Recent structure based comparisons suggest that coronavirus proteins mimic at least 140 human proteins, including those in the complement and coagulation pathways. The complement cascade leading to cell death and inflammation is part of the innate immune system, and may be overactive in patients with severe COVID-19. Inhibition of the complement system is being actively pursued in a number of clinical trials with COVID-19 patient participants.
Sagi D. Shapira of Columbia University, New York City, and colleagues, conducted a retrospective observational study of 11,116 patients with SARS-CoV-2 infection to see if dysregulation of the complement or coagulation systems impacted adverse clinical outcomes at New York-Presbyterian/ Columbia University Irving Medical Center. The results were released on the medRxiv preprint server.
Out of 11,116 patients presenting between February 1, and April 25, 2020 with suspected SARS-CoV-2 infection, 6,398 tested positive. Age and sex, hypertension, obesity, type 2 diabetes (T2D), coronary artery disease (CAD) were associated with a significant risk for a requirement of mechanical respiration and also mortality.
Patients with a history of macular degeneration (a proxy for complement activation disorders) and coagulation disorders (thrombocytopenia, thrombosis, and hemorrhage) were also at significantly increased risk of adverse clinical outcomes following SARS-CoV-2 infection.
The mechanical respiration rate was 16% with a mortality rate of 25% among patients with a history of macular degeneration, and rates of 9% and 15% for mechanical respiration and mortality, respectively, among patients with coagulation disorders.
The study may be limited by small sample size and its retrospective nature.
“Our study highlights the value of combining molecular information from virus protein structure-function analysis with orthogonal clinical data analysis to reveal determinants and/or predictors of immunity, susceptibility, and clinical outcome associated with infection. Such a framework can help refine large scale genomics efforts and help power genomics studies based on informed biological and clinical conjectures. While identification of CoV encoded structural mimics guided the retrospective clinical studies, a molecular and functional link between those observations and our discovery of complement and coagulation functions as risk factors for SARS-CoV-2 pathogenesis remains to be elucidated,” stated the authors.
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