PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：首次感染后超过1年的SARS-CoV-2特异性适应性免疫尚未得到很好的表征。这项研究的目的是调查感染后2年从COVID-19中恢复的个体对SARS-CoV-2的自然感染获得的免疫记忆的持久性和交叉反应性。
方法：在这项纵向队列研究中，我们招募了从实验室确诊的COVID-19中康复并从金银滩医院出院的患者(武汉，中国）2020年1月7日至5月29日。我们在2020年6月16日至9月3日(6个月)之间连续进行了三次随访，2020年12月16日和2021年2月7日（1年），2021年11月16日和2022年1月10日（2年），其中采集了血液样本。我们包括没有再次感染或接受SARS-CoV-2疫苗接种（感染-未接种）的参与者，以及在感染后1-2年接受1-3剂灭活疫苗的参与者（感染-接种疫苗）。我们评估了IgG抗体的存在，中和抗体，以及针对原型菌株以及δ和omicron变体的记忆B细胞和记忆T细胞反应。
结果：在未接种疫苗的参与者中，中和抗体滴度从6个月到2年的随访持续下降，半衰期约为141·2天。中和抗体对omicron亚谱系（BA.1，BA.1.1，BA.2，BA.4/5，BF.7，BQ.1和XBB）的反应较差。记忆B细胞对原型菌株的反应在2年时保留，并表现出与δ和omicronBA.1变体的交叉反应性。感染后1年和2年之间，干扰素γ和T细胞对SARS-CoV-2的反应程度没有显着差异。在大多数参与者中检测到针对SARS-CoV-2刺突蛋白和核蛋白的多功能T细胞反应。记忆T细胞对BA.1变体的识别在大多数个体中不受影响。抗体滴度和记忆B细胞的频率，但不是记忆T细胞，在接受灭活疫苗接种后，受感染接种疫苗的参与者数量增加。
结论：这项研究提高了对SARS-CoV-2特异性免疫持续时间的理解，这对疫苗接种方案和计划的设计有影响。我们的数据表明，由最初的病毒感染引发的记忆T细胞反应在2年后仍然具有高度的交叉反应性。随着变体的不断出现,应引入有效的疫苗以增强中和抗体和对新出现的SARS-CoV-2变体的整体T细胞反应。
背景:中国医学科学院,国家自然科学基金,北京协和医学院中央大学基础研究基金，北京市自然科学基金,英国医学研究委员会。
方法：在这项纵向队列研究中，我们招募了从实验室确诊的COVID-19中康复并从金银滩医院出院的患者(武汉，中国）2020年1月7日至5月29日。我们在2020年6月16日至9月3日(6个月)之间连续进行了三次随访，2020年12月16日和2021年2月7日（1年），2021年11月16日和2022年1月10日（2年），其中采集了血液样本。我们包括没有再次感染或接受SARS-CoV-2疫苗接种（感染-未接种）的参与者，以及在感染后1-2年接受1-3剂灭活疫苗的参与者（感染-接种疫苗）。我们评估了IgG抗体的存在，中和抗体，以及针对原型菌株以及δ和omicron变体的记忆B细胞和记忆T细胞反应。
结果：在未接种疫苗的参与者中，中和抗体滴度从6个月到2年的随访持续下降，半衰期约为141·2天。中和抗体对omicron亚谱系（BA.1，BA.1.1，BA.2，BA.4/5，BF.7，BQ.1和XBB）的反应较差。记忆B细胞对原型菌株的反应在2年时保留，并表现出与δ和omicronBA.1变体的交叉反应性。感染后1年和2年之间，干扰素γ和T细胞对SARS-CoV-2的反应程度没有显着差异。在大多数参与者中检测到针对SARS-CoV-2刺突蛋白和核蛋白的多功能T细胞反应。记忆T细胞对BA.1变体的识别在大多数个体中不受影响。抗体滴度和记忆B细胞的频率，但不是记忆T细胞，在接受灭活疫苗接种后，受感染接种疫苗的参与者数量增加。
结论：这项研究提高了对SARS-CoV-2特异性免疫持续时间的理解，这对疫苗接种方案和计划的设计有影响。我们的数据表明，由最初的病毒感染引发的记忆T细胞反应在2年后仍然具有高度的交叉反应性。随着变体的不断出现,应引入有效的疫苗以增强中和抗体和对新出现的SARS-CoV-2变体的整体T细胞反应。
背景:中国医学科学院,国家自然科学基金,北京协和医学院中央大学基础研究基金，北京市自然科学基金,英国医学研究委员会。
