Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies.
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ABSTRACT:
SUBMITTER: Dufloo J
PROVIDER: S-EPMC8057765 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The immune responses to SARS-CoV-2 infections are very complex and remain to be further characterized. In this study, we performed the single-cell B-cell receptor (BCR) sequencing (scBCR-seq) of the PBMC samples from the healthy controls and SARS-CoV-2 infected individuals with various clinical presentations, and subsequently analyzed the abundance, diversity and difference of BCR repertoire in different groups of COVID-19 patients and the healthy controls, respectively. We identified a number of unique heavy or light chain VDJ genes pairs and combinational preference in each group, such as IGKV3-7 enriched in the asymptomatic subjects, whereas IGHV3-23-IGHJ4, IGHV1-18–IGLV3-19, IGHV1-18–IGLV3-21, and IGHV1-1–IGLV3-25 enriched in the recovery patients from the severe diseases. These findings may advance our understanding of the B-cell mediated immune responses to SARS-CoV-2 infections and help develop novel vaccine candidates and therapeutic antibodies against COVID-19.
2022-09-15 | GSE180118 | GEO
Project description:BackgroundThe immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population.MethodsOf 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1-3.7) and 6.1 (5.3-7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR).ResultsOverall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes.ConclusionsAdults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.
| S-EPMC8515185 | biostudies-literature
Project description: Not available
| S-BSST379 | biostudies-other
Project description:A hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection gravely worsens the clinical progression of coronavirus disease 2019 (COVID-19). Although the undesirable effects of inflammasome activation have been correlated to the severity of COVID-19, the mechanisms of this process in the asymptomatic infection and disease progression have not yet been clearly elucidated. Our results indicate potential preventive targets for COVID-19 disease development and progression.
2023-07-11 | GSE236651 | GEO
Project description:We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.
| S-EPMC7774548 | biostudies-literature
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.
| S-EPMC8604724 | biostudies-literature
Project description:BackgroundThe huge surge in COVID-19 cases in Karnataka state, India, during early phase of the pandemic especially following return of residents from other states and countries required investigation with respect to transmission dynamics, clinical status, demographics, comorbidities and mortality. Knowledge on the role of symptomatic and asymptomatic cases in transmission of SARS-CoV-2 was not available.MethodsThe study included all the cases reported from March 8 - May 31, 2020. Individuals with a history of international or domestic travel from high burden states, Influenza-like Illness or Severe Acute Respiratory Illness and high-risk contacts of COVID-19 cases were included. Detailed analysis based on contact tracing data available from the line-list of state surveillance unit was performed using cluster network analysis software.FindingsAmongst the 3404 COVID-19 positive cases, 3096 (91%) were asymptomatic while 308 (9%) were symptomatic. Majority of asymptomatic cases were in the age range of 16 and 45 years while symptomatic cases were between 31 and 65 years. Mortality rate was especially higher among middle-aged and elderly cases with co-morbidities, 34/38 (89·4%). Cluster network analysis of 822 cases indicated that the secondary attack rate, size of the cluster and superspreading events were higher when the source case was symptomatic as compared to an asymptomatic.InterpretationOur findings indicate that both asymptomatic and symptomatic SARS-CoV-2 cases transmit the infection, although symptomatic cases were the main driving force within the state during the beginning of the pandemic. Considering the large proportion of asymptomatic cases, their ability to spread infection cannot be overlooked. Notwithstanding the limitations and bias in identifying asymptomatic cases, the findings have major implications for testing policies. Active search, early testing and treatment of symptomatic elderly patients with comorbidities should be prioritized for containing the spread of COVID-19 and reducing mortality.FundingIntermediate Fellowship, Wellcome Trust-DBT India Alliance to Giridhara R Babu, Grant number: IA/CPHI/14/1/501499.
| S-EPMC7831811 | biostudies-literature
Project description:ImportanceRandomized clinical trials have provided estimates of the effectiveness of the BNT162b2 vaccine against symptomatic SARS-CoV-2 infection, but its effect on asymptomatic infections remains unclear.ObjectiveTo estimate the association of vaccination with the Pfizer-BioNTech BNT162b2 vaccine with symptomatic and asymptomatic SARS-CoV-2 infections among health care workers.Design, setting, and participantsThis was a single-center, retrospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. Data were collected on symptomatic and asymptomatic SARS-CoV-2 infections confirmed via polymerase chain reaction (PCR) tests in health care workers undergoing regular screening with nasopharyngeal swabs between December 20, 2020, and February 25, 2021. Logistic regression was used to calculate incidence rate ratios (IRRs) comparing the incidence of infection between fully vaccinated and unvaccinated participants, controlling for demographics and the number of PCR tests performed.ExposuresVaccination with the BNT162b2 vaccine vs unvaccinated status was ascertained from the employee health database. Full vaccination was defined as more than 7 days after receipt of the second vaccine dose.Main outcomes and measuresThe primary outcome was the regression-adjusted IRR for symptomatic and asymptomatic SARS-CoV-2 infection of fully vaccinated vs unvaccinated health care workers. The secondary outcomes included IRRs for partially vaccinated health care workers (days 7-28 after first dose) and for those considered as late fully vaccinated (>21 days after second dose).ResultsA total of 6710 health care workers (mean [SD] age, 44.3 [12.5] years; 4465 [66.5%] women) were followed up for a median period of 63 days; 5953 health care workers (88.7%) received at least 1 dose of the BNT162b2 vaccine, 5517 (82.2%) received 2 doses, and 757 (11.3%) were not vaccinated. Vaccination was associated with older age compared with those who were not vaccinated (mean age, 44.8 vs 40.7 years, respectively) and male sex (31.4% vs 17.7%). Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated health care workers and 38 unvaccinated health care workers (incidence rate, 4.7 vs 149.8 per 100 000 person-days, respectively, adjusted IRR, 0.03 [95% CI, 0.01-0.06]). Asymptomatic SARS-CoV-2 infection occurred in 19 fully vaccinated health care workers and 17 unvaccinated health care workers (incidence rate, 11.3 vs 67.0 per 100 000 person-days, respectively, adjusted IRR, 0.14 [95% CI, 0.07-0.31]). The results were qualitatively unchanged by the propensity score sensitivity analysis.Conclusions and relevanceAmong health care workers at a single center in Tel Aviv, Israel, receipt of the BNT162b2 vaccine compared with no vaccine was associated with a significantly lower incidence of symptomatic and asymptomatic SARS-CoV-2 infection more than 7 days after the second dose. Findings are limited by the observational design.
| S-EPMC8220476 | biostudies-literature
Project description:Asymptomatic transmission of the coronavirus disease and the infected individual prediction has become very important in the COVID-19 outbreak study. The asymptomatic and symptomatic transmission studies are still ongoing to assess their impacts on disease monitoring and burden. However, there has been limited research on how asymptomatic and symptomatic transmissions together can affect the coronavirus disease outbreak. A mathematical model is therefore needed to be developed in order to assess the effect of these transmissions on the coronavirus disease dynamics. This paper develops a mathematical model concerning asymptomatic and symptomatic disease transmission processes in the COVID-19 outbreak. The model sensitivity has been analysed in terms of the variance of each parameter, and the local stability at two equilibrium points have been discussed in terms of the basic reproduction number (R0). It is found that the disease-free equilibrium gets stable for R0 < 1 whereas the endemic equilibrium becomes stable for R0 > 1 and unstable otherwise. The proportion of the effect of asymptomatic and symptomatic transmission rates on R0 is calculated to be approximately between 1 and 3. The results demonstrate that asymptomatic transmission has a significant impact compared to symptomatic transmission in the disease outbreak. Outcomes of this study will contribute to setting an effective control strategy for the COVID-19 outbreak.
| S-EPMC8788092 | biostudies-literature
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.
| S-EPMC8364143 | biostudies-literature