Prolonged adaptive immune activation in COVID-19: implications for maintenance of long-term immunity?

Abstract

Ongoing observational clinical research has prioritized understanding the human immune response to SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. Several recent studies suggest that immune dysregulation with early and prolonged adaptive immune system activation can result in cellular exhaustion. In this issue of the JCI, Files et al. compared cellular immune phenotypes during the first two months of COVID-19 in hospitalized and less severe, non-hospitalized patients. The authors utilized flow cytometry to analyze circulating peripheral blood mononuclear cells. Both patient cohorts maintained B and T cell phenotypes consistent with activation and cellular exhaustion throughout the first two months of infection. Additionally, follow-up samples from the non-hospitalized patient cohort showed that activation markers and cellular exhaustion increased over time. These findings illustrate the persistent nature of the adaptive immune system changes that have been noted in COVID-19 and suggest longer term effects that may shape the maintenance of immunity to SARS-CoV-2.

Figure 1. Response to human viral respiratory infections.

(A) In a typical influenza infection, symptoms and viral replication peak within a few days and resolve after the first week; serologic response peaks within the first two weeks and remains high. Notably, with influenza, the cellular immune activation peaks at week one and resolves by week three. (B) In contrast, with SARS-CoV-2 infection, the cellular immune system remains activated despite viral clearance. The persistence of viral antigens, development of T cell exhaustion, and increased risk of secondary infections set SARS-CoV-2 infection apart from other viral respiratory infections.