Genetic justification of severe COVID-19 using a rigorous algorithm

Authors

• Eleni Gavriilaki
• Panagiotis G. Asteris
• Tasoula Touloumenidou
• Evaggelia-Evdoxia Koravou
• Maria Koutra
• Penelope Georgia Papayanni
• Vassiliki Karali
• Apostolia Papalexandri
• Christos Varelas
• Fani Chatzopoulou
• Maria Chatzidimitriou
• Dimitrios Chatzidimitriou
• Anastasia Veleni
• Savvas Grigoriadis
• Evdoxia Rapti
• Diamantis Chloros
• Ioannis Kioumis
• Evaggelos Kaimakamis
• Milly Bitzani
• Dimitrios Boumpas
• Argyris Tsantes
• Damianos Sotiropoulos
• Ioanna Sakellari
• Ioannis G. Kalantzis
• Stefanos T. Parastatidis
• Mohammadreza Koopialipoor
• Liborio Cavaleri
• Danial J. Armaghani
• Anastasia Papadopoulou
• Robert Alan Brodsky

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

Publication Title

Clinical Immunology

Recommended Citation

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; and Brodsky, Robert Alan, "Genetic justification of severe COVID-19 using a rigorous algorithm" (2021). Research Publications (2021 to 2025). 12041.
https://knova.um.edu.my/research_publications_2021_2025/12041

Funders

Pfizer

Volume

226

Publisher

Academic Press

Publisher Location

525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA