Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures

Abstract

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. Objective: 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 anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, 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 anti-viral humoral immune responses and inflammatory immune signatures.

Autoimmunity and SARS‐CoV‐2 infection: Unraveling the link in neurological disorders

“…On the other hand, it is becoming increasingly clear that SARS-CoV-2 infection can trigger the de novo development of autoantibodies targeting a broad spectrum of autoantigens. Increased titers of anti-nuclear antibodies (ANA), hallmarks of systemic autoimmunity, have been identified in COVID-19 patients compared to healthy controls and seem to correlate with disease severity and systemic inflammation [73,[76][77][78][79][80][81][82]. Approximately 50% of hospitalized COVID-19 patients and less than 15% of healthy controls had detectable serum autoantibodies against self-antigens traditionally associated with rare autoimmune diseases, such as autoimmune myositis, systemic erythematous lupus (SLE), and Sjogren's syndrome [73,81].…”

Unlocking the Mysteries of Long COVID in Children and Young People: Insights from a Policy Review and Social Media Analysis in the UK

“…The condition was then recognised as a problem by key international bodies such as the World Health Organization (WHO) and the Centre for Disease Control and Prevention (CDC) in the latter half of 2020 (Miyake & Martin, 2021). In February 2021, Anthony Fauci gave Long COVID further medical recognition and de nition by renaming it 'post-acute sequelae of COVID' (PASC) (Taeschler et al, 2022). Yet, there is still much unknown about the long-term consequences of COVID-19 (World Health Organization (WHO), 2021a) and both the condition and the term are regularly questioned as researchers and healthcare professionals learn to identify and treat the wide range of symptoms caused by COVID-19 over time.…”

Unlocking the Mysteries of Long COVID in Children and Young People: Insights from a Policy Review and Social Media Analysis in the UK

“…The condition was then recognised as a problem by key international bodies such as the World Health Organization (WHO) and the Centre for Disease Control and Prevention (CDC) in the latter half of 2020 (Miyake & Martin, 2021). In February 2021, Anthony Fauci gave Long COVID further medical recognition and definition by renaming it 'post-acute sequelae of COVID' (PASC) (Taeschler et al, 2022). Yet, there is still much unknown about the long-term consequences of COVID-19 (World Health Organization (WHO), 2021a) and both the condition and the term are regularly questioned as researchers and healthcare professionals learn to identify and treat the wide range of symptoms caused by COVID-19 over time.…”