Autoantibodies in COVID-19 Correlate with Antiviral Humoral Responses and Distinct Immune Signatures

Overview

Journal Allergy

Specialty Allergy & Immunology

Date 2022 Apr 1

PMID 35364615

Authors

Patrick Taeschler

Carlo Cervia

Yves Zurbuchen

Sara Hasler

Christian Pou

Ziyang Tan

Sarah Adamo

Miro E Raeber

Esther Bachli

Alain Rudiger

Melina Stussi-Helbling

Lars C Huber

Petter Brodin

Jakob Nilsson

Elsbeth Probst-Muller

Onur Boyman

Affiliations

Soon will be listed here.

Abstract

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19.

Methods: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls.

Results: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery.

Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.

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References

Angileri F, Legare S, Marino Gammazza A, de Macario E, Macario A, Cappello F . Molecular mimicry may explain multi-organ damage in COVID-19. Autoimmun Rev. 2020; 19(8):102591. PMC: 7289093. DOI: 10.1016/j.autrev.2020.102591. View

Pou C, Nkulikiyimfura D, Henckel E, Olin A, Lakshmikanth T, Mikes J . The repertoire of maternal anti-viral antibodies in human newborns. Nat Med. 2019; 25(4):591-596. DOI: 10.1038/s41591-019-0392-8. View

Kaneko N, Kuo H, Boucau J, Farmer J, Allard-Chamard H, Mahajan V . Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19. Cell. 2020; 183(1):143-157.e13. PMC: 7437499. DOI: 10.1016/j.cell.2020.08.025. View

Bastard P, Rosen L, Zhang Q, Michailidis E, Hoffmann H, Zhang Y . Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020; 370(6515). PMC: 7857397. DOI: 10.1126/science.abd4585. View

Zhang H, Li P, Wu D, Xu D, Hou Y, Wang Q . Serum IgG subclasses in autoimmune diseases. Medicine (Baltimore). 2015; 94(2):e387. PMC: 4602543. DOI: 10.1097/MD.0000000000000387. View

Petersen E, Koopmans M, Go U, Hamer D, Petrosillo N, Castelli F . Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020; 20(9):e238-e244. PMC: 7333991. DOI: 10.1016/S1473-3099(20)30484-9. View

Wang Z, Muecksch F, Schaefer-Babajew D, Finkin S, Viant C, Gaebler C . Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature. 2021; 595(7867):426-431. PMC: 8277577. DOI: 10.1038/s41586-021-03696-9. View

Adamo S, Michler J, Zurbuchen Y, Cervia C, Taeschler P, Raeber M . Signature of long-lived memory CD8 T cells in acute SARS-CoV-2 infection. Nature. 2021; 602(7895):148-155. PMC: 8810382. DOI: 10.1038/s41586-021-04280-x. View

Wang E, Mao T, Klein J, Dai Y, Huck J, Jaycox J . Diverse functional autoantibodies in patients with COVID-19. Nature. 2021; 595(7866):283-288. DOI: 10.1038/s41586-021-03631-y. View

10.

Wiersinga W, Rhodes A, Cheng A, Peacock S, Prescott H . Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324(8):782-793. DOI: 10.1001/jama.2020.12839. View

11.

Baglaenko Y, Chang N, Johnson S, Hafiz W, Manion K, Ferri D . The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease. Arthritis Res Ther. 2018; 20(1):264. PMC: 6263058. DOI: 10.1186/s13075-018-1752-3. View

12.

Chang S, Minn D, Kim Y . Autoantibodies in moderate and critical cases of COVID-19. Clin Transl Sci. 2021; 14(5):1625-1626. PMC: 8239866. DOI: 10.1111/cts.13036. View

13.

Xu G, Kula T, Xu Q, Li M, Vernon S, Ndungu T . Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome. Science. 2015; 348(6239):aaa0698. PMC: 4844011. DOI: 10.1126/science.aaa0698. View

14.

Nakazawa D, Kumar S, Desai J, Anders H . Neutrophil extracellular traps in tissue pathology. Histol Histopathol. 2016; 32(3):203-213. DOI: 10.14670/HH-11-816. View

15.

Jog N, Young K, Munroe M, Harmon M, Guthridge J, Kelly J . Association of Epstein-Barr virus serological reactivation with transitioning to systemic lupus erythematosus in at-risk individuals. Ann Rheum Dis. 2019; 78(9):1235-1241. PMC: 6692217. DOI: 10.1136/annrheumdis-2019-215361. View

16.

Chan E, Damoiseaux J, Carballo O, Conrad K, Cruvinel W, Francescantonio P . Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015. Front Immunol. 2015; 6:412. PMC: 4542633. DOI: 10.3389/fimmu.2015.00412. View

17.

Cervia C, Nilsson J, Zurbuchen Y, Valaperti A, Schreiner J, Wolfensberger A . Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol. 2020; 147(2):545-557.e9. PMC: 7677074. DOI: 10.1016/j.jaci.2020.10.040. View

18.

Guan W, Ni Z, Hu Y, Liang W, Ou C, He J . Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020; 382(18):1708-1720. PMC: 7092819. DOI: 10.1056/NEJMoa2002032. View

19.

Fujinami R, von Herrath M, Christen U, Whitton J . Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev. 2006; 19(1):80-94. PMC: 1360274. DOI: 10.1128/CMR.19.1.80-94.2006. View

20.

Lerma L, Chaudhary A, Bryan A, Morishima C, Wener M, Fink S . Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19). J Transl Autoimmun. 2020; 3:100073. PMC: 7691817. DOI: 10.1016/j.jtauto.2020.100073. View