. 2022 Jul 23;94(11):5128–5148. doi: 10.1002/jmv.28000

Table 2.

Overview of adaptive immune reactions to SARS‐CoV‐2

Adaptive immune response	Reaction	Outcome	Reference
T CD4 lymphocyte	According to the research findings that examined CD4⁺ T cell reaction to proteins of SARS‐CoV‐2 in recovered COVID‐19 patients, reactions were identified toward approximately all SARS‐CoV‐2 proteins, with CD4⁺ T‐cell responses being unrecognizable only for one of the smallest proteins. Remarkably, CD4⁺ T cells special for SARS‐CoV‐2 were reported to significantly correlate with reduced COVID‐19 disease severity. IFNγ is the prevailing cytokine generated by SARS‐CoV‐2‐specific CD4⁺ T cells from cases with COVID‐19, with a distinguishable IFNγ, TNF, and IL‐2 protein signature of classical Th1 cells. A subset of T CD4+ expressed CCR6 specific to SARS‐CoV‐2 indicates underlying Th17 characteristics of those cells, but the reports have suggested the low or undetectable levels of IL‐17α protein expression in COVID‐19 patients. T CD4⁺ cells (SARS‐CoV‐2‐specific) can express a high level of IL‐22.	B‐cell affinity maturation and antibody production, Initiation of CD8 T‐cell proliferation and differentiation, direct cytotoxic activity, regulation of primary SARS‐CoV‐2 disease, reduction in COVID‐19 pathogenicity, and increased viral removal	¹⁷ , ³⁴ , ¹⁴⁷ , ¹⁵⁰ , ¹⁵¹ , ¹⁵²
T CD8 lymphocyte	The existence of virus‐specific CD8⁺ T cells has now been linked to improved COVID‐19 consequences. T CD8⁺ cells recognize various SARS‐CoV‐2 antigens, including spike, nucleocapsid, M, and ORF3a. Specific CD8⁺ T for SARS‐CoV‐2 express many molecules related to potent cytotoxic activity, including IFNγ, perforin, CD107, and granzyme B. Furthermore, depending on the increased expression of inhibitory receptors, several researchers have described exhaustion phenotypes of CD8⁺ T cells in severe COVID‐19 cases.	Protection against the expansion of severe COVID‐19, the killing of virus‐infected cells, the production of effector cytokines, and the impairment of host defense mechanisms	¹⁷ , ¹⁵⁰ , ¹⁵³ , ¹⁵⁴ , ¹⁵⁵ , ¹⁵⁶ , ¹⁵⁷ , ¹⁵⁸ , ¹⁵⁹
B lymphocyte	Upon infection with SARS‐CoV‐2, the naive B cells, or possibly pre‐existing memory B cells from previous HCoVs illnesses, are stimulated by antigen identification, and CD4⁺ T cells support. Definitions of circulatory B cells in the early weeks of an acute SARS‐CoV‐2 disease have revealed moderate relative B cell lymphopenia and changeable enhancement in plasmablasts frequencies, which in some cases exceeded 30% of total B cells. Plasma cells and memory B cells that secrete antibodies can access the blood and (presumably) the mucosa. They assisted in the battle against viral illness and defended against reinfection. Indeed, severe COVID‐19 cases exhibited higher rates of the DN2 B cells as opposed to those with mild cases and additionally had higher plasmablast numbers.	Affinity maturation, resulting in long‐lived plasma cells and memory B cells, particular antibody generation, rise in secondary reactions	¹⁶⁰ , ¹⁶¹ , ¹⁶² , ¹⁶³ , ¹⁶⁴

Adaptive immune response

Reaction

Outcome

Reference

T CD4 lymphocyte

According to the research findings that examined CD4⁺ T cell reaction to proteins of SARS‐CoV‐2 in recovered COVID‐19 patients, reactions were identified toward approximately all SARS‐CoV‐2 proteins, with CD4⁺ T‐cell responses being unrecognizable only for one of the smallest proteins.

Remarkably, CD4⁺ T cells special for SARS‐CoV‐2 were reported to significantly correlate with reduced COVID‐19 disease severity.

IFNγ is the prevailing cytokine generated by SARS‐CoV‐2‐specific CD4⁺ T cells from cases with COVID‐19, with a distinguishable IFNγ, TNF, and IL‐2 protein signature of classical Th1 cells.

A subset of T CD4+ expressed CCR6 specific to SARS‐CoV‐2 indicates underlying Th17 characteristics of those cells, but the reports have suggested the low or undetectable levels of IL‐17α protein expression in COVID‐19 patients.

T CD4⁺ cells (SARS‐CoV‐2‐specific) can express a high level of IL‐22.

B‐cell affinity maturation and antibody production,

Initiation of CD8 T‐cell proliferation and differentiation, direct cytotoxic activity, regulation of primary SARS‐CoV‐2 disease, reduction in COVID‐19 pathogenicity, and increased viral removal

¹⁷ , ³⁴ , ¹⁴⁷ , ¹⁵⁰ , ¹⁵¹ , ¹⁵²

T CD8 lymphocyte

The existence of virus‐specific CD8⁺ T cells has now been linked to improved COVID‐19 consequences.

T CD8⁺ cells recognize various SARS‐CoV‐2 antigens, including spike, nucleocapsid, M, and ORF3a.

Specific CD8⁺ T for SARS‐CoV‐2 express many molecules related to potent cytotoxic activity, including IFNγ, perforin, CD107, and granzyme B.

Furthermore, depending on the increased expression of inhibitory receptors, several researchers have described exhaustion phenotypes of CD8⁺ T cells in severe COVID‐19 cases.

Protection against the expansion of severe COVID‐19, the killing of virus‐infected cells, the production of effector cytokines, and the impairment of host defense mechanisms

¹⁷ , ¹⁵⁰ , ¹⁵³ , ¹⁵⁴ , ¹⁵⁵ , ¹⁵⁶ , ¹⁵⁷ , ¹⁵⁸ , ¹⁵⁹

B lymphocyte

Upon infection with SARS‐CoV‐2, the naive B cells, or possibly pre‐existing memory B cells from previous HCoVs illnesses, are stimulated by antigen identification, and CD4⁺ T cells support.

Definitions of circulatory B cells in the early weeks of an acute SARS‐CoV‐2 disease have revealed moderate relative B cell lymphopenia and changeable enhancement in plasmablasts frequencies, which in some cases exceeded 30% of total B cells.

Plasma cells and memory B cells that secrete antibodies can access the blood and (presumably) the mucosa. They assisted in the battle against viral illness and defended against reinfection.

Indeed, severe COVID‐19 cases exhibited higher rates of the DN2 B cells as opposed to those with mild cases and additionally had higher plasmablast numbers.

Affinity maturation, resulting in long‐lived plasma cells and memory B cells, particular antibody generation, rise in secondary reactions

¹⁶⁰ , ¹⁶¹ , ¹⁶² , ¹⁶³ , ¹⁶⁴

Abbreviations: COVID‐19, coronavirus disease 2019; DN2 B cells, double‐negative (DN) B cells; HcoVs, human coronaviruses; IL, interleukin; Th17, T helper 17 cells; TNF, tumor necrosis factor; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.