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 COVID-19. 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; Complement; Eculizumab; Genetic susceptibility; Rigorous algorithm; SARS-CoV2.
【저자키워드】 COVID-19, SARS-CoV2, eculizumab, complement, genetic susceptibility, Rigorous algorithm, 【초록키워드】 coronavirus disease, SARS-CoV2, severe COVID-19, thrombomodulin, Hospitalization, disease severity, Genetic, variant, Gender, eculizumab, complement, risk factor, variants, ICU, Complement activation, Characteristics, Coronavirus disease-19, ADAMTS13, Patient, genetic susceptibility, patients, thrombotic microangiopathy, Combination, complement inhibitors, Activation, Clinical data, severe coronavirus disease, thrombotic, specific treatment, patient population, recent, benefit, highlight, analyzed, patients hospitalized, 【제목키워드】 Algorithm,