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Genetic justification of severe COVID-19 using a rigorous algorithm

Gavriilaki E 1 , Asteris PG 2 , Touloumenidou T 3 , Koravou EE 3 , Koutra M 3 , Papayanni PG 3 Show all authors , Karali V 4 , Papalexandri A 3 , Varelas C 3 , Chatzopoulou F 5 , Chatzidimitriou M 6 , Chatzidimitriou D 5 , Veleni A 7 , Grigoriadis S 8 , Rapti E 9 , Chloros D 10 , Kioumis I 11 , Kaimakamis E 12 , Bitzani M 12 , Boumpas D 4 , Tsantes A 9 , Sotiropoulos D 3 , Sakellari I 3 , Kalantzis IG 13 , Parastatidis ST 2 , Koopialipoor M 14 , Cavaleri L 15 , Armaghani DJ 16 , Papadopoulou A 3 , Brodsky RA 17 , Kokoris S 9 , Anagnostopoulos A 3

Affiliations 

  • 1 Hematology Department - BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece. Electronic address: elenicelli@yahoo.gr
  • 2 Computational Mechanics Laboratory, School of Pedagogical and Technological Education, Athens, Greece
  • 3 Hematology Department - BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece
  • 4 Rheumatology and Clinical Immunology Unit, "Attikon" University Hospital, Athens, Greece
  • 5 Microbiology Department, Aristotle University of Thessaloniki, Greece
  • 6 Biomedical Sciences, Alexander Campus International Hellenic University, Thessaloniki, Greece
  • 7 Infectious Disease Committee, G Papanicolaou Hospital, Thessaloniki, Greece
  • 8 Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 9 Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital "Attikon", NKUA, Medical School, Greece
  • 10 Pneumonology Department, G Papanicolaou Hospital, Thessaloniki, Greece
  • 11 Respiratory Failure Department, G Papanicolaou Hospital-Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 12 1st Intensive Care Unit, G Papanicolaou Hospital, Thessaloniki, Greece
  • 13 Gastroenterology Department, Hellenic Red Cross Hospital, Athens, Greece
  • 14 Faculty of Civil and Environmental Engineering, Amirkabir University of Technology, Tehran, Iran
  • 15 Department of Civil, Environmental, Aerospace and Materials Engineering, University of Palermo, Palermo, Italy
  • 16 Department of Civil Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia
  • 17 Hematology Division, Department of Internal Medicine, Johns Hopkins University, Baltimore, USA
Clin Immunol, 2021 May;226:108726.
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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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