Durability and cross-reactive immune memory to SARS-CoV-2 in individuals 2 years after recovery from COVID-19: a longitudinal cohort study.

Publication date: Dec 01, 2023

SARS-CoV-2-specific adaptive immunity more than 1 year after initial infection has not been well characterised. The aim of this study was to investigate the durability and cross-reactivity of immunological memory acquired from natural infection against SARS-CoV-2 in individuals recovered from COVID-19 2 years after infection. In this longitudinal cohort study, we recruited patients who had recovered from laboratory-confirmed COVID-19 and were discharged from Jinyintan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We carried out three successive follow-ups between June 16 and Sept 3, 2020 (6 months), Dec 16, 2020, and Feb 7, 2021 (1 year), and Nov 16, 2021, and Jan 10, 2022 (2 years), in which blood samples were taken. We included participants who did not have re-infection or receive a SARS-CoV-2 vaccination (infected-unvaccinated), and participants who received one to three doses of inactivated vaccine 1-2 years after infection (infected-vaccinated). We evaluated the presence of IgG antibodies, neutralising antibodies, and memory B-cell and memory T-cell responses against the prototype strain and delta and omicron variants. In infected-unvaccinated participants, neutralising antibody titres continually declined from 6-month to 2-year follow-up visits, with a half-life of about 141.2 days. Neutralising antibody responses to omicron sublineages (BA. 1, BA. 1.1, BA. 2, BA. 4/5, BF. 7, BQ. 1, and XBB) were poor. Memory B-cell responses to the prototype strain were retained at 2 years and presented cross-reactivity to the delta and omicron BA. 1 variants. The magnitude of interferon γ and T-cell responses to SARS-CoV-2 were not significantly different between 1 year and 2 years after infection. Multifunctional T-cell responses against SARS-CoV-2 spike protein and nucleoprotein were detected in most participants. Recognition of the BA. 1 variant by memory T cells was not affected in most individuals. The antibody titres and the frequencies of memory B cells, but not memory T cells, increased in infected-vaccinated participants after they received the inactivated vaccine. This study improves the understanding of the duration of SARS-CoV-2-specific immunity without boosting, which has implications for the design of vaccination regimens and programmes. Our data suggest that memory T-cell responses primed by initial viral infection remain highly cross-reactive after 2 years. With the increasing emergence of variants, effective vaccines should be introduced to boost neutralising antibody and overall T-cell responses to newly emerged SARS-CoV-2 variants. Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities for Peking Union Medical College, Beijing Natural Science Foundation, UK Medical Research Council.

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Concepts Keywords
Beijing Antibody
Inactivated Ba
June Cell
Vaccinated Cov
Cross
Infected
Infection
Memory
Neutralising
Participants
Sars
Variants
Year
Years

Semantics

Type Source Name
disease MESH COVID-19
disease MESH infection
disease IDO blood
disease MESH re-infection
disease VO vaccination
disease VO unvaccinated
disease VO inactivated vaccine
disease VO vaccinated
disease IDO cell
disease MESH viral infection
disease VO effective
drug DRUGBANK Coenzyme M
drug DRUGBANK Guanosine
drug DRUGBANK Troleandomycin
disease IDO pathogen
disease MESH Respiratory Diseases
disease MESH psychotic disorder
disease MESH dementia
disease VO volume
disease VO USA
disease IDO assay
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Amino acids
disease MESH influenza
disease VO Viruses
disease VO vaccine dose
disease VO vaccine
disease VO dose
disease IDO production
disease VO report
disease VO time

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