Age and Location in Severity of COVID‐19 Pathology: Do Lactoferrin and Pneumococcal Vaccination Explain Low Infant Mortality and Regional Differences?

Abstract

Two conundrums puzzle COVID-19 investigators: 1) morbidity and mortality is rare among infants and young children and 2) rates of morbidity and mortality exhibit large variances across nations, locales, and even within cities. It is found that the higher the rate of pneumococcal vaccination in a nation (or city) the lower the COVID-19 morbidity and mortality. Vaccination rates with Bacillus Calmette-Guerin, poliovirus, and other vaccines do not correlate with COVID-19 risks, nor do COVID-19 case or death rates correlate with number of people in the population with diabetes, obesity, or adults over 65. Infant protection may be due to maternal antibodies and antiviral proteins in milk such as lactoferrin that are known to protect against coronavirus infections. Subsequent protection might then be conferred (and correlate with) rates of Haemophilus influenzae type B (Hib) (universal in infants) and pneumococcal vaccination, the latter varying widely by geography among infants, at-risk adults, and the elderly. Also see the video abstract here https://youtu.be/GODBYRbPL00.

Possible Cross-Reactivity between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death

“…The results point specifically to potential cross-reactivity between SARS-CoV-2 proteins and the pneumococcal proteins PspA and PsaA, which are known to contaminate polysaccharide-based pneumococcal vaccines [ 5 , 6 , 7 ] as well as PspC, which it is reasonable to assume is another such contaminant since it derives from the same outer membrane protein complex and is highly cross-reactive with the antibodies against PspA used to demonstrate the presence of PspA in vaccines [ 10 , 11 ]. Such cross-reactivity would be consistent with epidemiological studies suggesting a protective effect of pneumococcal vaccination against SARS-CoV-2 [ 1 , 2 ]. Since the CRM197 protein is used to conjugate some Haemophilus and meningitis vaccines, these vaccines may also provide some cross-reactive protection against SARS-Cov-2 proteins ( Figure 1 ), a result that is consistent with the findings of Pawlowski, et al [ 2 ].…”

“…The almost completely negative results reported here for antigenic mimicry between SARS-CoV-2 proteins and proteins from measles, mumps, diphtheria, pertussis and tetanus at E = 0.1 ( Table 1 ), and the relatively low rate of similarities with poliovirus at E = 1.0 ( Table 2 ), are consistent with the lack of association between these vaccines and SARS-CoV-2 rates of disease or death [ 1 ], although Pawlowski, et al [ 2 ] found some protective effect from polio vaccination and the measles–mumps–rubella (MMR) combination vaccine. The current study would suggest that the rubella component of MMR is the major protective agent, though measles also exhibits some high-quality antigenic similarities to SARS-CoV-2.…”

“…In light of the data presented here, it is therefore possible that at least some proportion of individuals with cross-reactive immunity developed it through exposure to pneumococcal vaccinations. Such cross-reactivity would also explain the epidemiological observation that pneumococcal vaccination rates correlate inversely with rates of serious SARS-CoV-2 disease and death, but that vaccination rates with other commonly used vaccines (DTP, MMR, polio, meningitis, and BCG), do not [ 1 ].…”

“…Various studies have indicated that some vaccines may protect against symptomatic SARS-CoV-2 infection and death. A very significant inverse correlation has been found between rates of pneumococcal vaccination at both the national and local population levels and rates of SARS-CoV-2 infections and death [ 1 ]. The study found no such correlations to the tuberculosis vaccine BCG (Bacillus Calmette–Guerin), Haemophilus influenzae type B (Hib), diphtheria–tetanus–pertussis, measles–mumps–rubella, or poliovirus vaccinations.…”

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

“…In murine models of fatal coronavirus (MERS and SARS) and influenza pneumonias, TLR3–TLR4 synergism is universal, such that antagonizing or deleting TLR4, which is specifically activated by bacterial lipopolysaccharides, prevents death [ 231 , 232 , 233 , 234 ]. Indeed, there are multiple reports that vaccinations against S. pneumonia [ 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 ] and, possibly, Haemophilus influenzae as well [ 239 , 240 , 241 ] significantly decreases the probability of contracting and dying from COVID-19. In this context, it is too bad that there are not vaccines against Klebsiella pneumoniae, Mycoplasma pneumoniae and Aspergillus fungal infections, as well.…”