Abstract
BackgroundCOVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population.MethodsWe collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays.ResultsWe found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age.ConclusionsWe concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.
Highlights
Coronavirus disease 2019 (COVID-19), caused by a newly discovered beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with no end in sight
All COVID-19 cases were diagnosed according to the guidelines for the diagnosis and treatment of new coronavirus pneumonia issued by the Chinese government, and were confirmed to be infected with SARS-CoV-2 by RT-PCR test of nasopharyngeal swabs
Among the 150 COVID-19 patients who participated in this study, 43 sera were obtained in 1– 2.5 months, 62 sera were obtained in 10–11 months, and 45 sera were obtained in 17–18 months after the onset of illness
Summary
Coronavirus disease 2019 (COVID-19), caused by a newly discovered beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with no end in sight. Specific T-cell immune responses are usually directed against virus-infected cells, accelerate viral clearance, and restrict viral spread in vivo (Feng et al, 2021). Studies have indicated a protective role of NAbs and antigen-specific memory T-cell responses in COVID19 patients (Addetia et al, 2020; Huang et al, 2020). Previous studies reported that SARS-CoV-2-specific T-cell responses occurred in virtually all patients (Grifoni et al, 2020; Feng et al, 2021; Sandberg et al, 2021). The long-term role of NAbs and cellular immunity against SARS-CoV-2 is unknown due to the recent outbreak of COVID-19, which may contribute to protection against reinfection. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population
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