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

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-1ß. 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.

Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients.

PURPOSE: Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-ß ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. METHODS: In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-ß, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. RESULTS: Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-ß mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. CONCLUSION: VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.

Switching Host Metabolism as an Approach to Dampen SARS-CoV-2 Infection.

BACKGROUND: COVID-19 pandemic, a global threat, adversely affects all daily lives, altered governmental plans around the world, and urges the development of therapeutics and prophylactics to avoid the expansion of the viral infection. With the recent gradual opening after long lockdown, several recommendations have been placed, with dietary modification as one of the most important approaches that have been appraised. SUMMARY: Here, we are reviewing how changing the host metabolism, particularly changing the host metabolic state from the carbohydrate-dependent glycolytic state to a fat-dependent ketogenic state, may affect viral replication. Furthermore, the impact of intermittent fasting (IF) in triggering metabolic switch along with the impact of supplementation with medium-chain triglycerides (MCTs) such as lauric acid in repressing the envelope formation and viral replication is also addressed. The amalgamation of IF and a ketogenic diet rich in MCTs is thought to work as a prophylactic measure for normal people and adjunct therapy for infected persons. Key Message: A diet regimen of ketogenic breakfast along with supplementation with two doses of lauric acid-rich MCTs at breakfast and lunch times, followed by 8-12-h IF and a dinner rich with fruits and vegetables, could be a potential prophylactic strategy and adjuvant therapy to combat SARS-CoV-2 infections.