Repeated Exposure to Subinfectious Doses of SARS-CoV-2 May Promote T Cell Immunity and Protection against Severe COVID-19

Abstract

Europe is experiencing a third wave of COVID-19 due to the spread of highly transmissible SARS-CoV-2 variants. A number of positive and negative factors constantly shape the rates of COVID-19 infections, hospitalization, and mortality. Among these factors, the rise in increasingly transmissible variants on one side and the effect of vaccinations on the other side create a picture deeply different from that of the first pandemic wave. Starting from the observation that in several European countries the number of COVID-19 infections in the second and third pandemic wave increased without a proportional rise in disease severity and mortality, we hypothesize the existence of an additional factor influencing SARS-CoV-2 dynamics. This factor consists of an immune defence against severe COVID-19, provided by SARS-CoV-2-specific T cells progressively developing upon natural exposure to low virus doses present in populated environments. As suggested by recent studies, low-dose viral particles entering the respiratory and intestinal tracts may be able to induce T cell memory in the absence of inflammation, potentially resulting in different degrees of immunization. In this scenario, non-pharmaceutical interventions would play a double role, one in the short term by reducing the detrimental spreading of SARS-CoV-2 particles, and one in the long term by allowing the development of a widespread (although heterogeneous and uncontrollable) form of immune protection.

High Frequencies of PD-1+TIM3+TIGIT+CTLA4+ Functionally Exhausted SARS-CoV-2-Specific CD4+ and CD8+ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients

“…Even human interactions with various animal coronaviruses might trigger SARS-CoV-2 cross-reactive T cell responses (80)(81)(82)(83)(84)(85)(86)(87)(88). Finally, confirming previous reports (25,35,36,75,89), we found a significant agedependent and comorbidities-associated susceptibility COVID-19 disease with patient over 60, and those with pre-existing diabetic and hypertension comorbidities, being the most susceptible to severe COVID-19…”

Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant

“…This means that immunity induced to the prototype virus has less reactivity to some of these epitopes. [48]. To address the impact of these emerging variants, in vitro assessment of antibodies in live virus neutralisation assays has proven an effective predictor of homologous versus heterologous P<0.001) rechallenge hamsters compared to those that received single infection.…”

Convalescence from prototype SARS-CoV-2 protects Syrian hamsters from disease caused by the Omicron variant

“…Two important questions arising from the emergence of variants of SARS-CoV-2 are whether they will circumvent naturally acquired immunity or that induced by vaccines 36,37 . During the course of the pandemic, the amino acid sequence of important viral epitopes of VOCs and VUIs against which previous naturally acquired or vaccination-induced immunity has been raised has changed 38 . As of December 2021, all approved vaccines are designed according to the sequence of the prototype virus.…”