Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?

Abstract

Since its declaration as a pandemic in March 2020, SARS-CoV-2 has infected more than 217 million people worldwide and despite mild disease in the majority of the cases, more than 4.5 million cases of COVID-19-associated death have been reported as of September 2021. The question whether recovery from COVID-19 results in prevention of reinfection can be answered with a “no” since cases of reinfections have been reported. The more important question is whether during SARS-CoV-2 infection, a protective immunity is built and maintained afterwards in a way which protects from possibly severe courses of disease in case of a reinfection. A similar question arises with respect to vaccination: as of September 2021, globally, more than 5.2 billion doses of vaccines have been administered. Therefore, it is of utmost importance to study the cellular and humoral immunity toward SARS-CoV-2 in a longitudinal manner. In this study, reconvalescent COVID-19 patients have been followed up for more than 1 year after SARS-CoV-2 infection to characterize in detail the long-term humoral as well as cellular immunity. Both SARS-CoV-2-specific T cells and antibodies could be detected for a period of more than 1 year after infection, indicating that the immune protection established during initial infection is maintained and might possibly protect from severe disease in case of reinfection or infection with novel emerging variants. Moreover, these data demonstrate the opportunity for immunotherapy of hospitalized COVID-19 patients via adoptive transfer of functional antiviral T cells isolated from reconvalescent individuals.

Longitudinal Tracking of Immune Responses in COVID-19 Convalescents Reveals Absence of Neutralization Activity Against Omicron and Staggered Impairment to Other SARS-CoV-2 Variants of Concern

“…Along these lines, CD8 + effector/memory type 1 cells (CD38 + HLA-DR + ) have been shown to contain Spike-responsive T cells ( 18 , 19 ) and our results also demonstrate a strong decrease of this cell pool following late convalescence, implying the contraction of Spike-specific T cells from circulation. Similar kinetics for Spike-reactive T cells have been described in recent reports ( 33 – 35 ).…”

Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy

“…All donors had initially been infected early in 2020 and have been vaccinated meanwhile. In accordance with previous reports, frequencies of T cells against M and N proteins slightly decreased throughout the time of convalescence, yet remained detectable ( Gussarow et al, 2021 ). In contrast, T cell frequencies against PepTivator SARS-CoV-2 Select remained stable, suggesting an increased fraction of T cells against the S protein after vaccination.…”

“…Throughout recovery and convalescence, significant numbers of SARS-CoV-2-specific memory T cells reactive against Spike (S), Nucleocapsid (N), and Membrane (M) proteins of SARS-CoV-2 are detectable ( Peng et al, 2020 ; Bonifacius et al, 2021 ). Particularly in convalescent individuals recovering from mild or even asymptomatic disease, a robust, broad and highly functional T cell response can be detected suggesting effective protection from SARS-CoV-2 reinfection ( Bonifacius et al, 2021 ; Gussarow et al, 2021 ; Le Bert et al, 2021 ; Marcotte et al, 2022 ). In contrast to neutralizing antibodies, antiviral T cells developed during SARS-CoV-2 infection with wild type or earlier VOCs, were shown to efficiently recognize antigens from Omicron variant ( Gao et al, 2022 ).…”

Immune Profiling Uncovers Potent Adjuvant Capacities of Sars-Cov-2 Infection to Vaccination Leading to Memory T Cell Responses With a Th17 Signature in Cancer Patients

“…Vaccination mainly induced CD4 T cells, in contrast to SARS CoV-2 infection, which could explain its potency of raising antibody responses possibly through activated CD4 T helper cells (49). T cell responses towards M and S proteins were found previously (50,51), but we extended this observation to O patients. In general, M protein was found to be a potent target for CD8 T cell responses even when compared to the S protein.…”