tetano
Editor, Senior Moderator
Clin Immunol
. 2021 Apr 9;108726.
doi: 10.1016/j.clim.2021.108726. Online ahead of print.
Genetic justification of severe COVID-19 using a rigorous algorithm
Eleni Gavriilaki[SUP] 1 [/SUP], Panagiotis G Asteris[SUP] 2 [/SUP], Tasoula Touloumenidou[SUP] 3 [/SUP], Evaggelia-Evdoxia Koravou[SUP] 3 [/SUP], Maria Koutra[SUP] 3 [/SUP], Penelope Georgia Papayanni[SUP] 3 [/SUP], Vassiliki Karali[SUP] 4 [/SUP], Apostolia Papalexandri[SUP] 3 [/SUP], Christos Varelas[SUP] 3 [/SUP], Fani Chatzopoulou[SUP] 5 [/SUP], Maria Chatzidimitriou[SUP] 6 [/SUP], Dimitrios Chatzidimitriou[SUP] 5 [/SUP], Anastasia Veleni[SUP] 7 [/SUP], Savvas Grigoriadis[SUP] 8 [/SUP], Evdoxia Rapti[SUP] 9 [/SUP], Diamantis Chloros[SUP] 10 [/SUP], Ioannis Kioumis[SUP] 11 [/SUP], Evaggelos Kaimakamis[SUP] 12 [/SUP], Milly Bitzani[SUP] 12 [/SUP], Dimitrios Boumpas[SUP] 4 [/SUP], Argyris Tsantes[SUP] 9 [/SUP], Damianos Sotiropoulos[SUP] 3 [/SUP], Ioanna Sakellari[SUP] 3 [/SUP], Ioannis G Kalantzis[SUP] 13 [/SUP], Stefanos T Parastatidis[SUP] 2 [/SUP], Mohammadreza Koopialipoor[SUP] 14 [/SUP], Liborio Cavaleri[SUP] 15 [/SUP], Danial J Armaghani[SUP] 16 [/SUP], Anastasia Papadopoulou[SUP] 3 [/SUP], Robert Alan Brodsky[SUP] 17 [/SUP], Styliani Kokoris[SUP] 9 [/SUP], Achilles Anagnostopoulos[SUP] 3 [/SUP]
Affiliations
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.
. 2021 Apr 9;108726.
doi: 10.1016/j.clim.2021.108726. Online ahead of print.
Genetic justification of severe COVID-19 using a rigorous algorithm
Eleni Gavriilaki[SUP] 1 [/SUP], Panagiotis G Asteris[SUP] 2 [/SUP], Tasoula Touloumenidou[SUP] 3 [/SUP], Evaggelia-Evdoxia Koravou[SUP] 3 [/SUP], Maria Koutra[SUP] 3 [/SUP], Penelope Georgia Papayanni[SUP] 3 [/SUP], Vassiliki Karali[SUP] 4 [/SUP], Apostolia Papalexandri[SUP] 3 [/SUP], Christos Varelas[SUP] 3 [/SUP], Fani Chatzopoulou[SUP] 5 [/SUP], Maria Chatzidimitriou[SUP] 6 [/SUP], Dimitrios Chatzidimitriou[SUP] 5 [/SUP], Anastasia Veleni[SUP] 7 [/SUP], Savvas Grigoriadis[SUP] 8 [/SUP], Evdoxia Rapti[SUP] 9 [/SUP], Diamantis Chloros[SUP] 10 [/SUP], Ioannis Kioumis[SUP] 11 [/SUP], Evaggelos Kaimakamis[SUP] 12 [/SUP], Milly Bitzani[SUP] 12 [/SUP], Dimitrios Boumpas[SUP] 4 [/SUP], Argyris Tsantes[SUP] 9 [/SUP], Damianos Sotiropoulos[SUP] 3 [/SUP], Ioanna Sakellari[SUP] 3 [/SUP], Ioannis G Kalantzis[SUP] 13 [/SUP], Stefanos T Parastatidis[SUP] 2 [/SUP], Mohammadreza Koopialipoor[SUP] 14 [/SUP], Liborio Cavaleri[SUP] 15 [/SUP], Danial J Armaghani[SUP] 16 [/SUP], Anastasia Papadopoulou[SUP] 3 [/SUP], Robert Alan Brodsky[SUP] 17 [/SUP], Styliani Kokoris[SUP] 9 [/SUP], Achilles Anagnostopoulos[SUP] 3 [/SUP]
Affiliations
- PMID: 33845193
- DOI: 10.1016/j.clim.2021.108726
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.