Cross-reactive memory T cells and herd immunity to SARS-CoV-2

Abstract

Immunity is a multifaceted phenomenon. For T cell-mediated memory responses to SARS-CoV-2, it is relevant to consider their impact both on COVID-19 disease severity and on viral spread in a population. Here, we reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2, which largely originates from previous exposure to circulating common cold coronaviruses. We propose four immunological scenarios for the impact of cross-reactive CD4⁺ memory T cells on COVID-19 severity and viral transmission. For each scenario, we discuss its implications for the dynamics of herd immunity and on projections of the global impact of SARS-CoV-2 on the human population, and assess its plausibility. In sum, we argue that key potential impacts of cross-reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. The implications of immunological processes on other aspects of SARS-CoV-2 epidemiology are worthy of future study.

Fig. 1. Schematic models of the three major scenarios wherein cross-reactive CD4⁺ memory T cells have a positive impact on control of SARS-CoV-2 replication in an individual and reduce COVID-19 disease severity.

Timelines of viral burden in the lungs and upper respiratory tract (URT) and of immune responses, which differ according to the magnitude and type of pre-existing cross-reactive CD4⁺ T cell memory. Model 1 makes no specific prediction about antibody response kinetics or magnitude, because it could be mediated by different types of immune response with equivalent disease outcomes (see main text). Under scenario 4, there would be no infection in individuals with cross-reactive immunity (scenario therefore not shown). Each of these models is currently hypothetical for SARS-CoV-2. T_FH cell, T follicular helper cell; T_RM, tissue-resident memory cell.