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Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons

Saheb Sharif-Askari et al., Scientific Reports, doi:10.1038/s41598-023-43675-w
Oct 2023  
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Cytometric analysis of the blood of 62 COVID-19 patients. Patients with severe COVID-19 had higher levels of regulatory T cells (Tregs) and regulatory B cells (Bregs) compared to patients with mild disease. Tregs and Bregs help control inflammation. High dose vitamin D treatment increased Tregs and Bregs and lowered inflammatory cytokines IL-6, IL-17, TNFα, IL-1β (statistically significant for IL-6 and IL-1β) in severe COVID-19 patients.
Saheb Sharif-Askari et al., 13 Oct 2023, United Arab Emirates, peer-reviewed, 10 authors.
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Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons
Fatemeh Saheb Sharif-Askari, Narjes Saheb Sharif-Askari, Shirin Hafezi, Hawra Ali Hussain Alsayed, Balachandar Selvakumar, Mariam Wed Abdelaziz Eladham, Bushra Mdkhana, Ola Salam Bayram, Mohamad-Hani Temsah, Rabih Halwani
Scientific Reports, doi:10.1038/s41598-023-43675-w
The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. While regulatory T (Treg) and B (Breg) cells, as the main elements of immune homeostasis, contribute to the control of hyperinflammation during COVID-19 infection, we hypothesized change in their levels in relation to disease severity and the presence of autoantibodies (auto-Abs) to type I IFNs. Cytometric analysis of blood of 62 COVID-19 patients with different severities revealed an increased proportion of conventional (cTreg; CD25 + FoxP3 + ) and unconventional (uTreg; CD25 -FoxP3 + ) Tregs, as well as the LAG3 + immune suppressive form of cTreg/ uTreg, in the blood of severe COVID-19 cases compared to the milder, non-hospitalized cases. The increase in blood levels of cTreg/uTreg, but not LAG3 + cTreg/uTreg subtypes, was even higher among patients with severe COVID-19 and auto-Abs to type I IFNs. Regarding Bregs, compared to the milder, non-hospitalized cases, the proportion of IL-35 + and IL-10 + Bregs was elevated in the blood of severe COVID-19 patients, and to a higher extent in those with auto-Abs to type I IFNs. Moreover, blood levels of cTreg, LAG3 + cTreg/uTreg, and IL-35 + and IL-10 + Breg subtypes were associated with lower blood levels of proinflammatory cytokines such as IL-6, IL-17, TNFα, and IL-1β. Interestingly, patients who were treated with either tocilizumab and/or a high dose of Vitamin D had higher blood levels of these regulatory cells and better control of the proinflammatory cytokines. These observations suggest that perturbations in the levels of immunomodulatory Tregs and Bregs occur in COVID-19, especially in the presence of auto-Abs to type I IFNs.
Author contributions Competing interests The authors declare no competing interests.
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