Cross-Reactivity Between SARS-CoV-2 Proteins and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death

A significant inverse correlation exists between rates of pneumococcal vaccination, at both national and local levels, and symptomatic cases of SARS-CoV-2 infection and death. No correlations exist to BCG, Hib, diphtheria-tetanus-pertussis, measles-mumps-rubella, or poliovirus vaccinations. This paper explored the possibility that pneumococcal vaccines contain antigens that might be cross-reactive with SARS-CoV-2 antigens and that such cross-reactive antigens are absent from other vaccines. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, they also contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. These proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. Equivalently similarities were found at statistically significantly lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Appropriate data were not available for testing Hib and BCG similarities. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.