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The Lancet

Infectious Disease

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

Last Revised:
PMID: 38048805
PII: S2666-5247(23)00255-0
PII: S2666-5247(23)00255-0


The study investigates the long-term adaptive immunity to SARS-CoV-2 in individuals recovered from COVID-19 two years post-infection. It was found that neutralising antibody titres gradually declined over the two-year period, with poor response to certain omicron sublineages. However, Memory B-cell responses remained at two years and showed cross-reactivity to the delta and omicron BA.1 variants. There was no significant difference in T-cell responses between the first and second year. Vaccinated participants showed increased antibody titres and memory B-cell frequencies. The findings suggest that initial viral infection primes highly cross-reactive memory T-cell responses that persist for two years.

Key Takeaways

  • Neutralising antibody titres continually decline over a two-year period post-infection, with inadequate response to omicron sublineages.
  • Memory B-cell responses are retained for two years post-infection and exhibit cross-reactivity to the delta and omicron BA.1 variants.
  • Following vaccination, infected individuals display increased antibody titres and frequencies of memory B cells.

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Li Guo, Qiao Zhang, Xiaoying Gu, Lili Ren, Tingxuan Huang, Yanan Li, Hui Zhang, Ying Liu, Jingchuan Zhong, Xinming Wang, Lan Chen, Yin Zhang, Danyang Li, Meiyu Fang, Liuhui Xu, Haibo Li, Zai Wang, Hui Li, Tao Bai, Wen Liu, Yanchun Peng, Tao Dong, Bin Cao, Jianwei Wang

Full Abstract

  • BACKGROUND: 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.
  • METHODS: 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.
  • FINDINGS: 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.
  • INTERPRETATION: 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.
  • FUNDING: 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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