Background:

Previous reports showed a 40% reduction in the odds of being HIV-positive in RH2-heterozygotes. In addition, those lacking the gene were 24 times and 33 times more likely to be HIV-infected than heterozygotes or homozygotes, respectively. A four-year longitudinal study observed lower HIV viral load and slower disease progression in RH2-positive individuals. Thus, the current study sought to establish if the same phenomenon applied to SARS-CoV-2 infections. We also compared the plasma levels of SARS-CoV-2 anti-spike and anti-nucleocapsid protein antibodies following full vaccination against COVID-19.

Materials and Methods:

Erythrocytes were phenotyped using anti-C and anti-c. Antibodies against SARS-CoV-2 were also measured in plasma of fully vaccinated persons (Oxford Astra-Zeneca, Johnson & Johnson, Pfizer/BioNTech, Sinovac, and Moderna vaccines) and compared across RH2 phenotypes.

Results:

RH2 expression on erythrocytes (n=319) was associated with lower odds for SARS-CoV-2 infection (OR= 0.42, 95%CI: 0.22-0.80, p=0.008). The strength of the serological reaction between anti-C and erythrocytes was predictive of a COVID-19 diagnosis (Mantel-Haenszel Chi Square = 9.44, p=0.002). However, there was no difference in the levels of anti-SARS-CoV-2 antibodies across categories of RH2, regardless of the vaccine taken.

Discussion:

RH2-positivity and stronger anti-C reaction were associated with protection against SARS-CoV-2, practically duplicating previous observations regarding HIV infection. Since both pathogens are ssRNA viruses, the primary mechanism likely involves Toll-like receptors that favor a TH1 response. The TH1 polarization is also suggested by protection against infection devoid of a superior humoral response. Further investigations could potentially provide a new approach to treat or prevent both viruses and other single-stranded RNA viruses.

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