Host determinants of inflammatory escalation remain incompletely defined in COVID-19. Vitamin D receptor (VDR) signaling regulates immune activation and cytokine responses, yet the contribution of VDR genetic variation to severe disease is unclear. We investigated two common VDR polymorphisms (rs7975232 and rs1544410) in a prospective, clinically stratified Indian cohort (
n
= 323), integrating genotype–phenotype associations, inflammatory biomarkers, interaction modeling, and polygenic risk stratification. Both variants were independently associated with severe disease under additive genetic models (per-risk allele adjusted OR 1.69 for rs7975232 and 1.82 for rs1544410) and demonstrated allele-dose relationships across severity categories. Risk alleles correlated with elevated IL-6, C-reactive protein, and ferritin levels, indicating amplified inflammatory signaling. A statistically significant gene–gene interaction between rs7975232 and rs1544410 (OR 2.48,
p
= 0.006) was observed; however, this finding should be considered exploratory pending independent replication. Vitamin D deficiency (< 20 ng/mL) further amplified genotype-associated risk, supporting a biologically relevant gene-environment interaction. Integration of genetic information into multivariable clinical models improved model discrimination within this cohort (AUC 0.83 vs. 0.72), although external validation is required. In silico functional annotation was performed using RegulomeDB, HaploReg, and GTEx (Supplementary Table S7). Together, these findings identify a genetically associated inflammatory risk profile characterized by VDR risk alleles, vitamin D deficiency, and heightened inflammatory responses, providing a framework for precision risk stratification targeting the vitamin D-VDR axis.
The policy question for COVID-19 vaccination has shifted from whether vaccines induce protection to how long clinically meaningful protection persists and how immune information should guide preparedness. This question is especially relevant to Saudi Arabia, where Hajj and Umrah create predictable periods of dense population mixing among pilgrims with diverse vaccination histories, prior infection exposures, ages, and comorbidity profiles. This structured narrative review synthesizes evidence on durability of COVID-19 vaccine-induced immunity, Saudi epidemiological and serological data, heterologous booster strategies, hybrid immunity, and operational implications for mass-gathering preparedness. A structured search of biomedical databases and public-health sources was undertaken for evidence published from January 2020 to May 2026. The review highlights those circulating antibodies and neutralizing activity decline after vaccination, particularly against antigenically divergent variants, whereas memory B-cell responses and CD4+ and CD8+ T-cell immunity generally provide more durable protection against severe disease. Saudi evidence remains limited but informative: national seroprevalence studies, vaccine-rollout data, clinical-effectiveness analyses, and recent serological work indicate substantial prior exposure, strong post-vaccination antibody responses, and meaningful protection against hospitalization and intensive-care admission, particularly after booster dosing. Heterologous schedules and hybrid immunity appear to broaden immune protection, but their policy relevance lies in flexible risk-based planning rather than in promoting infection as a strategy. For Hajj and Umrah, the main implication is a shift from simple dose counting toward immune durability, risk stratification, booster timing, vaccination documentation, genomic surveillance, and integrated respiratory-virus monitoring.
Leena E. Azhar, A. Alsaieedi, Mariam Aleissa et al.· Frontiers in Public Health· 0 citations
Respiratory viral infections caused by seasonal influenza, respiratory syncytial virus (RSV), and pandemic-potential coronaviruses are responsible for several million hospitalisations and an estimated several hundred thousand deaths each year, a burden underscored by the severe 2024–2025 influenza season and the continued emergence of zoonotic threats such as clade 2.3.4.4b H5N1. This review critically examines the pharmacological basis for targeting host cell-surface receptors as a strategy for the treatment and prophylaxis of respiratory viral infections, evaluates the current evidence for each major receptor axis, and identifies the key translational gaps that must be addressed. Respiratory viruses, including influenza, RSV, SARS-CoV-2, and MERS-CoV, collectively cause millions of hospitalisations annually, and the persistent challenges of antigenic drift, zoonotic emergence, and antiviral resistance highlight the need for mechanistically distinct strategies. Host-directed therapies (HDTs) targeting conserved receptors (ACE2, DPP4, sialic acids, TMPRSS2) exploit genetically stable host factors required for viral entry. Across the receptor axes reviewed here, we appraise more than a dozen candidate agents spanning preclinical development through Phase III evaluation, including TMPRSS2 inhibitors, soluble ACE2 decoys, anti-CD147 and receptor-blocking monoclonal antibodies, the sialidase fusion protein DAS181, and avian IgY preparations. This evidence reveals a consistent gap between robust preclinical activity and as-yet-limited clinical efficacy. We conclude that host receptor targeting is a mechanistically rational but still clinically unproven component of the respiratory antiviral landscape; its value is most plausibly realised in defined niches—prophylaxis, early outpatient treatment, and combination with direct-acting antivirals—and within pandemic preparedness frameworks, provided that the safety, delivery, and trial-design challenges identified here are resolved.
Sherif A. El-Kafrawy, Norah A. Othman, M. Zeyadi et al.· Frontiers in Cellular and In...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
