Basics of antibody and cell-mediated immunity. After encounter with the virus, immune cells known as antigen-presenting cells activate antigen-specific T cells that act either as support to other cell types by producing cytokines and stimulatory molecules (CD4+, also referred to as helper T cells) or attack the infected cells participating in infection clearance (CD8+, also referred to as cytotoxic T cells). Helper T cells can be further divided in Th1, Th2, or other subtypes, which differentially affect the immune effector response. Antigen-specific B cells, also acting as antigen-presenting cells, are activated by helper T cells and either immediately start producing antibodies or undergo affinity maturation into the germinal center of secondary lymphoid tissues (not represented in the figure) before differentiating into plasma cells that produce high affinity antibodies that neutralize the virus (Abbas et al., 2012).

Immunity to SARS-CoV-2. (A) Immunologic targets of SARS-CoV-2, highlighting the four main viral antigens. (B) Plot of putative correlation of neutralizing antibody levels with protection from infection and disease. A first wave of IgM and IgA antibodies might confer a degree of protection against SARS-CoV-2, but their levels rapidly decrease. On the contrary, IgG antibodies, appearing later during natural infection, are mostly correlated with protection. In case of active immunization, neutralizing IgG responses are induced in naïve individuals, with levels varying depending on the vaccine platform and immunization strategy used. In the case of vaccination of previously infected individuals, neutralizing IgG levels are much higher, boosting memory B cell responses developed during natural infection. In time, IgG levels might decrease below a protective threshold, requiring booster vaccination.

Clinical features of COVID-19. SARS-CoV-2 infection is characterized by three stages of acute infection of progressive severity. After the acute phase, a period of persistent disease can occur (Brodin, 2021; Hu et al., 2021; Sudre et al., 2021). *Postacute sequalae in <5% of patients (Sudre et al., 2021).

Origin and timeline of appearance for notable SARS-CoV-2 variants. The origin of viral variants across the world and the date of their earliest documentation during the COVID-19 pandemic (World Health Organization, 2021c).

Terminology of SARS-CoV-2 variants. Brief description of the terminology used in the manuscript referred to SARS-CoV-2 virus (Rambaut et al., 2020; Mascola et al., 2021).