Pitfalls in Understanding and Handling of Covid-19 Vaccination (“Any Fool Can Know. The Point Is to Understand”)

Abstract

The aim of this article is to critically review the managing of vaccination over the course of the present COVID-19 pandemic against the knowledge that had already been at hand and the scientific data that had yet to be learned. In the period before vaccines for COVID-19 became available, the startling similarity in epidemiologic behavior between COVID-19 and the Spanish flu could be observed. The development of vaccines against COVID-19 has evolved at an unprecedented speed resulting in highly immunogenic vaccines with incredible protective characteristics covering a relatively short follow-up time in clinical trials. The rollout in the general population turned out to take significantly longer time than the duration of immunity conferred by a 2-dose vaccination schedule (about 3-4 months). Therefore, the SARS-CoV-2 was left with the opportunity for random mutations with each replication cycle, resulting in immune evasion, shortened incubation, shortened serial interval, and increased transmissibility. The short incubation period of COVID-19 requires a steady protective antibody titer to be maintained to avert infection, achieve herd immunity, and terminate the pandemic spread. The protective neutralization titer needed to avert symptomatic infection and infection altogether is about 3% and 20%, respectively, of the mean convalescent titer. The latter corresponds to an absolute titer of 1:10–1:30. The intensity and duration of protective vaccinal and hybrid humoral immunity are explored. From the present perspective, it was naive to believe that a 2-dose vaccination would suffice to counter COVID-19 primarily due to its short incubation and a roll-out that was not catching up with the waning protective vaccinal antibody levels. Besides, the spacing of doses and boosters with respect to previous infection or vaccination, and differences in natural immunity and vaccine-induced immunity (adenovirus-vectored and mRNA) are discussed. The issue of vaccination and multisystem inflammatory syndrome in children is briefly presented. Finally, ethical points are discussed as some vaccine production platforms and neutralization tests use human cell lines derived from aborted fetuses.Conclusion – If the COVID-19 vaccines had been licensed as 3-dose vaccines, with more generous spacing, e.g. 0-2-6 months, providing for quantitatively larger and temporally more durable humoral immunity, that would have enabled attaining a steadier herd immunity and probably a paradoxical earlier effect on stopping the transmission.