SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study.
SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study.
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DOI：
10.1016/s2213-2600(21)00158-2
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
Sealfon SC
中科院分区：
文献类型：
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作者：
Letizia AG;Ge Y;Vangeti S;Goforth C;Weir DL;Kuzmina NA;Balinsky CA;Chen HW;Ewing D;Soares-Schanoski A;George MC;Graham WD;Jones F;Bharaj P;Lizewski RA;Lizewski SE;Marayag J;Marjanovic N;Miller CM;Mofsowitz S;Nair VD;Nunez E;Parent DM;Porter CK;Santa Ana E;Schilling M;Stadlbauer D;Sugiharto VA;Termini M;Sun P;Tracy RP;Krammer F;Bukreyev A;Ramos I;Sealfon SC
感染SARS-CoV-2的年轻人是否有随后感染的风险尚不确定。我们调查了先前感染血清学阳性的年轻成年人随后感染SARS-CoV-2的风险。这项分析是作为海军陆战队前瞻性COVID-19健康行动应对研究（CHARM）的一部分进行的。CHARM主要包括美国海军陆战队新兵，年龄在18-20岁之间，在家中进行了为期2周的无人监督隔离。居家隔离期后，在抵达海军监督的为期2周的隔离设施（大学校园或酒店）时，参与者被招募并评估基线SARS-CoV-2 IgG血清阳性，定义为受体结合域和全长刺突蛋白ELISA上1：150或更高的稀释度。参与者还完成了一份调查问卷，包括人口统计学信息、风险因素、14种特定COVID-19相关症状或任何其他未指明症状的报告以及简短病史。在隔离的第0周、第1周和第2周通过PCR评估SARS-CoV-2感染，参与者完成了一份随访问卷，其中包括自上次研究访问以来有关相同COVID-19相关症状的问题。如果受试者在隔离期间PCR检测呈阳性，则在此阶段将其排除。参与者在检疫期间有三个阴性拭子PCR结果，在监督检疫开始时进行基线血清学检测，确定他们为SARS-CoV-2血清阴性或血清阳性，然后继续在海军陆战队新兵仓库进行基本训练。在第2、4和6周对血清阳性和血清阴性组进行三次PCR检测，沿着对所有随后感染的血清阳性和选定的血清阳性未感染参与者进行随访症状问卷调查和基线中和抗体滴度（前瞻性研究期）。在2020年5月11日至2020年11月2日期间，我们招募了3249名参与者，其中3168名（98%）继续进入为期2周的隔离期。3076名（95%）参与者，其中2825名（92%）为男性，在隔离6周后的前瞻性研究期间进行了随访。在189名血清阳性参与者中，19名（10%）在6周随访期间至少有一次SARS-CoV-2 PCR检测阳性（1.1例/人年）。相比之下，2247名血清阴性参与者中有1079名（48%）检测为阳性（每人每年6·2例）。发病率比值为0.18（95%CI 0.11 ~ 0.28; p<0.001）。在血清反应阳性的新兵中，基线全长刺突蛋白IgG滴度较低的人比基线全长刺突蛋白IgG滴度较高的人更容易感染（风险比0.45 [95%CI 0.32 - 0.65]; p<0.001）。感染的血清阳性参与者的病毒载量比感染的血清阴性参与者低约10倍（ORF 1ab基因周期阈值差异3.95 [95%CI 1.23 - 6.67]; p= 0.004）。在血清阳性参与者中，在6周的观察期间，在54名未感染者中的45名（83%）和19名感染者中的6名（32%）中检测到基线中和滴度（ID 50差异p<0.0001）。与血清阴性个体相比，血清阳性的年轻人随后感染的风险约为五分之一。尽管初始感染诱导的抗体在很大程度上具有保护性，但它们不能保证有效的SARS-CoV-2中和活性或对后续感染的免疫力。这些发现可能与优化大规模疫苗接种策略有关。国防部卫生局和国防部高级研究计划局。
Whether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection. This analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18–20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot—Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period). Between May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11–0·28; p<0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32–0·65]; p<0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23–6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p<0·0001). Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies. Defense Health Agency and Defense Advanced Research Projects Agency.