Genetic justification of severe COVID-19 using a rigorous algorithm
Document Type
Article
Publication Date
5-1-2021
Abstract
Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (p = 0.022). Analysis of almost infinite variant combinations showed that patients with rs1042580 in thrombomodulin and without rs800292 in complement factor H did not require ICU hospitalization. We also observed gender differences in ADAMTS13 and complement-related variants. In light of encouraging results by complement inhibitors, our study highlights a patient population that might benefit from early initiation of specific treatment.
Keywords
COVID-19, SARS-CoV2, Complement, Genetic susceptibility, Eculizumab, Rigorous algorithm
Funders
Pfizer
Publication Title
Clinical Immunology
Volume
226
Publisher
Academic Press
Publisher Location
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA