Adaptive immunity to SARS-CoV-2 and COVID-19

Abstract

The adaptive immune system is important for control of most viral infections. The three fundamental components of the adaptive immune system are B cells (the source of antibodies), CD4⁺ T cells, and CD8⁺ T cells. The armamentarium of B cells, CD4⁺ T cells, and CD8⁺ T cells has differing roles in different viral infections and in vaccines, and thus it is critical to directly study adaptive immunity to SARS-CoV-2 to understand COVID-19. Knowledge is now available on relationships between antigen-specific immune responses and SARS-CoV-2 infection. Although more studies are needed, a picture has begun to emerge that reveals that CD4⁺ T cells, CD8⁺ T cells, and neutralizing antibodies all contribute to control of SARS-CoV-2 in both non-hospitalized and hospitalized cases of COVID-19. The specific functions and kinetics of these adaptive immune responses are discussed, as well as their interplay with innate immunity and implications for COVID-19 vaccines and immune memory against re-infection.

Figure 1

The major components of adaptive immunity in viral immune responses Virus-specific CD4⁺ T cells, CD8⁺ T cells, and antibodies (produced by B cells) constitute the three major components of acute adaptive immunity to a viral infection. Immune memory consists of memory B cells, antibodies, virus-specific CD4⁺ T cells, and virus-specific CD8⁺ T cells constitute the four major components of immune memory to a viral infection.

Figure 2

An integrated working model of COVID-19 immunology and disease severity Immune response trajectories in COVID-19. Conceptual schematics of the kinetics of immune responses to SARS-CoV-2 under conditions of average COVID-19 (non-hospitalized cases) and severe or fatal COVID-19. “Innate immunity” line specifically refers to the peak kinetics of innate cytokines and chemokines detectable in blood; innate immune responses occur locally throughout the course of an infection. “T cells” refers to virus-specific CD4⁺ and CD8⁺ T cells. “Antibodies” refers to virus-specific neutralizing antibodies. Arrows indicate a time point with important differences in the presence or absence of T cell responses and the magnitude of the viral load, comparing (B) and (C). (A) An example of a generic viral infection. (B) Average SARS-CoV-2 infection. (C) Severe or fatal SARS-CoV-2 infection. The period of severe COVID-19 clinical disease is shaded gray. See also Figure S1 for additional features.

Figure 3

CD4⁺ T cell functions observed in COVID-19 Virus-specific CD4⁺ T cells may differentiate into multiple distinct cell types in response to SARS-CoV-2, and exhibit a range of helper and effector functions. These include Tfh cells, which provide help to B cells for affinity maturation and antibody production; Th1 cells, which can have direct antiviral functions through cytokine secretion plus recruitment of innate cells; CD4 T cells, that help CD8 T cells to proliferate and differentiate; CD4-CTL, which can have direct cytotoxic activity against virally infected cells in a class II antigen presentation restricted manner; and CD4 T cells that produce IL-22, which has roles in wound healing.

Figure 4

Components of local immunity Human immune responses are most often measured in blood, but immune responses at local sites of infection and/or portals of entry are important and may not be directly reflected by blood measurements. Local immunity in lungs, nasal passages, and the oral cavity and salivary glands can consist of Trm CD8⁺ T cells, CD4⁺ T cells, and IgG and IgA antibodies constitutively present in those tissues as immune memory, which can be supplemented by additional cells and antibodies upon infection.