Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 12, 2026 55 minutes ago
Researchers have uncovered a potential “dual-hit” mechanism by which SARS-CoV-2 may intensify harmful inflammation: the virus activates a major inflammatory pathway while weakening vitamin D receptor signaling that normally helps restrain immune responses.
Researchers found that SARS-CoV-2 may disrupt vitamin D receptor signaling while driving IL-6 inflammation, with
calcitriol suppressing IL-6 in laboratory cell models
The research was conducted by scientists from the Grupo Gastrohepatología, Grupo Inmunovirología, and Grupo de Inmunología Celular e Inmunogenética (GICIG), all within the Faculty of Medicine at Universidad de Antioquia in Medellín, Colombia.
How the virus may remove an immune “brake”
The team examined gene-expression data from monocytes and myeloid dendritic cells taken from healthy people and patients with moderate or severe COVID-19, including patients with and without detectable virus in the blood. They also reanalyzed experiments involving human monocyte-derived macrophages exposed to infectious SARS-CoV-2 or virus-like particles.
The results showed strong activation of pattern-recognition receptors and the NF-κB inflammatory pathway, particularly in monocytes. TLR2 and TLR8 were increased in monocytes from COVID-19 patients, while severe disease was associated with increased expression of key NF-κB components. IL-6 expression was elevated across COVID-19 groups, alongside components of its signaling machinery.
Importantly, monocytes showed increased expression of IL-6 receptor components and downstream genes, including STAT3, SOCS3, JAK3, MYC, BCL2L1, MMP2, and IL10. In infected macrophages, infectious SARS-CoV-2 triggered strong increases in IL-6, IL6R, JAK1, JAK2, STAT3, and SOCS3, with peaks mainly four to 12 hours after infection.
Vitamin D pathway showed signs of dysfunction
At the same time, researchers found evidence that vitamin D receptor, or VDR, signaling was functionally impaired. Although VDR expression increased in patient monocytes, several genes normally controlled by VDR, including LYZ and IRF5, were reduced, indicating that increased receptor expression did not translate into normal downstream activity.
In laboratory-infected macrophages, the pattern was clearer: SARS-CoV-2 reduced VDR and CYP2R1 expression and suppressed VDR targets including CAMP/LL37 and IRF5. These changes were largely absent with virus-like particles, suggesting active infection or viral replication-related processes may be important.
Calcitriol selectively lowered IL-6
For this
Thailand Medical News report, one of the most striking findings came from experiments using U937-derived monocyte- and macrophage-like cells. Calcitriol, the active form of vitamin D, significantly reduced IL-6 production when given at the same time as UV-inactivated SARS-CoV-2 particles or two hours afterward. Other measured inflammatory cytokines were not broadly suppressed, suggesting a more selec
tive effect on the IL-6 axis.
The findings do not establish vitamin D as a COVID-19 treatment. The study used an ancestral viral strain, cell-line models have important limitations, and the patient analyses were cross-sectional. The researchers said clinical trials are needed to determine appropriate dosing and timing.
Conclusion
The study suggests SARS-CoV-2 may worsen inflammation by simultaneously accelerating NF-κB/IL-6 signaling and weakening VDR-mediated immune regulation. Calcitriol’s selective suppression of IL-6 provides a biologically plausible therapeutic lead, but confirmation in primary human cells, newer variants, longitudinal studies, and carefully designed clinical trials remains essential before clinical recommendations can be made.
The study findings were published in the peer reviewed journal: PLOS One.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357030
Read Also:
https://www.thailandmedical.news/articles/coronavirus
https://www.thailandmedical.news/articles/long-covid
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