{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T05:01:43Z","timestamp":1794373303795,"version":"4.9.0"},"reference-count":240,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The coronavirus disease (COVID-19) is a pandemic disease that threatens worldwide public health, and rheumatoid arthritis (RA) is the most common autoimmune disease. COVID-19 and RA are each strong risk factors for the other, but their molecular mechanisms are unclear. This study aims to investigate the biomarkers between COVID-19 and RA from the mechanism of pyroptosis and find effective disease-targeting drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained the common gene shared by COVID-19, RA (GSE55235), and pyroptosis using bioinformatics analysis and then did the principal component analysis(PCA). The Co-genes were evaluated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ClueGO for functional enrichment, the protein-protein interaction (PPI) network was built by STRING, and the k-means machine learning algorithm was employed for cluster analysis. Modular analysis utilizing Cytoscape to identify hub genes, functional enrichment analysis with Metascape and GeneMANIA, and NetworkAnalyst for gene-drug prediction. Network pharmacology analysis was performed to identify target drug-related genes intersecting with COVID-19, RA, and pyroptosis to acquire Co-hub genes and construct transcription factor (TF)-hub genes and miRNA-hub genes networks by NetworkAnalyst. The Co-hub genes were validated using GSE55457 and GSE93272 to acquire the Key gene, and their efficacy was assessed using receiver operating curves (ROC); SPEED2 was then used to determine the upstream pathway. Immune cell infiltration was analyzed using CIBERSORT and validated by the HPA database. Molecular docking, molecular dynamics simulation, and molecular mechanics-generalized born surface area (MM-GBSA) were used to explore and validate drug-gene relationships through computer-aided drug design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>COVID-19, RA, and pyroptosis-related genes were enriched in pyroptosis and pro-inflammatory pathways(the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex, death-inducing signaling complex, regulation of interleukin production), natural immune pathways (Network map of SARS-CoV-2 signaling pathway, activation of NLRP3 inflammasome by SARS-CoV-2) and COVID-19-and RA-related cytokine storm pathways (IL, nuclear factor-kappa B (NF-\u03baB), TNF signaling pathway and regulation of cytokine-mediated signaling). Of these, CASP1 is the most involved pathway and is closely related to minocycline. YY1, hsa-mir-429, and hsa-mir-34a-5p play an important role in the expression of CASP1. Monocytes are high-caspase-1-expressing sentinel cells. Minocycline can generate a highly stable state for biochemical activity by docking closely with the active region of caspase-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Caspase-1 is a common biomarker for COVID-19, RA, and pyroptosis, and it may be an important mediator of the excessive inflammatory response induced by SARS-CoV-2 in RA patients through pyroptosis. Minocycline may counteract cytokine storm inflammation in patients with COVID-19 combined with RA by inhibiting caspase-1 expression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1058884","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T17:52:55Z","timestamp":1669917175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["SARS-CoV-2 induces \u201ccytokine storm\u201d hyperinflammatory responses in RA patients through pyroptosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Qingcong","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjie","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical 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