Demographic and Clinical Factors Associated with Reactivity of Anti-SARS-CoV-2 Antibodies in Serbian Convalescent Plasma Donors.
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ABSTRACT:
SUBMITTER: Grujic J
PROVIDER: S-EPMC8751168 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesCharacterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms.MethodsWe measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling.ResultsAll donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay.ConclusionThe result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.
| S-EPMC8126762 | biostudies-literature
Project description:BackgroundConvalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma.MethodsPatients who had recovered from CO-VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed.ResultsA series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels.ConclusionWe demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.
| S-EPMC8216018 | biostudies-literature
Project description:Convalescent plasma therapy has been described as an attractive approach to treat critically ill patients with COVID-19 (Coronavirus disease 2019). The selection of convalescent plasma donors (CPD) is commonly based on neutralizing antibody titer. A better understanding of the quality of immune responses following COVID-19 will enable the optimization of convalescent donors' selection in convalescent plasma programs. The involvement of SARS-CoV-2 specific T cells in the induction and persistence of high affinity anti-SARS-CoV-2 neutralizing antibody is still poorly investigated. In this study, 115 CPD who presented SARS-CoV-2 and who were eligible for plasma donation were included. Comprehensive analysis of T cells together with humoral responses were performed in regards of sex, age and blood group type. High frequency of T cell responses against SARS-CoV-2 related protein such as spike glycoprotein (80.0%), nucleocapsid (NCAP) (70.4%) and membrane protein (VME1) (74.8%) were detected in CPD by ex vivo IFN-γ and TNF-α ELISpot assays. Among CPD responders, most exhibited poly-specific T cell responses (75%) defined by the ability to mount responses against at least two SARS-CoV-2 antigens. We found a positive correlation between the magnitude and the poly-specificity of anti-SARS-CoV-2 T cell responses in CPD. Notably, both the magnitude and poly-specificity of SARS-CoV-2 T cell responses were highly correlated with neutralizing antibody titer in CPD. The present study highlights that the poly-specificity and strength of SARS-CoV-2 specific T cell responses predicts neutralizing antibody titer following COVID-19. These observations show the interest to combine T cell assays and antibody titer for the selection of CPD and to a latter extend to assess COVID-19 vaccine efficacy in at-risk patients.
| S-EPMC8965758 | biostudies-literature
Project description:Aim: More data is required regarding the association between HLA allele and red blood cell (RBC) antigen expression in regard to SARS-CoV-2 infection and COVID-19 susceptibility. Methods: ABO, RhD, 37 other RBC antigens and HLA-A, B, C, DRB1, DQB1 and DPB1 were determined using high throughput platforms in 90 Caucasian convalescent plasma donors. Results: The AB group was significantly increased (1.5×, p = 0.018) and some HLA alleles were found to be significantly overrepresented (HLA-B*44:02, C*05:01, DPB1*04:01, DRB1*04:01 and DRB1*07:01) or underrepresented (A*01:01, B51:01 and DPB1*04:02) in convalescent individuals compared with the local bone marrow registry population. Conclusion: Our study of infection-susceptible but non-hospitalized Caucasian COVID-19 patients contributes to the global understanding of host genetic factors associated with SARS-CoV-2 infection and severity.
| S-EPMC9941981 | biostudies-literature
Project description:BackgroundConvalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19-susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood.MethodsSARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression.ResultsAntibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19-2.12]), independent of age, sex, and hospitalization.ConclusionsSARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.
| S-EPMC7499592 | biostudies-literature
Project description:The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.
| S-EPMC7877634 | biostudies-literature
Project description:The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.
| S-EPMC8903276 | biostudies-literature
Project description:Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.
| S-EPMC8489294 | biostudies-literature
Project description:BackgroundThe vast majority of COVID-19 cases both symptomatic and asymptomatic develop immunity after COVID-19 contagion. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The aim of this study was to determine how long total anti-SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting.Material and methodsA series of 2421 donations either of SARS-CoV-2 convalescent plasma or whole blood from 1107 repeat donors from January 2020 to March 2021 was analysed. An automated chemiluminescence immunoassay for total antibodies recognizing the nucleocapsid protein of SARS-CoV-2 in human serum and plasma was performed. Sex, age, blood group, blood cell counts and percentages and immunoglobulin concentrations were extracted from electronic recordings. Blood donation is allowed after a minimum of one-month post symptom's relapse. Donors were 69.7% males and their average age was 46. The 250 donors who had later donations after a positive one underwent further analysis. Both qualitative (positivity) and quantitative (rise or decline of optical density regarding consecutive donations) outcomes were evaluated.Results and discussionIn 97.6% of donors with follow-up, anti-SARS-CoV-2 protein N total antibodies remained positive at the end of a follow-up period of 12.4 weeks median time (1-46, SD = 9.65) after the first positive determination. The blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils would help predict future waning or decay of antibodies. Most recovered donors maintain their total anti-SARS-CoV-2 N protein antibodies for at least 16 weeks (at least one month must have been awaited from infection resolution to blood donation). The 10 individuals that could be followed up longer than 40 weeks (approximately 44 weeks after symptom's relapse) were all still positive.
| S-EPMC8870513 | biostudies-literature
Project description:We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14-104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.
| S-EPMC7760522 | biostudies-literature