Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19

Vlachoyiannopoulos, Panayiotis G.; Magira, Eleni; Alexopoulos, Harry; Jahaj, Edison; Theophilopoulou, Katerina; Kotanidou, Anastasia; Tzioufas, Athanasios G.

doi:10.1136/annrheumdis-2020-218009

Cited by 170 publications

(174 citation statements)

References 8 publications

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“…With respect to baseline clinical characteristics, the investigated cohort is comparable to previous reports ( 2 , 19 ). Our result of autoantibodies in patients with severe COVD-19 is in line with first results from other groups ( 10 , 11 , 20 ); however, we are the first to put this observation into context with clinical, imaging, and histopathology findings. Furthermore, we confirm the association between higher age, male sex, and elevated LDH with severe course of COVID-19 in line with literature data ( 19 ).…”

Section: Discussionsupporting

confidence: 91%

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)

et al. 2020

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Background and Objectives Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.

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Section: Discussionsupporting

confidence: 91%

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)

et al. 2020

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“…Our data sustained that autoimmunity is linked to SARS-CoV-2 infection, since none of the patients had a previous autoimmune disease. This is in accordance with what has recently been described in the literature concerning the onset of autoimmune diseases upon COVID-19 infection11 .…”

supporting

confidence: 93%

“…Different autoantibodies are not only disease markers but can be also pathogenic, therefore transferring autoantibodies or performing transfusions with neutralizing antibodies might not be the best choice for these patients 11 .…”

Section: Accepted Articlementioning

confidence: 99%

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

Sacchi

Tamiazzo

Stobbione

et al. 2021

Clinical Translational Sci

124

109

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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...

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“…This finding suggests a post-SARS-CoV-2 or para-SARS-CoV-2 infectious autoimmune reactivation. The authors suggested that the presentation of cytokines, such as IL-6, in the cytokine storm, can lead to autoinflammatory activation and autoimmunity, probably through natural B-cells or molecular mimicry ( Vlachoyiannopoulos et al, 2020 ). Tocilizumab is being used in patients with COVID-19, mostly in the advanced disease stage, on the basis of the previous experience with chimeric antigen receptor (CAR) T-cell immunotherapy-induced cytokine release syndrome ( Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

Ikonomidis

Pavlidis

Katsimbri

et al. 2020

Food and Chemical Toxicology

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We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. Clinical trial registration url: https://www.clinicaltrials.gov . Unique identifier: NCT03288584.

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Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19

Cited by 170 publications

References 8 publications

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)

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

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

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