Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks.

Journal: Journal of cellular and molecular medicine
PMID: 35064759

Abstract

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.

Authors

  • Panagiotis G Asteris
    Computational Mechanics Laboratory, School of Pedagogical and Technological Education, Heraklion, 14121 Athens, Greece.
  • Eleni Gavriilaki
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Tasoula Touloumenidou
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Evaggelia-Evdoxia Koravou
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Maria Koutra
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Penelope Georgia Papayanni
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Alexandros Pouleres
    Biomedical Laboratories, Athens, Greece.
  • Vassiliki Karali
    Rheumatology and Clinical Immunology Unit, University General Hospital 'Attikon', Athens, Greece.
  • Minas E Lemonis
    Computational Mechanics Laboratory, School of Pedagogical and Technological Education, Athens, Greece.
  • Anna Mamou
    Computational Mechanics Laboratory, School of Pedagogical and Technological Education, Athens, Greece.
  • Athanasia D Skentou
    Computational Mechanics Laboratory, School of Pedagogical and Technological Education, Athens, Greece.
  • Apostolia Papalexandri
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Christos Varelas
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Fani Chatzopoulou
    Microbiology Department, Aristotle University of Thessaloniki, Greece.
  • Maria Chatzidimitriou
    Biomedical Sciences Alexander Campus International Hellenic University, Thessaloniki, Greece.
  • Dimitrios Chatzidimitriou
    Microbiology Department, Aristotle University of Thessaloniki, Greece.
  • Anastasia Veleni
    Infectious Disease Committee, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Evdoxia Rapti
    Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital 'Attikon', NKUA, Medical School, Athens, Greece.
  • Ioannis Kioumis
    Respiratory Failure Department, G Papanicolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Evaggelos Kaimakamis
    1st Intensive Care Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Milly Bitzani
    1st Intensive Care Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Dimitrios Boumpas
    Rheumatology and Clinical Immunology Unit, University General Hospital 'Attikon', Athens, Greece.
  • Argyris Tsantes
    Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital 'Attikon', NKUA, Medical School, Athens, Greece.
  • Damianos Sotiropoulos
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Anastasia Papadopoulou
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Ioannis G Kalantzis
    Gastroenterology Department, Hellenic Red Cross Hospital, Athens, Greece.
  • Lydia A Vallianatou
    Cath and EP Laboratory/Covid Intensive Care Unit, Hellenic Red Cross Hospital, Athens, Greece.
  • Danial J Armaghani
    Department of Civil Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia.
  • Liborio Cavaleri
    Department of Civil, Environmental, Aerospace and Materials Engineering (DICAM), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
  • Amir H Gandomi
    Faculty of Engineering Information Technology, University of Technology Sydney, Ultimo, NSW 2007, Australia.
  • Mohsen Hajihassani
    Construction Research Alliance, Universiti Teknologi Malaysia, 81310 UTM Skudai, Johor Bahru, Johor, Malaysia. mohsen_hajihassani@yahoo.com.
  • Mahdi Hasanipanah
    Department of Mining Engineering, University of Kashan, Kashan, Iran. Hasanipanah.m@grad.kashanu.ac.ir.
  • Mohammadreza Koopialipoor
    Faculty of Civil and Environmental Engineering, Amirkabir University of Technology, Tehran, Iran.
  • Paulo B Lourenço
    Department of Civil Engineering, ISISE, University of Minho, Guimarães, Portugal.
  • Pijush Samui
    Department of Civil Engineering, National Institute of Technology Patna, India.
  • Jian Zhou
    CTIQ, Canon Medical Research USA, Inc., Vernon Hills, 60061, USA.
  • Ioanna Sakellari
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.
  • Serena Valsami
    Hematology Laboratory - Blood Bank, Aretaieion Hospital, School of Medicine, NKUA, Athens, Greece.
  • Marianna Politou
    Hematology Laboratory - Blood Bank, Aretaieion Hospital, School of Medicine, NKUA, Athens, Greece.
  • Styliani Kokoris
    Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital 'Attikon', NKUA, Medical School, Athens, Greece.
  • Achilles Anagnostopoulos
    Hematology Department, BMT Unit, G Papanicolaou Hospital, Thessaloniki, Greece.

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