Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion

Simón, David; Tascilar, Koray; Krönke, Gerhard; Kleyer, Arnd; Zaiss, Mario M.; Heppt, Franz; Meder, Christine; Atreya, Raja; Klenske, E; Dietrich, Péter; Abdullah, Abdullah; Kliem, Thorsten; Corte, Giulia; Morf, Harriet; Leppkes, Moritz; Kremer, Andreas E.; Ramming, Andreas; Pachowsky, Milena; Schuch, Florian; Ronneberger, Monika; Kleinert, Stefan; Maier, Clara; Hueber, Axel J.; Manger, Karin; Manger, Bernhard; Berking, Carola; Tenbusch, Matthias; Überla, Klaus; Sticherling, Michael; Neurath, Markus F.; Schett, Georg

doi:10.1038/s41467-020-17703-6

Cited by 83 publications

(84 citation statements)

References 26 publications

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“…However, it is possible that such a correlation will be identified in critically ill patients especially if cytokine expression will be monitored at the site of infection (i.e., lungs) 19 . Another explanation for the correlation that we observed between cytokines and antibody responses in moderate/severe patients in comparison to mild ones is supported by the recent publication that patients receiving cytokine inhibitors had lower prevalence of SARS-CoV-2 seroconversion 30 . Using hierarchical clustering analysis, we identified that IgG in the moderate/severe patient population clustered with IL-33.…”

Section: Discussionsupporting

confidence: 73%

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Munitz

Edry-Botzer

Itan

et al. 2021

Sci Rep

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Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

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Section: Discussionsupporting

confidence: 73%

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Munitz

Edry-Botzer

Itan

et al. 2021

Sci Rep

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“…Immunosuppressive treatment before COVID-19 was not associated with greater mortality or AKI in GN patients. Although the published data regarding risks of COVID-19 and immunosuppression are still limited, 10 our finding is in accordance with other reports of infected patients on immunosuppressive medications for other autoimmune diseases 24 , 25 , 26 , 27 , 28 or underlying cancer. 29 However, prednisone dose ≥10 mg/day was associated with higher odds of hospitalization in the COVID-19 Global Rheumatology Alliance.…”

Section: Discussionsupporting

confidence: 91%

“…We can only speculate whether patients with GN practice better social distancing or if there is a potential “protective” role of certain immunosuppressive medications that prevents or limits the excessive immune activation responsible for severe clinical manifestations. 26 , 28 , 30 , 34 Thus far, there is no convincing evidence that any agents protect against severe COVID-19 infection, but these issues warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

Results from the IRoc-GN international registry of patients with COVID-19 and glomerular disease suggest close monitoring

Waldman

Soler

García-Carro

et al. 2021

Kidney International

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The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels.

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“…In the present cohort, patients receiving non-anti-TNF anti-cytokine therapy in monotherapy (i.e., IL-6, IL-12/IL-23, and IL-17 inhibitors) at baseline were less likely to require hospitalization. Recent data suggest that patients with IMID receiving cytokine inhibitors may not have an enhanced but at a lower risk for SARS-CoV-2 infection compared with the general population and IMID patients not receiving such drugs [ 36 ]. Our data show that baseline anti-TNF treatment had no impact on the need for hospital admission in patients with AI/IMID.…”

Section: Discussionmentioning

confidence: 99%

A multidisciplinary registry of patients with autoimmune and immune-mediated diseases with symptomatic COVID-19 from a single center

Sarmiento-Monroy

Espinosa

Londoño

et al. 2021

Journal of Autoimmunity

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Background and aim There is increasing interest regarding SARS-CoV-2 infection in patients with autoimmune and immune-mediated inflammatory diseases (AI/IMID) with some discrepancies in different cohorts about their risk and outcomes. The aim was to describe a multidisciplinary cohort of patients with AI/IMID and symptomatic SARS-CoV-2 infection in a single tertiary center and analyze sociodemographic, clinical, and therapeutic factors associated with poor outcomes. Methods A retrospective observational study was conducted from the 1st of March until May 29th, 2020 in a University tertiary hospital in Barcelona, Spain. Patients with an underlying AI/IMID and symptomatic SARS-CoV-2 infection were identified in our local SARS-CoV-2 infection database. Controls (2:1) were selected from the same database and matched by age and gender. The primary outcome was severe SARS-CoV-2 infection, which was a composite endpoint including admission to the intensive care unit (ICU), need for mechanical ventilation (MV), and/or death. Several covariates including age, sex, and comorbidities among others were combined into a multivariate model having severe SARS-CoV-2 as the dependent variable. Also, a sensitivity analysis was performed evaluating AID and IMID separately. Results The prevalence of symptomatic SARS-CoV-2 infection in a cohort of AI/IMID patients was 1.3%. Eighty-five patients with AI/IMID and symptomatic SARS-CoV-2 were identified, requiring hospitalization in 58 (68%) cases. A total of 175 patients admitted for SARS-CoV-2 (58 with AI/IMID and 117 matched-controls) were analyzed. In logistic regression analysis, a significant inverse association between AI/IMID group and severe SARS-CoV-2 (OR 0.28; 95% CI 0.12–0.61; p = 0.001), need of MV (OR 0.20; IC 95% 0.05–0.71; p = 0.014), and ICU admission (OR 0.25; IC 95% 0.10–0.62; p = 0.003) was found. Conclusions Patients with AI/IMID who require admission for SARS-CoV-2 infection have a lower risk of developing severe disease, including the need to stay in the ICU and MV.

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Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion

Cited by 83 publications

References 26 publications

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Results from the IRoc-GN international registry of patients with COVID-19 and glomerular disease suggest close monitoring

A multidisciplinary registry of patients with autoimmune and immune-mediated diseases with symptomatic COVID-19 from a single center

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