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Front Immunol . Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Diseas

tetano

Editor, Senior Moderator
Front Immunol


. 2020 Oct 2;11:587517.
doi: 10.3389/fimmu.2020.587517. eCollection 2020.
Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)


Daniel Gagiannis[SUP] 1 [/SUP], Julie Steinestel[SUP] 2 [/SUP], Carsten Hackenbroch[SUP] 3 [/SUP], Benno Schreiner[SUP] 4 [/SUP], Michael Hannemann[SUP] 4 [/SUP], Wilhelm Bloch[SUP] 5 [/SUP], Vincent G Umathum[SUP] 6 [/SUP], Niklas Gebauer[SUP] 7 [/SUP], Conn Rother[SUP] 8 [/SUP], Marcel Stahl[SUP] 1 [/SUP], Hanno M Witte[SUP] 6 7 8 [/SUP], Konrad Steinestel[SUP] 6 [/SUP]



Affiliations

Abstract

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.

Keywords: SARS-CoV-2; autoantibodies; autoimmunity; connective tissue disease; coronavirus disease 2019.
 
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