SARS‐CoV‐2 infection as a trigger of autoimmune response

Abstract

Currently, few evidences have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID‐19). In this study, we elucidate whether severe acute respiratory syndrome coronavirus disease 2 (SARS‐CoV‐2) stimulates autoantibody production and contributes to autoimmunity activation. We enrolled 40 adult patients (66.8 years mean age) admitted to Alessandria Hospital between March and April 2020. All the patients had a confirmed COVID‐19 diagnosis and no previously clinical record of autoimmune disease. Forty blood donors were analyzed for the same markers and considered as healthy controls. Our patients had high levels of common inflammatory markers, such as C reactive protein, lactate dehydrogenase, ferritin, and creatinine. Interleukin‐6 concentrations were also increased, supporting the major role of this interleukin during COVID‐19 infection. Lymphocyte numbers were generally lower compared with healthy individuals. All the patients were also screened for the most common autoantibodies. We found a significant prevalence of antinuclear antibodies, antineutrophil cytoplasmic antibodies, and ASCA immunoglobulin A antibodies. We observed that patients having a de novo autoimmune response had the worst acute viral disease prognosis and outcome. Our results sustain the hypothesis that COVID‐19 infection correlates with the autoimmunity markers. Our study might help clinicians to: (a) better understand the heterogeneity of this pathology and (b) correctly evaluate COVID‐19 clinical manifestations. Our data explained why drugs used to treat autoimmune diseases may also be useful for SARS‐CoV‐2 infection. In addition, we highly recommend checking patients with COVID‐19 for autoimmunity markers, mainly when deciding on whether to treat them with plasma transfer therapy. WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? ☑ Recent data sustain the idea that autoimmune phenomena exist in patients with coronavirus disease 2019 (COVID‐19), but other investigations are necessary to define the possible link between severe acute respiratory syndrome coronavirus disease 2 (SARS‐CoV‐2) infection and autoimmune disease onset. WHAT QUESTION DID THIS STUDY ADDRESS? ☑ In this monocentric study, we demonstrated how SARS‐CoV‐2 infection could be associated with an autoimmune response and development of autoantibodies. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? ☑ Patients with COVID‐19 having an increased level of inflammatory markers and strong autoantibodies positivity (i.e., antinuclear antibodies and antineutrophil cytoplasmic antibodies) presented the worst clinical outcome. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? ☑ These results suggest that the drugs normally used to treat autoimmune diseases should also be considered during SARS‐CoV‐2, improving public health. In addition, before starting a transfer plasma therapy, it is important to also evaluate the autoimmunity conditions of the patients with COVID‐19. Transferring antibodies or trying to neutrali...

Antibodies Against Angiotensin II Receptor Type 1 and Endothelin A Receptor Are Associated With an Unfavorable COVID19 Disease Course

“…Increased autoantibodies have been demonstrated in COVID19 patients (8,9). Recently, neutralizing IgG antibodies against several types of interferon were found in life-threatening COVID19, while no such autoantibodies were found in individuals with mild disease (10).…”

COVID-19-associated autoimmunity as a feature of acute respiratory failure

“…Coronavirus disease 2019 (COVID-19) has similarities to systemic autoimmune conditions, including an association with increased incidence of autoantibodies [1][2][3], including those directed toward cytokines [4]. However, reports to date lack longitudinal assessments and have inadequate controls (i.e., comparison to different severities within COVID-19 or to healthy individuals).…”

COVID-19 associated autoimmunity is a feature of severe respiratory disease - a Bayesian analysis

“…We analyzed disease severity and presence of AAB in 22 COVID + and 20 COVID -ICU patients with respiratory distress of similar severity, enrolled contemporaneously, over time. We used HEp2 IFA to typify ANAs, as well as solid-phase multi-analyte arrays and bead-based multiplexed immunoassays to typify specific autoreactive antigens such as those observed in autoimmune diseases such as systemic lupus erythematous, Sjögren syndrome, systemic sclerosis, autoimmune inflammatory myopathies, and others [4][5][6] .…”

“…A significant limitation of studies that have reported the emergence of autoantibodies (AAB) in COVID-19 4, 6, 10 has been the lack of control groups with similar clinical characteristics and the lack of longitudinal data monitoring the development of autoimmunity over time. Our study provides evidence that, when observed longitudinally, severe COVID-19 patients have similar AAB prevalence as a control cohort of critically ill patients.…”

“…The immune response in SARS-CoV2 infection shows evidence of immune dysregulation in patients with severe clinical manifestations 1 . While there is continued debate about the nature of the heightened inflammatory responses in severe COVID-19 patients 2,3 there is mounting evidence that some clinical and serological features bear remarkable similarities to systemic autoimmune conditions [4][5][6] . In addition, some COVID-19 patients continue to develop de novo clinical signs and symptoms reminiscent of autoimmune diseases during convalescence 7 .…”