Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis

Post-acute sequelae of Covid-19 (PASC) refer to persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. However, identifying biological mechanisms, potential therapeutic targets, and modifiable environmental risk factors remains necessary. Here, we analyzed cytokine levels in patients with PASC through a systematic literature search of the PubMed/MEDLINE, Web of Science, and Scopus databases, including articles published up to December 2024. A total of 33 studies (comprising 3294 patients) were included, addressing the long-term sequelae following acute Covid-19 infection. Levels of IL-6, IL-2, MCP-1/CCL2, TNF-α, IFN-γ, and IP-10/CXCL10 were higher in Covid-19 patients with PASC compared to those without PASC, suggesting an inflammatory basis for the persistence of symptoms. Conversely, little or no difference was observed for IL-1β, IL-7, IL-10, IL-4, IL-17A, IL-8, and IL-1α. To assess the duration of the sustained inflammatory response post-infection, cytokine measurements were categorized as < 6 months or ≥ 6 months after diagnosis. IL-6, MCP-1/CCL2, TNF-α, and IFN-γ remained elevated in both time windows, while IL-1β, IL-8, IP-10/CXCL10, IL-2, and IL-10 showed increased levels beyond 6 months post-Covid-19 diagnosis. Our findings indicate that persistent elevation of inflammatory cytokine is associated with PASC, contributing to a better understanding of the immune pathology underlying chronic dysfunction related to Covid-19.