Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort

Abstract

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

“…We then estimated the half-life of the decrease of the antibody titer directly from the seroprevalence data, using an extension of the classic Susceptible-Exposed-Infectious-Removed (SEIR) model 26 . Assuming an average time to seroconversion of 14 days 27-29 , an average generation interval of 5.2 days 30 and an average time from disease onset to death of 20.2 days 31 , the overall half-life observed on the level of the population is 75 (CrI95% 55-103) days (unadjusted) or 88 (CrI95%: 61-128) days (post-stratification for age and sex), similar to what was reported by others 32 . We then computed the cumulative incidence of CoV2, i.e.…”

“…If antibody titers were stable after infection, the seroprevalence would reflect the entirety of the population infected since inception of the pandemic. However, anti-CoV2 titers were found to decay in multiple studies [11][12][13][14][15]32 , with a half-life of approximately 106 (CI95% 89 to 132) days 11 , 76 to 156 days 32 , and others suggesting an even shorter half-life of 26 to 60 days 13 . This decrease in titers over time was confirmed in neutralization assays, shown in various studies 12,14,15 .…”

“…in some areas in the Amazonas state in Brazil 11 or in slums in Mumbai, India 56 . Yet, since antibody waning has been reported in multiple instances [10][11][12][13][14][15]32 , discrete seroestimates may reflect snapshots of the immunity status of a population at a certain time, rather than the true cumulative case incidence. Conversely, we have accounted for antibody waning, using a model fit developed by data obtained through continuous CoV2 seromonitoring.…”

The lymphatic system and COVID-19 vaccines

“…The transport of vaccine antigen to the draining LNs is crucial for the initiation of systemic immune responses against the relevant pathogen by T and B cells ( 23 ). Previous studies have indicated that protective immunity against COVID-19 is mediated by both key arms of the adaptive immune system, i.e., humoral immunity and cellular immunity ( 34 – 37 ), and that antibody and T-cell responses tend to work in a compensatory manner to provide protection ( 38 ). Humoral immunity generates antibodies and memory B cells, while cellular immunity leads to the activation of antigen-specific helper CD4 + T cells and cytotoxic CD8 + T cells ( 13 ), which both occur in the draining LNs ( 39 , 40 ).…”

Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona

“…There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection ( Karachaliou et al, 2021 ; Menges et al, 2022 ; Le Bert et al, 2021 ; Mazzoni et al, 2021 ). Personal characteristics, comorbidities, lifestyles, living conditions, and the shared environment only partly account for such variation; this is particularly clear among healthy individuals from the general population ( Kogevinas et al, 2021 ; Weaver et al, 2022 ; Patanavanich and Glantz, 2021 ).…”