Long-term humoral and cellular immunity after primary SARS-CoV-2 infection: a 20-month longitudinal study

Abstract

Background SARS-CoV-2 remains a world-wide health issue. SARS-CoV-2-specific immunity is induced upon both infection and vaccination. However, defining the long-term immune trajectory, especially after infection, is limited. In this study, we aimed to further the understanding of long-term SARS-CoV-2-specific immune response after infection. Results We conducted a longitudinal cohort study among 93 SARS-CoV-2 recovered individuals. Immune responses were continuously monitored for up to 20 months after infection. The humoral responses were quantified by Spike- and Nucleocapsid-specific IgG levels. T cell responses to Spike- and non-Spike epitopes were examined using both intercellular cytokine staining (ICS) assay and Activation-Induced marker (AIM) assay with quantification of antigen-specific IFNγ production. During the 20 months follow-up period, Nucleocapsid-specific antibody levels and non-Spike-specific CD4 + and CD8 + T cell frequencies decreased in the blood. However, a majority of participants maintained a durable immune responses 20 months after infection: 59% of the participants were seropositive for Nucleocapsid-specific IgG, and more than 70% had persisting non-Spike-specific T cells. The Spike-specific response initially decreased but as participants were vaccinated against COVID-19, Spike-specific IgG levels and T cell frequencies were boosted reaching similar or higher levels compared to 1 month post-infection. The trajectory of infection-induced SARS-CoV-2-specific immunity decreases, but for the majority of participants it persists beyond 20 months. The T cell response displays a greater durability. Vaccination boosts Spike-specific immune responses to similar or higher levels as seen after primary infection. Conclusions For most participants, the response persists 20 months after infection, and the cellular response appears to be more long-lived compared to the circulating antibody levels. Vaccination boosts the S-specific response but does not affect the non-S-specific response. Together, these findings support the understanding of immune contraction, and with studies showing the immune levels required for protection, adds to the knowledge of durability of protection against future SARS-CoV-2.

Impact of Prior COVID-19 Immunization and/or Prior Infection on Immune Responses and Clinical Outcomes

“…This supports the notion of enduring cellular immune memory akin to observations from the initial SARS-CoV outbreak. The humoral and cellular immune responses specific to the S-protein also declined within the first ten months after infection; however, vaccination subsequently induced a strong S-specific memory response [58]. These results corroborate those of other longitudinal studies that demonstrate waning antibody and T cell immunity after 12 months, while the potentiation of an S-specific memory response may be accomplished by subsequent immunization [61,62].…”

“…Interestingly, there is evidence that T cell memory correlates with the reduced severity of influenza in the absence of neutralizing antibodies [57]. Longitudinal assessments of antibody and T cell immunity to primary infection over 20 months revealed that more than 94% of participants seroconverted for IgG specific to Nucleocapsid (N) and Spike (S) proteins one-month post-infection [58]. Additionally, the majority of participants showed both non-S-and S-specific T cell detection, indicating an adaptive immune response to the infection [58].…”

“…Longitudinal assessments of antibody and T cell immunity to primary infection over 20 months revealed that more than 94% of participants seroconverted for IgG specific to Nucleocapsid (N) and Spike (S) proteins one-month post-infection [58]. Additionally, the majority of participants showed both non-S-and S-specific T cell detection, indicating an adaptive immune response to the infection [58]. The study observed that while the detectability of non-S-specific humoral and cellular immunity reduced over the 20-month period, it was still observable in most participants, implying the development of efficient long-term immune memory [59,60].…”

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

“…This is consistent with studies in the healthy population, where cellular immunity to COVID-19 vaccination and infection tends to be more durable than antibody responses. 43 Robust longitudinal cellular immunity in B-cell-depleted MS patients is a consistent finding across multiple studies. 26,33,[44][45][46][47] Booster further raised cytokine responses 4-5-fold.…”

Evaluation of Long-Term Adaptive Immune Responses Specific to SARS-CoV-2: Effect of Various Vaccination and Omicron Exposure

“…Previous longitudinal studies of SARS-CoV-2–specific immune responses have covered a period of up to one year after the completion of the primary two-dose series [ 5 , 11 , 12 , 13 , 14 , 15 , 16 ] or up to 20 months after infection [ 17 ]. However, the specific characteristics of long-term immune response metrics in infection-naive individuals remain largely unexplored.…”