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Autoantibodies Against Angiotensin-converting Enzyme 2 and Immune Molecules Are Associated with COVID-19 Disease Severity

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Journal Res Sq
Date 2023 Oct 16
PMID 37841848
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Abstract

Increased inflammation caused by SARS-CoV-2 infection can lead to severe coronavirus disease 2019 (COVID-19) and long-term disease manifestations referred to as post-acute sequalae of COVID (PASC). The mechanisms of this variable long-term immune activation are poorly defined. Autoantibodies targeting immune factors such as cytokines, as well as the viral host cell receptor, angiotensin-converting enzyme 2 (ACE2), have been observed after SARS-CoV-2 infection. Autoantibodies to immune factors and ACE2 could interfere with normal immune regulation and lead to increased inflammation, severe COVID-19, and long-term complications. Here, we deeply pro led the features of ACE2, cytokine, and chemokine autoantibodies in samples from patients recovering from severe COVID-19. We identified epitopes in the catalytic domain of ACE2 targeted by these antibodies, that could inhibit ACE2 function. Levels of autoantibodies targeting ACE2 and other immune factors could serve as determinants of COVID-19 disease severity, and represent a natural immunoregulatory mechanism in response to viral infection.

References
1.
Casanova J, Su H . A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection. Cell. 2020; 181(6):1194-1199. PMC: 7218368. DOI: 10.1016/j.cell.2020.05.016. View

2.
Jawad B, Adhikari P, Podgornik R, Ching W . Key Interacting Residues between RBD of SARS-CoV-2 and ACE2 Receptor: Combination of Molecular Dynamics Simulation and Density Functional Calculation. J Chem Inf Model. 2021; 61(9):4425-4441. DOI: 10.1021/acs.jcim.1c00560. View

3.
Dotan A, Muller S, Kanduc D, David P, Halpert G, Shoenfeld Y . The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev. 2021; 20(4):102792. PMC: 7892316. DOI: 10.1016/j.autrev.2021.102792. View

4.
Patel S, Juno J, Lee W, Wragg K, Hogarth P, Kent S . Plasma ACE2 activity is persistently elevated following SARS-CoV-2 infection: implications for COVID-19 pathogenesis and consequences. Eur Respir J. 2021; 57(5). PMC: 7830336. DOI: 10.1183/13993003.03730-2020. View

5.
Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q . The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proc Natl Acad Sci U S A. 2022; 119(21):e2200413119. PMC: 9173764. DOI: 10.1073/pnas.2200413119. View