Decoding the paradox: Understanding Elevated Hospitalization and Reduced Mortality in SARS-CoV-2 Variants

Abstract

Introduction and aim: SARS-CoV-2 outbreaks occur cyclically, aligning with winter when vitamin D levels are lowest, except after new variant outbreaks. Adequate vitamin D is crucial for robust immune function. Hypovitaminosis diminishes immune responses, increasing susceptibility to viral infections. The manuscript explores the discrepancy between increased SARS-CoV-2 hospitalizations and lower mortality. Method​: SARS-CoV-2 mutants, including Delta, BQ, and XBB Omicron lineages, developed immune evasion capabilities, reducing the effectiveness of COVID-19 vaccines and bivalent boosters. The failure of COVID-19 vaccines to prevent infections and spread to others, coupled with the immune evasion exhibited by mutant viruses, contributed to continued SARS-CoV-2 outbreaks. Interestingly, dominant new mutants, despite their increased transmissibility, have caused fewer deaths. This article scrutinizes the mentioned incongruity through an analysis of published data. Results: Achieving herd immunity and eradicating SARS-CoV-2 has proven elusive due to ongoing mutagenesis and immune evasion, leading to recurrent viral outbreaks. The failure to approve repurposed early therapies for COVID-19 by regulators, as well as misinformation and weak strategies undertaken by leading health authorities, exacerbated the situation. Repurposed agents, including vitamin D and ivermectin, have demonstrated high efficacy against SARS-CoV-2 from the beginning, and remain unaffected by mutations. Despite their cost-effectiveness and widespread availability, regulatory approval for these generic agents in COVID-19 treatment is pending. Conclusion: Regulators hesitated to approve cost-effective, repurposed generic agents primarily to safeguard the temporary approval status of COVID-19 vaccines and anti-viral agents under Emergency Use Authorization, which persists. This reluctance overlooked the opportunity to implement an integrated approach with repurposed agents alongside COVID-19 vaccines, potentially reducing hospitalizations and fatalities and preventing outbreaks; this led to the failure to eradicate SARS-CoV-2 and becoming endemic. It is imperative that regulators now reconsider approving affordable generics for SARS-CoV-2 to effectively control future viral outbreaks. Non-technical Importance (Lay Abstract) Adequate vitamin D levels significantly bolster the human immune system—deficiency compromises immune responses and increases susceptibility, particularly to viruses. While new SARS-CoV-2 mutations like Omicron are less severe, they are more infectious and adept at evading immunity from vaccines; thus, they offer a limited spectrum of protection and duration. Primary COVID-19 vaccines have reduced disease severity but have failed to prevent viral spread, contributing to outbreaks. Booster doses had little effect on the virus but caused immune paresis, thus increasing susceptibility to infections. Regulators should consider approving generic, repurposed agents like vitamin D and ivermectin as adjunct therapies to address this challenge and better prepare for future pandemics. Proactively integrating vitamin D supplementation to fortify the immune system can mitigate vital outbreaks, alleviate hospital burdens, and reduce healthcare costs.

Physiology of Vitamin D—Focusing on Disease Prevention

“…It can be utilized as an adjunct therapy in infections and metabolic disorders. For example, when used in SARS-CoV-2 infection, the cost is about USD 2 per person, compared to over USD 700 with anti-viral agents (https://c19early.org; accessed on 28 March 2024) [100,209,214]. Maintaining optimal circulatory levels of 25(OH)D, above 50 ng/mL, can be achieved through regular vitamin D supplements (e.g., 70-90 IU/kg body weight for a non-obese person [49] or through safe sun exposure.…”