospital Animal-Assisted Intervention Programs | BackgroundMicrobial sharing between humans and animals has been demonstrated in a variety of settings. However, the extent of microbial sharing that occurs within the healthcare setting during animal-assisted intervention programs, a validated and valuable part of holistic patient wellness, is unknown. Understanding microbial transmission between patients and therapy animals can provide important insights into potential health benefits for patients, in addition to addressing concerns regarding potential pathogen transmission that limits program utilization. This study evaluated the potential for microbial sharing between pediatric patients and therapy dogs, and tested whether patient-dog contact level and a dog decolonization protocol modified this sharing.
Methods and ResultsPatients, therapy animals, and the hospital environment were sampled before and after every group therapy session and samples underwent 16S rRNA sequencing to characterize microbial communities. Both patients and animals experienced changes in the relative abundance and overall diversity of their nasal microbiome, suggesting that exchange of microorganisms had occurred. Increased contact was associated with greater sharing between patients and therapy animals, as well as between patients. A topical chlorhexidine-based dog decolonization intervention was associated with decreased microbial sharing between therapy dogs and patients, particularly from the removal of rarer microbiota from the dog, but did not significantly affect sharing between patients.
ConclusionThese data suggest that the therapy animal is both a potential source of and a vehicle for the transfer of microorganisms to patients but not necessarily the only source. The relative contribution of other potential sources (e.g., other patients, the hospital environment) should be further explored to determine their relative importance. | public and global health |
10.1101/2021.02.01.21250950 | SARS-CoV-2 transmission from the healthcare setting into the home: a prospective longitudinal cohort study | ObjectiveTo assess the incidence of symptomatic and asymptomatic SARS-CoV-2 seropositivity in healthcare workers and subsequent transmission to their close contacts within their household. To assess changes in immunoglobulin (Ig) and neutralising antibodies (nAbs) in exposed participants.
SettingTwo acute National Health Service (NHS) hospitals within the East Midlands region of England.
BackgroundThe UK has been one of the most severely affected countries during the COVID-19 pandemic. Transmission from healthcare workers to the wider community is a potential major vector for spread of SARS-CoV-2 which is not well described in the current literature.
MethodsHealthcare workers (HCW) were recruited from two Hospitals within the East Midlands of England and underwent serial blood sampling for anti-SARS-CoV-2 antibodies (both nucleocapsid and spike protein for IgG, IgM and IgA) between 20 April and 30 July 2020, with the presence of neutralising antibodies (nAbs) assessed for positive participants. Cohabitees of the volunteers were invited to attend testing in July -August 2020 and underwent identical serological testing as the HCWs.
Results633 healthcare professionals were recruited. 178 household contacts of 137 professionals volunteered for the study. 18% of healthcare professionals (115 out of 633) tested as seropositive during the study period, compared to an estimated seroprevalence of 7% within the general population. The rate of symptomatic COVID-19 was 27.5% compared to an asymptomatic rate of 15.1%. Rates of positivity declined across the study period for all immunoglobulins (overall positivity from 16.7% to 6.9%).
7.2% of the cohabitees tested as seropositive. 58 cohabitees lived with a serologically positive HCW; this group had a seropositive rate of 15.5%, compared to 2.5% of cohabitees without a seropositive HCW, a six-fold increase in risk (Odds ratio 7.16 95% CI 1.86 to 27.59), p = 0.0025). Given the observed decay rates and data from Public Health England, we estimate that the proportion of seropositive cohabitees living with a seropositive HCW at the height of the first wave could have been as high as 44%.
110 out of 115 (95.7%) HCWs and 12 out of 13 (92.3%) cohabitees who tested positive developed detectable nAbs. 56.5% (65 out of 115) of SARS-CoV-2 positive HCWs developed a neutralising titre with an IC50[≥]1/300; no cohabitee achieved this level..
ConclusionsTransmission of SARS-CoV-2 between healthcare professionals and their home contacts appears to be a significant factor of viral transmission, but, even accounting for the decline in seropositivity over time, less than 44% of adult cohabitees of seropositive healthcare workers became seropositive. Routine screening and priority vaccination of both healthcare professionals and their close contacts should be implemented to reduce viral transmission from hospitals to the community.
SUMMARY BOXESO_ST_ABSSection 1: What is already known on this topicC_ST_ABSO_LIHealthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population due, at least in part, to high levels of occupational exposure.
C_LIO_LIIgA, IgM and IgG are detectable for most patients after 11 days post SARS-CoV-2 infection but all decline in the weeks following SAR-CoV-2 exposure.
C_LIO_LIRates of transmission to healthcare workers, and therefore subsequent transmission to their close contacts, may be reduced with effective PPE.
C_LI
Section 2: What this study addsO_LIThe amount of neutralising antibodies formed may be dependent on IgG response as it is much lower among seropositive cohabitees than seropositive healthcare workers.
C_LIO_LINHS Healthcare workers had a far greater seroprevalence of SARS-CoV-2 infection compared to the general population.
C_LIO_LICohabitees of positive healthcare workers have a 6-fold increased risk of developing serological evidence of SARS-CoV-2 infection compared to the general population.
C_LIO_LIDespite this increased risk, transmission at home is less than 50% even from highly exposed healthcare workers, but remains an important potential vector of transmission from hospitals to the wider community.
C_LI
Research into contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published between January 1 2020 and January 27, 2021 with the terms "Covid-19", "healthcare workers", and "transmission" "home {NOT nursing} or household". We did not restrict our search by language or type of publication. We identified 38 studies of which only one assessed the prevalence among HCW households using Canadian national databases. Our PubMed search yielded only one serological study within the German Healthcare system, which suggested very low transmission from healthcare workers to their close cohabitees.
Added value of this studyTo our knowledge, this is the largest longitudinal serological cohort study assessing transmission of SARS-CoV-2 infection from the UK healthcare environment to the home (n = 633 healthcare workers, 178 cohabitees). Our findings showed that serological evidence within the HCW was high with 18% of healthcare professionals (115 out of 633) tested as seropositive during the study period, compared to an estimated seroprevalence of 7% within the general population. A cohabitee of a seropositive HCW had a six-fold increase of being seropositive themselves compared to a baseline rate of 2.5%. Despite this increased risk, transmission at home is less than 50% even from highly exposed healthcare workers, but remains an important potential vector of transmission from hospitals to the wider community. Rates of positivity declined across the study period for all immunoglobulins (overall positivity from 16.7% to 6.9%). Given the observed decay rates and data from Public Health England, we estimate that the proportion of seropositive cohabitees living with a seropositive HCW at the height of the first wave could have been as high as 44%.
Implications of all available evidenceUnderstanding the transmission during the first wave from the healthcare setting into the home and the extent of such transmissions is essential to understand containment strategies of novel SARS-CoV-2 variants or to understand viral transmission of future respiratory viruses. NHS workers appeared to be at an increased risk of contracting of SARS-CoV-2 infection compared to the HCWs of other nations; we hypothesise that this may be related to a scarcity of appropriate personal protective equipment during the initial wave of SARS-CoV-2. Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. An infected HCW, whether symptomatic or not, appears to be a significant bridge for transmission of SARS-CoV-2 to their close home contacts. | public and global health |
10.1101/2021.02.01.21250936 | Inference on the dynamics of the COVID pandemic from observational data | AO_SCPLOWBSTRACTC_SCPLOWWe describe a time dependent stochastic dynamic model in discrete time for the evolution of the COVID-19 pandemic in various states of USA. The proposed multi-compartment model is expressed through a system of difference equations that describe their temporal dynamics. Various compartments in our model is connected to the social distancing measures and diagnostic testing rates. A nonparametric estimation strategy is employed for obtaining estimates of interpretable temporally static and dynamic epidemiological rate parameters. The confidence bands of the parameters are obtained using a residual bootstrap procedure. A key feature of the methodology is its ability to estimate latent compartments such as the trajectory of the number of asymptomatic but infected individuals which are the key vectors of COVID-19 spread. The nature of the disease dynamics is further quantified by the proposed epidemiological markers, which use estimates of such key latent compartments. | public and global health |
10.1101/2021.02.02.21250986 | Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort | Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, however the precise nature of SVD-related cognitive deficits, and their associations with structural brain changes, remain unclear. We combined computational volumes and visually-rated MRI markers of SVD to quantify total SVD burden, using data from the Lothian Birth Cohort 1936 (n=540; age:72.6{+/-}0.7 years). We found negative associations between total SVD burden and general cognitive ability (standardised {beta}: -0.363; 95%CI: [-0.49, -0.23]; p(FDR)<0.001), processing speed (-0.371 [-0.50, -0.24]; p(FDR)<0.001), verbal memory (-0.265; [-0.42, -0.11]; p(FDR)=0.002), and visuospatial ability (-0.170; [-0.32, -0.02]; p(FDR)=0.029). Only the association between SVD burden and processing speed remained after accounting for covariance with general cognitive ability (-0.325; [-0.61, -0.04]; p(FDR)=0.029). This suggests that SVDs association with poorer processing speed is not driven by, but is independent of its association with poorer general cognitive ability. Tests of processing speed may be particularly sensitive to the cognitive impact of SVD, but all major cognitive domains should be tested to determine the full range of SVD-related cognitive characteristics. | radiology and imaging |
10.1101/2021.02.02.21250825 | Evaluation of Depression, Anxiety and Sleep Quality in the Brazilian Population During Social Isolation Due to the New Coronavirus (SARS-CoV-2) pandemic: the DEGAS-CoV Study | IntroductionThe new coronavirus infection (COVID-19) has caused distress and repercussions in mental and physical health of individuals. Depression, anxiety and worsening of sleep quality have been reported in several recent articles that surveyed populations all over the globe. Our work meant to access, through a cross-sectional study, these disorders in the Brazilian population, through the application of an online questionnaire conducted on the second trimester of 2020.
Materials and MethodsWe applied an online questionnaire, filled with questions regarding social, economic, financial, educational and health status, as well as questions from the Hospital Anxiety and Depression Scale (HAD), and from the Pittsburgh Sleep Quality Index (PSQI).
ResultsWe collected 2,695 valid answers, from April 24th to May 31st, 2020. Age ranged from 18 to 79 years, mean of 31.3. Women were 76.3%, men 23.7%. Symptoms of Anxiety were found in 56.5%, of depression in 46.1%, and of bad sleep in 49.2%. Some groups were more prone than others to one or more of those conditions, such as: younger people, women, mestizos, Northeasterners, people with lesser years of education, of lower income or whose income dropped significantly during the pandemic, caregivers, students, sedentary or people practicing less physical activity, people who followed more hours of news of COVID-19 and those less engaged in social and instrumental activities.
Conclusionanxiety, depression and bad sleep quality were significantly high in our survey. Mental and sleep health is heterogeneously affected among individuals, depending on social, economic, financial, educational and health status.
O_TEXTBOXHIGHLIGHTS
- An online survey (DEGAS-CoV) was conducted between April 30th and May 31st, 2020, with people living in Brazil, aged 18 or more. The study obtained 2,695 valid answers.
- Rates of possible anxiety, possible depression and bad sleep quality were 56.5%, 46.1% and 49.2%, respectively. Rates are similar to another Brazilian survey, with 45,161 participants, conducted in a similar time window.
- Were more prone to mental and/or sleep conditions: younger participants, women, mestizos, unemployed, students, people with less years of education, people with lower income or with considerable drops of income during the virus outbreak, caregivers, people who followed more news of COVID-19, people less engaged in social and instrumental activities, smokers, sedentary or those who practiced less physical activity, and people who had symptoms suspected (confirmed or not) of SARS-CoV-2 infection.
- Alcohol drinkers were slightly less likely to be possibly depressed. That finding needs more clarification and may be due to confounders.
C_TEXTBOX | neurology |
10.1101/2021.02.02.21250817 | Effective subthalamic and pallidal deep brain stimulation - are we modulating the same network? | The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinsons disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common network. To test this hypothesis, we calculated connectivity profiles seeding from deep brain stimulation electrodes in 94 patients that underwent subthalamic treatment and 28 patients with pallidal treatment based on a normative connectome atlas calculated from 1,000 healthy subjects. In each cohort, we calculated connectivity profiles that were associated with optimal clinical improvements. The two maps showed striking similarity and were able to cross-predict outcomes in the respective other cohort (R = 0.38 at p < 0.001 & R = 0.35 at p = 0.027). Next, we calculated an agreement map which retained regions common of both target sites. Crucially, this map was able to explain an additional amount of variance in clinical improvements of either cohort when compared to the maps calculated on the two cohorts alone. Finally, we tested profiles and predictive utility of connectivity maps calculated from different motor symptom subscores with a specific focus on bradykinesia and rigidity. While our study is based on retrospective data and indirect connectivity metrics, it delivers empirical data to support the hypothesis of a largely overlapping network associated with effective deep brain stimulation in Parkinsons disease irrespective of the specific target. | neurology |
10.1101/2021.02.02.21251017 | Home Food Procurement Impacts Food Security and Diet Quality during COVID-19 | BackgroundHome food procurement (HFP) (i.e. gardening, fishing, foraging, hunting, backyard livestock and canning) have historically been important ways that people obtain food. Recently, some HFP activities have grown (e.g. gardening), while other activities (e.g. hunting) have become less common in the United States. Anecdotally, COVID-19 has sparked an increase in HFP evidenced by increased hunting licenses and shortages in seeds and canning supplies. HFP may have positive benefits for food security and diet quality, though research beyond gardening is especially limited in high-income countries.
MethodsWe examine HFP activities before and since the COVID-19 pandemic, and their relationship to food security and dietary quality using multivariable logit models and matching analysis with a statewide representative survey (n=600) of residents of Vermont, United States.
ResultsWe find 29% of respondent households classified as food insecure since COVID-19, and more prevalence among those experiencing a negative job change since COVID-19, households earning less than $50,000 annually, Hispanic and multi-race respondents. Forty-two percent of respondents engaged in HFP activities; the majority of those gardened, and more than half pursued HFP activities more intensely than before the pandemic. HFP was more common among food insecure households, who were more likely to fish, forage, hunt and have backyard livestock. Respondents who were food insecure, Black, Indigenous, People of Color and/or Hispanic, those with a negative job disruption, and larger households all had greater odds of increased intensity of HFP since COVID-19. HFP were significantly associated with eating greater amounts of fruits and vegetables, especially if gardening and canning, while respondents hunting or having backyard livestock were significantly more likely to have higher red meat intake.
ConclusionOverall, these results suggest that HFP activities have increased since the start of the COVID-19 pandemic, and may be an important safety net for food insecure households, and provide diet quality impacts. Long-term, HFP activities may have important food security and diet quality impacts, as well as conservation implications, which should be more thoroughly explored. Regardless, the increased interest and intensity of HFP demonstrates multiple opportunities for educational and outreach efforts. | nutrition |
10.1101/2021.02.01.21250943 | Seroprevalence of SARS-CoV-2 during pregnancy and associated outcomes: results from an ongoing prospective cohort study, New York City | BackgroundIn May-July 2020 in the New York City area, up to 16% of pregnant women had reportedly been infected with SARS-CoV-2. Prior studies found associations between SARS-CoV-2 infection during pregnancy and certain adverse outcomes (e.g., preterm birth, cesarean delivery). These studies relied on reverse transcription polymerase chain reaction (RT-PCR) testing to establish SARS-CoV-2 infection. This led to overrepresentation of symptomatic or acutely ill cases in scientific studies.
ObjectiveTo expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology and stage of infection, by using serological tests to measure IgG antibody levels.
Study DesignThe Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant women receiving obstetrical care at the Mount Sinai Hospital and Mount Sinai West Hospital from April 20, 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before August 15, 2020. Blood was drawn as part of routine clinical care; for each woman, we tested the latest sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labor and delivery. Pregnancy outcomes of interest (i.e., gestational age at delivery, birth weight, mode of delivery, Apgar score, ICU/NICU admission, and neonatal hospital length of stay) and covariates were extracted from electronic medical records. Among all Generation C participants who had given birth by August 15, 2020 (n=708), we established the SARS-CoV-2 seroprevalence. Excluding women who tested RT-PCR positive at delivery, we conducted crude and adjusted linear and logistic regression models to compare antibody positive women without RT-PCR positivity at delivery with antibody negative women without RT-PCR positivity at delivery. We stratified analyses by race/ethnicity to examine potential effect modification.
ResultsThe SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (n=116, 95% CI 13.7-19.3). Twelve women (1.7%) were SARS-CoV-2 RT-PCR positive at delivery (11 of these women were seropositive). Seropositive women were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative women. SARS-CoV-2 seropositivity without RT-PCR positivity at delivery was associated with decreased odds of caesarean delivery (aOR 0.48, 95%CI 0.27; 0.84) compared with seronegative women without RT-PCR positivity at delivery. Stratified by race/ethnicity, the association between seropositivity and decreased odds of caesarean delivery remained for non-Hispanic Black/African-American and Hispanic women, but not for non-Hispanic White women. No other pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity.
ConclusionSeropositivity for SARS-CoV-2 without RT-PCR positivity at delivery, suggesting that infection occurred earlier during pregnancy, was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample of women from New York City. While non-Hispanic Black and Latina women in our cohort had a higher rate of SARS-CoV-2 seropositivity compared with non-Hispanic White women, we found no increase in adverse maternal or neonatal outcomes among these groups due to infection. | obstetrics and gynecology |
10.1101/2021.02.01.21250952 | Wastewater surveillance for SARS-CoV-2 on college campuses: Initial efforts, lessons learned and research needs | BackgroundWastewater surveillance for SARS-CoV-2 is an emerging approach to help identify the risk of a COVID-19 outbreak. This tool can contribute to public health surveillance at both community (wastewater treatment system) and institutional (e.g., colleges, prisons, nursing homes) scales.
ObjectivesThis research aims to understand the successes, challenges, and lessons learned from initial wastewater surveillance efforts at colleges and university systems to inform future research, development and implementation.
MethodsThis paper presents the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period. We describe the broad range of approaches, findings, resource needs, and lessons learned from these initial efforts. These institutions range in size, social and political geographies, and include both public and private institutions.
DiscussionOur analysis suggests that wastewater monitoring at colleges requires consideration of information needs, local sewage infrastructure, resources for sampling and analysis, college and community dynamics, approaches to interpretation and communication of results, and follow-up actions. Most colleges reported that a learning process of experimentation, evaluation, and adaptation was key to progress. This process requires ongoing collaboration among diverse stakeholders including decision-makers, researchers, faculty, facilities staff, students, and community members. | occupational and environmental health |
10.1101/2021.02.01.21250963 | Risk factors for SARS-CoV-2 infection among farmworkers in Monterey County, California | ImportanceEssential workers in agriculture and food production have been severely affected by the ongoing COVID-19 pandemic.
ObjectiveTo identify risk factors associated with SARS-CoV-2 shedding and antibody response in farmworkers in California.
DesignThis cross-sectional study collected survey data and determined current SARS-CoV-2 shedding and seropositivity among 1,107 farmworkers in Californias Salinas Valley from 16 July to 30 November 2020.
SettingFarmworkers receiving transcription-mediated amplification (TMA) tests for SARS-CoV-2 infection at federally qualified community clinics and community sites were invited to participate in our study.
ParticipantsIndividuals were eligible if they were not pregnant, [≥]18 years old, had conducted farm work since the pandemic started, and were proficient in English or Spanish.
ExposuresSociodemographic, household, community, and workplace characteristics.
Main Outcome(s) and Measure(s)Current (as indicated by TMA positivity) and historical (as indicated by IgG seropositivity) SARS-CoV-2 infection.
ResultsMost farmworkers enrolled in the study were born in Mexico, had primary school or lower levels of educational attainment, and were overweight or obese. Current SARS-CoV-2 shedding was associated in multivariable analyses with attained only primary or lower educational levels (RR=1.32; 95% CI: 0.99-1.76), speaking an indigenous language at home (RR=1.30; 0.97-1.73), working in the fields (RR=1.60; 1.03-2.50), and exposure to known or suspected COVID-19 case at home (RR=2.98; 2.06-4.32) or in the workplace (RR=1.59; 1.18-2.14). Antibody detection was associated with residential exposures including living in crowded housing (RR=1.23; 0.98-1.53), with children (RR=1.40; 1.1-1.76) or unrelated roommates (RR=1.40; 1.19-1.64), and with a known or suspected COVID-19 case (RR=1.59; 1.13-2.24). Those who were obese (RR=1.65; 1.01-2.70) or diabetic (RR=1.31; 0.98-1.75) were also more likely to be seropositive. Farmworkers who lived in rural areas other than Greenfield (RR=0.58; 0.47-0.71), worked indoors (RR=0.68; 0.61-0.77), or whose employer provided them with information on how to protect themselves at work (RR=0.59; 0.40-0.86) had lower risk of prior infection.
Conclusions and RelevanceOur findings suggest both residential and workplace exposures are contributing to SARS-CoV-2 infection among farmworkers in California. Urgent distribution of COVID-19 vaccines is warranted given this populations increased risk of infection and the essential nature of their work. | occupational and environmental health |
10.1101/2021.02.02.21250330 | DEFINING THE DIVERSITY OF HNRNPA1 MUTATIONS IN CLINICAL PHENOTYPE AND PATHOMECHANISM | Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form ribonucleoproteins. hnRNPs are a major subclass of evolutionarily conserved RBPs that are primarily concentrated in the nucleus and are heavily involved in pre-mRNA splicing, mRNA stability and transcriptional/translational regulation. During times of stress, standard translational programming is interrupted, and hnRNPs, mRNA, and other RBPs condense in the cytoplasm, forming liquid-liquid phase separated (LLPS) membraneless organelles termed stress granules (SGs). SGs are central to the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). hnRNPs and other RBPs are critical components of SGs. Indeed, the link between SGs, hnRNPs, and neurodegenerative diseases has been established by the identification of additional mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, each of which can directly lead to ALS, IBM and other related neurodegenerative diseases. Here, we report and characterize four novel HNRNPA1 mutations and two known HNRNPA1 mutations, previously reported as being causal for ALS, in a broad spectrum of patients with hereditary motor neuropathy (HMN), ALS, and myopathy. Our results show the different effects of mutations on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics, indicating the possibility of different underlying pathomechanisms for HNRNPA1 mutations with a possible link to the clinical phenotypes. | genetic and genomic medicine |
10.1101/2021.02.02.21250796 | Scientists' opinion, attitudes, and consensus towards immunity passports | ObjectivesWe measured attitudes towards "immunity passports" in the context of COVID-19 of a large sample of scientists. Consensus of scientists opinions on a different aspect of immunity passports was assessed.
MethodsWe designed and implemented a survey to capture what scientists from around the world and different scientific background think about immunity certification. The survey was sent to the corresponding authors of scholarly articles published in the last five years in the top 20-ranked journals in each of the 27 subject areas between May and June 2020. Responses from 12,738 scientists were captured, and their distribution was tabulated by participants in health science and other fields. Consensus of responses was calculated using a variant of Shannon Entropy, made suitable for the ordinal response variables.
ResultsHalf of the scientists surveyed, regardless of academic background agree that a potential immunity passport program will be good for public health (50.2%) and the economy (54.4%), with 19.1% and 15.4% of participants disagree, respectively. A significant proportion of scientists raised concerns about immunity certification over fairness to others (36.5%) and social inequality (45.5%). There is little consensus in the different aspects of immunity passport among scientists. Overall, scientists with health background hold a more conservative view towards immunity certification.
ConclusionsOur findings suggest a lack of general agreement regarding the potential health and economic benefits, societal costs, and ethical issues of an immunity certification program within the scientific community. Given the relevant and important implications of immunity passport due to the increasing vaccine availability and efficacy, more attention should be given to the discussion of the design and implementation of immunity certification program.
Strengths and limitations of this studyO_LIFirst cross-disciplinary survey with a large and international sample size that enables mapping of scientists opinions and attitudes towards COVID-19 immunity certificates.
C_LIO_LIFrom the survey responses, we measured, reported, and compared the levels of consensus of scientists between health-related and non-health-related discipline.
C_LIO_LIResponse rate and sample representativeness are moderate.
C_LI | health policy |
10.1101/2021.02.01.21250775 | Single-cell spatial analysis of tumor immune architecture in diffuse large B cell lymphoma | Multiplexed immune cell profiling of the tumor microenvironment (TME) in cancer has improved our understanding of cancer immunology, but complex spatial analyses of tumor-immune interactions in lymphoma are lacking. Here we used imaging mass cytometry (IMC) on 33 cases of diffuse large B cell lymphoma (DLBCL) to characterize tumor and immune cell architecture and correlate it to clinicopathological features such as cell of origin, gene mutations, and responsiveness to chemotherapy. To understand the poor response of DLBCL to immune check point inhibitors (ICI), we compared our results to IMC data from Hodgkin lymphoma (HL), a cancer highly responsive to ICI, and observed differences in the expression of PD-L1, PD-1, and TIM-3. We created a spatial classification of tumor cells and identified sub-regions of immune activation, immune suppression, and immune exclusion within the topology of DLBCL. Finally, the spatial analysis allowed us to identify markers such as CXCR3, which are associated with penetration of immune cells into immune desert regions, with important implications for engineered cellular therapies.
SIGNIFICANCEThis is the first study to integrate tumor mutational profiling, cell of origin classification, and multiplexed immuno-phenotyping of the TME into a spatial analysis of DLBCL at the single cell level. We demonstrate that, far from being histo-pathologically monotonous, DLBCL has a complex tumor architecture, and that changes in tumor topology can be correlated with clinically relevant features. This analysis identifies candidate biomarkers and therapeutic targets such as TIM-3, CCR4, and CXCR3 that are relevant for combination treatment strategies in immuno-oncology and cellular therapies such as CAR-T cells. | hematology |
10.1101/2021.02.02.21250758 | Timing of Convalescent plasma administration and 28-day mortality for COVID-19 pneumonia. | Convalescent plasma administration (CPA) is widely used to treat Covid-19, but its effectiveness remains controversial. Here we report the results of an Expanded Access Program of CPA in the province of Buenos Aires, Argentina. We evaluated the relationship between the timing of CPA and 28-day mortality in 4719 hospitalized patients with COVID-19 pneumonia. Early ([≤]3 days from admission) CPA was associated to decreased mortality in patients in the general ward and in the Intensive Care Unit not requiring mechanical ventilation. This suggests that the favorable effect of CPA might be related both to disease acuity and to the therapeutic window. | hematology |
10.1101/2021.02.02.21251008 | Modelling the Impact of Prevention and Treatment Interventions on HIV and Hepatitis C Virus Transmission Among People Who Inject Drugs in Kenya | BackgroundPeople who inject drugs (PWID) in Kenya have a high prevalence of HIV (14-26%) and HCV (11-36%). Needle and syringe programmes (NSP) and antiretroviral therapy (ART) have high coverage among PWID, while HCV treatment and opioid substitution therapy (OST) access is low.
MethodsA dynamic model of HIV (sexual and injecting-related) and HCV (injecting-related) transmission among PWID was calibrated using Bayesian methods to data from Nairobi and the Coastal region. We projected the impact of existing coverage levels of interventions (ART: 64-66%; OST: 4-7%; NSP: 54-56%) in each setting, and the impact over 2020-2030 of increasing the coverage of OST (50%) and NSP (75%; full HR), ART (UNAIDS 90-90-90 target), HCV treatment (1000 over 5 years), and reducing HIV sexual risk by 75%. We estimated HCV treatment levels needed to reduce HCV incidence by 90% with or without full HR.
FindingsSince 2013, HR has averted 15.1-20.6% (range in medians across settings) of HIV infections and 29.0-31.6% of HCV infections across Nairobi and the Coastal region, with most impact being due to NSP. Conversely, ART has only averted <5% of HIV infections since 2004 because of sub-optimal viral suppression (28-48%). Going forward, Full HR and ART could reduce HIV incidence by 58.2-62.0% and HCV incidence by 62.6-81.6% by 2030 across these settings. If sexual risk is also reduced, HIV incidence would reduce by 77.1-81.4%. Alongside full HR, treating 896 PWID over 2020-2025 could reduce HCV incidence by 90% by 2030.
InterpretationExisting interventions have had moderate impact on HIV and HCV transmission in Kenya, but may have substantial impact if scaled-up. However, to achieve HIV and HCV elimination, reductions in sexual risk are needed and a scale-up in HCV treatment.
FundingGlobal Fund, MDM | hiv aids |
10.1101/2021.02.02.21251020 | SEVERE COVID-19 IS MARKED BY DYSREGULATED SERUM LEVELS OF CARBOXYPEPTIDASE A3 AND SEROTONIN | The immune response plays a critical role in the pathophysiology of SARS-CoV-2 infection ranging from protection to tissue damage. This is observed in the development of acute respiratory distress syndrome when elevated levels of inflammatory cytokines are detected. Several cells of the immune response are implied in this dysregulated immune response including innate immune cells and T and B cell lymphocytes. Mast cells are abundant resident cells of the respiratory tract, able to rapidly release different inflammatory mediators following stimulation. Recently, mast cells have been associated with tissue damage during viral infections, but little is known about their role in SARS-CoV-2 infection. In this study we examined the profile of mast cell activation markers in the serum of COVID-19 patients. We noticed that SARS-CoV-2 infected patients showed increased carboxypeptidase A3 (CPA3), and decreased serotonin levels in their serum. CPA3 levels correlated with C-reactive protein, the number of circulating neutrophils and quick SOFA. CPA3 in serum was a good biomarker for identifying severe COVID-19 patients, while serotonin was a good predictor of SARS-CoV-2 infection. In summary, our results show that serum CPA3 and serotonin levels are relevant biomarkers during SARS-CoV-2 infection, suggesting that mast cells are relevant players in the inflammatory response in COVID-19, might represent targets for therapeutic intervention. | infectious diseases |
10.1101/2021.02.02.21250960 | Colchicine use in patients with COVID-19: a systematic review and meta-analysis | IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.
MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.
ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality - HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not - OR of 0.26 (95% CI: 0.06, 1.09).
ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care. | infectious diseases |
10.1101/2021.02.02.21250960 | Colchicine use in patients with COVID-19: a systematic review and meta-analysis | IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.
MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.
ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality - HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not - OR of 0.26 (95% CI: 0.06, 1.09).
ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care. | infectious diseases |
10.1101/2021.02.02.21250960 | Colchicine use in patients with COVID-19: a systematic review and meta-analysis | IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.
MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.
ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality - HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not - OR of 0.26 (95% CI: 0.06, 1.09).
ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care. | infectious diseases |
10.1101/2021.02.02.21250960 | Colchicine use in patients with COVID-19: a systematic review and meta-analysis | IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.
MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.
ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality - HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not - OR of 0.26 (95% CI: 0.06, 1.09).
ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care. | infectious diseases |
10.1101/2021.02.01.21250846 | Deleterious effects of SARS-CoV-2 infection on human pancreatic cells | COVID-19 pandemic has infected more than 46 million people worldwide and caused more than 1.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, SARS-CoV-2 is capable of infecting iPSC-derived pancreatic cells, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key inflammatory cytokine, CXCL12, known to be involved in pancreas dysfunction. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas is confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate for the first time that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening. | infectious diseases |
10.1101/2021.02.01.21250973 | A Remote Household-Based Approach to Influenza Self-Testing and Antiviral Treatment | BackgroundHouseholds represent important settings for transmission of influenza and other respiratory viruses. Current influenza diagnosis and treatment relies upon patient visits to healthcare facilities, which may lead to under-diagnosis and treatment delays. This study aimed to assess the feasibility of an at-home approach to influenza diagnosis and treatment via home testing, telehealth care, and rapid antiviral home delivery.
MethodsWe conducted a pilot interventional study of remote influenza diagnosis and treatment in Seattle-area households with children during the 2019-2020 influenza season using pre-positioned nasal swabs and home influenza tests. Home monitoring for respiratory symptoms occurred weekly; if symptoms were reported within 48 hours of onset, participants collected mid-nasal swabs and used a rapid home-based influenza immunoassay. An additional home-collected swab was returned to a laboratory for confirmatory influenza RT-PCR testing. Baloxavir antiviral treatment was prescribed and delivered to symptomatic and age-eligible participants, following a telehealth encounter.
Results124 households comprising 481 individuals self-monitored for respiratory symptoms, with 58 home tests administered. 12 home tests were positive for influenza, of which 8 were true positives confirmed by RT-PCR. The sensitivity and specificity of the home influenza test was 72.7% and 96.2%, respectively. There were 8 home deliveries of baloxavir, with 7 (87.5%) occurring within 3 hours of prescription, and all within 48 hours of symptom onset.
ConclusionsWe demonstrate the feasibility of self-testing combined with rapid home delivery of influenza antiviral treatment. This approach may be an important control strategy for influenza epidemics and pandemics.
SummaryIn this pilot study, 481 individuals self-monitored for respiratory symptoms. Of 58 home tests, 12 were influenza-positive. There were 8 baloxavir home deliveries within 48 hours of illness onset. A home-based approach to influenza diagnosis and treatment could be feasible. | infectious diseases |
10.1101/2021.02.02.21250989 | Short report: Ethnicity and COVID-19 death in the early part of the COVID-19 second wave in England: an analysis of OpenSAFELY data from 1st September to 9th November 2020 | Black and minority ethnic groups were at raised risk of dying from COVID-19 during the first few months of the COVID-19 epidemic in England. We aimed to investigate whether ethnic inequalities in COVID-19 deaths were similar in the more recent "second wave" of the epidemic. Working on behalf of NHS England, we used primary care and linked ONS mortality data within the OpenSAFELY platform. All adults in the database at 1st September 2020 and with at least 1 year of prior follow-up and a record of ethnicity were included. The outcome was COVID-19-related death (death with COVID-19 listed as a cause of death on the death certificate). Follow-up was to 9th November 2020. Hazard ratios for ethnicity were calculated using Cox regression models adjusted for age and sex, and then further adjusted for deprivation. 13,223,154 people were included. During the study period, people of South Asian ethnicity were at higher risk of death due to COVID-19 than white people after adjusting for age and sex (HR = 3.47, 95% CI 2.99-4.03); the association attenuated somewhat on further adjustment for index of multiple deprivation (HR = 2.86, 2.46-3.33, Table 2). In contrast with the first wave of the epidemic, we found little evidence of a raised risk in black or other ethnic groups compared to white (HR for black vs white = 1.28, 0.87-1.88 adjusted for age and sex; and 1.01, 0.69-1.49 further adjusted for deprivation). Our findings suggest that ethnic inequalities in the risk of dying COVID-19-related death have changed between the first and early second wave of the epidemic in England.
O_TBL View this table:
[email protected]@1a8a141org.highwire.dtl.DTLVardef@1f2de56org.highwire.dtl.DTLVardef@1e2f9b8org.highwire.dtl.DTLVardef@78bfcc_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 2:C_FLOATNO O_TABLECAPTIONAssociation between ethnicity and COVID-19 death 1st Sept - 9th Nov 2020
C_TABLECAPTION C_TBL | infectious diseases |
10.1101/2021.02.02.21251016 | Adult vaccination in Brazil: a cross-sectional survey on physicians prescription habits | OBJECTIVETo characterize adult and older adult vaccination practices of physicians, from various medical specialties, in Brazil; identify barriers influencing prescription of vaccines to these populations, and evaluate the physicians knowledge on routinely prescribed vaccines.
METHODSCross-sectional survey conducted in Brazil between June-August 2018. Eligible physicians included those from general practice/family medicine, geriatrics, cardiology, gynecology, endocrinology, infectious disease and pulmonology. The surveys questions addressed the physicians prescription habits, sociodemographic and clinical practice characteristics, barriers to vaccines prescription, and physicians knowledge regarding routinely prescribed vaccines. The study focused on the vaccines recommended by the Brazilian Society of Immunization (SBIm) for adults and older adults (years 2017-2018). Study sample was stratified according to the number of physicians per specialty and Brazilian region.
RESULTSA total of 1068 surveys were completed. The vaccines prescribed by the highest proportions of physicians were Influenza (>90% of physicians for adults and older adults), Hepatitis B (adults: 87%; older adults: 59%) and Yellow Fever (adults: 77.7%; older adults: 58.5%). Underprescription was reported by less than 20% of prescribing physicians for all adult and older adult recommended vaccines. The most common barriers to vaccination were the high vaccine cost, lack of time during appointments and lack of patient interest. Knowledge on target populations, dosage schedule and availability in the Unified Public Health System (SUS) was generally low.
CONCLUSIONSThe results showed a considerable variability of prescribing habits across recommended vaccines. Although most prescribing physicians seem to be aware of the importance of adult and older adult vaccination, knowledge deficits on vaccines target populations, dosage schedule and availability in the SUS may hamper their ability to prescribe vaccines to all patients with an indication. | infectious diseases |
10.1101/2021.02.02.21251016 | Adult vaccination in Brazil: a cross-sectional survey on physicians prescription habits | OBJECTIVETo characterize adult and older adult vaccination practices of physicians, from various medical specialties, in Brazil; identify barriers influencing prescription of vaccines to these populations, and evaluate the physicians knowledge on routinely prescribed vaccines.
METHODSCross-sectional survey conducted in Brazil between June-August 2018. Eligible physicians included those from general practice/family medicine, geriatrics, cardiology, gynecology, endocrinology, infectious disease and pulmonology. The surveys questions addressed the physicians prescription habits, sociodemographic and clinical practice characteristics, barriers to vaccines prescription, and physicians knowledge regarding routinely prescribed vaccines. The study focused on the vaccines recommended by the Brazilian Society of Immunization (SBIm) for adults and older adults (years 2017-2018). Study sample was stratified according to the number of physicians per specialty and Brazilian region.
RESULTSA total of 1068 surveys were completed. The vaccines prescribed by the highest proportions of physicians were Influenza (>90% of physicians for adults and older adults), Hepatitis B (adults: 87%; older adults: 59%) and Yellow Fever (adults: 77.7%; older adults: 58.5%). Underprescription was reported by less than 20% of prescribing physicians for all adult and older adult recommended vaccines. The most common barriers to vaccination were the high vaccine cost, lack of time during appointments and lack of patient interest. Knowledge on target populations, dosage schedule and availability in the Unified Public Health System (SUS) was generally low.
CONCLUSIONSThe results showed a considerable variability of prescribing habits across recommended vaccines. Although most prescribing physicians seem to be aware of the importance of adult and older adult vaccination, knowledge deficits on vaccines target populations, dosage schedule and availability in the SUS may hamper their ability to prescribe vaccines to all patients with an indication. | infectious diseases |
10.1101/2021.02.02.21250910 | Elevated mucosal antibody responses against SARS-CoV-2 are correlated with lower viral load and faster decrease in systemic COVID-19 symptoms | Mucosal antibodies play a key role in protection against SARS-CoV-2 exposure, but their role during primary infection is not well understood. We assessed mucosal antibody responses during primary infection with SARS-CoV-2 and examined their relationship with viral load and clinical symptoms. Elevated mucosal IgM was associated with lower viral load. RBD and viral spike protein-specific mucosal antibodies were correlated with decreases in systemic symptoms, while older age was associated with an increase in respiratory symptoms. Up to 42% of household contacts developed SARS-CoV-2-specific mucosal antibodies, including children, indicating high transmission rates within households in which children might play an important role. | infectious diseases |
10.1101/2021.02.02.21250985 | Rapid vaccination and early reactive partial lockdown will minimize deaths from emerging highly contagious SARS-CoV-2 variants | The goals of SARS-CoV-2 vaccination programs are to maximally reduce cases and deaths, and to limit the amount of time required under lockdown. Using a mathematical model calibrated to data from King County Washington but generalizable across states, we simulated multiple scenarios with different vaccine efficacy profiles, vaccination rates, and case thresholds for triggering and relaxing partial lockdowns. We assumed that a contagious variant is currently present at low levels. In all scenarios, it rapidly becomes dominant by early summer. Low case thresholds for triggering partial lockdowns during current and future waves of infection strongly predict lower total numbers of COVID-19 infections, hospitalizations and deaths in 2021. However, in regions with relatively higher current seroprevalence, there is a predicted delay in onset of a subsequent surge in new variant infections. For all vaccine efficacy profiles, increasing vaccination rate lowers the total number of infections and deaths, as well as the total number of days under partial lockdown. Due to variable current estimates of emerging variant infectiousness, vaccine efficacy against these variants, vaccine refusal, and future adherence to masking and physical distancing, we project considerable uncertainty regarding the timing and intensity of subsequent waves of infection. Nevertheless, under all plausible scenarios, rapid vaccination and early implementation of partial lockdown are the two most critical variables to save the greatest number of lives. | infectious diseases |
10.1101/2021.02.01.21250839 | Extremely high SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK | BackgroundEthnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand how COVID-19 had spread within this community.
MethodsWe performed a household-focused cross-sectional SARS-CoV-2 serosurvey specific to three antigen targets. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and gender. We used random-effects models to identify factors associated with infection and antibody titres.
FindingsA total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres.
InterpretationIn this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required.
FundingThis work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust. The funders had no role in the design, conduct or analysis of the study or the decision to publish. The authors have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Research In ContextO_ST_ABSEvidence before the studyC_ST_ABSIn January 2020, we searched PubMed for articles on rates of SARS-CoV-2 infection amongst ethnic minority groups and amongst the Jewish population. Search teams included "COVID-19", "SARS-CoV-2", seroprevalence, "ethnic minority", and "Jewish" with no language restrictions. We also searched UK government documents on SARS-CoV-2 infection amongst minority groups. By January 2020, a large number of authors had reported that ethnic minority groups experienced higher numbers of cases and increased hospitalisations due to COVID-19. A small number of articles provided evidence that strictly-Orthodox Jewish populations had experienced a high rate of SARS-CoV-2 infection but extremely limited data was available on overall population level rates of infection amongst specific ethnic minority population groups. There was also extremely limited data on rates of infection amongst young children from ethnic minority groups.
Added value of the studyWe report findings from a population representative, household survey of SARS-CoV-2 infection amongst a UK strictly Orthodox Jewish population. We demonstrate an extremely high seroprevalence rate of SARS-CoV-2 in this population which is more than five times the estimated seroprevalence nationally and five times the estimated seroprevalence in London. In addition the large number of children in our survey, reflective of the underlying population structure, allows us to demonstrate that in this setting there is a significant burden of disease in all age groups with secondary school aged children having an equivalent seroprevalence to adults.
Implications of the available evidenceOur data provide clear evidence of the markedly disproportionate impact of SARS-CoV-2 in minority populations. In this setting infection occurs at high rates across all age groups including pre-school, primary school and secondary school-age children. Contextually appropriate measures to specifically reduce the impact of SARS-CoV-2 amongst minority populations are urgently required. | infectious diseases |
10.1101/2021.02.02.21250995 | Effect of co-infection with parasites on severity of COVID-19 | BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a spectrum of clinical presentations. The effect of co-infection with parasites on the clinical features of COVID-19 is unknown.
MethodsWe prospectively enrolled consecutive COVID-19 patients and screened them for intestinal parasitic infections. Patients were followed during hospitalization for clinical outcomes. Patients with parasitic co-infection were compared to those without parasitic co-infection. The primary outcome was the proportion of COVID-19 patients who developed severe disease. Factors associated with the development of severe disease were determined by logistic regression.
ResultsA total of 515 patients with PCR-confirmed SARS-CoV-2 infection were screened for intestinal parasites, of whom 267 (51.8%) were co-infected with one or more parasites. Parasitic co-infection correlated inversely with COVID-19 severity. Severe COVID-19 was significantly higher in patients without parasites [47/248 (19.0%, CI: 14.52-24.35)] than in those with parasites [21/267 (7.9%, CI: 5.17-11.79)]; p<0.0001. There was a significantly higher proportion of patients who developed severe COVID-19 in the non-protozoa group [56/369 (15.2%, CI: 11.85-19.23)] as compared to the protozoa group [12/146 (8.2%, CI: 4.70-14.00)]; p=0.036. Significant higher proportion of the patients presented at baseline with severe COVID-19 in the helminth negative group [57/341 (16.7%, CI: 13.10 - 21.08)] than in the group with pre-existing helminth infection [11/174 (6.3%, CI: 3.51 - 11.11)]; p=0.001. In addition, after adjustment for age and presence of comorbidities, COVID-19 patients with any parasite co-infection [aOR 0.41 (95% CI: 0.22-0.77); p=0.006], or with protozoa co-infection [aOR 0.45 (95% CI: 0.21-0.98); p=0.044] as well as those with helminth co-infection [aOR 0.37 (95% CI: 0.17-0.80); p=0.011] had lower probability of developing severe COVID-19 compared with those without parasite, protozoa or helminth co-infection.
ConclusionOur results suggest that co-infection with parasitic co-infection appears to be associated with reduced COVID-19 severity. The results suggest that parasite-driven immunomodulatory responses may mute hyperinflammation associated with severe COVID-19. | infectious diseases |
10.1101/2021.02.01.21250972 | The role of the SwissCovid digital contact tracing app during the pandemic response: results for the Canton of Zurich | ImportanceDigital proximity tracing (DPT) apps were released in several countries to help interrupt SARS-CoV-2 transmission chains in the population. However, the impact of DPT on pandemic mitigation still remains to be demonstrated.
ObjectiveTo estimate key populations and performance indicators along the DPT app notification cascade in a clearly defined regional (Canton of Zurich, using all of Switzerland as a comparison) and temporal context (September/October 2020).
DesignPublicly available administrative and research data, including key DPT performance indicators, SARS-CoV-2 testing statistics, infoline call statistics, and observational study data, were compiled. A model of the DPT notification cascade was developed and key performance indicators for DPT processes were defined. Subpopulation sizes at each cascade step were estimated using data triangulation. Resulting estimates were systematically checked for internal consistency and consistency with other up- or downstream estimates in the cascade. Stochastic simulations were performed to explore robustness of results.
ResultsFor the Canton of Zurich, we estimate that 537 app users received a positive SARS-CoV-2 test in September 2020, of whom 324 received and entered a CovidCode. This triggered an app notification for an estimated 1374 proximity contacts and led to 722 infoline calls. In total, 170 callers received a quarantine recommendation, and 30 app users tested positive for SARS-CoV-2 after an app notification, reflecting a performance above the national level.
Based on this quantification, key performance indicators were evaluated. For September 2020, these analyses suggest that SwissCovid triggered quarantine recommendations in the equivalent of 5% of all exposed contacts placed in quarantine by manual contact tracing. Per 11 CovidCodes entered in the app, we estimate that almost 1 contact tested positive for SARS-CoV-2 upon app notification.
However, longitudinal indicator analyses demonstrate bottlenecks in the notification cascade, as capacity limits were reached due to large increases in SARS-CoV-2 incidence in October 2020.
ConclusionAlthough requiring confirmation, our estimations on the number of notified proximity contacts receiving quarantine recommendations or testing positive after notification suggest relevant contributions to mitigating the pandemic. Increasing SwissCovid app uptake and improving notification cascade performance may further enhance its impact.
Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the real-life impact of Digital proximity tracing (DPT) apps on interrupting SARS-CoV-2 transmission chains?
FindingsThis data-informed simulation study found that, in the canton of Zurich, the number of app notified persons receiving a quarantine recommendation corresponds to the equivalent of up to 5% of all mandatory quarantined contacts identified by manual contact tracing. Furthermore, about 1 in 11 notification triggers led to SARS-CoV-2 testing of an exposed proximity contact who was consecutively tested positive.
MeaningDPT apps exert a measurable impact that will further scale as more persons use the apps. | infectious diseases |
10.1101/2021.02.01.21250933 | Identifying Heart Failure from Electronic Health Records: A Systematic Evidence Review | BackgroundHeart failure (HF) is a complex syndrome associated with significant morbidity and healthcare costs. Electronic health records (EHRs) are widely used to identify patients with HF and other phenotypes. Despite widespread use of EHRs for phenotype algorithm development, it is unclear if the characteristics of identified populations mirror those of clinically observed patients and reflect the known spectrum of HF phenotypes.
MethodsWe performed a subanalysis within a larger systematic evidence review to assess the different methods used for HF algorithm development and their application to research and clinical care. We queried PubMed for articles published up to November 2020. Out of 318 studies screened, 25 articles were included for primary analysis and 15 studies using only International Classification of Diseases (ICD) codes were evaluated for secondary analysis. Results are reported descriptively.
ResultsHF algorithms were most often developed at academic medical centers and the V.A. One health system was responsible for 8 of 10 HF algorithm studies. HF and congestive HF were the most frequent phenotypes observed and less frequently, specific HF subtypes and acute HF. Diagnoses were the most common data type used to identify HF patients and echocardiography was the second most frequent. The majority of studies used rule-based methods to develop their algorithm. Few studies used regression or machine learning methods to identify HF patients. Validation of algorithms varied considerably: only 52.9% of HF and 44.4% of HF subtype algorithms were validated, but 75% of acute HF algorithms were. Demographics of any study population were reported in 68% of algorithm studies and 53% of ICD-only studies. Fewer than half reported demographics of their HF algorithm-identified population. Of those reporting, most identified majority male (>50%) populations, including both algorithms for HF with preserved ejection fraction.
ConclusionThere is significant heterogeneity in phenotyping methodologies used to develop HF algorithms using EHRs. Validation of algorithms is inconsistent but largely relies on manual review of patient records. The concentration of algorithm development at one or two sites may reduce potential generalizability of these algorithms to identify HF patients at non-academic medical centers and in populations from underrepresented regions. Differences between the reported demographics of algorithm-identified HF populations those expected based on HF epidemiology suggest that current algorithms do not reflect the full spectrum of HF patient populations. | cardiovascular medicine |
10.1101/2021.02.02.21251010 | Periodontal inflammation mediates the link between homocysteine and high blood pressure | BackgroundHere, we assess the association between Hcy serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES).
MethodsWe included 4,021 participants with a periodontal examination, medical self-reported data, BP and blood samples to determine complete blood count, C-reactive protein (CRP) and Hcy levels. We then calculated the periodontal inflamed surface area (PISA) and the periodontal epithelial surface area (PESA). Multivariable regression analysis explored the association between Hcy, periodontal measures and blood pressure. Mediation analysis was performed to understand the effect of age on the association of periodontitis with BP. Mediation analysis assessed the effect of PISA and PESA in the link between Hcy and BP.
Results4,021 participants fulfilled the inclusion criteria. Hcy levels showed significant correlations with systolic BP, diastolic BP, PISA, PESA and age. PESA showed to be significantly associated with Hcy both for the crude and adjusted models (p<0.01), but not PISA (p>0.05). In the association of Hcy with systolic BP, PISA significantly mediated 17.4% and PESA 0.9%. In the association of Hcy with diastolic BP, PISA significantly mediated 16.3% and PESA 47.2%.
ConclusionsThis report shows that Hcy and periodontitis are associated. Also, both PISA and PESA significantly mediated the association of Hcy with systolic BP and diastolic BP. Future studies shall deepen the mechanisms by which homocysteine levels increase in a clinical situation of periodontitis.
One-sentence summary describing the key finding(s) from the studyHomocysteine and periodontitis are associated. The periodontal inflamed and epithelial surface areas significantly mediate the association of homocysteine with systolic and diastolic blood pressures. | dentistry and oral medicine |
10.1101/2021.02.01.21250802 | Recognition of Diabetes in a Multi-ethnic Population: Results from a Nationally Representative Population-Based Study | BackgroundThe prevalence of diabetes is on the rise in developed countries. Yet discrepancies exist in reports regarding the level of knowledge of diabetes. This study evaluates the recognition of diabetes among residents in the Singapore population. Sociodemographic characteristics associated with the ability to correctly recognise diabetes were also examined.
MethodsThis was a nationwide cross-sectional vignette-based study. Data were collected from 2895 residents aged 18 years and above through face-to-face interviews, of which 436 are persons with diabetes. Descriptive statistics, chi-square tests, and binary logistic regression were used in the analyses.
ResultsIn total, 82.7% (2418/2895) of respondents recognised diabetes correctly. In adjusted models, correct recognition was significantly higher among respondents aged 35-49 years (OR, 1.85; 95% CI, 1.15 to 2.98; P= 0.01), 50-64 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.19 to 3.56; P= 0.01), ethnic Malays (OR, 1.39; 95% CI, 1.02 to 1.89; P= 0.04) (vs. Chinese) and persons with diagnosed diabetes (OR, 2.64; 95% CI, 1.38 to 5.08; P < 0.01). Being male (OR, 0.64; 95% CI, 0.46 to 0.90; P < 0.01), ethnic Others (OR, 0.59; 95% CI, 0.37 to 0.93; P < 0.01), and being unemployed (OR, 0.48; 95% CI, 0.25 to 0.92; P= 0.03), were significantly associated with poor recognition of diabetes.
ConclusionOverall public recognition of diabetes is high, but the significant gaps in knowledge in certain demographic groups are of concern. Public health interventions aimed at preventing and controlling diabetes should continue to target all members of the population with accurate and appropriate information. Ongoing efforts of diabetes awareness and educational programs need to be improved, particularly for young adults, males, and the unemployed. | endocrinology |
10.1101/2021.02.02.21250630 | First indication of the effect of COVID-19 vaccinations on the course of the COVID-19 outbreak in Israel | Concomitantly with rolling out its rapid COVID-19 vaccine program, Israel is experiencing its third, and so far largest, surge in morbidity. We aimed to estimate whether the high vaccine coverage among individuals aged over 60 years old creates an observable change in disease dynamics. Using observed and simulated data, we suggest that the shape of the outbreak as measured by daily new moderate and severe cases, and in particular of patients aged over 60, has changed because of vaccination, bringing the decline in new moderate and severe cases earlier than expected, by about a week. Our analyses is consistent with the assumption that vaccination lead to higher than 50% protection in preventing clinical disease and with at least some effectiveness in blocking transmission of elderly population, and supports the importance of prioritizing vulnerable population. This is the first indication of the effectivity of COVID-19 vaccine in changing the course of an ongoing pandemic outbreak.
One Sentence SummaryWe show, by data analysis and modelling of the dynamics of COVID-19 pandemic in Israel, that the current nationwide outbreak, that had up to 0.1% of the population confirmed daily, is clearly affected by the vaccination program, that reached a coverage of more than 80% among people [≥] 60 years old. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful adoption of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful adoption of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful adoption of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful adoption of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful adoption of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful adoption of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.02.21251022 | Quantifying meaningful usage of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona | ObjectiveTo measure meaningful, local exposure notification usage without in-app analytics.
MethodsWe surveyed app usage via case investigation interviews at the University of Arizona, with a focus on the period from September 9 to November 28, 2020, after automating the issuance of secure codes to verify positive test results. As independent validation, we compared the number of verification codes issued to the number of local cases.
ResultsForty six percent (286/628) of infected persons interviewed by university case investigators reported having the app, and 55% (157/286) of these app users shared their positive SARS-CoV-2 test result in the app prior to the case investigation interview, comprising 25% (157/628) of those interviewed. This is corroborated by a 33% (565/1,713) ratio of code issuance (inflated by some unclaimed codes) to cases. Combining the 25% probability that those who test positive rapidly share their test result with a 46% probability that a person they infected can receive exposure notifications, an estimated 11.4% of transmission pairs exhibit meaningful app usage. High usage was achieved without the use of "push" notifications, in the context of a marketing campaign that leveraged social influencers.
ConclusionsUsage can be assessed, without in-app analytics, within a defined local community such as a college campus rather than an entire jurisdiction. With marketing, high uptake in dense social networks like universities makes exposure notification an impactful complement to traditional contact tracing. Integrating verification code delivery into patient results portals was successful in making the exposure notification process rapid.
3 question summary box1) What is the current understanding of this subject?The extent to which exposure notification technology reduces SARS-CoV-2 transmission depends on usage among infected persons.
2) What does this report add to the literature?A novel metric estimates meaningful usage, and demonstrates potential transmission reduction on a college campus. Clear benefit was seen from simplifying verification of positive test results with automation.
3) What are the implications for public health practice?Defined communities can benefit from local deployment and marketing even in the absence of statewide deployment. Lifting current restrictions on deployment would allow more entities such as campuses to copy the model shown here to be successful. | epidemiology |
10.1101/2021.02.01.21250621 | Targeting fronto-limbic dysfunctions via intermittent theta burst stimulation as a novel treatment for Functional Movement Disorders | BackgroundNeuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD), although there is no direct causal evidence of this relationship. Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, in this proof-of-concept study, we investigated safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD.
MethodsSix subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day, for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. FMD symptom severity was assessed at baseline, during treatment and 24 hours after receiving the last iTBS session.
ResultsMultiples doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and also influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a significant decrease in negative valence and an increase in positive valence levels following iTBS. Furthermore, we also observed a marked reduction in FMD symptom severity post stimulation.
ConclusionsCorticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research. | psychiatry and clinical psychology |
10.1101/2021.02.02.21250043 | Toward a geography of community health workers in Niger: a geospatial analysis | BackgroundLittle is known about the geography of community health workers (CHWs), their contribution to geographical accessibility of primary health care (PHC) services, and strategies for optimizing efficiency of CHW deployment in the context of universal health coverage (UHC).
MethodsUsing a complete georeferenced census of front-line health facilities and CHWs in Niger and other high resolution spatial datasets, we modelled travel times to front-line health facilities and CHWs between 2000-2013, accounting for training, essential commodities, and maximum population capacity. We estimated additional CHWs needed to maximize geographical accessibility of the population beyond the reach of existing front-line health facilities and CHWs. We assessed the efficiency of geographical targeting of the existing CHW network compared to modelled CHW networks designed to optimize geographical targeting of the estimated population, under-five deaths, and plasmodium falciparum malaria cases.
ResultsThe percent of the population within 60 minutes walking to the nearest CHW increased from 0{middle dot}0% to 17{middle dot}5% between 2000-2013, with 15{middle dot}5% within 60 minutes walking to the nearest CHW trained on integrated community case management (iCCM) - making PHC services and iCCM, specifically, geographically accessible for an estimated 2{middle dot}3 million and 2{middle dot}0 million additional people, respectively. An estimated 10{middle dot}4 million people (59{middle dot}0%) remained beyond a 60-minute catchment of front-line health facilities and CHWs. Optimal deployment of 8064 additional CHWs could increase geographic coverage of the estimated total population from 41{middle dot}5% to 73{middle dot}6%. Geographical targeting of the existing CHW network was inefficient but optimized CHW networks could improve efficiency by 55{middle dot}0%-81{middle dot}9%, depending on targeting metric.
InterpretationsWe provide the first high-resolution maps and estimates of geographical accessibility to CHWs at national scale, highlighting improvements between 2000-2013 in Niger, geographies where gaps remained, approaches for improving targeting, and the importance of putting CHWs on the map to inform planning in the context of UHC.
O_TEXTBOXKEY QUESTIONSO_ST_ABSWhat is already known?C_ST_ABSO_LIPrevious studies have estimated geographical accessibility (as travel time) to CHWs for subnational areas only1-4 and have assessed efficiency of the distribution of hospitals in low and middle-income countries.5
C_LI
What are the new findings?O_LIThe percent of the population within 60 minutes walking to the nearest CHW increased from 0{middle dot}0% to 17{middle dot}5% between 2000-2013, with 15{middle dot}5% within 60 minutes walking to the nearest CHW trained on integrated community case management (iCCM) - making PHC services and iCCM, specifically, geographically accessible for an estimated 2{middle dot}3 million and 2{middle dot}0 million additional people, respectively.
C_LIO_LIAn estimated 10{middle dot}4 million people (59{middle dot}0%) remained beyond a 60-minute catchment of front-line health facilities and CHWs in 2013, with important variation across subnational geographies, training of CHWs, and availability of essential commodities.
C_LIO_LIOptimal deployment of 8064 additional CHWs could increase geographic coverage of the estimated total population from 41{middle dot}5% to 73{middle dot}6%, providing physical access to PHC services for an additional 5{middle dot}7 million people not covered in 2013.
C_LIO_LIOptimized CHW networks increased efficiency of geographical targeting compared to the existing CHW network by 55{middle dot}0%-81{middle dot}9%, depending on targeting metric.
C_LI
What do the new findings imply?O_LIGeographical accessibility to primary health care services, including iCCM, improved in Niger between 2000-2013 with important contributions by CHWs.
C_LIO_LIGaps in geographical accessibility remained as of 2013 but scale-up of the CHW network, using the scale-up approach described in this study, could substantially increase geographical accessibility of PHC services.
C_LIO_LIThe efficiency of geographical targeting of the existing network of CHWs was suboptimal. The approach for optimizing efficiency of geographical targeting described in this study could be used to improve geographical targeting of CHW deployment in Niger and other countries.
C_LIO_LIThis work is a first step toward establishing a geography of CHWs in Niger and is a call to action to put CHWs on the map globally to inform health system planning and maximize geographical accessibility, efficiency, and impact of investments in the context of UHC.
C_LI
C_TEXTBOX | public and global health |
10.1101/2021.02.02.21251013 | Association Between Preparedness and Response Measures and COVID-19 Incidence and Mortality | The COVID-19 pandemic is the most disruptive global health threat in a century. We analyzed publicly available data on preparedness capacity, COVID-19 incidence and mortality, governance, and testing. Although other analyses have suggested that preparedness assessments do not correlate with effective pandemic response, we found that testing rates correlate with both COVID-19 incidence and mortality and strongly correlated with country preparedness capacity as measured by the Joint External Evaluation (JEE). There is a statistically significant association between preparedness capacities and COVID-19 case incidence and an independent association between governance and COVID-19 case and mortality rates. Legislation, surveillance, and risk communication capacities were associated with lower COVID-19 case incidence and mortality. Preparedness and governance are independently associated with COVID-19 pandemic severity. Preparedness capacities are not sufficient -- capacity and governance are both critical to pandemic control. Countries must improve public health systems and implement strong government leadership.
Article SummaryCountry preparedness capacities and country leadership policy response (governance) are both critically important to control pandemics. Without appropriate policy action, public health preparedness is insufficient for effective pandemic response. | public and global health |
10.1101/2021.02.02.21250897 | Impact of the COVID-19 Pandemic on anxiety and depression symptoms of young people in the Global South: evidence from a four-country cohort study | ObjectiveTo provide evidence on the effect of the COVID-19 pandemic on the mental health of adolescents and young adults who grew up in poverty in Low and Middle Income Countries (LMICs).
DesignA phone survey implemented August-October 2020 to participants of a population-based cohort study since 2002 comprising two cohorts born in 1994-5 and 2001-2 in Ethiopia, India (Andhra Pradesh and Telangana), Peru and Vietnam. We examined associations between mental health and pandemic-related stressors, as well as structural factors (gender, location, wealth); and lifelong protective/risk factors (parent and peer relationship, past household wealth, long-term health problems, past emotional problems and subjective well-being) measured at younger ages.
SettingA diverse, poverty focused sample, reaching those without mobile phones or internet access.
Participants10,496 individuals were approached, 9,730 participated. Overall, 8,988 individuals were included in this study, 4,610 (51%) male and 4,378 (49%) female. Non-inclusion was due to non-location or missing data.
Main outcome measuresAt least mild anxiety and depression were measured by Generalized Anxiety Disorder-7 (GAD-7, [≥]5) and Patient Health Questionnaire-8 (PHQ-8, [≥]5).
ResultsRates of symptoms of at least mild anxiety (depression) were highest in Peru at 41% (32%) [95% CI, 38.63-43.12; (29.49-33.74)], and lowest in Vietnam at 9% (9%) [95% CI, 8.16-10.58; (8.33-10.77)], mirroring COVID-19 mortality rates. Females were most affected in all countries but Ethiopia. In all countries, pandemic-related stressors were associated with increased rates of anxiety and depression, though with varying levels of importance across countries. Prior parent and peer relationships were protective factors for mental health while having a long-term health problem or prior emotional problems were risk factors.
ConclusionThe COVID-19 pandemic presents significant risks to the mental health of young people. Mental health support is limited in LMICs and young people have to date been lower priority for COVID-19 interventions.
Strengths and limitations of this studyO_LIThe study uses data from adolescents and young adults who grew up in poverty in four LMICs which were diversely affected by the COVID-19 pandemic, therefore investigating a globally vulnerable, but understudied group both in terms of age and wealth.
C_LIO_LIThis study reaches a broad sample of young people who grew up in poverty, including those without internet or mobile phone access.
C_LIO_LIA key strength is combining a broad range of pandemic-related stressors from survey data on experiences of COVID-19 with previously measured information on longer-term risk and protective factors, therefore contributing to a more complete picture of COVID-19 effects.
C_LIO_LIA limitation of the study is that it does not have a directly comparable pre-COVID baseline for depression/anxiety, however, proxy variables are used as a baseline and the explanatory variables capture dynamics that happened during the pandemic.
C_LIO_LIA further limitation is possible underreporting due to stigma associated with mental health, despite piloting and validation, as well as possible bias in self-reported experiences of pandemic-related stressors due to feelings of anxiety or depression.
C_LI | public and global health |
10.1101/2021.02.01.21250914 | Diagnostic performance of standard and inverted grey-scale CXR in detection of lung lesions in COVID-19 patients. A single institution study in the region of Abu Dhabi. | PurposeTo evaluate diagnostic performance of greyscale and inverted greyscale Chest X-ray (CXR) using Computed Tomography (CT) scan as a gold standard.
MethodsIn this retrospective study, electronic medical records of 120 patients who had valid CXR and High-resolution CT (HRCT) within less than 24 hours after having a positive COVID-19 RT-PCR test during the period from May 19 th to May 23 rd 2020 in a single tertiary care center were reviewed.
PA chest radiographs were presented on 2 occasions to 5 radiologists to evaluate the role and appropriateness of greyscale and inverted greyscale chest radiographs (CXR). The images were viewed on high-specification viewing systems using a primary display monitors and compared it to computed tomography (CT) findings for screening and management of suspected or confirmed COVID-19 patients.
ResultsNinety-six (80%) patients had positive CT findings, 81 (67.5%) had positive grey scale CXR lesions, and 25 (20.8%) had better detection in the inverted grey scale CXR. The CXR sensitivity for COVID-19 pneumonia was 93.8% (95% CI (86.2% - 98.0%) and the specificity was 48.7% (95% CI (32.4% - 65.2%). The CXR sensitivity of detection of lung lesions was slightly higher in male (95.1% (95% CI (86.3% - 99.0%)) than female (90.0% (95% CI (68.3% - 98.8%)), while the specificity was 48.0% (95% CI (27.8% - 68.7%) and 50.0% (95% CI (23.0% - 77.0%) in males and females, respectively. However, no significant difference was detected in ROC area between men and women.
ConclusionsThe sensitivity of detection of lung lesions of CXR was relatively high, particularly in men. The results of the study support the idea of considering conventional radiographs as an important diagnostic tool in suspected COVID-19 patients especially in healthcare facilities where there is no access to HRCT scans.
HighlightsO_LICXR shows high sensitivity for detecting lung lesions in HRCT confirmed COVID-19 patients.
C_LIO_LIBetter detection of lesions was noted in the inverted grey scale CXR in (20.8%) of cases with positive findings in standard greyscale CXR.
C_LIO_LIConventional radiographs can be used as diagnostic tools in suspected COVID-19 patients especially in healthcare facilities where there is no access to HRCT scans.
C_LI | radiology and imaging |
10.1101/2021.02.02.21250855 | A novel biomechanical injury risk score demonstrates correlation with lower limb posterior chain injury in fifty elite level rugby union athletes | ObjectivesLower limb posterior chain injury (PCI) is common amongst athletic populations, with multi-factorial risk factors including age, previous injury, strength measurements, range of motion and training load. Biomechanics are commonly considered in the prevention and rehabilitation of PCI by performance staff. However, there is no documented testing method to assess for associations between biomechanics and PCI. The aim of this study was to investigate whether there is an association between an easily applicable, novel biomechanical assessment tool and PCI.
MethodsFifty male elite-level rugby union athletes (age 22.83{+/-}5.08) participating in the highest tier of England were tested at the start of the 2019 pre-season period and PCIs (N=48) were recorded over the 2019/20 playing season. Participants biomechanics were analysed using two-dimensional video analysis against an Injury Risk Score (IRS) system in the performance of the combined movement - prone hip extension and knee flexion. Participants biomechanics in carrying out this movement were scored against the 10-point IRS, where the more compensatory movement recorded sees an increase in an individuals IRS. Participants IRS were then compared against the number of PCI sustained and Spearmans correlation coefficient was utilised for analysis.
ResultsThere is a good significant association between IRS and PCI (R=0.573, p<0.001). Linear Regression demonstrated that an increase of 1 in IRS was associated with a 35% increase in PCI incidence (R2=0.346).
ConclusionA good significance between the IRS and PCI provides preliminary support for its use as an injury risk assessment tool. | sports medicine |
10.1101/2021.02.01.21250820 | Site-specific decrease in cortical reactivity during sensory trick in cervical dystonia patients. | BackgroundSensory tricks (SeT) are various maneuvers that can alleviate dystonic contractions and are a characteristic feature of cervical dystonia (CD). The neurophysiology underlying SeT, however, remains largely unknown. Reducing the abnormal cortical facilitation and modulating the abnormal cortical and subcortical oscillatory activity are mechanisms that have been proposed. The supplementary motor area (SMA) and primary sensorimotor cortices are thought to be relevant to this phenomenon.
ObjectiveIn the current study, using concurrent EEG recording during transcranial magnetic stimulation (TMS) of the SMA and primary motor cortex (M1), we aimed at determining the changes in cortical reactivity and oscillatory changes induced by SeT.
MethodsWe recruited 13 patients with CD who exhibited SeT and equal number of age- and gender-matched healthy controls. Single TMS pulses were delivered over the SMA and M1 either at rest or during SeT. 32-channel EEG was recorded, and TMS-evoked potentials (TEP) were obtained. Further, time-frequency analysis was performed on the induced data. Correlation analysis for significant neurophysiological parameters was done with clinical measures.
ResultsWe found that SeT induced a significant decrease in the amplitude of TEP elicited from M1 stimulation at [~]210-260ms in patients, which correlated with symptom duration. Post hoc analysis of EMG activity in the neck muscles revealed that this effect on TEP was present only in the subset of patients with effective SeT.
ConclusionOur results suggest that SeT reduces cortical reactivity over M1 approximately 200ms after stimulation. This adds support to the idea that reduced cortical facilitation underlies the phenomenon. | neurology |
10.1101/2021.02.02.21250685 | The Value of Self-Reported Cognitive Performance in low, medium and high EDSS | ObjectivesThe patient-reported Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is inconsistently related to objective cognitive tests in multiple sclerosis (MS), while being strongly correlated with depression. In this study we test whether the relation between subjective and objective cognitive performance is moderated by physical disability, assessed by the Expanded Disability Status Scale (EDSS).
Materials & MethodsFrom 275 MS patients who completed the patient-report MSNQ and the two-question screening tool for depression, we collected Symbol Digit Modalities Test (SDMT) and EDSS scores, indicators of respectively objective cognitive performance and physical disability. We analysed correlations between these variables in the total group and in three EDSS subgroups: Low 0.0 - 3.0, Medium 3.5 - 6.0 and High 6.5 - 9.0. We also investigated the use of a composite measure of cognitive impairment and depression.
ResultsWe found no significant correlations between patient-reported MSNQ and SDMT scores in the total group or the EDSS subgroups. MSNQ scores correlated significantly with depression in all subgroups. After correcting for several variables, MSNQ scores contributed adversely to SDMT scores in the total group, not in any subgroup. MSNQ scores contributed significantly to the prediction of the composite measure of impairment in the total group and in all EDSS subgroups.
ConclusionsThe relationship between measures of subjective and objective cognitive performance is not influenced by the patients level of physical disability. MSNQ scores are substantially influenced by depression, and reflect cognitive function to some degree. The patient-report MSNQ can be useful to identify patients requiring further (neuro)psychological assessment. | neurology |
10.1101/2021.02.02.21250685 | Correlates of patient-reported cognitive performance with regard to disability | ObjectivesThe patient-reported Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is inconsistently related to objective cognitive tests in multiple sclerosis (MS), while being strongly correlated with depression. In this study we test whether the relation between subjective and objective cognitive performance is moderated by physical disability, assessed by the Expanded Disability Status Scale (EDSS).
Materials & MethodsFrom 275 MS patients who completed the patient-report MSNQ and the two-question screening tool for depression, we collected Symbol Digit Modalities Test (SDMT) and EDSS scores, indicators of respectively objective cognitive performance and physical disability. We analysed correlations between these variables in the total group and in three EDSS subgroups: Low 0.0 - 3.0, Medium 3.5 - 6.0 and High 6.5 - 9.0. We also investigated the use of a composite measure of cognitive impairment and depression.
ResultsWe found no significant correlations between patient-reported MSNQ and SDMT scores in the total group or the EDSS subgroups. MSNQ scores correlated significantly with depression in all subgroups. After correcting for several variables, MSNQ scores contributed adversely to SDMT scores in the total group, not in any subgroup. MSNQ scores contributed significantly to the prediction of the composite measure of impairment in the total group and in all EDSS subgroups.
ConclusionsThe relationship between measures of subjective and objective cognitive performance is not influenced by the patients level of physical disability. MSNQ scores are substantially influenced by depression, and reflect cognitive function to some degree. The patient-report MSNQ can be useful to identify patients requiring further (neuro)psychological assessment. | neurology |
10.1101/2021.01.31.21250867 | Standard and anomalous second waves in the COVID-19 pandemic | We apply a generalised logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit a second wave of infections. The model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterise the first and second waves, respectively. We show that the theoretical curves are in excellent agreement with the empirical data for all cases considered. The model also allows for predictions about the time of occurrence and relative severity of the second wave, in comparison to the first wave. It is shown furthermore that the COVID-19 second waves can be generically classified in two main types, namely, standard and anomalous second waves, according as to whether the second wave starts well after or still during the first wave, respectively. We have also observed that the standard second waves tend, in their majority, to be more severe than the corresponding first wave, whereas for anomalous second waves the opposite occurs. | infectious diseases |
10.1101/2021.01.31.21250867 | Standard and anomalous second waves in the COVID-19 pandemic | We apply a generalised logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit a second wave of infections. The model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterise the first and second waves, respectively. We show that the theoretical curves are in excellent agreement with the empirical data for all cases considered. The model also allows for predictions about the time of occurrence and relative severity of the second wave, in comparison to the first wave. It is shown furthermore that the COVID-19 second waves can be generically classified in two main types, namely, standard and anomalous second waves, according as to whether the second wave starts well after or still during the first wave, respectively. We have also observed that the standard second waves tend, in their majority, to be more severe than the corresponding first wave, whereas for anomalous second waves the opposite occurs. | infectious diseases |
10.1101/2021.01.31.21250867 | Standard and anomalous second waves in the COVID-19 pandemic | We apply a generalised logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit a second wave of infections. The model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterise the first and second waves, respectively. We show that the theoretical curves are in excellent agreement with the empirical data for all cases considered. The model also allows for predictions about the time of occurrence and relative severity of the second wave, in comparison to the first wave. It is shown furthermore that the COVID-19 second waves can be generically classified in two main types, namely, standard and anomalous second waves, according as to whether the second wave starts well after or still during the first wave, respectively. We have also observed that the standard second waves tend, in their majority, to be more severe than the corresponding first wave, whereas for anomalous second waves the opposite occurs. | infectious diseases |
10.1101/2021.01.31.21250867 | Standard and anomalous waves of COVID-19: A multiple-wave growth model for epidemics | We apply a generalised logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit a second wave of infections. The model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterise the first and second waves, respectively. We show that the theoretical curves are in excellent agreement with the empirical data for all cases considered. The model also allows for predictions about the time of occurrence and relative severity of the second wave, in comparison to the first wave. It is shown furthermore that the COVID-19 second waves can be generically classified in two main types, namely, standard and anomalous second waves, according as to whether the second wave starts well after or still during the first wave, respectively. We have also observed that the standard second waves tend, in their majority, to be more severe than the corresponding first wave, whereas for anomalous second waves the opposite occurs. | infectious diseases |
10.1101/2021.02.02.21250909 | Muscle strength is associated with COVID-19 hospitalization in adults 50 years of age and older | BackgroundWeak muscle strength has been associated with a wide range of adverse health outcomes. Yet, whether individuals with weaker muscle strength are more at risk for hospitalization due to severe COVID-19 is still unclear. The objective of this study was to investigate the independent association between muscle strength and COVID-19 hospitalization.
MethodsData from adults 50 years of age or older were analyzed using logistic models adjusted for several chronic conditions, body-mass index, age, and sex. Hand-grip strength was repeatedly measured between 2004 and 2017 using a handheld dynamometer. COVID-19 hospitalization during the lockdown was self reported in summer 2020 and was used as an indicator of COVID-19 severity.
ResultsThe study was based on the Survey of Health, Ageing and Retirement in Europe (SHARE) and included 3600 older adults (68.8 {+/-} 8.8 years, 2044 females), amongst whom 316 were tested positive for the severe acute respiratory syndrome coronavirus 2 (8.8%) and 83 (2.3 %) were hospitalized due to COVID-19. Results showed that higher grip strength was associated with a lower risk of COVID-19 hospitalization (adjusted odds ratio [OR] per increase of 1 standard deviation in grip strength = .64, 95% confidence interval [95% CI] = .45-.87, p = .015). Results also showed that age (OR for a 10-year period = 1.70, 95% CI = 1.32-2.20, p < .001) and obesity (OR = 2.01, 95% CI = 1.00-3.69, p = .025) were associated with higher risk of COVID-19 hospitalization. Sensitivity analyses using different measurements of grip strength as well as robustness analyses based on rare-events logistic regression and a different sample of participants (i.e., COVID-19 patients) were consistent with the main results.
ConclusionMuscle strength is an independent risk factor for COVID-19 severity in adults 50 years of age or older. | epidemiology |
10.1101/2021.02.02.21250909 | Muscle strength is associated with COVID-19 hospitalization in adults 50 years of age and older | BackgroundWeak muscle strength has been associated with a wide range of adverse health outcomes. Yet, whether individuals with weaker muscle strength are more at risk for hospitalization due to severe COVID-19 is still unclear. The objective of this study was to investigate the independent association between muscle strength and COVID-19 hospitalization.
MethodsData from adults 50 years of age or older were analyzed using logistic models adjusted for several chronic conditions, body-mass index, age, and sex. Hand-grip strength was repeatedly measured between 2004 and 2017 using a handheld dynamometer. COVID-19 hospitalization during the lockdown was self reported in summer 2020 and was used as an indicator of COVID-19 severity.
ResultsThe study was based on the Survey of Health, Ageing and Retirement in Europe (SHARE) and included 3600 older adults (68.8 {+/-} 8.8 years, 2044 females), amongst whom 316 were tested positive for the severe acute respiratory syndrome coronavirus 2 (8.8%) and 83 (2.3 %) were hospitalized due to COVID-19. Results showed that higher grip strength was associated with a lower risk of COVID-19 hospitalization (adjusted odds ratio [OR] per increase of 1 standard deviation in grip strength = .64, 95% confidence interval [95% CI] = .45-.87, p = .015). Results also showed that age (OR for a 10-year period = 1.70, 95% CI = 1.32-2.20, p < .001) and obesity (OR = 2.01, 95% CI = 1.00-3.69, p = .025) were associated with higher risk of COVID-19 hospitalization. Sensitivity analyses using different measurements of grip strength as well as robustness analyses based on rare-events logistic regression and a different sample of participants (i.e., COVID-19 patients) were consistent with the main results.
ConclusionMuscle strength is an independent risk factor for COVID-19 severity in adults 50 years of age or older. | epidemiology |
10.1101/2021.02.02.21250909 | Muscle strength is associated with COVID-19 hospitalization in adults 50 years of age and older | BackgroundWeak muscle strength has been associated with a wide range of adverse health outcomes. Yet, whether individuals with weaker muscle strength are more at risk for hospitalization due to severe COVID-19 is still unclear. The objective of this study was to investigate the independent association between muscle strength and COVID-19 hospitalization.
MethodsData from adults 50 years of age or older were analyzed using logistic models adjusted for several chronic conditions, body-mass index, age, and sex. Hand-grip strength was repeatedly measured between 2004 and 2017 using a handheld dynamometer. COVID-19 hospitalization during the lockdown was self reported in summer 2020 and was used as an indicator of COVID-19 severity.
ResultsThe study was based on the Survey of Health, Ageing and Retirement in Europe (SHARE) and included 3600 older adults (68.8 {+/-} 8.8 years, 2044 females), amongst whom 316 were tested positive for the severe acute respiratory syndrome coronavirus 2 (8.8%) and 83 (2.3 %) were hospitalized due to COVID-19. Results showed that higher grip strength was associated with a lower risk of COVID-19 hospitalization (adjusted odds ratio [OR] per increase of 1 standard deviation in grip strength = .64, 95% confidence interval [95% CI] = .45-.87, p = .015). Results also showed that age (OR for a 10-year period = 1.70, 95% CI = 1.32-2.20, p < .001) and obesity (OR = 2.01, 95% CI = 1.00-3.69, p = .025) were associated with higher risk of COVID-19 hospitalization. Sensitivity analyses using different measurements of grip strength as well as robustness analyses based on rare-events logistic regression and a different sample of participants (i.e., COVID-19 patients) were consistent with the main results.
ConclusionMuscle strength is an independent risk factor for COVID-19 severity in adults 50 years of age or older. | epidemiology |
10.1101/2021.01.30.21250811 | Bladder Cancer Immunotherapy by BCG is associated with a significantly reduced risk of Alzheimer disease | IMPORTANCEDespite years of investigation and billions of dollars, there is no cure or even a disease-slowing remedy for Alzheimers disease (AD). Most studies thus far have focused on amyloid beta plaques (A{beta}) and neurofibrillary tangles as therapeutic targets, and only a few on modulating the associated inflammatory process.
OBJECTIVETo determine if exposure to Bacillus Calmette-Guerin (BCG) during treatment of non-muscle-invasive bladder cancer (NMIBC) is associated with a lower risk of developing AD.
DESIGN, SETTING AND PARTICIPANTSMulticenter retrospective study of 12,185 bladder cancer patients including 2301 BCG-treated patients between 2000 and 2019 meeting all inclusion criteria. Data was retrieved from two tertiary hospital systems in Israel and the United States, and the largest Israeli health provider database, with a median follow up of 3.5 to 7 years.
MAIN OUTCOMES AND MEASURESThe primary outcome was time to the first occurrence of AD/Dementia events following a diagnosis of bladder cancer by trans-urethral resection (TURBT) in BCG treated patients, and in bladder cancer patients not receiving BCG (control group).
RESULTSBCG treatment was associated with a significantly reduced risk of developing AD in bladder cancer patients of [≥]75 years following BCG treatment. A competing risk model using Cox Proportional-Hazard (PH) analysis applied to the largest medical records data showed a Hazard Ratio (HR) of 0.726 (95% CI: 0.529 - 0.996, P = 0.0473). The results were duplicated in analyzing NMIBC patients from a tertiary hospital with a HR of 0.416 (95% CI: 0.203 - 0.853, P = 0.017). A reduction in the risk (by 28%) for developing Parkinsons disease (PD) was also shown in bladder cancer patients subjected to BCG immunotherapy.
CONCLUSIONS AND RELEVANCEBCG treatment for bladder cancer patients was associated with a significantly reduced risk for developing AD and PD in the elderly population (>75 years), and in NMIBC patients from a tertiary hospital. Prospective studies in elderly inoculated with intradermic BCG should be initiated to evaluate the potential protective effect of BCG against AD and PD.
KEY POINTSO_ST_ABSQuestionC_ST_ABSWhether bladder cancer patients treated with BCG immunotherapy have a lower risk to develop AD than bladder cancer patients that do not receive such treatment.
FindingsIn a multicenter retrospective study composed of three cohorts covering >12,000 bladder cancer patients, those receiving intravesical BCG immunotherapy had a significantly lower risk of developing AD.
MeaningIntradermal inoculation of BCG to elderly people should be tested as a potential preventive approach against AD. | public and global health |
10.1101/2021.02.01.21250977 | Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation with cognitive functioning | Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but knowledge on its role in deep gray matter regions is limited and previous studies have yielded heterogeneous results. The aim was to evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction and post-processing techniques. A 7 tesla MRI scanner combined with a unique lipid suppression coil and subject specific water signal suppression pulses were used to acquire high-resolution magnetic resonance spectroscopic imaging data. Anatomical scans were used to perform tissue fraction correction and registration to a standard brain for group comparison in specifically delineated brain regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. Average glutamate levels across deep gray matter structures (i.e. caudate, pallidum, putamen, and thalamus) in patients with a psychotic disorder (n=16, 4 females) were lower compared to healthy controls (n=23, 7 females). Stratified analyses showed lower glutamate levels in the caudate and putamen but not in the pallidum or thalamus. Average glutamate levels across deep gray matter structures were positively correlated with cognition, particularly to psychomotor speed. We find reduced glutamate levels across deep brain structures such as the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Our results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in patients with psychotic disorders. | radiology and imaging |
10.1101/2021.02.02.21251000 | Neurofilament light protein as a blood biomarker for Huntington's disease in children | Juvenile-onset Huntingtons disease (JoHD) is a rare, particularly devastating form of Huntingtons Disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD. We report that plasma NfL is elevated in JoHD and premanifest HD mutation-carrying children. Quantifying plasma NfL may improve clinical diagnosis and therapeutic trial design in the pediatric population. | neurology |
10.1101/2021.02.02.21250991 | The effect of Alzheimer's disease-associated genetic variants on longevity | The genetics underlying human longevity is influenced by the genetic risk to develop -or escape- age-related diseases. As Alzheimers disease (AD) represents one of the most common conditions at old age, an interplay between genetic factors for AD and longevity is expected.
We explored this interplay by studying the prevalence of 38 AD-associated single-nucleotide-polymorphisms (SNPs) identified in AD-GWAS, in self-reported cognitively healthy centenarians, and we replicated findings in the largest GWAS on parental-longevity.
We found that 28/38 SNPs identified to associate with increased AD-risk also associated with decreased odds of longevity. For each SNP, we express the imbalance between AD- and longevity-risk as an effect-size distribution. When grouping the SNPs based on these distributions, we found three groups: 17 variants increased AD-risk more than they decreased the risk of longevity (AD-group): these variants were functionally enriched for {beta}-amyloid metabolism and immune signaling, and they were enriched in microglia. 11 variants reported a larger effect on longevity as compared to their AD-effect (Longevity-group): these variants were enriched for endocytosis/immune signaling, and at the cell-type level were enriched in microglia and endothelial cells. Next to AD, these variants were previously associated with other aging-related diseases, including cardiovascular and autoimmune diseases, and cancer. Unexpectedly, 10 variants associated with an increased risk of both AD and longevity (Unexpected-group). The effect of the SNPs in AD- and Longevity-groups replicated in the largest GWAS on parental-longevity, while the effects on longevity of the SNPs in the Unexpected-group could not be replicated, suggesting that these effects may not be robust across different studies.
Our study shows that some AD-associated variants negatively affect longevity primarily by their increased risk of AD, while other variants negatively affect longevity through an increased risk of multiple age-related diseases, including AD. | genetic and genomic medicine |
10.1101/2021.01.30.21250727 | BurnNet: An Efficient Deep Learning Framework for Accurate Dermal Burn Classification | AO_SCPLOWBSTRACTC_SCPLOWBurns are the fourth most prevalent unintentional injury around the world, and when left untreated can become permanent and sometimes fatal. An important aspect of treating burn injuries is accurate and efficient diagnosis. Classifying the three primary types of burns - superficial dermal, deep dermal, and full thickness - is essential in determining the necessity of surgery, which is often critical to the afflicted patients survival. Unfortunately, reconstructive burn surgeons and dermatologists are merely able to diagnose these types of burns with approximately 50-75% accuracy. As a result, we propose the use of an eight-layer convolutional neural network, BurnNet, for rapid and precise burn classification with 99.87% accuracy. We applied affine transformations to artificially augment our dataset and found that our model attained near perfect metrics across the board, demonstrating the high propensity of deep learning architectures in burn classification. | health informatics |
10.1101/2021.02.02.21250984 | Point-of-care evaluation of a rapid antigen test (CLINITEST Rapid COVID-19 Antigen Test) for diagnosis of SARS-CoV-2 infection in symptomatic and asymptomatic individuals | Rapid antigen assays (RAD) based on lateral flow immunochromatography (LFIC) technology have emerged as a valuable tool for the control of COVID-19 pandemic. Manufacturer{square}independent, real{square}world evaluation of these assays is crucial given the considerable heterogeneity reported in their clinical and analytical performances. Here, we report for the first time on the point-of-care performance of the CLINITEST(R) Rapid COVID-19 Antigen Test (Siemens, Healthineers, Erlangen, Germany) to detect SARS-CoV-2 infection in presumptive COVID-19 cases or asymptomatic close contacts of COVID-19 patients. When compared to RT-PCR, the overall sensitivity of the assay was 80.2 (95% CI, 70.9-87.1) for symptomatic patients sampled (nasopharyngeal specimens) within five days after the onset of symptoms and 60% (95% CI, 40.7-76.6%) for asymptomatic participants. The overall specificity was 100% in both population groups. | infectious diseases |
10.1101/2021.02.01.21250878 | The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS):Rationale, Objectives, and Design | BackgroundInfluenza viruses pose significant disease burdens through annual seasonal outbreaks and unpredictable pandemics. Existing influenza surveillance programs have relied heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness-specific student absenteeism (a-ILI) in pre-kindergarten through grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.
MethodsStarting in September 2014, ORCHARDS combined automated reporting of daily absenteeism within 6 schools and home visits to school children with acute respiratory infections (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing, long-standing, and highly effective influenza surveillance program, based on MAI at 5 primary care clinics in the same geographical area.
ResultsOver the first 5 years, a-ILI occurred on 6,634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of the 1,728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Influenza (p<0.001) and adenovirus (P=0.004) were significantly associated with a-ILI.
ConclusionORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives. | infectious diseases |
10.1101/2021.02.02.21250902 | PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship | BackgroundThe Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) trial has provided in-pandemic evidence of what does not work in the early primary care management of coronavirus-2019 disease (COVID-19). PRINCIPLEs first finding was that azithromycin and doxycycline were not effective.
AimTo explore the extent to which azithromycin and doxycycline were being used in-pandemic, and the scope for trial findings impacting on practice.
Design and SettingWe compared crude rates of prescribing and respiratory tract infections (RTI) in 2020, the pandemic year, with 2019, using the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).
MethodsWe used a negative binomial model including age-band, gender, socioeconomic status, and NHS region to compare azithromycin and doxycycline lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like-illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years and 95% confidence intervals (95%CI).
ResultsAzithromycin prescriptions increased 7% in 2020 compared to 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4% respectively) while ILI rose slightly (6.4%). The overall percentage of RTI prescribed azithromycin rose by 42.1% between 2019 and 2020, doxycycline increased by 33%.
Our adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR=1.22, 95%CI:1.19-1.26, p<0.0001), for every unit rise in confirmed COVID there was an associated 3% rise in prescription (IRR=1.026, 95%CI 1.024-1.0285, p<0.0001); whereas these measures were static for doxycycline.
ConclusionPRINCIPLE trial flags scope for improvement in antimicrobial stewardship. | primary care research |
10.1101/2021.02.02.21250987 | Role of Inflammation in Depression and Anxiety: Tests for Disorder Specificity, Linearity and Potential Causality of Association in the UK Biobank | BackgroundConcentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.
MethodsUsing data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety.
FindingsCRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.
InterpretationAltered activity of the IL-6/IL-6R pathway could be causally linked to depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.
FundingMQ (MQDS17/40); Wellcome Trust (201486/Z/16/Z). | psychiatry and clinical psychology |
10.1101/2021.02.01.21250946 | Usability of saliva collection devices for SARS-CoV-2 diagnostics | There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems, as it can be completed without specialized training and uses generic materials. In this study, we observed thirty individuals who self-collected saliva using four different collection devices and analyzed their feedback. Two of these devices, a funnel and bulb pipette, were used to evaluate at-home saliva collection by 60 individuals. All devices enabled the safe, unsupervised self-collection of saliva. The quantity and quality of the samples received were acceptable for SARS-CoV-2 diagnostic testing, as determined by RNase P detection. Here, we demonstrate inexpensive, generic, buffer free collection devices suitable for unsupervised and home saliva self-collection. | public and global health |
10.1101/2021.02.01.21250946 | Evaluation of saliva self-collection devices for SARS-CoV-2 diagnostics | There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems, as it can be completed without specialized training and uses generic materials. In this study, we observed thirty individuals who self-collected saliva using four different collection devices and analyzed their feedback. Two of these devices, a funnel and bulb pipette, were used to evaluate at-home saliva collection by 60 individuals. All devices enabled the safe, unsupervised self-collection of saliva. The quantity and quality of the samples received were acceptable for SARS-CoV-2 diagnostic testing, as determined by RNase P detection. Here, we demonstrate inexpensive, generic, buffer free collection devices suitable for unsupervised and home saliva self-collection. | public and global health |
10.1101/2021.02.01.21250971 | Estimation of infection rate and the population size potentially exposed to SARS-CoV-2 in Japan during 2020 | BackgroundThe infectious respiratory disease COVID-19, caused novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reached pandemic status during 2020. The primary statistic data are important to survey the actual circumstances of COVID-19. Here, we report the analysis of the primary data of COVID-19 in Japan during 2020.
MethodsData were collected and released systematically under Japan domestic law. Machine learning was conducted to estimate the positive rate in Japan and four prefectures (Tokyo, Osaka, Chiba, and Fukuoka).
ResultsPrimary data analysis revealed there were at least two peaks of infection in Japan; the first one was during April 2020 and the second one started from November 1, 2020. Estimating the positive rate in Japan as well as in the four prefectures reinforced the above observations. The positive rate in Japan during 2020 was estimated to be around 6% to 8%. We also estimated that 1.95 million people were possibly exposed to the novel virus on October 31, 2020. The numbers of related deaths were over 3,000 people at the end of 2020.
ConclusionWe estimated the infection rate of SARS-CoV-2 in Japan to be 6-8% in 2020. We also concluded that Japan had at least two infection-spreading periods, the first one being from Jan 19, 2020 until May 2020, and the second one beginning from November 1, 2020. Importantly, our analysis supports the need for clear definition of the criteria for conducting confirmation tests before embarking on data analysis. | public and global health |
10.1101/2021.02.02.21250980 | Performance of a Computational Phenotyping Algorithm for Sarcoidosis Using Diagnostic Codes in Electronic Medical Records: A Pilot Study from Two Veterans Affairs Medical Centers | BackgroundThe accuracy of identifying sarcoidosis cases in electronic medical records (EMR) using diagnostic codes is unknown.
MethodsTo estimate the statistical performance of using diagnostic codes, ICD-9 and ICD-10 diagnostic codes in identifying sarcoidosis cases in EMR, we searched the San Francisco and Palo Alto Veterans Affairs (VA) medical centers EMR and randomly selected 200 patients coded as sarcoidosis. To further improve diagnostic accuracy, we developed an "index of suspicion" algorithm to identify probable sarcoidosis cases based on clinical and radiographic features. We then determined the positive predictive value (PPV) of diagnosing sarcoidosis by two computational methods using ICD only and ICD plus the "index of suspicion" against the gold standard developed through manual chart review based on the American Thoracic Society (ATS) practice guideline. Finally, we determined healthcare providers adherence to the guidelines using a new scoring system.
ResultsThe PPV of identifying sarcoidosis cases in VA EMR using ICD codes only was 71% (95%CI=64.7%-77.3%). The inclusion of our construct of "index of suspicion" along with the ICD codes significantly increased the PPV to 90% (95%CI=85.2%-94.6%). The care of sarcoidosis patients was more likely to be classified as "Fully" or "Substantially" adherent with the ATS practice guideline if their managing provider was a specialist (45% of primary care providers vs. 74% of specialists; P=0.008).
ConclusionsAlthough ICD codes can be used as reasonable classifiers to identify sarcoidosis cases within EMR, using computational algorithms to extract clinical and radiographic information ("index of suspicion") from unstructured data could significantly improve case identification accuracy.
HighlightsO_LIIdentifying sarcoidosis cases using diagnostic codes in EMR has low accuracy.
C_LIO_LI"Unstructured data" contain information useful in identifying cases of sarcoidosis.
C_LIO_LIComputational algorithms could improve the accuracy and efficiency of case identification in EMR.
C_LIO_LIWe introduce a new scoring system for assessing healthcare providers compliance with the American Thoracic Society (ATS) practice guideline.
C_LIO_LICompliance scoring could help automatically assess sarcoidosis patients care delivery.
C_LI | respiratory medicine |
10.1101/2021.02.02.21250980 | Performance of a Computational Phenotyping Algorithm for Sarcoidosis Using Diagnostic Codes in Electronic Medical Records: A Pilot Study from Two Veterans Affairs Medical Centers | BackgroundThe accuracy of identifying sarcoidosis cases in electronic medical records (EMR) using diagnostic codes is unknown.
MethodsTo estimate the statistical performance of using diagnostic codes, ICD-9 and ICD-10 diagnostic codes in identifying sarcoidosis cases in EMR, we searched the San Francisco and Palo Alto Veterans Affairs (VA) medical centers EMR and randomly selected 200 patients coded as sarcoidosis. To further improve diagnostic accuracy, we developed an "index of suspicion" algorithm to identify probable sarcoidosis cases based on clinical and radiographic features. We then determined the positive predictive value (PPV) of diagnosing sarcoidosis by two computational methods using ICD only and ICD plus the "index of suspicion" against the gold standard developed through manual chart review based on the American Thoracic Society (ATS) practice guideline. Finally, we determined healthcare providers adherence to the guidelines using a new scoring system.
ResultsThe PPV of identifying sarcoidosis cases in VA EMR using ICD codes only was 71% (95%CI=64.7%-77.3%). The inclusion of our construct of "index of suspicion" along with the ICD codes significantly increased the PPV to 90% (95%CI=85.2%-94.6%). The care of sarcoidosis patients was more likely to be classified as "Fully" or "Substantially" adherent with the ATS practice guideline if their managing provider was a specialist (45% of primary care providers vs. 74% of specialists; P=0.008).
ConclusionsAlthough ICD codes can be used as reasonable classifiers to identify sarcoidosis cases within EMR, using computational algorithms to extract clinical and radiographic information ("index of suspicion") from unstructured data could significantly improve case identification accuracy.
HighlightsO_LIIdentifying sarcoidosis cases using diagnostic codes in EMR has low accuracy.
C_LIO_LI"Unstructured data" contain information useful in identifying cases of sarcoidosis.
C_LIO_LIComputational algorithms could improve the accuracy and efficiency of case identification in EMR.
C_LIO_LIWe introduce a new scoring system for assessing healthcare providers compliance with the American Thoracic Society (ATS) practice guideline.
C_LIO_LICompliance scoring could help automatically assess sarcoidosis patients care delivery.
C_LI | respiratory medicine |
10.1101/2021.02.01.21250939 | Trends in Technology Usage for Parkinson's Disease Assessment: A Systematic Review | Parkinsons disease (PD) is a neurological disorder with complicated and disabling motor and non-motor symptoms. The complexity of PD pathology is amplified further due to its dependency on patient diaries and the neurologists subjective assessment of clinical scales. This challenge can be addressed by the advances in mobile technology, which can enable objective, accurate, and continuous patient monitoring. Indeed, a significant amount of recent work explores new cost-effective and subjective assessment methods of PD symptoms. For example, smart technologies, such as wearable sensors, have been used to analyze a PD patients symptoms to assess their disease progression and even to detect signs in their nascent stage for early diagnosis of PD.
This review focuses on the use of modern wearable and mobile equipment for PD applications in the last decade. Four significant fields of research were identified: Assistance to Diagnosis, Prognosis or Monitoring of Symptoms and their Severity, Predicting Response to Treatment, and Assistance to Therapy or Rehabilitation. This study starts with 31,940 articles published between January 2008 and December 2019 in the following four databases: Pubmed Central, Science Direct, IEEE Xplore and MDPI. A total of 976 papers are manually investigated and included in this review after removing unrelated articles, duplicate entries, publications in languages other than English, and other articles that did not fulfill the selection criteria. Our analysis shows that the numbers of published papers every year has increased at a constant rate from 2008 to 2015, while the rate of increase has significantly grown from 2016 to 2019. Majority of the papers (62%) were published in the last four years, and 21% papers in just 2019. In terms of the symptoms, gait and tremor are two major ones that researchers have focused on. The trend shows the growing interest in assessing Parkinsons Disease with wearable devices in the last decade, particularly in the last 4 years. Our automated script makes the review easily reproducible for publications published in the future. | neurology |
10.1101/2021.02.02.21249720 | Salivary profiles of 11 oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia | ContextSeveral studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD).
ObjectiveTo analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD.
Design, Setting, and ParticipantsCross-sectional single center study including 34 patients with classic 21OHD (men=14; women=20) and 32 BMI- and age-matched controls (men=15; women=17).
Outcome MeasuresSalivary concentrations of the following steroids were analyzed by LC-MS/MS: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11{beta}-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT).
ResultsSimilar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: male patients {Delta}mean = 79 %; male controls {Delta}mean = 81%; female patients {Delta}mean = 33 %; female controls {Delta}mean = 91 %; 11KT: male patients {Delta}mean = 64 %; male controls {Delta}mean = 60 %; female patients {Delta}mean = 49 %; female controls {Delta}mean = 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p)male = 0.741**; r(p)female = 0.842****), and 11OHA4 (r(p)male = 0.385n.s.; r(p)female = 0.527*) were observed in patients but not in controls.
ConclusionsAdrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control. | endocrinology |
10.1101/2021.02.03.21250992 | Using a household structured branching process to analyse contact tracing in the SARS-CoV-2 pandemic | We explore strategies of contact tracing, case isolation and quarantine of exposed contacts to control the SARS-CoV-2 epidemic using a branching process model with household structure. This structure reflects higher transmission risks among household members than among non-household members, and is also the level at which physical distancing policies have been applied. We explore implementation choices that make use of household structure, and investigate strategies including two-step tracing, backwards tracing, smartphone tracing and tracing upon symptom report rather than test results. The primary model outcome is the effect on the growth rate of the epidemic under contact tracing in combination with different levels of physical distancing, and we investigate epidemic extinction times to indicate the time period over which interventions must be sustained. We consider effects of non-uptake of isolation/quarantine, non-adherence, and declining recall of contacts over time. We find that compared to self-isolation of cases but no contact tracing, a household-based contact tracing strategy allows for some relaxation of physical distancing measures; however, it is unable to completely control the epidemic in the absence of other measures. Even assuming no imported cases and sustainment of moderate distancing, testing and tracing efforts, the time to bring the epidemic to extinction could be in the order of months to years. | epidemiology |
10.1101/2021.02.02.21251039 | Could the new COVID-19 mutant strain undermine vaccination efforts? A mathematical modelling approach for estimating the spread of the UK mutant strain using Ontario, Canada, as a case study | BackgroundInfections represent highly dynamic processes, characterized by evolutionary changes and events that involve both the pathogen and the host. Among infectious agents, viruses, such as the "Severe Acute Respiratory Syndrome-related Coronavirus type 2" (SARS-CoV-2), the infectious agent responsible for the currently ongoing "Coronavirus disease 2019" (COVID-2019) pandemic, have a particularly high mutation rate. Taking into account the mutational landscape of an infectious agent, it is important to shed light on its evolution capability over time. As new, more infectious strains of COVID-19 emerge around the world, it is imperative to estimate when these new strains may overtake the wild-type strain in different populations. Therefore, we developed a general-purpose framework to estimate the time at which a mutant variant is able to takeover a wild-type strain during an emerging infectious diseases outbreak. In this study, we used COVID-19 as a case-study, but the model is adaptable to any emerging pathogens.
Methods and findingsWe devise a two-strain mathematical framework, to model a wild- and a mutant-type viral population and fit cumulative case data to parameterize the model, using Ontario as a case study. We found that, in the context of under-reporting and the current case levels, a variant strain is unlikely to dominate until March/April 2021. Current non-pharmaceutical interventions in Ontario need to be kept in place longer even with vaccination in order to prevent another outbreak. The spread of a variant strain in Ontario will mostly likely be observed by a widened peak of the daily reported cases. If vaccine efficacy is maintained across strains, then it is still possible to have an immune population by end of 2021.
ConclusionsOur findings have important practical implications in terms of public health as policy-and decision-makers are equipped with a mathematical tool that can enable the estimation of the take-over of a mutant strain of an emerging infectious disease. | epidemiology |
10.1101/2021.02.02.21250515 | Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank | BackgroundThe causal relevance of elevated blood pressure for several cardiovascular diseases is uncertain, as is the population impact of blood pressure lowering on risk of cardiovascular diseases more broadly. This study systematically assesses evidence of causality for various cardiovascular diseases in a two-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP).
Methods and ResultsWe investigated associations of genetically-predicted SBP as predicted by 256 genetic variants with 21 cardiovascular diseases in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376,703 participants of European ancestry aged 40-69 years at baseline. Genetically-predicted SBP was positively associated with 14 of the outcomes (p<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease, population reductions in SBP were predicted to result in an overall 16.9% (95% confidence interval (CI): 12.2-21.3%) decrease in morbidity for a 5 mmHg decrease from a population mean of 137.7 mmHg, 30.8% (95% CI: 22.8-38.0%) for a 10 mmHg decrease, and 56.2% (95% CI: 43.7-65.9%) decrease for a 22.7 mmHg decrease in SBP (22.7 mmHg represents a shift from the current mean SBP to 115 mmHg).
ConclusionsRisk of many cardiovascular diseases is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure. | epidemiology |
10.1101/2021.02.02.21250515 | Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank | BackgroundThe causal relevance of elevated blood pressure for several cardiovascular diseases is uncertain, as is the population impact of blood pressure lowering on risk of cardiovascular diseases more broadly. This study systematically assesses evidence of causality for various cardiovascular diseases in a two-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP).
Methods and ResultsWe investigated associations of genetically-predicted SBP as predicted by 256 genetic variants with 21 cardiovascular diseases in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376,703 participants of European ancestry aged 40-69 years at baseline. Genetically-predicted SBP was positively associated with 14 of the outcomes (p<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease, population reductions in SBP were predicted to result in an overall 16.9% (95% confidence interval (CI): 12.2-21.3%) decrease in morbidity for a 5 mmHg decrease from a population mean of 137.7 mmHg, 30.8% (95% CI: 22.8-38.0%) for a 10 mmHg decrease, and 56.2% (95% CI: 43.7-65.9%) decrease for a 22.7 mmHg decrease in SBP (22.7 mmHg represents a shift from the current mean SBP to 115 mmHg).
ConclusionsRisk of many cardiovascular diseases is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure. | epidemiology |
10.1101/2021.02.02.21250515 | Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank | BackgroundThe causal relevance of elevated blood pressure for several cardiovascular diseases is uncertain, as is the population impact of blood pressure lowering on risk of cardiovascular diseases more broadly. This study systematically assesses evidence of causality for various cardiovascular diseases in a two-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP).
Methods and ResultsWe investigated associations of genetically-predicted SBP as predicted by 256 genetic variants with 21 cardiovascular diseases in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376,703 participants of European ancestry aged 40-69 years at baseline. Genetically-predicted SBP was positively associated with 14 of the outcomes (p<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease, population reductions in SBP were predicted to result in an overall 16.9% (95% confidence interval (CI): 12.2-21.3%) decrease in morbidity for a 5 mmHg decrease from a population mean of 137.7 mmHg, 30.8% (95% CI: 22.8-38.0%) for a 10 mmHg decrease, and 56.2% (95% CI: 43.7-65.9%) decrease for a 22.7 mmHg decrease in SBP (22.7 mmHg represents a shift from the current mean SBP to 115 mmHg).
ConclusionsRisk of many cardiovascular diseases is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure. | epidemiology |
10.1101/2021.02.01.21249903 | Quantifying transmissibility of COVID-19 and impact of intervention within long-term health care facilities | Estimates of the basic reproduction number (R0) for Coronavirus disease 2019 (COVID-19) are particularly variable in the context of transmission within locations such as long-term health care (LTHC) facilities. We sought to characterise the heterogeneity of R0 across known outbreaks within these facilities. We used a unique comprehensive dataset of all outbreaks that have occurred within LTHC facilities in British Columbia, Canada. We estimated R0 with a Bayesian hierarchical dynamic model of susceptible, exposed, infected, and recovered individuals, that incorporates heterogeneity of R0 between facilities. We further compared these estimates to those obtained with standard methods that utilize the exponential growth rate and maximum likelihood. The total size of an outbreak varied dramatically, with a range of attack rates of 2%-86%. The Bayesian analysis provides more constrained overall estimates of R0 = 2.19 (90% CrI [credible interval] 0.19-6.69) than standard methods, with a range within facilities of 0.48-10.08. We further estimated that intervention led to 57% (47%-66%) of all cases being averted within the LTHC facilities, or 73% (63%-78%) when using a model with multi-level intervention effect. Understanding the risks and impact of intervention are essential in planning during the ongoing global pandemic, particularly in high-risk environments such as LTHC facilities. | epidemiology |
10.1101/2021.02.01.21249903 | Quantifying transmissibility of COVID-19 and impact of intervention within long-term health care facilities | Estimates of the basic reproduction number (R0) for Coronavirus disease 2019 (COVID-19) are particularly variable in the context of transmission within locations such as long-term health care (LTHC) facilities. We sought to characterise the heterogeneity of R0 across known outbreaks within these facilities. We used a unique comprehensive dataset of all outbreaks that have occurred within LTHC facilities in British Columbia, Canada. We estimated R0 with a Bayesian hierarchical dynamic model of susceptible, exposed, infected, and recovered individuals, that incorporates heterogeneity of R0 between facilities. We further compared these estimates to those obtained with standard methods that utilize the exponential growth rate and maximum likelihood. The total size of an outbreak varied dramatically, with a range of attack rates of 2%-86%. The Bayesian analysis provides more constrained overall estimates of R0 = 2.19 (90% CrI [credible interval] 0.19-6.69) than standard methods, with a range within facilities of 0.48-10.08. We further estimated that intervention led to 57% (47%-66%) of all cases being averted within the LTHC facilities, or 73% (63%-78%) when using a model with multi-level intervention effect. Understanding the risks and impact of intervention are essential in planning during the ongoing global pandemic, particularly in high-risk environments such as LTHC facilities. | epidemiology |
10.1101/2021.02.02.21251042 | Mental Health, Substance Use, and Suicidal Ideation Among Unpaid Caregivers in the United States During the COVID-19 Pandemic: Relationships to Age, Race/Ethnicity, Employment, and Caregiver Intensity | ObjectivesTo estimate the prevalence of unpaid caregiving during the coronavirus disease 2019 (COVID-19) pandemic, and to identify factors associated with adverse mental health symptoms, substance use, and suicidal ideation in this population, which provides critical support in health care systems by providing care to older adults and those with chronic conditions.
MethodsIn June 2020, Internet-based surveys with questions about demographics, caregiving responsibilities, and mental health were administered to US adults aged [≥]18 years. Demographic quota sampling and survey weighting to improve cross-sectional sample representativeness of age, gender, and race/ethnicity. Prevalence ratios for adverse mental health symptoms were estimated using multivariable Poisson regressions.
ResultsOf 9,896 eligible invited adults, 5,412 (54.7%) completed surveys; 5,011 (92.6%) respondents met screening criteria and were analysed, including 1,362 (27.2%) caregivers. Caregivers had higher prevalences of adverse mental health symptoms than non-caregivers, including anxiety or depressive disorder symptoms (57.6% vs 21.5%, respectively, p<0.0001) having recently seriously considered suicide (33.4% vs 3.7%, p<0.0001). Symptoms were more common among caregivers who were young vs older adults (e.g., aged 18-24 vs [≥]65 years, aPR 2.75, 95% CI 1.95-3.88, p<0.0001), Hispanic or Latino vs non-Hispanic White (1.14, 1.04-1.25, p=0.0044), living with vs without disabilities (1.18, 1.10-1.26, p<0.0001), and with moderate and high vs low Caregiver Intensity Index scores (2.31, 1.65-3.23; 2.81, 2.00-3.94; both p<0.0001). Suicidal ideation was more prevalent among non-Hispanic Black vs non-Hispanic White caregivers (1.48, 1.15-1.90, p=0.0022).
ConclusionsCaregivers, who accounted for one in four US adult respondents in this nationally representative sample, more commonly reported adverse mental health symptoms than non-caregivers. Increased visibility of and access to mental health care resources are urgently needed to address mental health challenges of caregiving. | psychiatry and clinical psychology |