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. 2024 Mar 6:11:1332716.
doi: 10.3389/fmed.2024.1332716. eCollection 2024.

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries

Rebecca Hasseli #  1   2 , Frank Hanses #  3 , Melanie Stecher  4 , Christof Specker  5 , Tobias Weise  6 , Stefan Borgmann  7 , Martina Hasselberger  8 , Bernd Hertenstein  9 , Martin Hower  10 , Bimba F Hoyer  11 , Carolin Koll  4 , Andreas Krause  12 , Marie von Lilienfeld-Toal  13 , Hanns-Martin Lorenz  14 , Uta Merle  15 , Susana M Nunes de Miranda  16 , Mathias W Pletz  17 , Anne C Regierer  18 , Jutta G Richter  19   20 , Siegbert Rieg  21 , Christoph Roemmele  22 , Maria M Ruethrich  13 , Tim Schmeiser  23 , Hendrik Schulze-Koops  24 , Anja Strangfeld  18 , Maria J G T Vehreschild  25 , Florian Voit  26 , Reinhard E Voll  27 , Jörg Janne Vehreschild  4   28 , Ulf Müller-Ladner  2 , Alexander Pfeil  29
Affiliations

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries

Rebecca Hasseli et al. Front Med (Lausanne). .

Abstract

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared.

Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total.

Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19.

Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.

Keywords: COVID-19; general population; inflammatory rheumatic diseases; severe disease; tumor necrosis factor-alpha inhibitors.

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Conflict of interest statement

TW was employed by company Biocontrol Jena. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Flowchart regarding the excluded patients or missing value for matching of the patients from both registries.
FIGURE 2
FIGURE 2
Results of the univariate (A) and multivariate regression analysis (B,C) for the verification of comorbidities, IRD and rheumatic treatment on the outcome of COVID-19 infection based on the LEOSS Registry and IRD registry. Significant independent variable’s influence (p-values <0.05) on the COVID-19 severity outcome marked bold and colored blue. (LEOSS Registry, Lean European Open Survey on SARS-CoV-2; BMI, body mass index; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; IRD, inflammatory rheumatic diseases; DSA, disease activity; bDMARD biological disease-modifying antirheumatic drugs, csDMARD, conventional synthetic disease-modifying antirheumatic drug; TNF Inhibitors, tumor necrosis factor-alpha inhibitors).
FIGURE 3
FIGURE 3
Results of the univariate (A) and multivariate regression (B,C) sub-analysis for the IRD cohort on the outcome of COVID-19 infection using the data of the IRD registry (significant variable were marked bold and colored blue. LEOSS Registry, Lean European Open Survey on SARS-CoV-2; BMI, body mass index; COPD, Chronic obstructive pulmonary disease; ILD, interstitial lung disease; IRD, inflammatory rheumatic diseases; DSA, disease activity; bDMARD, biological disease-modifying antirheumatic drugs; csDMARD, conventional synthetic disease-modifying antirheumatic drug; TNF inhibitors, tumor necrosis factor-alpha inhibitors).
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