We propose a top-down approach for elucidating novel COVID-19 disease which caused unprecedented social and economic devastations globally. Detrimental outcome of antioxidant enzyme deficiency and synergism between SARS-CoV-2 virus and a bacterial pathogen, Streptococcus pneumoniae is the most likely cause of COVID-19-associated mortalities. As we age, production of the antioxidant catalase enzyme, which catalyzes the decomposition of hydrogen peroxide (H2O2) to water and oxygen, tails off;as a result, H2O2 starts to accumulate in body. Additional production of H2O2 by the bacteria increases H2O2 concentration up to a critical level in respiratory tract. The elevated H2O2 causes damages in lungs and oxidizes key components of the innate immune system, halts inflammasome activation process, and eventually suppresses it. Having suppressed innate immune response along with substantial lung injuries, synergic viral-bacterial co-infection leads to fast colonization of pathogens at the respiratory tract. The adaptive immune system kicks in too early and overreacts, and which results in overwhelming local and systemic cytokines release and hyperinflammations in the lungs. We have tested the validity of our proposal by analyzing recent clinical data on COVID-19, age- and gender-dependent COVID-19 death rates, H2O2 accumulation and antioxidant enzyme activities in cells, and the correlation between antioxidant-rich intake and COVID-19 death rate in various countries. Based on our analysis, it might be possible to explain COVID-19 peculiarities including why and how the immune system fails, why some infected people do not develop severe respiratory illness, why older people are affected the most, why male death rate is significantly higher than female death rate, why certain comorbidities are related with COVID-19 mortality, and why some Asian countries have very low death rates. We anticipate that the proposed mechanism might uncover the mystery of COVID-19 and may pave the way for finding a cure and vaccine for the coronavirus pandemic, and for understanding the viral-bacterial co-pathogenesis and related respiratory tract diseases.
Synergic Viral-Bacterial Co-Infection in Catalase-Deficient COVID-19 Patients Causes Suppressed Innate Immunity and Lung Damages Due to Detrimental Elevation of Hydrogen Peroxide Concentration