Among the different drugs involved in pediatric exposures and poisonings, opioids are the most important, given their rise in nonmedical use. Opioid poisonings in children can result in serious symptoms or complications, including respiratory disorders such as apnea, respiratory failure, and respiratory depression; psychiatric or nervous system disorders such as agitation, seizures, and coma; and cardiac disorders such as tachycardia, bradycardia, and cardiac arrest. Opioid poisonings in children can have delayed onset of symptoms as well as severe and prolonged toxic effects. Many studies have examined the economic burden of opioid poisoning in the general population, but very little is known about the pediatric population.To estimate the economic burden associated with pediatric prescription opioid poisonings.This study examined opioid poisonings in pediatric patients, defined as patients aged less than 18 years, for the 2012 base year. Costs were estimated using the 2012 Nationwide Emergency Department Sample (NEDS), Kids’ Inpatient Database (KID), Multiple Cause-of-Death (MCOD) file, and other published sources, while applying a societal perspective. The Bottom Up approach was used to estimate the total cost of pediatric prescription opioid poisonings. Direct costs included costs associated with emergency department (ED) visits, hospitalizations, and ambulance transports. Indirect costs were estimated using the human capital method and included productivity costs due to caregivers’ absenteeism and premature mortality among children. Descriptive statistics were employed in calculating costs.The total costs of pediatric prescription opioid poisonings and exposure in the United States were $230.8 million in 2012. Total direct costs were estimated to be over $21.1 million, the majority resulting from prescription opioid poisoning-related inpatient stays. Total indirect (productivity) costs were calculated at $209.7 million, and 98.6% of these costs were attributed to opioid poisoning-related mortality. Pediatric prescription opioid poisoning-related ED visits, inpatient stays, and deaths were most common in patients aged 13-17 years and those in mid to large urban areas. Most were unintentional.Pediatric prescription opioid poisonings resulted in direct and indirect costs of $230.8 million in 2012. While these costs are low in comparison with the costs of prescription opioid poisoning in the general population, the number of pediatric poisonings represents only a small fraction of total poisonings. Quantified costs associated with pediatric prescription opioid poisonings can help decision makers to understand the economic trade-offs in planning interventions. What is already known about this subjectAlthough pediatric fatalities related to unintentional drug poisonings have decreased over the years, the number of pediatric unintentional drug exposures and poisonings reported to poison centers and the associated morbidity  have risen.Some studies have examined the economic burden of opioid poisoning in the general population (including adults), but very little is known about the pediatric population.Presentation of opioid poisonings in children can differ from adults.What this study addsThis study examines the economic burden of opioid poisonings in pediatric patients by examining direct and indirect costs.Indirect costs associated with pediatric prescription opioid poisonings are substantial due to the productivity losses incurred, and total inpatient costs were about twice the total ED costs.Pediatric prescription opioid poisoning-related ED visits, inpatient stays, and deaths were most common in patients aged 13-17 years and those in mid to large urban areas; most were unintentional.2 In the pediatric population, prescription and illicit opioid-related mortality rates increased from 0.22 to 0.81 per 100,000 between 1999 and 2016, an increase of 268.2%.3 The 5-year prevalence rates of pediatric prescription opioid exposures from 2010 to 2014 was 22.6 per 100,000 children and decreased from 25.5 to 20 per 100,000 children. During this time, the pediatric prescription opioid poisonings rate was 11.8 per 100,000 children.4The Centers for Disease Control and Prevention reported that drug overdoses increased more than 4 times between 1999 and 2017. About 399,230 people died from an overdose involving a prescription or illicit opioid during this time period. In 2017 alone, more than 70,000 people died from drug overdoses in the United States, and about 68% of these involved a prescription or illicit opioid.4 They often result in symptoms such as respiratory depression and are typically managed with opioid antagonists and oxygen supplementation.5 According to the Council of Economic Advisers, the total economic burden of the opioid crisis in the United States was estimated to be $696 billion in 2018, 3.4% of the gross domestic product, and over $2.5 trillion from 2015 to 2018. These estimates include “the value of lost lives, as well as increases in healthcare and substance abuse treatment costs, increases in criminal justice costs, and reductions in productivity.”6 According to Gaither et al. (2016), about 8,986 children and adolescents died from prescription and illicit opioid poisonings between 1999 and 2016.3 Pediatric hospitalization rates increased by 2-fold across age all groups between 1997 and 2012, and the number of pediatric opioid-related hospitalizations requiring critical care doubled from 797 in 2004 to 1,504 in 2015.8 Yokell et al. (2014) examined mean charges for emergency department (ED) visits in 2010 U.S. dollars.9 They reported 92,209 ED visits for prescription opioid poisonings with a mean charge of $3,640. A total of 4,998 visits were for pediatric patients.Opioid poisonings involve an opioid exposure resulting in a corresponding clinical symptom or medical effect.9 Despite the data on the economic burden of the opioid crisis in the general population, very little is known about the total economic burden of opioid poisonings, specifically, in the pediatric population. As a result, the objective of this study was to estimate the direct and indirect costs associated with pediatric prescription opioid poisonings. We defined pediatric patients as those aged less than 18 years.The epidemiology, health care resources use (HCRU), and costs of opioid poisonings can vary based on age.10 The KID is the largest publicly available all-payer pediatric inpatient care database in the United States. It yields national estimates on inpatient stays for patients aged younger than 21 years.11 The MCOD is a county-level mortality and population database that provides information on demographics and the underlying cause of all deaths among U.S. residents, including pediatric patients.12 NEDS and KID are samples of the relevant populations that include hospital-level weights that allow the researcher to develop nationally representative estimates. To do so, each observation  is multiplied by its respective weight. MCOD does not need weights to provide nationally representative estimates because it records all U.S. deaths.This was a retrospective, cross-sectional study that applied a societal perspective. Study data came from the Healthcare Cost and Utilization Project (HCUP) 2012 Nationwide Emergency Department Sample (NEDS), the 2012 Kids’ Inpatient Database (KID), and the National Vital Statistics System’s 2012 Mortality Multiple Cause-of-Death (MCOD) files. The NEDS is the largest all-payer ED database in the United States. It captures information on all ED visits including those that resulted in hospital admissions.International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in any listed diagnosis field . Several studies have used data from NEDS and KID databases in a similar manner to evaluate prescription opioid abuse-related events, including opioid poisonings.16 Intentionality of opioid poisonings was identified as unintentional, intentional, or undetermined using these ICD-9-CM codes (E-codes). Data are recorded for up to 4 E-codes for each visit or stay. Records that did not have a specific E-code were initially classified as missing. This resulted in about 7% of ED visits with a missing or unknown intentionality in NEDS. However, NEDS contains certain injury-related variables including intent  on every record. Information from these injury-related variables was used to impute intentionality to the extent possible. For instance, if the record was classified as undetermined (using E-code 980.0) or missing, but had an indicator for self-harm, then the record was reclassified as intentional. Such injury-related variables are not recorded in the KID, and inpatient stays that did not have a specific E-code were classified as unknown.Discharge records from NEDS and KID were extracted for pediatric patients with 1 or more opioid poisoning-related 18We estimated direct medical costs and indirect costs. Direct costs included costs associated with ED visits, hospitalizations, and ambulance transports. Indirect costs were estimated using the human capital method and included productivity costs due to caregivers’ absenteeism and premature mortality among children. All cost calculations were made for the 2012 base year, since that was the most recent data available at the time of data acquisition. Costs from other years were adjusted to 2012 U.S. dollars (USD) using the Bureau of Labor Statistics’ (BLS) medical care component of the Consumer Price Index or the BLS Employment Cost Index for civilian workers.19 NEDS does not provide CCRs for ED charges. However, HCUP has estimated ED CCRs by grouping hospitals by characteristics such as hospital ownership and location. We used these group average ED CCRs to convert ED charges to costs.19 Information on pediatric prescription opioid poisoning ED visits, inpatient stays, and deaths are shown in Inpatient stay costs were obtained by multiplying inpatient charges with hospital-specific cost-to-charge ratios (CCR) provided by HCUP.20 The most common codes were for other diagnostic procedures ; other therapeutic procedures; microscopic examination ; laboratory-chemistry and hematology; and medications . The sum of payment amounts for all CPT codes was calculated for each ED visit. Total ED costs were calculated as the sum of facility and physician costs. Outliers in ED charge data were examined (top/bottom 5%). Upon manual inspection, these charges looked reasonable.Costs of ED visits and inpatient stays included a facility charge and a physician charge. The facility charge covered all components of care, such as nursing services, rent and utilities, medications, and other supplies, except for physician charges. Total ED facility costs were calculated as the product of the total number of ED visits and the mean facility cost per visit. Physician costs were calculated by linking Current Procedural Terminology (CPT) codes from NEDS to the Centers for Medicare & Medicaid Services (CMS) 2012 Physician Fee Schedule.ED facility charges were missing for 182 (17.4%) ED visits. We tried several different imputation methods for these missing data . ImputatImputation 4 used Markov Chain Monte Carlo (MCMC), a multiple imputation method, to impute missing charges. After examining the several imputation methods for missing data , we usedCPT codes were missing for 340 (32.4%) ED visits. Missing physician costs were imputed using techniques similar to those previously described . MCMC wa21 This consisted of calculating the average charge per day for each stay and identifying the top 1% of charges per day. The difference between the 75th percentile and median charge per day was multiplied by 4 and added to the median. This value, $45,600 per day, was the cutoff value for suspiciously high charges. Two observations were above this cutoff value and were excluded from cost analyses.Total inpatient facility costs were calculated as the product of the number of inpatient stays and the estimated mean cost of hospitalization from KID. Outliers were examined using the approach described by Friedman et al. (2008).Inpatient facility charges were missing for 20 (1.5%) inpatient stays. MCMC was used to impute missing values for inpatient stays . The imp20 Inpatient stays ≤ 1 day were assigned CPT codes for initial care (99222) and discharge day care (99238). Inpatient stays > 1 day were also assigned the CPT code for subsequent care (99231) for every day between admission and discharge. Total inpatient costs were calculated as the sum of inpatient facility and physician costs.KID does not include CPT codes for inpatient physician costs, so 3 standard CPT codes and their national payment amounts were assumed for all inpatient stays: 99222 “initial hospital care” billed at $133.09 per day; 99231 “subsequent hospital care” billed at $38.12 per day; and 99238 “hospital discharge day” billed at $69.78 per day. The national payment amounts for these codes were taken from the CMS 2012 Physician Fee Schedule.22 Friedman et al. used a similar estimate.21 However, these analyses were not specific to the pediatric population. Adults with opioid poisoning may avoid ED transport for reasons such as fear of legal involvement or discrimination. These reasons may not be a concern for children. Hence, we assumed ambulance runs for the base case to be slightly higher at 50%. This estimate was multiplied by cost per ambulance run, $429 in 2010, to compute total ambulance costs.23 Total direct medical costs were calculated as the sum of total ED costs and total inpatient costs.Ambulance costs, a direct medical cost, were not available in HCUP databases, so we used estimates from the literature. Larkin et al. (2006) estimated ambulance use in about 39% of injury-related ED visits.24 A discount rate of 3% was used.25 The 2012 MCOD was used to estimate pediatric deaths from opioid poisonings. Records of decedents aged less than 18 years with a poisoning-related International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code in the cause of death field were extracted . From these records, decedents who had an indication of opioid as a contributing cause of death were identified using the opioid-specific ICD-10-CM code in the record axis fields .We estimated indirect costs for pediatric patients who died from opioid poisoning as the present value of expected future productivity (PVFP), which included earnings and household services. PVFPs were obtained from Grosse et al. (2009).24 DPV is the sum of daily market production and daily household production, and it was obtained from Grosse et al.24 Indirect costs for ED visits and inpatient stays were calculated as the product of absent days, DPV, and the weighted number of visits. DPV values were reported in 2007 USD and inflated to 2012 USD using the BLS Employment Cost Index for all civilian workers.18 The DPV in 2012 USD was estimated at $142.99. We assumed 1 recovery day per ED visit. Recovery days for inpatient stays were based on the severity of the opioid poisoning. Severity was identified using the APR-DRG severity index in the KID. Average length of stay for inpatient stay was calculated by severity group . One, 3, and 7 recovery days were assumed for none to minor, moderate, and major to extreme severity groups, respectively. A maximum of 1 week of recuperation time was assumed based on previous poisoning-related hospital analyses.27We estimated indirect costs for caregivers as the product of days lost from productive activity and average daily production value (DPV).Multiple one-way sensitivity analyses were performed to examine the effects of assumptions on our estimates . The upper and lower bounds of each parameter were determined based on confidence intervals provided by the data. When a confidence interval was unavailable, the base case was varied based on reasonable assumptions. All analyses were done in SAS version 9.4  and Microsoft Excel 2013 .Pediatric prescription opioid poisoning-related ED visits, inpatient stays, and deaths were most common in patients aged 13-17 years and those in mid to large urban areas. Most were unintentional: 64.6% of ED visits, 41.7% of inpatient stays, and 77.2% of deaths in the weighted population .There was a weighted total of 4,584  ED visits and 1,874  inpatient stays for pediatric prescription opioid poisonings in 2012. Mean hospital and physician costs for ED and inpatient visits as calculated by various imputation methods are summarized in Total morbidity-related indirect costs in 2012 due to caregiver absenteeism were estimated to be over $2.9 million. Inpatient stays constituted about 55.5% of morbidity-related costs and ED visits accounted for the remainder .The MCOD file indicated that there were 123 pediatric prescription opioid poisoning-related deaths in the United States in 2012. About 69.9% were teenagers, and 26% were under the age of 6 years. Total mortality costs were estimated to be $206.8 million. Total indirect costs for pediatric prescription opioid poisonings were estimated at approximately $209.7 million. Mortality-related costs constituted about 98.6% of this amount. The total costs of pediatric prescription opioid poisonings in the United States were calculated at $230.8 million.Cost estimates were most sensitive to the discount rate of PVFP  estimated mean charges for drug poisoning-related ED visits at $2,208, in 2012 USD.29 Yokell et al. calculated mean charges for prescription opioid poisoning ED visits at $3,833-$4,339 and mean hospitalization charges at $31,058-$34,374, in 2012 USD.9 Tadros et al. (2016) estimated mean ED charges at $1,840 and mean inpatient charges to be $14,325 based on NEDS data from 2006 to 2012.14 Inocencio et al. (2013) estimated the mean ED cost to be $1,967 and inpatient stay costs to be $9,696 in 2011 USD.26The estimated mean cost for ED visits and inpatient stays related to pediatric prescription opioid poisonings in the United States were $1,496 and $7,045, respectively, in 2012. As a rough comparison, pediatric opioid poisoning-related inpatient costs are higher than the national mean costs of $6,415 for all-hospital stays among pediatric patients.29 It is well known that hospital and ED charges are substantially higher than costs. Inocencio et al.’s estimates were somewhat higher than those of the current study. However, Inocencio et al.’s estimates were for the general population, not just those aged under 18 years, and included poisonings due to heroin.26 Prognosis and management of opioid poisonings in adults can vary considerably from those in children because of factors such as higher prevalence of multiple health conditions, chronic opioid use and misuse, substance use disorders, or polypharmacy.30 These factors may result in higher cost of treatment following an opioid poisoning in adults compared with children.Yokell et al., Tadros et al., and Xiang et al. reported charges rather than costs.26 Indirect costs consisted of absenteeism costs of $261 million and costs due to premature mortality of about $14 billion in 2012 USD. A major factor explaining the large differences is that our estimates represented only pediatric patients, while Inocencio et al.’s estimates represented all ages. The pediatric population represents a very small percentage of the total economic burden of opioid poisoning. Yokell et al. reported that only 4.4% of patients presenting to EDs for opioid poisonings were aged less than 18 years.9 Similarly, Gomes et al. (2018) reported that only 0.2% of opioid-related deaths in 2016 were in the 0-14 years age group and that 9.5% were in the 15-24 years group.31 A recently released report suggests that 0.1% of opioid-related deaths in 2018 were in those aged 0-14 years and 8.4% in those aged 15-24 years.32 In addition, opioid poisonings in adults are more likely to be intentional and severe, resulting in more expensive hospital visits compared with children.35We estimated total direct costs of pediatric prescription opioid poisoning to be $21 million and total indirect costs to be nearly $210 million. Indirect costs consisted of $2.9 million due to absenteeism and $207 million due to premature mortality. In comparison, Inocencio et al. estimated the total direct cost of prescription opioid poisoning in the general population to be $1.8 billion and the total indirect cost at $14.1 billion.36While our estimates of direct and indirect costs are small compared with costs in the general population, it seems likely that the intangible costs of poisonings are particularly high in the pediatric population. Poisonings of children result in fear and anxiety in parents and caregivers; poisoning-related deaths cause overwhelming grief and suffering. Feigelman et al. (2011) have reported that parents who lost a child to a drug overdose experience substantially more grief, stigmatization, and depression than those have lost children to nondrug-related accidents or natural causes.4 Many interventions that could decrease unintentional poisonings, such as safety locks on cabinets, storage of prescription opioids in areas that young children cannot reach, and prescription drug take-back and disposal programs, are relatively inexpensive. As a result, these interventions could be cost-effective despite the relatively low economic burden of pediatric prescription opioid poisonings.Patel et al. (2019) found that the majority of pediatric prescription opioid exposures are unintentional.These analyses have several limitations. The summary CCR data used for ED analyses were from the 2003 HCUP preliminary report. CCRs may have changed since 2003, but there are no updated CCRs. Outcomes and costs related to long-term disability or postdischarge care following an opioid poisoning hospitalization could not be examined in the current data; hence, our study underestimated the true economic burden of pediatric prescription opioid poisonings. CPT codes were not available in the inpatient database, so physician costs associated with hospitalizations were estimated based on several fundamental hospital stay-related CPT codes. Some hospitalizations may have required more physician services. This had minimal effect on the cost estimates, since physician costs were less than 4% of inpatient costs and less than 0.1% of direct medical costs. Our study did not include direct nonmedical costs such as meals and accommodations for caregivers. We made assumptions about the proportion of poisonings that would require ambulance runs and the days of productivity caregivers would miss. Our sensitivity analyses indicated these assumptions had negligible effects on our results.The data used in the study were from 2012. While the prevalence of opioid-related poisonings and the unit cost of medical resources may have changed since then, the results are still useful. For example, our results point out that the vast majority of the costs of opioid-related poisonings is related to premature mortality. By comparison, the costs of ED visits and inpatient stays are relatively small. Further, in the absence of more recent data, the mean cost estimates from this study could be adjusted to current figures using the Consumer Price Index.Quantifying the costs of pediatric prescription opioid poisonings can help decision makers understand economic trade-offs in planning interventions. Our study estimated the total economic burden of pediatric prescription opioid poisonings at $230.8 million in 2012, of which $21.1 million were from direct medical costs and $209.7 million from productivity losses. Decision makers should also consider the unmeasured, but probably large, intangible costs in this population.


Quarantine is a common public health intervention that is often used to curb pandemics of infectious diseases. Quarantine is the intentional separation of people who are either suspected or confirmed to be infected with a contagious virus from the uninfected population. The goal of this study was to determine the expected economic cost for healthcare systems due to quarantine in the case of the monkeypox virus. A systematic literature review of studies on similar virus outbreaks was performed. The findings affirm that quarantine effectively mitigates the spread of a virus outbreak, but it has high direct and indirect costs that can only be justifiable for a dangerous virus with high mortality. The monkeypox virus presents moderate risk, unlike high-risk diseases for which quarantine is mandatory. The study recommends the introduction of mass vaccination programs and public awareness and sensitization forums to inform the population about the best behavioral practices to curb the spread of monkeypox virus. Since May 13, 2022, monkeypox infections have been reported in various nations worldwide, affecting more people outside of Africa than ever before. As of June 6, 2022, a total of 1019 cases of monkeypox were reported from 29 nations. Regions such as North America, Europe, and Australia, where the virus is not endemic, have reported alarming cases. To date, the United Kingdom (UK) has reported a majority of the infections, with 302 suspected and confirmed cases, followed by Spain (198 cases), Portugal (153 cases), Canada (80 cases), and the United States (US) (30 cases). Monkeypox is prevalent in its endemic regions of West and Central Africa. Countries such as the Democratic Republic of Congo (which has the highest infection rate), Central African Republic, Cameroon, Ivory Coast, Liberia, Gabon, the Democratic Republic of the Congo, Nigeria, and Sierra Leone have reported high rates of infections in the past. Although epidemiological investigations are still in progress, researchers have not correlated current infections with travel links to endemic areas. Consequently, the uncharacteristic spread of monkeypox outside of Africa with no travel links to the continent has created a sense of panic that the virus is now spreading globally.Monkeypox is a viral zoonosis that occurs when a person or animal is exposed to the monkeypox virus. Symptoms include rashes, swelling, head and muscle aches, fever, and back pain.The Centers for Disease Control and Prevention (CDC) in the US reported that the risk to the general public is currently low, but they encourage people to avoid close contact with those infected. These include people with genital and skin lesions, as well as infected or dead animals. The CDC also urges people exhibiting symptoms of the virus, such as unexplained skin rashes or lesions, to isolate themselves and reach out to the closest healthcare provider for guidance. The WHO recommends that people with suspected or confirmed infection be promptly isolated in a room with sufficient ventilation, a clean and dedicated bathroom, and staff. The CDC advises that isolation precautions be continued until all lesions have resolved, the scabs have eroded, and a new layer of skin has grown.Current available evidence from the World Health Organization (WHO) suggests the risk is greatest for those who have made close physical contact with those infected with the virus while they are symptomatic. The UK and Germany followed suit soon afterward, adding that people with a high risk of contracting the virus should self-isolate for at least 21 days. The UK Health Security Agency (UKHSA) notes that individuals like sexual partners, persons living within the same house, or any other person coming in contact with an infected person’s bodily fluids (notably sneeze or cough) should self-isolate.On May 20, 2022, Belgium became the first nation to enact a compulsory 21-day quarantine for patients confirmed to have been infected by the monkeypox virus. The president and government officials downplayed the spread and expected the impact of monkeypox to be minimal, especially provided that it has been monitored for decades and has existing vaccine doses and medications. The purpose of the current study was to investigate the expected economic cost for healthcare systems due to quarantine in the case of the monkeypox virus through a systematic review of literature.However, critics have described the move to quarantine monkeypox patients as unnecessary. President Joe Biden recently said that quarantines are not necessary to mitigate the spread of the monkeypox virus in the US.5 He further explained that the new pandemic does not warrant the same kind of concern as in the case of COVID-19.The current study was a systematic review of current literature. The goal was to find research the estimated economic cost burden for healthcare systems due to quarantine in the case of monkeypox virus outbreak. Different previous studies that focused on different virus outbreaks where quarantining was used as the primary virus mitigation method were reviewed. Conclusions were arrived at on the basis of the information found from the various studies and resources that were reviewed.The articles used in this literature review were obtained from different academic databases and peer reviewed open-source online research publishing websites. A total of 38 resources were first collected and after evaluation for their suitability in creating the necessary knowledge and findings for this study, only 29 of these were suitable for use in forming the basis for the findings of the current study.Different authors have researched the cost of quarantine, particularly the economic impact on the different aspects of the healthcare system. Despite these studies, there has not been a study that compares the overall economic impact of the monkeypox quarantine as the current study sought to investigate. Below is a systematic analysis of literature focused on the cost and benefit of quarantine strategies and the impact on the healthcare sector. In general, quarantine strategies have effectively reduced infection rates and delayed new infections over time. After modeling the 2003 severe acute respiratory syndrome (SARS) pandemic, Hsieh et al determined that quarantine prevented about 461 additional SARS infections and 62 more deaths in Taiwan. After studying SARS data from Hong Kong, Riley et al determined that public health interventions implemented during the SARS outbreak effectively reduced the contact rates among infectious people and the entire population.In a pandemic, quarantine and similar social distancing strategies are often enforced to curb viral spread, particularly when there are no vaccines or medicines to manage symptoms. Importantly, the research also showed that a reduced infection rate has a strong positive correlation with socioeconomic status. Indeed, quarantine is an effective measure to mitigate the spread of an infectious virus/disease. While quarantines have proved effective in curbing viral infections, critics have questioned the economic feasibility of such measures. Hence, it is vital to perform a cost-benefit analysis to assess the efficacy of quarantine in responding to the current monkeypox outbreak.Marshall evaluated the impact of quarantine on the infection and modified the SIR, a conventional epidemiology model used to mathematically simulate the spread of infectious diseases. The findings revealed that quarantines drastically minimize the rates of infection, thus limiting spikes that can overwhelm the health system. In research to determine the economic burden of COVID-19 in China, Jin et al calculated the unit costs of treatment in different regions using the healthcare industry salary index. The State Council reported that a total of 42,600 frontline workers attended to suspected or confirmed COVID-19 cases.The researchers estimated that the average risk subsidy per day for every frontline professional was Yen (¥) 300.Moreover, the researchers estimated that the healthcare cost of suspected cases of COVID-19 was ¥584.08 (US dollars [$] 84.53) for every individual. The average cost for the treatment of an individual confirmed to have contracted the virus was ¥22,061.94. The researchers calculated the routine healthcare expenses to be $0.31 billion. Inpatient treatment constituted 44.2% of routine healthcare expenses, while medications represented 32.5% (¥0.70 billion/¥2.15 billion). Overall, the healthcare expenses of the outbreak of COVID-19 in China for the initial 3 months of 2020 were estimated to amount to 0.62 billion USD.Direct healthcare costs include those associated with the creation and implementation of control programs, such as facility construction and frontline workers’ salaries. assessed the direct and indirect costs incurred due to quarantine for COVID-19 in Sri Lanka. The direct cost of quarantine was determined to be Rupees (Rs) 1610 per patient every day, and accommodation expenses accounted for 54% of the costs. The mean income loss from quarantining an informal sector worker for 14 days was Rs 13,800, and for a government-sector worker was Rs 30, 000. The loss of output as a result of placing primary contacts in quarantine was Rs 166 billion. The researchers concluded that as a disease evolves, quarantine guidelines must accommodate resource availability and disease burden.Gamage et al sought to calculate both the indirect and direct expenses of treating COVID-19 patients within a referral hospital setting and the economic burden of the COVID-19 pandemic in Iran in 2020.They concluded that the direct healthcare expenses amounted to $1,791,172, averaging $3,755 per person. Mubayi et al studied the relationship between quarantine, isolation, and financial implications using dynamical models. They compared 3 distinct quarantine methods implemented in addition to a single isolation approach, and analysis proved that a single policy (either quarantine or isolation) was enough to control an outbreak. Since isolation costs more than quarantine, mainly due to the cost and time spent constructing isolating facilities, the researchers recommended using a joint quarantine-isolation policy.Ghaffari et al In order do so, they compared the associated costs of quarantine in 2 different outbreak cases. In the first scenario, SARS was allowed to propagate throughout the study population without taking mitigation intervention. In the second scenario, quarantine was implemented at the beginning of the outbreak to contain the virus. The latter proved more rational, and the authors concluded that quarantine is effective in slowing the spread of infectious outbreaks while reducing expenditure compared to taking a passive approach.Those supporting quarantine measures suggest that such measures have a positive economic impact since expenses incurred lessen direct and indirect costs in the future. Gupta, Moyer, and Stern assessed the economic implications that Toronto experienced following the implementation of quarantine for patients suspected or confirmed to have SARS in the 2003 outbreak. The government spent an additional $1 million for protecting the jobs of individuals who had been quarantined. The government also had to set up an assistance office for SARS to look into the interests of quarantined or isolated employees, which came at a cost of $1 million. From these figures, Gupta at al estimated the direct expenses of the epidemic to be $12 million. On average, the study findings indicated that a SARS patient spent approximately 14 days in the hospital. The average cost of a single night in the intensive care unit in Canada was estimated to be $1,836.16 Findings from the study revealed that contagious and infectious diseases can effectively be contained through quarantine, which also reduces costs compared to not adopting any containment measure.Ontario’s finances for the first quarter of the 2003-2004 fiscal year indicate that the provincial government incurred costs amounting to $10 million for administrative activities for the containment of the SARS virus. estimated the productivity losses from COVID-19 in China to amount to ¥2641.61 billion (US $ 382.29 billion). This loss was attributed to the lost working time as the population’s movement was restricted, regardless of their status. The productivity loss was highest in areas with the greatest numbers of employed people, such as Guangdong, Jiangsu, and Beijing. The researchers concluded that contact tracing and quarantine measures reduce the number of infections but result in great inconvenience to the general population, as well as subsequent indirect costs.Indirect cost to the healthcare system comprises productivity losses from quarantining patients as well as restriction of movement of people who have not contracted the disease. Jin et al calculated average indirect expenses, particularly those associated with income that is lost due to premature death, the productivity lost due to a patient being hospitalized, and absenteeism from work due by COVID-19. They estimated the cost to be $11,634 per person. The inpatient costs at the national level amounted to $1,439,083,784.Ghaffari et al measured the costs indirectly associated with SARS by reviewing the productivity that is lost within the economy or the opportunity cost of the disease. In Ontario, the income per capita was valued at $30,702. These costs were quantified as lost productivity after people who were exposed failed to attend work for at least 10 days. In Toronto, the researchers successfully used the average daily wage to value the loss of productivity at $1140 for every individual isolated person. Using a mortality rate of 11% and the average life expectancy of 71 years in Canada, the researchers computed society’s economic cost per premature death.Gupta et alThey estimated that the average age of death was 56 years. Consequently, this indicated a mean lost life time of 15 years. They examined average worker wages in Ontario and came up with an average of $30,702 lost for every worker per every year of life. Hence, the mortality of SARS led to productivity loss with approximately $460,530 for every single life that was lost. Hence, the researchers concluded that quarantine would help to minimize the cost that the economy would incur from premature deaths. Common issues to address include coordinating emergency responses and establishing necessary quarantine measures. The health sector  plays a role in advocacy and leadership in the preparedness and response efforts geared towards managing the pandemic. In coordination with other departments and in support of the central government, the health department creates awareness about the risks and the likely health consequences of the outbreak and provides leadership and guidance on the required measures. As Berman explains, efforts at the federal level include.During a healthcare pandemic, the government has a responsibility to protect its citizens from the various adverse effects of the disease outbreak. During public health crises and the cascading social and economic consequences, governments are required to respond swiftly and effectively to a series of challenges.Stockpiling supplies such as vaccines, drugs, and medical equipmentTesting and diagnostic development of innovative equipment and medicationsFunding research for vaccines and antiviralsFacilitating public education on best practices with regard to the pandemicDirect versus (vs.) indirect cost of quarantine on the healthcare system. Generally, economic researchers quantify the cost of a pandemic with the inclusion of direct expenditures, the indirect health and non-health costs, and the fall in GDP. Direct healthcare costs include protective equipment, vaccines, medication, and contact tracing, and testing. Direct costs also include the construction and maintenance of quarantine facilities, as well as special measures enforced by institutions to prevent the spread of infections. Mulligan also estimated an annual welfare loss of $7 billion in the US. Another study determined that in the US, an estimated cost amounting to $286,000 was incurred.Indirect costs include productivity losses from mortality, morbidity, and quarantines. In the US, the indirect cost of COVID-19 was estimated to be approximately $13 trillion . sought to estimate the cost of the COVID-19 pandemic in Spain. They considered the macroeconomic losses of foregone GDP and the direct and indirect expenses of prevention and treatment. They explain that Spain was among the most-affected nations with a macroeconomic cost linked to COVID-19 amounting to 24% of the GDP in 2019. Nonetheless, they determined that the direct health costs of the pandemic were only an insignificant portion of the total cost of the pandemic.Analysts have sought to compare the cost of intervention strategies implemented to curb the spread of infections against the benefits yielded from such strategies. López-Valcárcel and Vallejo-Torres Monkeypox triggers a milder illness as compared to smallpox, which is fatal in approximately 30% of cases. The WHO estimates the general rate of fatalities for SARS patients at 14% to 15%. The COVID-19 statistics differ slightly among nations, but the average mortality rate is 2.7%, and the infection rate stands at 2%.Each virus has unique spreading patterns and mortality rates. Hence, interventions should be adopted rationally to effectively curb the spread and deaths caused by the virus while also economically protecting the healthcare sector and society. Compared to other virus pandemics, the current monkeypox outbreak only poses a reasonable risk to general public health across the world. Monkeypox has estimated transmission rates of 3.3% to 30%, while its fatality rate is estimated to be between 1% and 10%.Conclusion, despite the transmission rate of the monkeypox virus being high compared to other virus infections, the current risk to the general public remains low. A majority of infected people report relatively mild symptoms that do not create an urgent need for hospitalization. Many reviewed studies affirm that quarantine strategies effectively reduce the infection rate and delay new infections over time, but the healthcare departments of affected nations have to incur huge expenses, particularly from the indirect costs of quarantine. While a significant budget is required to cater to the direct expenses of quarantine, the mentioned studies show that the indirect costs of quarantine by far exceed the direct costs. However; this depends on the rate of spread of the disease and its mortality rate. Non-pharmaceutical interventions such as quarantines are the main strategies used for ensuring that the spread of the disease is under control when there are no vaccines or clinical treatment for specific illnesses. However, since there are known and effective vaccines and medications to prevent and cure monkeypox, it is unjustifiable to incur exorbitant costs in quarantining infected people or their close contacts. The cost of quarantine of close contacts includes both direct and indirect costs.Those supporting quarantine measures suggest that such measures have a positive economic impact since expenses incurred in the present reduce future direct and indirect costs. In addition, public awareness and sensitization forums should be held to inform the population about the best behavioral practices, such as handling potentially infectious animals and following routine hygiene practices.As such, although quarantine would effectively mitigate the spread of the current strain of the monkeypox virus, it would cause significant economic disruptions to the world economy and healthcare ministries. Indeed, quarantining suspected people would adversely affect the GDPs of affected nations and cause immense productivity losses. Instead, governments across the world (including non-endemic counties) should immediately initiate mass vaccination programs to protect their populations. The WHO explains that the smallpox vaccine is 85% effective in preventing monkeypox infections. Rather than calling for isolation and quarantine programs, other nations should emulate the US, which has already ordered 13 million doses of the vaccines.


Chronic cases of chikungunya fever represent a public health problem in countries where the virus circulates. The disease is prolonged, in some cases, for years, resulting in disabling pain and bone erosion among other bone and joint problems. As time progresses, tissue damage is persistent, although the virus has not been found in blood or joints. The pathogenesis of these conditions has not been fully explained. Additionally, it has been considered that there are multiple factors that might intervene in the viral pathogenesis of the different conditions that develop. Other mechanisms involved in osteoarthritic diseases of non-viral origin could help explain how damage is produced in chronic conditions. The aim of this review is to analyze the molecular and cellular factors that could be involved in the tissue damage generated by different infectious conditions of the chikungunya virus. Aedes aegypti and Aedes albopictus . In. In84]. As for other disease-modifying antirheumatic drugs, trials with chloroquine showed unsatisfactory results. These studies not only failed to decrease the duration of viremia and arthralgias, but also increased the rate of chronic arthralgias and viral replication ,87. In cAdditionally, trials with monoclonal antibodies have been performed, but only for the acute phase of the disease . Most ofThe most recent research on the chikungunya virus has allowed us to learn more about the factors involved in the processes of bone erosion and about the pathogenic relationship it has with other non-infectious arthritic diseases. However, there are contradictory reports about what is known regarding the virus. These contradictions are especially related to the persistence and the physiological and viral mechanisms that lead to chronic condition progression in certain individuals. There are also some contradictions in the findings of how arthritis development leads to bone erosion. All of the knowledge obtained on non-infectious arthritis and other alphaviral infections, as well as on chikungunya fever, has certainly contributed to our understanding of the disease. However, there are different diseases with particularities, and hence, there is a need for specific research regarding CHIKV infections. It is important to continue with these viral pathogenesis studies to elucidate and propose new therapeutic targets that can help to prevent exacerbated bone resorption from occurring and significantly impacting the life quality of people suffering from chronic chikungunya fever.


Childhood Sjögren’s Disease (cSjD) is an underdiagnosed phenomenon with clinical and pathophysiological nuances in contrast to Sjögren’s Disease (SjD) in the adult population. While adults typically experience sicca symptoms, children with cSjD often present with recurrent parotitis, diverse autoantibody profiles, and renal and neurological manifestations. Diagnosis and classification in pediatric rheumatology remain controversial due to the reliance on adult-focused diagnostic criteria and the lack of standardized treatment and understanding of outcomes. The purpose of the paper is to propose a multimodal treatment plan and demonstrate the effectiveness of sialendoscopy in the management of cSjD.We present the case of a twelve-year-old female diagnosed with cSjD using the 2016 American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) diagnostic criteria for SjD. In addition to medical management, she underwent sialendoscopy with triamcinolone irrigation under sedation and was monitored for progress via salivary gland ultrasonography (SGUS). Over the course of one year, she demonstrated significant improvement in symptoms, with serial SGUS scores gradually decreasing by five points.This paper proposes a multimodal treatment plan involving sialendoscopy and medical management as a non-invasive and potentially more effective approach for cSjD. Standardized monitoring through SGUS scoring allows objective and quantifiable measurement of treatment progress, enabling better assessment of glandular tissue status. Recurrence is possible, and each cSjD patient may present differently. Nevertheless, our year-long observation of a patient with cSjD demonstrates that sialendoscopy, as seen in adults, can promote remission of recurrent parotitis in children as well. Sjögren’s Disease (SjD) is an autoimmune inflammatory condition that presents as a chronic, multisystem disease, often affecting women between the ages of 45–55 years of age. Characterized by immune-mediated exocrine gland destruction, adults with SjD often report sicca symptoms of xeropthalmia and xerostomia . HoweverIn 2016, the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) set forth criteria for the diagnosis of SjD in the adult population. According to the ACR/EULAR, a diagnosis of SjD is made through a point system in evaluation of the following clinical factors: serology detecting anti-SSA/Ro (SSA), focus score from labial biopsy, sialometry results for unstimulated saliva flow rate (USFR), Schirmer’s test, and ocular surface staining (OSS) . PositivChildren with cSjD often do not meet the ACR/EULAR criteria, and many authors have proposed creating more specific criteria for the diagnosis of cSjD. In addition to differing clinical presentations, other barriers can exist in evaluating the pediatric population. According to Thatayatikom et al., the documentation of sicca symptoms in children can vary depending upon a child’s ability to communicate any sensation of xerostomia or xerophthalmia . FurtherA twelve-year-old female with a history of type I diabetes mellitus presented with recurrent, tender parotitis refractory to antibiotics, xerostomia, and keratoconjunctivitis sicca since the age of five. Her parotitis was more pronounced on the right side, with the inflammation resulting in mild otalgia. Her lab work was negative for SSA (Ro) and SSB (La) autoantibodies, but positive for salivary protein 1 IgA autoantibody and antinuclear antibody (ANA). She also tested positive for labial biopsy with a focus score greater than one, and her sialometry measured below the cut-off for hyposalivation 0.099 ml/min). Her clinical symptoms, serologic markers, positive lip biopsy, and sialometry measurements warranted a formal diagnosis of childhood Sjögren’s Disease (cSjD). She underwent salivary gland ultrasonography (SGUS), with scoring criteria as proposed by Hocevar et al. [9 ml/min.In the months following sialendoscopy, her SGUS score decreased to 10 or 11 at all subsequent appointments, indicating significant improvement in glandular inflammation Fig. . The imaFew reports adequately estimate the effectiveness of sialendoscopy in halting recurrence of childhood Sjögren’s Disease (cSjD). Sialendoscopy is a safe, minimally invasive procedure which can be effective for addressing salivary issues in SjD. Benefits include direct visualization of ductal pathologies, including inflammation, stenosis, and stricture diagnosis. In addition to gathering images, the physician can also administer a treatment when indicated . The impCurrently, no guidelines establish sialendoscopy with irrigation as part of the standard of care for treatment, as both cSjD and SjD are often medically managed with anti-inflammatory treatments or immunomodulatory therapy. When reviewing outcomes in patients with recurrent juvenile parotitis, Schwarz et al. determined it is unclear whether steroid administration or sialendoscopy itself relieves severity of inflammatory symptoms . Du et aThe 2002 American-European Consensus Group (AECG) criteria , 2012 AmPatients diagnosed with cSjD present with a unique pathophysiology of the parotid glands in comparison to the adult population. Karagozoglu noted that the improvement of salivary flow is most likely dependent upon the presence of saliva-producing acinar cells, which may be lacking in patients with fibrotic tissue, secondary to long-standing disease . TherefoIorio et al. evaluated the long-term impacts of sialendoscopy with corticosteroid irrigation in children aged 6 to 13, and improvement in salivary flow was noticeable during an 18-month observation period . The bioNumerous studies have evaluated the efficacy of sialendoscopy over different timeframes. Karagozoglu et al. conducted follow-ups with patients for up to sixty weeks after undergoing sialendoscopy with triamcinolone acetate . Their rOur patient experienced recurrence of right-sided parotitis at eleven months. However, overall improvement was noted over 48 weeks after her hydroxychloroquine dosage was increased to 300 mg. While cSjD is a rare condition, recurrence is not uncommon in other cases. Iorio reported recurrences of parotitis in two patients at five and three years. It is important to note that sialendoscopy is a treatment modality for managing salivary gland disorders and is focused on addressing specific concerns related to the salivary glands. Therefore, the optimal treatment plan for a patient with cSjD should remain multifactorial, encompassing both medical and procedural management, as each patient with an autoimmune condition presents uniquely with their own respective clinical presentation.In 2005, Hocevar et al. set forth a novel scoring system through SGUS. Through SGUS, the inflammation of glandular tissue is quantified via observation of parenchymal echogenicity in comparison to the thyroid, homogeneity of tissue parenchyma, hypoechoic areas, hypoechoic foci, and delineation . AccordiIn our patient, SGUS was utilized to offer not only a visual imaging but also provide a quantified score in assessing efficacy of treatment post-sialendoscopy. Our patient’s SGUS score decreased from 16 to 11, and she reported being asymptomatic without flares after one year. Her clinical improvement was reflected by subsequent SGUS results and a normal physical exam upon follow-up. We conclude SGUS is best utilized to monitor each patient’s individual progress via comparison of imaging and scoring with the first established baseline.Notably, our patient presented with a baseline score of 16 in her SGUS, which is one point below the cutoff for Hocevar for SjD. With that said, half of the subjects with SjD in Hocevar et al’s study scored below 17 in their SGUS assessment. In addition, in Hocevar’s study all subjects were adults between the ages of 23–84 with a mean age of 51.5. As discussed, cSjD presents with unique pathophysiology. Therefore, further investigation is warranted on whether the cutoff or parameters for a diagnosis of cSjD via SGUS should be modified for the pediatric population. As seen in our patient, a reduction in five points suggested a curtailment of inflammatory processes within her parotid tissue. However, the degree of point reduction should be compared to more patients with cSjD who have undergone sialendoscopy. In addition, a modified SGUS for the pediatric population might reflect a greater difference in scoring.It should be noted that SGUS does present with other limitations. Drawbacks can include missing early disease if disease severity is mild, and SGUS monitoring should be executed with the same technique, machine, technician, and standardized scoring system if long-term follow-up is planned. Since cSjD is a systematic inflammatory disease process, clinicians should also continue to monitor renal, neurologic, and musculoskeletal function in a thorough workup.Along with medical management, sialendoscopy can be utilized as a therapeutic treatment with low morbidity for treatment of parotitis secondary to cSjD. Its success in the treatment of inflammatory processes is likely due to the dilation of the ductal system under direct visualization in combination with corticosteroid irrigation. Further studies are warranted over whether the addition of sialendoscopy can provide improved long-term remission of recurrent parotitis in patients with cSjD. As no criteria exist for diagnosing pediatric patients with cSjD, it is our opinion that sialendoscopy and SGUS can be beneficial when incorporated in the management of cSjD, especially when a patient presents with recurrent parotitis.


This A/H5N6 virus was not transmitted between ferrets via the air but was of unexpectedly high pathogenicity compared to other described A/H5N6 viruses. The virus replicated and caused severe lesions not only in respiratory tissues but also in multiple extra-respiratory tissues, including brain, liver, pancreas, spleen, lymph nodes, and adrenal gland. Sequence analyses demonstrated that the well-known mammalian adaptation substitution D701N was positively selected in almost all ferrets. In the in vitro experiments, no other known viral phenotypic properties associated with mammalian adaptation or increased pathogenicity were identified. The lack of transmission via the air and the absence of mammalian adaptation markers suggest that the public health risk of this virus is low. The high pathogenicity of this virus in ferrets could not be explained by the known mammalian pathogenicity factors and should be further studied.Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of other avian influenza A viruses have been detected. As a result, various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8 have been identified. As of January 2023, 83 humans have been infected with A/H5N6 viruses, thereby posing an apparent risk for public health. Here, as part of a risk assessment, the in vitro and in vivo, in ferrets. The virus was not transmissible via the air but caused severe disease and spread to extra-respiratory organs. Apart from the detection in ferrets of a mutation that increased virus replication, no other mammalian adaptation phenotypes were identified. Our results suggest that the risk of this avian A/H5N6 virus for public health is low. The underlying reasons for the high pathogenicity of this virus are unexplained and should be further studied.Avian influenza A/H5 viruses can cross the species barrier and infect humans. These infections can have a fatal outcome, but fortunately these influenza A/H5 viruses do not spread between humans. However, the extensive circulation and reassortment of A/H5N6 viruses in poultry and wild birds warrant risk assessments of circulating strains. Here an in-depth characterization of the properties of an avian A/H5N6 influenza virus isolated from a black-headed gull in the Netherlands was performed  Highly pathogenic avian influenza (HPAI) A/H5 viruses of the A/goose/Guangdong/1/1996 (GsGd) lineage first emerged in Hong Kong in 1997 , 3. In 2https://www.who.int/docs/default-source/wpro---documents/emergency/surveillance/avian-influenza/ai_20230331.pdf?sfvrsn=5bc7c406_23).Clade 2.3.4.4 A/H5N6 viruses were first detected in China in a live poultry market in 2013 8. By lahttps://food.ec.europa.eu/animals/animal-diseases/diseases-and-control-measures/avian-influenza_en).The first European detection of an HPAI A/H5N6 virus, carrying the clade 2.3.4.4b HA, was detected in a duck farm in the Netherlands in December 2017. The virus was subsequently detected in wild birds in close proximity to the infected farm  and in tChroicocephalus ridibundus) on 18 December 2017  route between ferrets was assessed, as well as its pathogenicity in the ferret model. A/H5N6 BHG was found to not be transmissible via the airborne route but showed a remarkable tropism for extra-respiratory organs and was lethal in the ferret model.Several research groups previously reported on the relatively low pathogenicity and lack of airborne transmissibility of the A/H5N8 clade 2.3.4.4a and clade 2.3.4.4b viruses in the ferret model -16. Seber 2017  as part ber 2017 . In vitr6 median tissue culture infectious dose (TCID50) of virus. Body weight and clinical signs were recorded daily. Nose and throat swabs were collected daily. Three animals were scheduled to be sacrificed and necropsied at day 3 and 6 days post-inoculation (dpi) each; however, one animal that was scheduled to be necropsied at 6 dpi had to be euthanized at 5 dpi because of a predefined humane endpoint of this experiment (20% weight loss compared to day 0). To be able to compare lesions and virus distribution at 3 and 6 dpi with an equal number of animals, the donor animal from the transmission experiment  that died at 6 dpi was included in these analyses.To assess the pathogenicity of A/H5N6 BHG, six adult female ferrets were inoculated intranasally with 10A/H5N6 BHG-inoculated animals had lost on average 12% of their starting bodyweight at 3 dpi. The two remaining animals at 6 dpi had lost 19% and 20% of their starting body weight . At 3 dp6,6 and 107,3 TCID50/g of tissue, respectively) (Virus titers in nose and throat swabs were determined by endpoint titration in Madin-Darby canine kidney (MDCK) cells. Infectious virus shedding was demonstrated from 1 dpi onward and continued with a small increase in titer until 6 dpi in both samples . A/H5N6 ctively) . MoreoveThe upper respiratory tract was the body site that most consistently expressed abundant virus antigen. Virus antigen was detected in the upper respiratory tract of all ferrets at 3, 5, and 6 dpi. Within the upper respiratory tract, virus antigen was located in the nasal turbinates and the larynx in all ferrets. The cells that expressed virus antigen in the nasal turbinates were mainly clusters of olfactory and respiratory epithelial cells, and few individual submucosal gland epithelial cells and submucosal mononuclear cells . The virThe lower respiratory tract inconsistently expressed virus antigen on day 3. Virus antigen was only present in 2/3 ferrets at 3 dpi, and in just one ferret at 6 dpi. The cells that expressed virus antigen in the lower respiratory tract were few clusters of adjacent bronchial and bronchiolar epithelial cells with occasional bronchial gland epithelial cells, also individual type I and type II pneumocytes and few individual alveolar macrophages expressed virus antigen . These cThe lymphoid  and nervIn the nervous tissue, virus antigen was present in locations suggesting virus had spread there via neuronal connections: virus was most consistently present in the olfactory bulbs, which are directly connected with the olfactory epithelium in the nose. Virus was also present in the trigeminal ganglion, which contains the cell bodies of the sensory neurons that innervate the head. Furthermore, at 5 and 6 dpi, several distinct, well-demarcated foci of antigen-positive cells were present in the brainstem. The sagittal plane of the brain section differed for these four ferrets, and therefore comparison was not always possible for all regions. If a brain region was positive in one ferret, and this brain region was also present in the brain slide of another ferret, it was mostly also positive in that other ferret. This strongly suggests that the distribution was not random and that virus did not disseminate to the brain via the circulation. Aside from the reticular formation, all mentioned nuclei contain second- or third-order neurons from sensory cranial neurons innervating the nose, mouth, or ear, suggesting this influenza virus did not only spread via the olfactory epithelium to the brain but also via other sensory neuron routes. To examine the possibility that virus might have disseminated via neurons from the taste buds on the tongue to the brainstem, retrospective examination of taste buds in the vallate papillae of tongue tissues was performed. Vallate papillae (tongue) were sampled in formalin for five of the seven ferrets. Antigen-positive cells were detected in the epithelial layer in an area with taste buds and co-localized with necrotic cells and neutrophils in one ferret . FurtherIn the lymphoid tissue, virus antigen was detected in all ferrets. The cells that expressed virus antigen in lymphoid tissues were individual or groups of variably shaped mononuclear cells with large nuclei and abundant cytoplasm. Based on morphology, these cells were likely macrophages or dendritic cells . AdrenalAssociation of histological lesions and A/H5N6 BHG infection was based on co-localization of lesions and virus-antigen expression. Lesions associated with A/H5N6 BHG infection generally consisted of a central area of advanced necrosis , bordered by an area where fewer cells showed necrosis and the presence of small numbers of neutrophils. This outer area generally had virus-antigen-positive cells.Lesions associated with virus antigen in the upper respiratory tract consisted of a mild to moderate multifocal necrotizing rhinitis  and laryIn the lower respiratory tract, lesions associated with virus antigen were mild and multifocal and were centered around bronchioles. Bronchioles and alveoli showed necrosis and infiltration of neutrophils, and there was an increase in the number of intra-alveolar macrophages in affected areas. The ferrets that were euthanized at 5 and 6 dpi showed no lung lesions, suggesting that lower respiratory tract infection had not been more severe at 3 dpi than scored at time of euthanasia in these two ferrets .Lesions associated with virus antigen in the nervous tissues were present in the olfactory bulb , trigemiAlso associated with virus antigen were lesions in spleen- and larynx-associated lymphoid tissue, liver, pancreas, and adrenal gland. These lesions consisted of necrosis of parenchymal cells and infiltration with neutrophils . In the Lesions indirectly associated with A/H5N6 BHG-positive cells were present in one ferret (6 dpi). This ferret had a lesion in the gut-associated lymphoid tissue (GALT) of the jejunum that was most likely related to A/H5N6 BHG infection because the character of the lesion fitted with the lesions in other lymphoid tissues, where antigen-positive cells were present. The overlying mucosa of the jejunum was ulcerated allowing the necrotic GALT to have direct contact with the intestinal lumen. Coccoid bacteria were present in between necrotic cells in the GALT. Within the same section of jejunum, bacteria, both rods and cocci, were present in blood vessels, suggesting bacteremia had occurred prior to euthanasia.Other histological lesions not associated with A/H5N6 BHG infection were present in liver, kidney, adrenal gland, skin, intestine, and spleen. All ferrets had a chronic mild , moderate , or marked (1/3 ferrets at 3 dpi) lymphoplasmacytic portal hepatitis. All ferrets had hepatic lipidosis. One ferret (3 dpi) had chronic moderate multifocal lymphoplasmacytic perivascular infiltrates in the adrenal gland. One ferret (3 dpi) had mild multifocal mineralization in the interstitium of the kidney. One ferret (5 dpi) had a multifocal superficial necropurulent dermatitis. Two ferrets (6 dpi) showed villus blunting and fusion in duodenum and jejunum. All ferrets had mild to moderate extramedullary hematopoiesis in the spleen, characterized by the presence of megakaryocytes in the spleen.N <5%), two other substitutions emerged in PB2, which were exclusively detected in this sample, G590S and I647M  as described previously . The MDCnd I647M . It is p5,25 TCID50/mL  and α2,6-linked sialic acids , respectively. To assess the receptor specificity of A/H5N6-BHG, a resialylated turkey red blood cell (TRBC) assay was performed using recombinant A/Puerto Rico/8/1934 (H1N1) viruses harboring the HA protein of interest. Briefly, TRBCs were treated with sialidase to strip off SA and subsequently modified to contain either α2,3-SA or α2,6-SA, using specific sialytransferases. Both control viruses, harboring the avian A/H5N1 virus A/Indonesia/5/2005 (Indo/05) HA and the human A/H3N2 virus A/Netherlands/213/2003 (NL/03) HA, displayed the expected receptor attachment pattern by binding exclusively to α2,3-SA and α2,6-SA, respectively . A/H5N6-Influenza virus attachment to SA receptors on the host cell surface is followed by receptor-mediated endocytosis. In endosomes, a low-pH-triggered conformational change of HA mediates fusion of the viral and endosomal membranes to release the viral genome in the cytoplasm . In ordeThe irreversible conformational change of HA from a metastable non-fusogenic to a stable fusogenic state can also be triggered at neutral pH when the HA is exposed to increasing temperatures . TherefoRenilla luciferase as an internal control. The experiment was performed at 37°C. Polymerase activities were expressed as fold increase compared to the negative control. The polymerase activity of the A/H5N6-BHG was only approximately sevenfold higher than the control, which is much lower than the human and avian control polymerase complex activities   and the nucleoprotein (NP) of different A/H5 viruses, firefly (FF) luciferase as a reporter gene and ncrease) . Introduncrease) -32. Nencrease) .in vitro and in vivo characterization of a clade 2.3.4.4 A/H5N6 virus, that was isolated from a black-headed gull in the Netherlands in 2017 (A/H5N6-BHG), to assess the potential risk for humans. We first assessed the pathogenicity and transmissibility of A/H5N6-BHG in the ferret model. Ferrets generally show similar susceptibility to infection with human and avian influenza viruses and develop respiratory disease similar to that observed in humans .Careful extrapolation from animal models to humans suggests that the public health threat of the HPAI H5N6 viruses is low. However, given the rapid geographical spread of HPAI clade 2.3.4.4 A/H5Nx viruses, including recent clade 2.3.4.4b A/H5N1 viruses, their ability to infect various species of birds and mammals including humans, and the tendency of influenza A viruses to mutate and reassort, the phenotypic properties of HPAI H5Nx viruses should be monitored closely  , 10 mM HEPES (Lonza), and 1× non-essential amino acids .MDCK cells (ATCC) were cultured in Eagle’s minimal essential medium  supplemented with 10% fetal bovine serum , 100 U/mL penicillin , 100 U/mL streptomycin , 2 mM L-glutamine , 1.5 mg/mL sodium bicarbonate (NaHCOA/black-headed gull/Netherlands/29/2017 virus (EPI_ISL_289714) was isolated from a combined oropharyngeal and cloacal swab. The virus was then propagated for two passages in MDCK cells. Clade 2.3.4.4 viruses A/H5N6 A/Guangzhou/39715/2014 (GZ/14) and A/H5N8 A/chicken/Netherlands/EMC-3/2014 (ck/NL/14) have been described previously , 18.3, 10 mM HEPES, 1× NEAA, and 20 µg/mL trypsin (Lonza). Three days after inoculation, supernatants of cell cultures were tested for agglutinating activity using turkey erythrocytes as an indicator of virus replication. Infectious virus titers were calculated from four replicates each of the homogenized tissue samples, nose swabs, and throat swabs and for 10 replicates of the virus stocks by the method of Spearman-Karber.Virus titrations were performed as described previously . Briefly6 TCID50 of virus by applying 250 µL of virus suspension to each nostril. Each donor ferret was then placed in a transmission cage. One day after inoculation, one naïve recipient ferret was placed opposite each donor ferret. Each transmission pair was housed in a separate transmission cage designed to prevent direct contact but allowing airflow from the donor to the recipient ferret. Nose and throat swabs were collected every other day from donor ferrets until the humane endpoint was reached and at 1, 3, 5, 7, and 9 dpe from the recipient ferrets and subjected to virus titration. Recipient ferrets were euthanized at 14 dpe to allow assessment of seroconversion.Airborne transmission experiments were performed as described previously , 48. In 6 TCID50 of HPAI A/black-headed gull/Netherlands/29/2017. Clinical scores were assessed every day. Activity status was scored as follows: 0, alert and playful; 1, alert and playful only when stimulated; 2, alert but not playful when stimulated; 3, neither alert nor playful when stimulated. Body weight was monitored daily. Animals were euthanized when one or more humane endpoint criteria were met: the animal no longer eats or drinks, a decrease in body weight >20% from original weight, presence of severe circulation or respiratory problems, the animal’s behavior and locomotion are severely abnormal, the infection causes severe clinical signs, evidence of mouth breathing or an activity score of 3. Throat and nose swabs were collected every day and were stored at −80°C in transport medium  for endpoint titration in MDCK cells. Three animals were euthanized at 3 and 6 dpi by exsanguination under anesthesia to allow comparison with historical experiments, unless for ethical reasons ferrets needed to be euthanized earlier. Tissues harvested for virological examination were homogenized in transport medium using the FastPrep system  with two one-quarter-inch ceramic sphere balls, centrifuged 1500 × g for 10 minutes aliquoted, and stored at −80°C for endpoint titration in MDCK cells. Tissues harvested for histological examination to examine the type of lesions associated with virus presence were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned at 4 m, and stained with hematoxylin and eosin (HE) for examination by light microscopy.Six adult female ferrets were inoculated intranasally with 10For detection of influenza A virus antigen, sequential slides of all tissues were stained with a primary antibody against the influenza A NP as described previously , 50. In GTTACGCGCCAGCAAAAGCAGG), Opti1-F2 (5′-GAAAGCAGGGTTACGCGCCAGC), and Opti1-R1 (5′-GTTACGCGCCAGTAGAAACAAGG). DNA amplicons were purified using an Agencourt AMPure XP 5 mL Kit . Library preparation and fragmentation were done using the Roche KAPA Hyperplus Kit, followed by sequencing on the MiSeq instrument, according to the instructions of the manufacturer . Raw sequence data were analyzed and mapped using the CLC Genomics software package, workbench 11 . The sequences were trimmed to improve quality using a Phred score of 20. Reads were aligned to reference sequence A/Black-headed gull/Netherlands/29/2017 (EPI1131093-EPI1131100). The threshold for mutation detection was manually set at 1% and 5%, for the virus inoculum and ferret samples, respectively.RNA was extracted using a QIAamp viral RNA minikit . M-RTPCR amplification was performed with a SuperScript III high-fidelity RT-PCR Kit  according to the manufacturer’s instructions using the Opti1 primer set, consisting of primers Opti1-F1  at 37°C and incubated at 56°C for 1 h the next day. Twofold serial dilutions of the antisera, starting at a 1:20 dilution, were mixed with 25 µL of a virus stock containing four hemagglutinating units and were incubated at 37°C for 30 minutes. Subsequently, 25 µL of 1% turkey erythrocytes was added, and the mixture was incubated at 4°C for 1 h. Hemagglutination inhibition was read and was expressed as the reciprocal value of the highest dilution of the serum that completely inhibited agglutination of virus and erythrocytes.Ferret antisera were prepared as previously described . Ferret Modified TRBCs were prepared as described  with sliVirus solutions were incubated for 30 minutes at different temperatures before performing an HA assay using TRBCs. Twofold dilutions of virus in PBS containing 0.25% red blood cells were prepared in a U-shaped 96-well plates and were incubated for 1 h at 4°C, and agglutination was recorded.The open reading frames (coding region) of the HA genes of virus isolates were cloned into the pCAGGS expression vector using Gibson Assembly . Fusion was tested as previously described  in a celRenilla luciferase, served as an internal control to normalize variation in transfection efficiency and sample processing.The open reading frames (coding region) of the PB2, PB1, PA, and NP genes of virus isolates were cloned into the pPPI4 expression vector  using GiRenilla luciferase expression plasmid in 50 μL Opti-MEM  was mixed with 50 μL Optim-mem containing Lipofectamine 2000  or TransIT-X2 Transfection Reagent  in a 1:3 ratio and incubated for 20 minutes at room temperature. An amount of 20 μL of the transfection mixture was added to each well. Each transfection was performed in quadruplo in at least two independent experiments. Twenty-four hours post-transfection luminescence was measured using the Dual-Luciferase Reporter Assay System (Promega) using a GloMax Luminometer according to the manufacturer’s instructions .Human HEK-293T was seeded 1 day prior to the experiment into 96-well plates. An amount of 25 ng of the FF reporter plasmid, 50 ng of each of the plasmids encoding PB2, PB1, and PA, 100 ng of NP, and 2 ng of the


Aim: The present study addressed overcoming the lacunae in the literature of psychiatric manifestations associated with rhino-orbital mucormycosis. The current study aimed to assess the symptoms of depression, anxiety, stress, coping measures, suicidal intent, and visual disability in patients of rhino-orbital mucormycosis (ROM) during the epidemic of the disease at the nodal tertiary care center in North India.Methods: Fifty-four inpatients of laboratory-proven rhino-orbital mucor-mycosis (ROM) were included for an observational, cross-sectional study at nodal, designated COVID-19, and mucormycosis treating tertiary care hospital. Patients with Hindi Mini-Mental State Examination score <24, prior psychiatric illness, and severely ill requiring ventilator support were excluded. The psychological variables were assessed using Depression, Anxiety, and Stress Scale 21 (DASS 21), Beck’s Suicide intent Scale, Coping Scale Questionnaire, and Visual disability scale (IND-VFQ33). Their socioeconomic status was assessed using the Modified Kuppuswamy Scale.Results: Ninety percent of patients with ROM had diabetes mellitus. The majority (44%) of patients belonged to lower socioeconomic strata. Higher frequencies of severe depression (28%), extremely severe anxiety (26%), and mild stress (17%) were noted in the study participants. On the Tukey test, depression score was higher in patients of ROM compared to COVID (with ROM) . On Tukey analysis, anxiety score was significantly higher in ROM patients compared to COVID (with ROM) patients . Coping scores were significantly higher in COVID (with ROM) patients compared to ROM patients . Mild to moderate visual disability was noted in the study participants. Conclusion: The current study reflects the association of higher depression and anxiety scores in cases with ROM that indicated higher mental health needs. Early assessment, early detection, and early intervention for psychological help, along with the multidisciplinary team, helped to improve the overall psychological outcome of the affected patients. Mucormycosis, a ubiquitous fungus belonging to the taxonomic order of Mucorales, is known to cause angio-invasive fungal infection in immunocompromised hosts like patients of uncontrolled diabetes, leukemia, lymphopenia, and organ transplantation .During the pre-COVID era, the annual prevalence of mucormycosis estimated by The Leading International Fungal Education (LIFE) portal was estimated to be around 10,000 cases, but with the inclusion of Indian data, the cases escalated to 910,000 . During Due to the sudden surge in cases reaching epidemic levels, the Government of India declared mucormycosis to be a notifiable disease in May 2021. Guru Teg Bahadur hospital (GTBH), the largest tertiary care teaching hospital in East Delhi, was declared a nodal center for the treatment of both COVID-19 cases as well as mucormycosis.Desai et al. found the following treatment measures, such as control of diabetes mellitus, intravenous infusion of intravenous amphotericin B, and surgical debridement of sinuses, useful for rhino-orbital mucormycosis (ROM) seen in post-COVID-19 . In a reDuring the second wave of the pandemic, a web-based online survey was conducted on 500 participants using GAD7, Centre for Epidemiology Scale of Depression. They reported 25.4% of GAD and 18.8% of depressive symptoms, respectively. The study also noted that the younger age group had a higher risk of developing depressive symptoms . In a reAs per the media reports, a large number of suicides were committed among students probable reason cited was the delay in examination (due to the lockdowns implemented by the authorities to contain the spread of COVID-19), resulting in their career-related uncertainty . The masThe current study aimed to assess the symptoms of depression, anxiety, and stress along with coping capabilities, suicidal intent, and visual disability in patients of ROM during the epidemic of the disease at the nodal tertiary care center in North India. The early detection and assessment of the psychological manifestations can aid in early intervention.Study design and populationThe present study was an observational cross-sectional study jointly conducted by the Department of Psychiatry and Ophthalmology on ROM patients recruited between July 2021 and September 2021 during the second wave of COVID-19 pandemic and the epidemic of mucormycosis reported from India. The study was approved by the institution’s ethics committee and adhered to tenets of the Declaration of Helsinki.Sample sizeTo the best of the knowledge of the authors, no study had been conducted before the start of the present study to assess the psychological impact on patients of mucormycosis. Hence, a convenient sample of a minimum of 50 patients with mucormycosis was decided for the present work.During the study period from July 2021 to September 2021, 450 patients of ROM utilized emergency hospital services. Guru Teg Bahadur Hospital (GTBH), a tertiary care hospital affiliated with a medical school, was turned into a COVID designated facility completely in line with the Government of India guidelines. An additional healthcare facility for less severe cases of COVID-19 was made at Ramlila ground which was also being managed by the staff of GTBH.One hundred seventy patients were transferred to an additional healthcare facility. Out of the remaining 280 patients, 64 were shifted to Intensive Care Unit as they required ventilatory support. Eighty-four patients were shifted to the internal medicine department due to severe systemic derangement of electrolytes, blood sugars, or blood pressure, and 46 patients were shifted under the care of the neurosurgery department as they had poor cognitive scores . Eighty-six patients were admitted under the Department of Ophthalmology and Ear, Nose, Throat (ENT), out of which eight were excluded as they had a prior psychiatric illness, and 24 patients did not give consent to participate in the study. Finally, a total of 54 patients were included for analysis in the study Figure .Data collection and evaluationA detailed history, including presenting complaints, past history, personal history, family history, socio-demographic history, and detailed physical, mental state, and ophthalmological examination, were carried out for all study participants.Confirmed COVID-19 positive patients were defined as patients who tested positive for SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction (RT-PCR). COVID-19 suspects were defined as patients who had clinical symptoms suggestive of COVID-19 but whose RTPCR was negative or who were unable to get tested due to RT-PCR kit constraints.A patient of mucormycosis was defined as a patient who tested positive by microbiological evidence from scrapings taken by direct nasal endoscopy or tissue biopsy and stained with potassium hydroxide (KOH) stain. All patients were staged according to the staging of Rhino-Orbital-Cerebral mucormycosis given by Honavar et al. , who staPsychiatric questionnaires for assessment of depression, stress, anxiety symptom scale, coping scale, and visual disability scales were applied. The scales were applied within 24-48 hours of admission before the pharmacological intervention with amphotericin B. Cognitive functions were assessed for all participants, and informed consent was obtained.Hindi version of the Depression, Anxiety, and Stress scale 21 (DASS 21) was used for the assessment of depression, anxiety, and stress symptom scores. Each of the three DASS 21 scales contained seven items divided into subscales with similar content. After the application of the scales, a final score was obtained, which helped to classify patients into normal, mild, moderate, severe, and extremely severe classes of depression, anxiety, and stress .Beck’s suicide intent scale was used to assess suicide intent in patients in a psychometric/measurable way. It had 15 items; and each item was scored from 0 to 2. The final score calculated helped to classify the patients into low, medium, and high risk of suicide .A coping scale questionnaire was used to assess cognitive, emotional, and behavioral methods of dealing with problems in patients with mucormycosis. It comprised 13 items, and each item was scored from 1 to 4. The final score was achieved by adding all the scores. A higher score indicated a higher coping capability [Visual Disability scale (IND-VFQ33) had three scales: general functioning (21 items), psychosocial impact (five items), and visual symptoms (seven items). General functioning pertains to a person’s ability to move about, household chores, and activities of daily life on a 5-point scale. Visual symptoms pertained to the effect of quality of life due to visual loss on a 4-point scale. Psychosocial impact pertained to a person’s well-being as well as the quality of social and family interactions on a 4-point scale. A higher score meant poor functionality and, hence, poor vision-related quality of life. This scale was specially designed for the Indian population .HMMSE had components of orientation (10 points) which includes temporal orientation (five points) and spatial orientation (five points); Memory (six points) which consisted of immediate recall (three points) and delayed recall (three points); language (eight points) which had naming (two points), verbal repetition (one point), verbal comprehension (three points), writing (one point) and reading a sentence (one point); Attention and calculation (five points) and design copying (one point). The final score was calculated by adding all the scores. A score of 23 or < was taken as a poor cognitive score and, hence, was excluded from the study . All theStatistical testsQualitative data were presented as frequency and percentage. Quantitative data were analyzed using ANOVA and Post hoc Tukey’s test. For statistical significance, a p-value of <0.05 was considered statistically significant. Data analysis was done using IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.The study group comprised 54 patients of ROM, with mean age of 53.14 (range 35-70) years. Thirty-four (62.95%) belonged to the male gender, and 20 (37.04%) were females. All study participants (N=54) had a cognitive score of >24 on the administration of the HMMSE scale. The mean cognitive score by the HMMSE scale for the study participants was 27.35±1.43.Table Figure On comparing depression between three groups; group 1 as COVID suspect & ROM; group 2 as ROM, and group 3 as COVID confirmed & ROM; depression emerged as the statistically significant factor between the three groups   compared to group 3 (CC+ROM) . There was no statistically significant difference between other CS+ROM vs. ROM and CS+ROM vs. CC+ROM pairs in relation to depression scores . On further comparison between the groups using Tukey analysis, it was seen that the anxiety score was significantly higher in the MM group compared to the CC+ROM group . There was no statistically significant difference between other CS+ROM vs. ROM and CS+ROM vs. CC+ROM pairs in relation to anxiety parameters Tables .The coping parameter was seen to be statistically significant between the three groups  using ANOVA. On Tukey analysis, it was seen that the coping scale score was significantly higher in the CC+ROM group compared to the ROM group . There was no statistically significant difference between other CS+ROM vs. ROM and CS+ROM vs. CC+ROM pairs Tables , 3 with Between the three groups, the visual disability scale (IND-VFQ33), which included the general functioning scale, psychosocial scale, and visual symptom scale, was not statistically significant. The mean value for the general functioning scale (score range 21-105) was 26.20 for CS+ROM, 27.29 for ROM, and 27.36 for the CC+ROM group indicating that all patients had mild to moderate visual disability while pursuing their daily needs. The mean value for the psychosocial impact scale (score range 5-20) was 10.00 for the CS+ROM group, 8.86 for the ROM group, and 8.93 for the CC+ROM group indicating that mild to moderate disability due to vision affected their psychological and social well-being. The mean value for the visual symptom scale (score range 7-28) was 10.40 for CS+ROM, 10.57 for ROM, and 10.36 for the CC+ROM group indicating the satisfactory quality of life scale measures as measured on the visual disability scale.The present study was carried out in a tertiary care teaching hospital, which was declared a dedicated COVID care and mucormycosis facility by the Government of India. The majority of the patients recruited in this study belonged to the age group of 35-70 years, with a mean age of 53 years. This is in accordance with the data established by a previous study that compared the epidemiology of mucormycosis in India versus the world. Muthu et al. observed that the mean age of presentation in India was 56 years in comparison with 52 years worldwide . We alsoThe majority of patients in this study belonged to the lower socio-economic strata and were unemployed (44.44%), which is in agreement with a study that attributes the preponderance of mucormycosis cases in India to a large population belonging to the lower socioeconomic status . Another observation in this study was that a large population of the study were high school graduates. To the best of our knowledge, this factor has not been studied earlier with respect to mucormycosis. All the participants of this study were married, as seen in another study by Ahuja A et al. in 2021 . The risSteenblock's study  reportedThe majority of the participants were classified as Stage 3 and above. This is also in accordance with a multi-centric Indian study published in 2021 . The souPrevious evidence, literature, and media highlighted the need for assessment of suicidal risk, as the pandemic overall had set in a gloomy picture -9. The fThe study sample comprising ROM had stress symptoms in 100% of patients and depressive and anxiety symptoms in 92% and 96%, respectively. The depression  and anxiety (0.012) symptoms were significantly associated with COVID suspect (with ROM), COVID (with ROM), and only ROM. Previous studies also report a higher association between depression and anxiety symptoms during the COVID-19 pandemic . A previOur study was unique in highlighting the presence of Rhino-Orbital Mucormycosis (N=54) with higher mean scores of both depression and anxiety symptoms which was like the previous study by Nair et al.  that conPoorer coping methods were associated with ROM  in comparison with COVID cases in the study sample. This could be explained by the visual disability symptoms observed more in ROM cases that lead to impairment of day-to-day activities. One of the possible mechanisms for the higher association of depression and anxiety symptoms in ROM cases could be attributed to underlying physical ailments such as blindness in one eye, diabetes mellitus, hypertension, and higher stage of ROM 3 or above in the present study.Psychiatry consultations were made a norm at the COVID and mucormycosis designated study center for all ROM admitted patients, in liaison with the other departments managing the disease as a part of the multi-disciplinary team. Appropriate interventions involving both pharmacological measures and counseling/psycho-educative support sessions were executed for all screened positive ROM cases  by a trained senior psychiatrist who had expertise in dealing with COVID-19/mucormycosis cases.Follow-up counseling sessions were exclusively conducted in association with the department of ophthalmology to deal with patients with mild to moderate visual disability. This is the first study in the literature to assess visual disability due to mucormycosis in terms of how it affects their general functioning, social life, and its effect on quality of life. Apart from the study cases, psychological support sessions were also conducted for their primary caregivers for educating them on how to handle the patients and help them deal with the post-discharge complications/interventions of both COVID and ROM. The limitation of this study is that the results cannot be extrapolated to the entire Asian region, as the data is obtained from a nodal tertiary center in North India dealing with the cases of COVID and ROM. Further research work requires pooled data from different regional centers involving different geographical locations.Nevertheless, the current study reflects the association of higher depression and anxiety scores in cases with ROM, which emphasizes the need for early intervention to improve the mental health as well as the overall well-being of the affected patients. Early assessments, regular counselling sessions may have contributed to the low suicide risk in ROM cases. The study enabled early detection of cases with higher depression, anxiety, stress symptoms, poor coping methods, and visually disabling symptoms resulting in poor psychosocial and general functioning. Early intervention by trained mental health professionals in liaison with a dedicated multidisciplinary team of medical experts improved the overall outcome of these ROM cases.