Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection.
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ABSTRACT:
SUBMITTER: Choe PG
PROVIDER: S-EPMC7774548 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus-neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate that children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that can likely contribute to protection from reinfection.
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Project description:Waning humoral immunity in coronavirus disease patients has raised concern over usefulness of serologic testing. We investigated antibody responses of 58 persons 8 months after asymptomatic or mildly symptomatic infection with severe acute respiratory syndrome coronavirus 2. For 3 of 4 immunoassays used, seropositivity rates were high (69.0%-91.4%).
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Project description:Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming "herd-immunity" through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.
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Project description:The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.
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Project description:BackgroundHousehold transmission contributes to SARS-CoV-2 spread, but the role of children in transmission is unclear. We conducted a study that included symptomatic and asymptomatic children and adults exposed to SARS-CoV-2 in their households with the objective of determining how SARS-CoV-2 is transmitted within households.MethodsIn this case-ascertained antibody-surveillance study, we enrolled households in Ottawa, Ontario, in which at least 1 household member had tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction testing. The enrolment period was September 2020 to March 2021. Potentially eligible participants were identified if they had tested positive for SARS-CoV-2 at an academic emergency department or affiliated testing centre; people who learned about the study through the media could also self-identify for participation. At least 2 participants were required for a household to be eligible for study participation, and at least 1 enrolled participant per household had to be a child (age < 18 yr). Enzyme-linked immunosorbent assays were used to evaluate SARS-CoV-2-specific IgA, IgM and IgG against the spike-trimer and nucleocapsid protein. The primary outcome was household secondary attack rate, defined as the proportion of household contacts positive for SARS-CoV-2 antibody among the total number of household contacts participating in the study. We performed descriptive statistics at both the individual and household levels. To estimate and compare outcomes between patient subgroups, and to examine predictors of household transmission, we fitted a series of multivariable logistic regression with robust standard errors to account for clustering of individuals within households.ResultsWe enrolled 695 participants from 180 households: 180 index participants (74 children, 106 adults) and 515 of their household contacts (266 children, 249 adults). A total of 487 household contacts (94.6%) (246 children, 241 adults) had SARS-CoV-2 antibody testing, of whom 239 had a positive result (secondary attack rate 49.1%, 95% confidence interval [CI] 42.9%-55.3%). Eighty-eight (36.8%, 95% CI 29.3%-43.2%) of the 239 were asymptomatic; asymptomatic rates were similar for children (51/130 [39.2%, 95% CI 30.7%-48.5%]) and adults (37/115 [32.2%, 95% CI 24.2%-41.4%]) (odds ratio [OR] 1.3, 95% CI 0.8-2.1). Adults were more likely than children to transmit SARS-CoV-2 (OR 2.2, 95% CI 1.3-3.6). The odds of transmission from asymptomatic (OR 0.6, 95% CI 0.2-1.4) versus symptomatic (OR 0.9, 95% CI 0.6-1.4) index participants to household contacts was uncertain. Predictors of household transmission included household density (number of people per bedroom), relationship to index participant and number of cases in the household.InterpretationThe rate of SARS-CoV-2 transmission within households was nearly 50% during the study period, and children were an important source of spread. The findings suggest that children are an important driver of the COVID-19 pandemic; this should inform public health policy.
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Project description:Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
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Project description:Without an effective vaccine against SARS-CoV-2, the build-up of herd immunity through natural infection has been suggested as a means to control COVID-19. Although population immunity is typically estimated by the serological investigation of recovered patients, humoral immunity in asymptomatic subjects has not been well studied, although they represent a large proportion of all SARS-CoV-2 infection cases. In this study, we conducted a serosurvey of asymptomatic infections among food workers and performed serological and cellular response analyses of asymptomatic subjects in Wuhan, the original epicenter of the COVID-19 outbreak. Our data showed that up to 5.91% of the food workers carried SARS-CoV-2 IgG antibodies asymptomatically; however, in 90.4% of them, the antibody level declined over a 2-week period. IgM and IgG antibodies, including neutralizing antibodies, were significantly lower in asymptomatic subjects than in recovered symptomatic patients with similar disease courses. Furthermore, the asymptomatic subjects showed lymphopenia and a prominent decrease in the B-cell population, as well as a low frequency of antibody-secreting cells and a low cytokine response. These factors probably contributed to the low and unsustained antibody levels in asymptomatic subjects. Our results show that asymptomatic subjects are likely to be vulnerable to SARS-CoV-2 reinfection, and neither the proportion of population immunity nor the breadth of immune responses is sufficient for herd immunity.
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Project description:BackgroundInflammatory biomarkers have been used to portend disease severity in nonpregnant individuals with SARS-CoV-2 infection. However, currently, limited data are available, and with mixed results, to elucidate which inflammatory biomarkers may be most associated with clinical phenotype in pregnant patients.ObjectiveWe aimed to compare laboratory findings among pregnant patients with SARS-CoV-2 infection by symptom status and disease severity.Study designWe retrospectively evaluated pregnant patients with positive SARS-CoV-2 infection, confirmed through polymerase chain reaction testing, at an urban academic US hospital between March 2020 and October 2020, performed for reported symptoms or universal screening on admission. In our hospital, all patients with SARS-CoV-2 infection were recommended to have baseline laboratory testing, including leukocyte, neutrophil, and lymphocyte counts; aspartate aminotransferase and alanine aminotransferase; high-sensitivity C-reactive protein; procalcitonin; lactate dehydrogenase; D-dimer; and ferritin. We performed multivariable logistic regression to evaluate peak laboratory abnormalities significantly associated with symptomatic SARS-CoV-2 infection and disease severity with gestational age at diagnosis, maternal age, and obesity as covariates. The sensitivity and specificity of laboratory abnormalities were calculated to identify symptomatic vs asymptomatic infection and severe to critical disease vs mild to moderate disease.ResultsWe identified 175 pregnant patients with SARS-CoV-2 infection, of whom 100 (57%) were symptomatic; 17 (17%) of those who were symptomatic had a severe to critical disease. Laboratory data were available for 128 patients, of whom 67 (52%) were symptomatic. Compared with asymptomatic individuals, symptomatic individuals were more likely to exhibit elevated high-sensitivity C-reactive protein levels after adjusting for gestational age (adjusted odds ratio, 5.67; 95% confidence interval, 1.42-22.52; sensitivity, 81%; specificity, 43%). In symptomatic individuals, transaminitis (adjusted odds ratio, 5.67; 95% confidence interval, 1.27-25.43), elevated procalcitonin levels (adjusted odds ratio, 16.60; 95% confidence interval, 2.61-105.46), and elevated lactate dehydrogenase levels (adjusted odds ratio, 17.55; 95% confidence interval, 2.51-122.78) were independently associated with severe to critical disease rather than mild to moderate disease after adjusting for maternal age and obesity. For differentiating disease severity, sensitivity rates for transaminitis, procalcitonin elevation, and lactate dehydrogenase elevation were 47%, 87%, and 53%, respectively, whereas the specificity rates were 89%, 63%, and 90%, respectively.ConclusionInflammatory biomarkers in pregnant patients with SARS-CoV-2 infection exhibited vast heterogeneity, poor discriminative ability, and thereby limited clinical utility. Larger registry studies should evaluate which inflammatory biomarkers may be most useful for risk stratification and prognostication of pregnant patients with SARS-CoV-2 infection, taking into account the physiology of pregnancy.
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Project description:BackgroundThe development of memory B cells after asymptomatic SARS-CoV-2 infection is not well understood.MethodsWe compared Spike antibody titers, pseudovirus neutralizing antibody titers, and memory B cell responses among SARS-CoV-2 PCR positive Marine recruits who either reported asymptomatic or symptomatic infection.Results36 asymptomatic participants exhibited similar Spike IgG titers, Spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and Spike IgG titers showed significant positive correlations with frequency of memory B cells.ConclusionsAmong young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B cell responses comparable to mild symptomatic infection.
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Project description:We investigated serological responses following a SARS-CoV-2 outbreak in spring 2020 on a US Marine recruit training base. 147 participants that were isolated during an outbreak of respiratory illness were enrolled in this study, with visits approximately 6 and 10 weeks post-outbreak (PO). This cohort is comprised of young healthy adults, ages 18-26, with a high rate of asymptomatic infection or mild symptoms, and therefore differs from previously reported longitudinal studies on humoral responses to SARS-CoV-2, which often focus on more diverse age populations and worse clinical presentation. 80.9% (119/147) of the participants presented with circulating IgG antibodies against SARS-CoV-2 spike (S) receptor-binding domain (RBD) at 6 weeks PO, of whom 97.3% (111/114) remained positive, with significantly decreased levels, at 10 weeks PO. Neutralizing activity was detected in all sera from SARS-CoV-2 IgG positive participants tested (n=38) at 6 and 10 weeks PO, without significant loss between time points. IgG and IgA antibodies against SARS-CoV-2 RBD, S1, S2, and the nucleocapsid (N) protein, as well neutralization activity, were generally comparable between those participants that had asymptomatic infection or mild disease. A multiplex assay including S proteins from SARS-CoV-2 and related zoonotic and human endemic betacoronaviruses revealed a positive correlation for polyclonal cross-reactivity to S after SARS-CoV-2 infection. Overall, young adults that experienced asymptomatic or mild SARS-CoV-2 infection developed comparable humoral responses, with no decrease in neutralizing activity at least up to 10 weeks after infection.
| S-EPMC8220197 | biostudies-literature