Genetic justification of severe COVID-19 using a rigorous algorithm

Gavriilaki, Eleni and Asteris, Panagiotis G. and Touloumenidou, Tasoula and Koravou, Evaggelia-Evdoxia and Koutra, Maria and Papayanni, Penelope Georgia and Karali, Vassiliki and Papalexandri, Apostolia and Varelas, Christos and Chatzopoulou, Fani and Chatzidimitriou, Maria and Chatzidimitriou, Dimitrios and Veleni, Anastasia and Grigoriadis, Savvas and Rapti, Evdoxia and Chloros, Diamantis and Kioumis, Ioannis and Kaimakamis, Evaggelos and Bitzani, Milly and Boumpas, Dimitrios and Tsantes, Argyris and Sotiropoulos, Damianos and Sakellari, Ioanna and Kalantzis, Ioannis G. and Parastatidis, Stefanos T. and Koopialipoor, Mohammadreza and Cavaleri, Liborio and Armaghani, Danial J. and Papadopoulou, Anastasia and Brodsky, Robert Alan and Kokoris, Styliani and Anagnostopoulos, Achilles (2021) Genetic justification of severe COVID-19 using a rigorous algorithm. Clinical Immunology, 226. ISSN 1521-6616, DOI https://doi.org/10.1016/j.clim.2021.108726.

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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.

Item Type: Article
Funders: Pfizer
Uncontrolled Keywords: COVID-19;SARS-CoV2;Complement;Genetic susceptibility; Eculizumab;Rigorous algorithm
Subjects: R Medicine
R Medicine > RB Pathology
Depositing User: Ms Zaharah Ramly
Date Deposited: 30 May 2022 06:20
Last Modified: 30 May 2022 06:20
URI: http://eprints.um.edu.my/id/eprint/34693

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