Detection of Antinuclear Antibodies Targeting Intracellular Signal Transduction, Metabolism, Apoptotic Processes and Cell Death in Critical COVID-19 Patients
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Date
2022-10-29Author
Nasarallah, Gheyath K.Fakhroo, Aisha D.
Khan, Taushif
Cyprian, Farhan S.
Al Ali, Fatima
Ata, Manar M.A.
Taleb, Sara
Zedan, Hadeel T.
Al-Sadeq, Duaa W.
Amanullah, Fathima H.
Hssain, Ali A.
Eid, Ali H.
Abu-Raddad, Laith J.
Al-Khal, Abdullatif
Al Thani, Asmaa A.
Marr, Nico
Yassine, Hadi M.
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Background and Objectives: The heterogeneity of the coronavirus disease of 2019 (COVID-19) lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) is a leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Results: Initial screening for antinuclear antibodies (ANA) IgG using ELISA revealed that 1.58% (2/126) and 4% (5/126) of intensive care unit (ICU) COVID-19 cases expressed strong and moderate ANA levels, respectively. An additional sample was positive with immunofluorescence assays (IFA) screening. However, all the non-ICU cases (n=273) were ANA negative using both assays. Samples positive for ANA were further confirmed with large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). The majority of the ANA-positive samples showed "speckled" ANA pattern by microscopy and revealed autoantibody specificities that targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death by PhIP-Seq; further denoting reactivity to nuclear and cytoplasmic antigens. Conclusion: Our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of COVID-19.
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