# Immunoinflammatory evidence of rheumatoid arthritis caused by COVID-19

**Authors:** Zhiqiang Shao, Dan Xia, Liang Zhou, Zonghan Xu, Jiaqian Wang

PMC · DOI: 10.1186/s40659-025-00620-7 · Biological Research · 2025-06-10

## TL;DR

This study finds that immune inflammation from COVID-19 may lead to rheumatoid arthritis, showing similar immune responses in both diseases.

## Contribution

The study provides new evidence that immune inflammation from COVID-19 could cause rheumatoid arthritis.

## Key findings

- RA patients with COVID-19 had higher hospitalization and mortality rates.
- Interleukin 13 and specific immune cell markers are linked to both diseases.
- Both diseases show similar immune cell infiltration patterns and enriched immune pathways.

## Abstract

The relationship between coronavirus disease 2019 (COVID-19) and rheumatoid arthritis (RA) remains uncertain. We aimed to assess the association between COVID-19 and RA through immune inflammation.

First, we conducted a meta-analysis on the risk of COVID-19 infection, hospitalization rate, and mortality rate for patients with RA. Then, Mendelian randomization (MR) was used to evaluate the causal relationship between COVID-19 and RA, and further analyzed the cytokines and immune cells in COVID-19 and RA. Finally, we obtained microarray datasets of COVID-19, RA patients, and normal controls from the GEO database. And performed functional, pathway enrichment, and immune cell infiltration analysis on differentially expressed genes between each group.

The meta-analysis results suggested that the hospitalization rate and mortality rate of RA patients infected with COVID-19 were higher than those of the control population. MR analysis showed a positive correlation between COVID-19 infection and RA. We also found that interleukin 13 was associated with RA and COVID-19 infection. CD27 on IgD + CD24 + B cells and CD3 on CD39 + CD8 + T cells are common immune cell phenotypes in two diseases. In addition, COVID-19 function is enriched in immune responses mediated by leukocytes and neutrophils, while RA is significantly enriched in the proliferation of T and B lymphocytes. The results of immune cell infiltration showed that both diseases had more neutrophils and fewer CD8 T cells.

There are many similarities between COVID-19 and RA in immune inflammatory responses such as cytokines and immune cells. COVID-19 may lead to the development of RA through immune inflammation.

The online version contains supplementary material available at 10.1186/s40659-025-00620-7.

## Linked entities

- **Proteins:** CD27 (CD27 molecule), Igd (immunoglobulin delta heavy chain constant region), CD24 (CD24 molecule), cd.3 (Cd.3 conserved hypothetical protein), ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1), CD8A (CD8 subunit alpha)
- **Diseases:** rheumatoid arthritis (MONDO:0008383), coronavirus disease 2019 (MONDO:0100096), COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}
- **Diseases:** RA (MESH:D001172), inflammation (MESH:D007249), COVID-19 (MESH:D000086382)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12150480/full.md

## References

5 references — full list in the complete paper: https://tomesphere.com/paper/PMC12150480/full.md

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Source: https://tomesphere.com/paper/PMC12150480