Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

Cohen, Kristen W.; Linderman, Susanne L.; Moodie, Zoe; Czartoski, Julie; Lai, Lilin; Mantus, Grace; Norwood, Carson; Nyhoff, Lindsay E.; Edara, Venkata Viswanadh; Floyd, Katharine; Rosa, Stephen C. De; Ahmed, Hasan; Whaley, Rachael E.; Patel, Shivan; Prigmore, Brittany; Lemos, Maria P.; Davis, Carl W.; Furth, Sarah; O’Keefe, James B; Gharpure, Mohini P.; Gunisetty, Sivaram; Stephens, Kathy; Antia, Rustom; Zarnitsyna, Veronika I.; Stephens, David S.; Edupuganti, Srilatha; Rouphael, Nadine; Anderson, Evan J.; Mehta, Aneesh K; Wrammert, Jens; Suthar, Mehul S.; Ahmed, Rafi; McElrath, M. Juliana

doi:10.1101/2021.04.19.21255739

Cited by 105 publications

(156 citation statements)

References 50 publications

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“…Levels of IgA and IgG antibodies at the 6-month follow-up were approximately half that of their assumed maximum value measured 6 weeks after disease onset [23], and remained stable up to the 12-months follow-up, thereby showing a biphasic decrease as previously described [24,25]. In contrast to IgM antibodies, IgG antibodies specifically directed against the spike protein of SARS-CoV-2 persist relatively stable over time as described by Dan JM et al, who found a percentage of 90% spike IgG-positive convalescents half a year after COVID-19 [26].…”

Section: Discussionsupporting

confidence: 75%

One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

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Tzortzini

Kling

et al. 2021

JCM

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After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19.

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Section: Discussionsupporting

confidence: 75%

One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

Rank

Tzortzini

Kling

et al. 2021

JCM

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“…Although the difference between both groups continuously disappeared until 3 weeks after 2 nd vaccination, anti-spike antibody titers were still 2-4 times higher and neutralization capacities against the unmutated virus was almost twice as strong in COVID-19convalescent compared with COVID-19-negative individuals. Importantly, the interval between SARS-CoV-2 infection and vaccination did not affect the extent of the described responses, confirming that immune memory did not significantly decrease within the observed temporal range of up to one year between SARS-COV-2 infection and vaccination (26).…”

Section: Discussionsupporting

confidence: 55%

BNT162b2 Vaccination Elicits Strong Serological Immune Responses Against SARS-CoV-2 Including Variants of Concern in Elderly Convalescents

et al. 2021

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Elderly residents of long-term care facilities (LTCFs) have long been underrepresented in studies on vaccine efficacy, particularly in light of currently emerging variants of concern (VOCs). In this prospective observational cohort study, we analyzed serological immune responses in 190 individuals before, 3 weeks after 1st and 3 weeks after 2nd vaccination with BNT162b2. Unvaccinated COVID-19-convalescent subjects served as reference. End points comprised serum anti-spike IgG and IgA titers as well as neutralization capacities against unmutated and mutated SARS-CoV-2 receptor binding domains including B.1.1.7, B.1.351 and P.1. We found that antibody titers and neutralization capacities up to 3 weeks after 2nd vaccination with BNT162b2 were significantly higher in COVID-19-convalescent as compared to COVID-19-naive vaccinees. Moreover, pre-vaccination anti-NCP IgG titers, but not age or gender, had a high impact on the strength and kinetics of post-vaccination neutralization capacity development. Most importantly, BNT162b2-induced neutralization capacity was cross-reactive with VOCs. In contrast to unvaccinated convalescents, vaccinated convalescent individuals of all ages acquired strong neutralizing capacities against current VOCs. The present study suggests that COVID-19-convalescent individuals with a broad age range between 18 and 98 years benefit from BNT162b2 vaccination by developing strong and broad neutralizing immune responses against SARS-CoV-2 including current VOCs.

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“…Similar findings have been reported in healthcare workers, where older age (in those of working age) was associated with higher maximum anti-nucleocapsid IgG levels and longer half-lives 15 . Others have also reported associations between older age and higher immune responses, including IgG and memory B cells 37 . One postulated mechanism is that older adults exhibit higher IgG levels because they expand their catalogue of memory B and T cells through accumulated memory 38 .…”

Section: Discussionmentioning

confidence: 97%

Anti-spike antibody response to natural SARS-CoV-2 infection in the general population

Wei

Matthews

Stoesser

et al. 2021

Preprint

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We estimated the duration and determinants of antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as 'non-responders' not developing anti-spike antibodies. These seronegative non-responders were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.

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Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

Cited by 105 publications

References 50 publications

One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

BNT162b2 Vaccination Elicits Strong Serological Immune Responses Against SARS-CoV-2 Including Variants of Concern in Elderly Convalescents

Anti-spike antibody response to natural SARS-CoV-2 infection in the general population

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