Genetic justification of severe COVID-19 using a rigorous algorithm

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

Risultato della ricerca: Articlepeer review

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.
Lingua originaleEnglish
Numero di pagine9
RivistaClinical Immunology
Volume226
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2400.2403???

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