Genetic justification of severe COVID-19 using a rigorous algorithm

• Main Authors: Gavriilaki, Eleni, Asteris, Panagiotis G., Touloumenidou, Tasoula, Koravou, Evaggelia-Evdoxia, Koutra, Maria, Papayanni, Penelope Georgia, Karali, Vassiliki, Papalexandri, Apostolia, Varelas, Christos, Chatzopoulou, Fani, Chatzidimitriou, Maria, Chatzidimitriou, Dimitrios, Veleni, Anastasia, Grigoriadis, Savvas, Rapti, Evdoxia, Chloros, Diamantis, Kioumis, Ioannis, Kaimakamis, Evaggelos, Bitzani, Milly, Boumpas, Dimitrios, Tsantes, Argyris, Sotiropoulos, Damianos, Sakellari, Ioanna, Kalantzis, Ioannis G., Parastatidis, Stefanos T., Koopialipoor, Mohammadreza, Cavaleri, Liborio, Armaghani, Danial J., Papadopoulou, Anastasia, Brodsky, Robert Alan, Kokoris, Styliani, Anagnostopoulos, Achilles
• Format: Article
• Published: Academic Press 2021
• Subjects: R Medicine; RB Pathology
• Online Access: http://eprints.um.edu.my/34693/
• Institution: Universiti Malaya

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.