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Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels.

ABSTRACT: Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antiviral B cell frequencies were determined by indirect immunofluorescence screening on SARS-CoV-2 infected cells. Surprisingly, frequencies of SARS-CoV-2 specific clones from the two groups were not statistically different, despite higher antibody levels in hospitalized patients. Moreover, functional analyses revealed that several B cell clones from healthcare personnel with low antibody levels had neutralizing properties. This study reveals for the first time a key qualitative defect of antibody synthesis in severe patients and calls for caution regarding estimated protective immunity based only on circulating antiviral antibodies.

SUBMITTER: Coutant F

PROVIDER: S-EPMC8540683 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels.

Coutant Frédéric F Pin Jean-Jacques JJ Morfin-Sherpa Florence F Ferry Tristan T Paul Stéphane S Pozzetto Bruno B Normand Myriam M Miossec Pierre P

International journal of molecular sciences 20211014 20

Individuals with pre-existing chronic systemic low-grade inflammation are prone to develop severe COVID-19 and stronger anti-SARS-CoV-2 antibody responses. Whether this phenomenon reflects a differential expansion of antiviral B cells or a failure to regulate antibody synthesis remains unknown. Here, we compared the antiviral B cell repertoire of convalescent healthcare personnel to that of hospitalized patients with pre-existing comorbidities. Out of 277,500 immortalized B cell clones, antivira ...[more]

PMID: 34681752

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Project description:ImportanceThe factors associated with long-term serum levels of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy individuals have rarely been investigated.ObjectiveTo investigate factors associated with anti-SARS-CoV-2 antibody levels.Design, setting, and participantsThis prospective cohort study included health care workers at Kyungpook National University Chilgok Hospital (Daegu, Korea) with no history of SARS-CoV-2 infection who received 2 doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech; first dose, March 17-20, 2021; second dose, April 7-10, 2021). Serum samples were collected at 2, 4, and 6 months after the second injection.InterventionsSARS-CoV-2 BNT162b2 mRNA vaccine.Main outcomes and measuresAnti-SARS-CoV-2 specific antibodies were measured using enzyme-linked immunosorbent assay kits up to 6 months after the receipt of 2 doses of the BNT162b2 mRNA COVID-19 vaccine. The main outcome was factors associated with anti-SARS-CoV-2 antibody levels at 6 months.ResultsAll 50 participants (mean [SD] age, 34.7 [9.4] years; 10 [20.0%] male; mean [SD] body mass index, 21.8 [5.4]) acquired anti-SARS-CoV-2 antibodies and maintained positive antibody (cutoff ≥30%) up to 6 months. The mean serum antibody level decreased with time (91.9%, 89.3%, and 81.5% at 2, 4, and 6 months, respectively). Serum antibody levels at 6 months were correlated with antibody levels at 2 months (R = 0.944; P < .001). The anti-SARS-CoV-2-specific antibody level was inversely correlated with weight, body mass index, body fat amount, and body weight to height ratio in Spearman correlation analysis. A 1-SD increase in body weight, weight to height ratio, and body mass index was associated with a 4%- to 5%-decrease in anti-SARS-CoV-2 antibodies in multiple linear regression analysis for women. In multivariate analysis for categorized variables, lower serum level of antibody (ie, <81.5%) was associated with weight (weight ≥55 kg: odds ratio, 9.01; 95% CI, 1.44-56.40). The probabilities of less than 70% and less than 80% antibody at 6 months were 0% and 11% in participants weighing less than 55 kg, respectively, but 16% and 42% in participants weighing 55 kg or greater.Conclusions and relevanceIn this study, the inverse correlation of anti-SARS-CoV-2-specific antibody levels with weight was sustained up to 6 months after vaccination. A booster shot of BNT162b2 mRNA vaccination may be given later than 6 months after the second dose in young and middle-aged healthy persons with low body weight.

Project description:ObjectivesThe recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.MethodsThis was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.ResultsOf the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients.DiscussionA third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.

Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and caused a dramatic pandemic. Serological assays are used to check for immunization and assess herd immunity. We evaluated commercially available assays designed to quantify antibodies directed to the SARS-CoV-2 Spike (S) antigen, either total (Wantaï SARS-CoV-2 Ab ELISA) or IgG (SARS-CoV-2 IgG II Quant on Alinity, Abbott, and Liaison SARS-CoV-2 TrimericS IgG, Diasorin). The specificities of the Wantaï, Alinity, and Liaison assays were evaluated using 100 prepandemic sera and were 98, 99, and 97%, respectively. The sensitivities of all three were around 100% when tested on 35 samples taken 15 to 35 days postinfection. They were less sensitive for 150 sera from late infections (>180 days). Using the first WHO international standard (NIBSC), we showed that the Wantai results were concordant with the NIBSC values, while Liaison and Alinity showed a proportional bias of 1.3 and 7, respectively. The results of the 3 immunoassays were significantly globally pairwise correlated and for late infection sera (P < 0.001). They were correlated for recent infection sera measured with Alinity and Liaison (P < 0.001). However, the Wantai results of recent infections were not correlated with those from Alinity or Liaison. All the immunoassay results were significantly correlated with the neutralizing antibody titers obtained using a live virus neutralization assay with the B1.160 SARS-CoV-2 strain. These assays will be useful once the protective anti-SARS-CoV-2 antibody titer has been determined. IMPORTANCE Standardization and correlation with virus neutralization assays are critical points to compare the performance of serological assays designed to quantify anti-SARS-CoV-2 antibodies in order to identify their optimal use. We have evaluated three serological immunoassays based on the virus spike antigen that detect anti-SARS-CoV-2 antibodies: a microplate assay and two chemiluminescent assays performed with Alinity (Abbott) and Liaison (Diasorin) analysers. We used an in-house live virus neutralization assay and the first WHO international standard to assess the comparison. This study could be useful to determine guidelines on the use of serological results to manage vaccination and treatment with convalescent plasma or monoclonal antibodies.

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Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels.

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Impact of Host Immune Status on Discordant Anti-SARS-CoV-2 Circulating B Cell Frequencies and Antibody Levels.

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