Project description:Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.
Project description:BackgroundCharacterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence.MethodsWe measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic.ResultsBetween 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63.ConclusionsAmong symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.
Project description:BackgroundAssessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection.MethodsThis is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants.FindingsA total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine.InterpretationOur study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.
Project description:Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15-28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.
Project description:The COVID-19 pandemic has caused a severe global health and economic crisis, with significant consequences for human mortality and morbidity. Therefore, there is an urgent need for more studies on the immune response to SARS-CoV-2 infection, both to enhance its effectiveness and prevent its deleterious effects. This study presents the chronology of antibodies during six months after infection in hospitalized patients and the kinetics of serum soluble mediators of the cellular response triggered by SARS-CoV-2. Samples and clinical data from 330 patients hospitalized at the Hospital da Baleia in Belo Horizonte, Brazil, who were suspected of having COVID-19, were collected at the time of hospitalization and during 6 months after infection. The immune response was analyzed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. There was a significant difference in IgM specific antibody titers from the 7th to 60th days after infection between COVID-19 negative and positive patients. Soon after 60 days after infection, antibody levels started to reduce, becoming similar to the antibody levels of the COVID-19 negative patients. IgG specific antibodies started to be detectable after 9 days of infection and antibody levels were comparatively higher in positive patients as soon as after 7 days. Furthermore, IgG levels remained higher in these patients during the complete period of 180 days after infection. The study observed similar antibody profiles between different patient groups. The soluble systemic biomarkers evaluated showed a decrease during the six months after hospitalization, except for CCL11, CXCL8, CCL3, CCL4, CCL5, IL-6, IFN-g, IL-17, IL-5, FGF-basic, PDGF, VEGF, G-CSF, and GM-CSF. The results indicate that IgM antibodies are more prominent in the early stages of infection, while IgG antibodies persist for a longer period. Additionally, the study identified that patients with COVID-19 have elevated levels of biomarkers after symptom onset, which decrease over time.
Project description:BackgroundPersistence of antibodies to SARS-CoV-2 viral infection may depend on several factors and may be related to the severity of disease or to the different symptoms.MethodsWe evaluated the antibody response to SARS-CoV-2 in personnel from 9 healthcare facilities and an international medical school and its association with individuals' characteristics and COVID-19 symptoms in an observational cohort study. We enrolled 4735 subjects (corresponding to 80% of all personnel) for three time points over a period of 8-10 months. For each participant, we determined the rate of antibody increase or decrease over time in relation to 93 features analyzed in univariate and multivariate analyses through a machine learning approach.ResultsHere we show in individuals positive for IgG (≥12 AU/mL) at the beginning of the study an increase [p = 0.0002] in antibody response in paucisymptomatic or symptomatic subjects, particularly with loss of taste or smell (anosmia/dysgeusia: OR 2.75, 95% CI 1.753 - 4.301), in a multivariate logistic regression analysis in the first three months. The antibody response persists for at least 8-10 months.ConclusionsSARS-CoV-2 infection induces a long lasting antibody response that increases in the first months, particularly in individuals with anosmia/dysgeusia. This may be linked to the lingering of SARS-CoV-2 in the olfactory bulb.
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%).
Project description:BackgroundTesting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity.MethodsA SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract samples from individuals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of samples using a standard microneutralization assay.ResultsA total of 2753 individuals were eligible for the study (126 NAT-positive; prevalence, 4.6%). The median "window period" from illness onset to appearance of antibodies (range) was 10.2 (5.8-14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected ≥14 days after symptom onset were 91.3% (95% CI, 84.9%-95.6%) and 98.9% (95% CI, 98.4%-99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%-99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%-85.1%); this increased to 96.8% (95% CI, 90.7%-99.0%) for the combination of IgG and IgA.ConclusionsMeasurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NATs are suspected. The majority of individuals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.
Project description:Better understanding of antibody responses against SARS-CoV-2 after natural infection might provide valuable insights into the future implementation of vaccination policies. Longitudinal analysis of IgG antibody titers was carried out in 32 recovered COVID-19 patients based in the Umbria region of Italy for 14 months after Mild and Moderately-Severe infection.Two FDA-approved immunoassays against SARS-CoV-2 Nucleocapsid protein (NCP) and anti-spike-receptor binding domain (S-RBD) were used for sequential serological tests at different time points. The demographics,clinical history and symptom profile associated with the magnitude and longevity of antibody responses were also analyzed. Anti-S-RBD IgG persisted in 96.8% (31 of 32) subjects at 14 months. Patients reporting loss of smell and taste during the clinical course of the disease developed significantly higher antibody titers. Anti-NCP IgG seronegative patients(n=7) at 10 months, tested positive for anti-S-RBD IgG at 12,13 and 14 months emphasizing on a higher false-negative rate for NCP protein-based antibody assays. This study also highlights the importance of adopting specific immunoassays for routine estimation of antibody titers and the decreased rate of re-infections in recovered patients.
Project description:BackgroundCharacterizing the kinetics of the antibody response to SARS-CoV-2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over an 11-month period in order to determine how circulating antibody levels change over time following natural infection.MethodsFrom April 2020 to February 2021, we enrolled 228 donors. At each study visit, subjects either donated plasma or had study samples drawn only. Anti-SARS-CoV-2 donor testing was performed using the VITROS® Anti-SARS-CoV-2 Total and IgG assays, and an in-house fluorescence reduction neutralization assay (FRNA).ResultsAnti-SARS-CoV-2 antibodies were identified in 97% of COVID-19 convalescent donors at initial presentation. In follow up analyses, of the 116 donors presenting for repeat timepoints, 91.4% of donors had detectable IgG levels up to 11 months post-symptom recovery, while 63% had detectable neutralizing titers, however, we observed that 25% of donors had neutralizing levels that dropped to an undetectable titer over time.ConclusionOur data suggest that immunological memory is acquired in most individuals infected with SARS-CoV-2 and is sustained in a majority of patients for up to 11 months after recovery.