Anti-nucleocapsid Antibodies Research Articles

2080. Reduced risk of SARS-CoV-2 infection among household contacts with hybrid immunity from recent COVID-19 vaccination and SARS-CoV-2 infection

Abstract Background COVID-19 vaccines reduce the risk of symptomatic SARS-CoV-2 infection, but it is unclear the extent to which vaccines or prior infection reduce the risk of infection in high transmission settings like households. Methods We screened individuals who tested positive for SARS-CoV-2 (index cases) recruited at 7 sentinel testing sites and through a nationwide effort during Sep 2021–Apr 2023. Index cases and their households (HH) were enrolled ≤6 days after the index case’s illness onset. Household contacts (HHC) had daily self-collected nasal swabs or saliva samples tested by RT-PCR for SARS-CoV-2. We determined COVID-19 vaccination status by plausible self-report (with date) or vaccination records, and prior SARS-CoV-2 infection by self-reported prior positive test (with year) or anti-nucleocapsid antibodies assessed at enrollment. We considered HHC with prior COVID-19 and ≥2 COVID-19 vaccine doses as having “hybrid immunity”, and assessed the effects of ≥2 vaccine doses, prior COVID-19, or hybrid immunity on the risk of PCR-confirmed SARS-CoV-2 infection among HHC by GEE Poisson regression adjusted for age of the HHC, recruitment strategy, household density (ppl/bedroom), and enrollment month. Results We included 1,324 HHC (Fig 1); 73% enrolled May–Nov 2022, when Omicron BA.4/5 predominated; 28% were aged < 18 years (Table 1). Most (89%) had some immunity to COVID-19: 54% from vaccination only, 7% from infection only, and 26% from hybrid immunity. Most HHC without immunity to SARS-CoV-2 were children (64%). Of HHCs, 61% became SARS-CoV-2 positive during follow-up. In a model that accounted for all sources of immunity (figure 2), prior vaccination or prior infection alone did not provide significant protection, only HHC with hybrid immunity had significantly reduced risk of infection (adjusted relative risk: 0.80, 95% confidence interval: 0.68, 0.94; Fig 2). The risk of infection was lowest (43%) when the HHC’s last immunizing event (vaccination or infection) occurred ≤6 months before the index case’s illness onset. Eligibility and inclusion of HH contacts in analysis of COVID-19 transmission Figure 1 Table 1 Demographic characteristics of HH contacts by COVID-19 vaccination or prior COVID-19 Figure 2 Adjusted relative risk of infection among HH contacts by COVID-19 vaccination or prior COVID-19 Conclusion The risk of SARS-CoV-2 infection among HHCs continues to be high. While vaccination alone was not effective at preventing SARS-CoV-2 infection, HHCs with hybrid immunity from recent vaccination or prior infection had the lowest risk of infection. Disclosures Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support

The effectiveness of primary series CoronaVac vaccine in preventing COVID-19 illness: A prospective cohort study among healthcare workers in Azerbaijan, May-November 2021.

Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few studies have evaluated the CoronaVac vaccine effectiveness (VE), particularly in Eastern Europe, where the vaccine has been widely used. We conducted a prospective cohort study among HCWs in seven hospitals in Baku, Azerbaijan between May 17 and November 30, 2021, to evaluate primary series (two-dose) CoronaVac VE against symptomatic SARS-CoV-2 infection. Participants completed weekly symptom questionnaires, provided nasopharyngeal swabs for SARS-CoV-2 RT-PCR testing when symptomatic, and provided serology samples at enrollment that were tested for anti-spike and anti-nucleocapsid antibodies. We estimated VE as (1 - hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying exposure, adjusting for hospital and previous SARS-CoV-2 infection status. We enrolled 1582 HCWs. At enrollment, 1040 (66%) had received two doses of CoronaVac; 421 (27%) were unvaccinated. During the study period, 72 PCR-positive SARS-CoV-2 infections occurred; 36/39 (92%) sequenced samples were classified as Delta variants. Primary series VE against COVID-19 illness was 29% (95% CI: -51%; 67%) for the entire analysis period. For the Delta-only period (July 1-November 30, 2021), primary series VE was 19% (95% CI: -81%; 64%). For the entire analysis period, primary series VE was 39% (95% CI: -40%; 73%) for HCWs vaccinated within 14-149 days and 19% (95% CI: -81%; 63%) for those vaccinated ≥150 days. During a period in Azerbaijan characterized by mostly Delta circulation, VE point estimates suggested that primary series CoronaVac protected nearly 1 in 3 HCWs against COVID-19, but 95% confidence intervals were wide, with lower bounds that crossed zero, reflecting the limited precision of our VE estimates. Our findings underscore the need to consider booster doses for individuals who have received the primary series of CoronaVac.

A-365 Carbohydrate-binding Module Proteins to Functionalize Paper for Lateral Flow Applications

Abstract Background Lateral flow (LF) tests have employed nitrocellulose membrane since their introduction. Refinement of nitrocellulose and LF production techniques have led to substantial improvements in reproducibility, sensitivity, clarity, and speed of results. The recent surge in demand for LF tests during the COVID-19 pandemic has drawn increased attention to the consequences of using non-biodegradable or non-recyclable materials in test production, requiring disposal via landfill. The nitrocellulose substrate is a critical component for substitution with an equivalent or superior material to address environmental concerns. Additionally, nitrocellulose and the specific molecular recognition reagents, typically antibodies, contribute significantly to the test cost, and whilst LF tests are less expensive than most other formats, challenges remain with respect to providing affordable tests with adequate performance globally in low resource environments. Despite attempts to substitute cellulose for nitrocellulose, principally for reducing cost and more latterly, environmental impact, cellulose is not widely used due to inferior performance, especially in relation to the clarity and quality of the signal line and reagent requirements. Here, we present preliminary data supporting the use of cellulose membrane (paper) as an alternative substrate to nitrocellulose for LF assays. We demonstrate that cellulose-binding module (CBM)-streptavidin fusion proteins for the immobilisation of capture antibodies on cellulose addresses the performance limitations, yielding sensitivity, clarity and speed of result matching current clinical and industry requirements for a qualitative SARS-CoV-2 antigen LF test. Methods We expressed and purified CBM-streptavidin fusion proteins from E.coli to a purity of >90%. Binding to biotinylated proteins and cellulose material was confirmed. An inhouse SARS-CoV-2 antigen assay was adapted for use with the CBM-streptavidin fusion protein on cellulose material. Using methods compatible with current LF test production, we conjugated and dried down 40nm gold (BBI) with anti-nucleocapsid antibodies (Hytest). The biotinylated anti-nucleocapsid capture antibody was dried down on a separate pad. CBM-streptavidin fusion protein was plotted on Whatman 43 paper at the test line. We evaluated assay performance using SARS-CoV-2 nucleocapsid protein and UV-inactivated SARS-CoV-2 virus (NIBSC) in artificial mucus. We further evaluated accelerated stability of the CBM-paper system at 45°C. Results Plotting of the CBM-fusion protein on the test line (0.3 mg/mL, 1 uL/cm) resulted in a tightly focused line, while the control line antibody, without CBM-fusion protein (1 mg/mL, 1 uL/cm), diffused from its deposition line. Additionally, we were able to substantially reduce the amount of capture antibody needed using the CBM-fusion protein system. The cellulose-based assay exhibited a runtime of 30 minutes and an analytical sensitivity of 10^3 pfu/mL. No significant changes in performance were observed after 9 weeks of incubation at 45°C, representing an approximate accelerated shelf-life of 12 months. Conclusion Our results indicate that paper-based tests match sensitivity, clarity, and speed of current qualitative antigen tests on nitrocellulose, with a shelf-life of at least one year. This preliminary investigation demonstrates the viability of using paper as a replacement for nitrocellulose when coupled with CBM-fusion proteins for antibody immobilisation, offering significantly reduced material cost and environmental impact.

Post-acute sequelae of COVID-19 and longitudinal antibody levels in a community-based cohort.

Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases. The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18-89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete a follow-up questionnaire for PASC symptoms and repeat anti-nucleocapsid testing, and anti-spike antibody testing between July and December 2021. Of 3,917 adults invited to participate, 2260 (57.7%) completed the questionnaire- 1150 cases and 1110 controls. Persistent symptoms were reported in 21.1% of cases, with the most common being shortness of breath, fatigue, and loss of taste or smell. Among 292 cases with asymptomatic infection, >15% reported new fatigue and 8-10% reported new loss of taste/smell, myalgias, or headache. Median anti-nucleocapsid levels in cases decreased from 3.5U to 0.7U over a median follow-up of 8.6 months. Anti-spike antibody levels at 6-7 months post-vaccination in cases were similar to that of controls. More than 1 in 5 patients with COVID-19 infection, including those with mild infection, reported persistent symptoms during follow-up. Both nucleocapsid and spike protein antibody levels decreased within six months following a COVID-19 infection and vaccination.

Repeated COVID-19 vaccination to maximum antibody response yields very low mortality and hospitalisation rates in patients with CLL and MBL.

We analysed COVID-19 infection outcomes of 129/241 chronic lymphocytic leukaemia (CLL) (53.9%) and 22/55 monoclonal B-lymphocytosis (MBL) (40.0%) patients following multiple vaccine doses aiming for maximum measured anti-spike antibody response. Throughout the pandemic to date, there were 8/129 CLL (6.2%) patients hospitalised, with one death (0.8%). No MBL patients were hospitalised or died. CLL patients with COVID-19 had lower anti-spike levels (3778.8 AU/mL) than those without (13 486.8 AU/mL; p = 0.0061). Anti-nucleocapsid antibody was detected in 29.8% within 2 months and 17.5% >6 months. Of COVID-19-infected CLL patients, 47.3% received anti-viral therapy. A multiple vaccine dosing strategy to achieve measured maximum antibody is highly effective in preventing severe COVID-19.

Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia

IntroductionPeople who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine...

Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study.

Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD). Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls. Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03). Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.

Comparison of SARS-CoV-2 seroconversion in children with chronic diseases with healthy children and adults during the first waves of the COVID-19 pandemic.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically diverse, and children have a low risk of developing severe coronavirus disease 2019 (COVID-19). However, children with chronic diseases have a potentially increased risk. We performed a prospective surveillance study with longitudinal serum SARS-CoV-2 anti-nucleocapsid antibody quantification and questionnaires in pediatric tertiary care patients during the first waves of the COVID-19 pandemic (November 2020-September 2021). The results were compared with those of healthy children and adults from the same geographic area. We obtained 525 samples from 362 patients (M/F ratio of 1.3:1; median age of 11.1 years) comprising children with immune-suppressive or immune-modulating drugs (32.9%), inborn errors of immunity (23.5%), type 1 diabetes mellitus (15.2%), and rheumatic diseases (11.9%). A total of 51 (9.7%) samples were seropositive among 37/351 children (10.5%). Seropositivity increased from 5.8% in November-December 2020 to 21.6% in July-September 2021. Compared with adults, a longitudinal analysis revealed reduced seroprevalence but similar kinetics as in children from the same country. Demographic or social variables and disease characteristics did not correlate with seropositivity. Being obese and household contact with COVID-19-infected individuals significantly increased the odds of infection. The majority of seropositive patients had mild symptoms (21/37). One-third were asymptomatic and/or unaware of having COVID-19 (10/37). Four patients (4/37) needed hospitalization, with good clinical outcomes. Although harboring a chronic disease, we observed a low SARS-CoV-2 incidence in a cohort of pediatric tertiary care patients, comparable with healthy children during the first year of the pandemic. Infection was mostly associated with mild symptoms.

Evolution of seroprevalence to SARS-CoV-2 in blood donors in Sarajevo Canton, Federation of Bosnia and Herzegovina: Cross-sectional and longitudinal studies.

Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS-CoV-2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection- and vaccine-induced SARS-CoV-2 antibody response and persistence. We conducted repeated cross-sectional analyses of blood donors aged 18-65 years in Sarajevo Canton in November-December 2020 and 2021. We analyzed serum samples for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. One thousand fifteen participants were included in Phase 1 (November-December 2020) and 1152 in Phase 2 (November-December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2%-21.4%) in Phase 1 to 91.6% (95% CI: 89.8%-93.1%) in Phase 2. Anti-S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p < 0.001), though highest among those who received an mRNA vaccine. At 6months, 78/82 (95.1%) participants maintained anti-spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive, and 33 (56.9%) had completed the primary vaccine series within 6months. Among 11 unvaccinated participants who were not re-infected at 12 months, anti-S IgG declined from median 770.1 (IQR 615.0-1321.7) to 290.8 (IQR 175.7-400.3). Anti-N IgG antibodies waned earlier, from 35.4% seropositive at 6months to 24.1% at 12 months. SARS-CoV-2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID-19 vaccination is vital to strengthening population immunity.

Achievement of sufficient antibody response after a fourth dose of wild-type SARS-CoV-2 mRNA vaccine in nursing home residents.

Infection control during COVID-19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the fourth (second booster) dose of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in nursing home residents have not been fully characterized. This study included 112 individuals: 54 nursing home residents (mean age: 84.4 years; 35 SARS-CoV-2-naive and 19 previously infected) and 58 healthcare workers (mean age: 47.7 years; 25 SARS-CoV-2-naive and 33 previously infected). Antispike and antinucleocapsid antibody responses to messenger RNA vaccination were evaluated using serum samples collected shortly and 5 months after the third dose, and shortly after the fourth dose. The median immunoglobulin G (IgG) level in SARS-CoV-2-naive residents was similar to that in SARS-CoV-2-naive healthcare workers after the fourth dose (24,026.3 vs. 30,328.6 AU/mL, p = .79), whereas after the third dose the IgG level of SARS-CoV-2-naive residents was approximately twofold lower than that in SARS-CoV-2-naive healthcare workers. In residents with previous SARS-CoV-2 infection, timing of infection in relation to vaccination affected the kinetics of antibody responses. Residents infected after the third dose showed the highest IgG levels after the fourth dose among all groups (median: 64,328.8 AU/mL), in contrast to residents infected before initiating vaccination with antibody levels similar to those of SARS-CoV-2-naive residents. Advanced aged nursing home residents, poor responders in the initial SARS-CoV-2 vaccine series, could achieve sufficient antibody responses after the fourth (second booster) vaccination, comparable to those of younger adults.

Association between SARS-CoV-2 Symptoms, Ct Values, and Serological Response in Vaccinated and Unvaccinated Healthcare Personnel.

SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection. Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing. There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP. Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated.

The Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf): Risk Factors and Determinants of Immune Response in Healthcare Workers.

Antibody studies analyze immune responses to SARS-CoV-2 vaccination and infection, which is crucial for selecting vaccination strategies. In the KoCo-Impf study, conducted between 16 June and 16 December 2021, 6088 participants aged 18 and above from Munich were recruited to monitor antibodies, particularly in healthcare workers (HCWs) at higher risk of infection. Roche Elecsys® Anti-SARS-CoV-2 assays on dried blood spots were used to detect prior infections (anti-Nucleocapsid antibodies) and to indicate combinations of vaccinations/infections (anti-Spike antibodies). The anti-Spike seroprevalence was 94.7%, whereas, for anti-Nucleocapsid, it was only 6.9%. HCW status and contact with SARS-CoV-2-positive individuals were identified as infection risk factors, while vaccination and current smoking were associated with reduced risk. Older age correlated with higher anti-Nucleocapsid antibody levels, while vaccination and current smoking decreased the response. Vaccination alone or combined with infection led to higher anti-Spike antibody levels. Increasing time since the second vaccination, advancing age, and current smoking reduced the anti-Spike response. The cumulative number of cases in Munich affected the anti-Spike response over time but had no impact on anti-Nucleocapsid antibody development/seropositivity. Due to the significantly higher infection risk faced by HCWs and the limited number of significant risk factors, it is suggested that all HCWs require protection regardless of individual traits.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 IgG Is Present in the Amniotic Fluid of both Infected and Vaccinated Women at Second Trimester of Pregnancy: A Cohort Study

Introduction: Pregnant women are protected from the complications of COVID-19 infection, thanks to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The benefit of this vaccination to prevent morbidity and mortality in the fetus has not yet been completely elucidated. Our aim was to test the presence of anti-SARS-CoV-2 antibodies in the amniotic fluid during the second trimester of pregnancy and then to compare them to the antibody levels in maternal serum to evaluate their correlation and to improve amniotic fluid immunological characteristics knowledge. Methods: This cohort study took place at the Policlinico G. Martino of Messina from September 2021 to February 2022; 22 pregnant women had amniocentesis: we analyzed serum and amniotic fluid samples of women who contracted the SARS-CoV-2 infection or vaccinated against the same virus within 1 year, and women never infected or vaccinated against it. Amniotic fluids and peripheral blood were collected to evaluate IgG anti-SARS-CoV-2 nucleocapsid and spike S1 protein antibodies. Results: Patients vaccinated had higher S1 receptor-binding domain antibody levels both in amniotic fluid (p < 0.006; mean 68.70; standard deviation [SD] 85.46) and maternal blood (p < 0.005; mean 1,989.86; SD 3,777.15) than unvaccinated women. Anti-nucleocapsid antibodies were present in women who developed COVID infection both in amniotic fluid and maternal blood but not in unvaccinated women. There was a high correlation between the concentrations of anti-spike antibody levels in serum and amniotic fluid of vaccinated women (p < 0.001; R = 1.0) and of anti-nucleocapsid antibody levels in serum and amniotic fluid of women who developed COVID infection (p < 0.001; R = 0.93). Conclusion: Recent studies have shown that SARS-CoV-2 vaccination during pregnancy is safe. Moreover, we can assume that there is an early transplacental antibody transfer after anti-SARS-CoV-2 immunization to protect the fetus, and there is also a high correlation between levels of anti-nucleocapsid antibodies in blood and amniotic fluid of pregnant women previously infected.

The Difference in Anti-nucleocapsid Protein Antibody Responses Between Vaccinated and Unvaccinated Individuals After Asymptomatic, Mild, or Moderate COVID-19 Infection

Ji Yeun Kim, Hye Hee Cha, Ji Soo Kwon, Jun Ho Cha, Choi Young Jang, Hyun Jung Lee, So Yun Lim, Sung-Han Kim. Korean J healthc assoc Infect Control Prev 2023;28:92-8. https://doi.org/10.14192/kjicp.2023.28.1.92

Immune response to COVID-19 vaccination in a population with a history of elevated exposure to per- and polyfluoroalkyl substances (PFAS) through drinking water

BackgroundExposure to per- and polyfluoroalkyl substances (PFAS) has been linked to lower vaccine-induced antibody concentrations in children, while data from adults remains limited and equivocal. Characteristics of PFAS exposure and age at vaccination may modify such effects.ObjectiveWe used the mass administration of novel COVID-19 vaccines to test the hypothesis that prior exposure to environmentally-relevant concentrations of PFAS affect antibody response to vaccines in adolescents and adults.MethodsBetween April and June 2021, 226 participants aged 12–90 years with a history of exposure to PFAS in drinking water and who received an mRNA COVID-19 vaccine participated in our prospective cohort study. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies (IgG) were quantified before the first and second vaccine doses and again at two follow-ups in the following months (up to 103 days post dose 1). Serum PFAS concentrations (n = 39 individual PFAS) were measured once for each participant during baseline, before their first vaccination. The association between PFAS exposure and immune response to vaccination was investigated using linear regression and generalized estimating equation (GEE) models with adjustment for covariates that affect antibody response. PFAS mixture effects were assessed using weighted quantile sum and Bayesian kernel machine regression methods.ResultsThe geometric mean (standard deviation) of perfluorooctane sulfonate and perfluorooctanoic acid serum concentrations in this population was 10.49 (3.22) and 3.90 (4.90) µg/L, respectively. PFAS concentrations were not associated with peak anti-spike antibody response, the initial increase in anti-spike antibody response following vaccination, or the waning over time of the anti-spike antibody response. Neither individual PFAS concentrations nor their evaluation as a mixture was associated with antibody response to mRNA vaccination against COVID-19.Impact statementGiven the importance of understanding vaccine response among populations exposed to environmental contaminants and the current gaps in understanding this relationship outside of early life/childhood vaccinations, our manuscript contributes meaningful data from an adolescent and adult population receiving a novel vaccination.

Prepandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: Systematic review and meta-analysis

ObjectivesTo assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations. MethodsWe performed a systematic review and meta-analysis of studies evaluating prepandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity. ResultsIn total, 26 articles with 156 datasets were eligible, including 3437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-nucleocapsid (14%) and anti-spike antibodies (11%), higher for anti-spike1 (23%), and lower for anti-receptor-binding domain antibodies (7%). Positivity was similar, on average, for immunoglobulin M and immunoglobulin G. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% confidence interval, 12-15% vs 2%, 95% confidence interval 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in settings of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity. ConclusionPrepandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. At the country level, cross-reactivity tracks especially with malaria prevalence.

#4473 PREVALENCE OF POST-COVID-19 CONDITION IN PATIENTS WITH CHRONIC KIDNEY DISEASE, ON DIALYSIS AND LIVING WITH A KIDNEY TRANSPLANT

Abstract Background and Aims The prevalence of post-COVID-19 condition (PCC) is estimated to be 13% in healthy individuals. We analyzed the prevalence and disease burden of PCC in patients with chronic kidney disease (CKD) G4/5, dialysis patients and kidney transplant recipients (KTR). Method Patients participated in the RECOVAC study, in which SARS-CoV-2 antibodies were measured in CKD G4/5, dialysis patients and KTR after the second and third COVID-19 vaccination in the Netherlands. A questionnaire was sent to 4868 participants one year after initial vaccination asking for the presence of long-lasting symptoms after diagnosis in COVID-19 positive patients, or since the start of the pandemic in COVID-19 negative patients. PCC was defined according to the WHO clinical case definition. Blood samples at one month after the second and third vaccination were analysed with anti-RBD IgG ELISA. COVID-19 diagnosis was assessed by questionnaire or positive anti-nucleocapsid IgG antibodies. Logistic regression analysis was used to compare the presence of one or more long-lasting symptoms between COVID-19 positive and negative patients. In COVID-19 positive patients, we likewise identified predictors of PCC by backward selection and estimated the association between log-transformed antibody levels and PCC. Results 2747 patients were included, of which 222 patients with CKD G4/5, 390 dialysis patients and 2135 KTR. PCC was present in 25%, 16%, and 21% of CKD G4/5 patients, dialysis patients and KTR with high or very high symptom burden in 57%, 61% and 71%, respectively. In COVID-19 negative patients, long-lasting symptoms were present in 15%, 13% and 18%, respectively. COVID-19 positive patients (n = 1004) were at higher odds of having one or more long-lasting symptoms compared with COVID-19 negative patients (n = 1743) (OR: 1.33 [1.09–1.61], p = .005). Predictors of PCC were chronic lung disease (adjusted OR 2.04 [1.18#x2013;3.50], p = .01) and hospital/ICU admission (adjusted OR 5.03 [3.22-7.86], p &amp;lt; .001). Log anti-RBD IgG antibody level was negatively associated with PCC (adjusted OR: 0.79 [0.66#x2013;0.94], p = .008). Conclusion Patients with CKD G4/5, dialysis patients and KTR are at risk for PCC with a high symptom burden, especially if antibody levels after COVID-19 vaccination are low.

Assessment of Anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses — fall 2021, Wisconsin

BackgroundUniversity students commonly received COVID-19 vaccinations before returning to U.S. campuses in the Fall of 2021. Given likely immunologic variation among students based on differences in type of primary series and/or booster dose vaccine received, we conducted serologic investigations in September and December 2021 on a large university campus in Wisconsin to assess anti-SARS-CoV-2 antibody levels.MethodsWe collected blood samples, demographic information, and COVID-19 illness and vaccination history from a convenience sample of students. Sera were analyzed for both anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody levels using World Health Organization standardized binding antibody units per milliliter (BAU/mL). Levels were compared across categorical primary COVID-19 vaccine series received and binary COVID-19 mRNA booster status. The association between anti-S levels and time since most recent vaccination dose was estimated by mixed-effects linear regression.ResultsIn total, 356 students participated, of whom 219 (61.5%) had received a primary vaccine series of Pfizer-BioNTech or Moderna mRNA vaccines and 85 (23.9%) had received vaccines from Sinovac or Sinopharm. Median anti-S levels were significantly higher for mRNA primary vaccine series recipients (2.90 and 2.86 log [BAU/mL], respectively), compared with those who received Sinopharm or Sinovac vaccines (1.63 and 1.95 log [BAU/mL], respectively). Sinopharm and Sinovac vaccine recipients were associated with a significantly faster anti-S decline over time, compared with mRNA vaccine recipients (P <.001). By December, 48/172 (27.9%) participants reported receiving an mRNA COVID-19 vaccine booster, which reduced the anti-S antibody discrepancies between primary series vaccine types.ConclusionsOur work supports the benefit of heterologous boosting against COVID-19. COVID-19 mRNA vaccine booster doses were associated with increases in anti-SARS-CoV-2 antibody levels; following an mRNA booster dose, students with both mRNA and non-mRNA primary series receipt were associated with comparable levels of anti-S IgG.

One-Year Follow-Up of Seroprevalence of SARS-CoV-2 Infection and Anxiety among Health Workers of a French Cancer Center: The PRO-SERO-COV Study.

Infection of SARS-CoV-2 among health workers (HWs) in contact with cancer patients has been a major issue since the beginning of the pandemic. We aimed to assess the serological immune status of SARS-CoV-2 infection among these HWs. A prospective cohort study was initiated in the comprehensive cancer center of the Nouvelle-Aquitaine region (NA, France). Volunteer HWs working on March 2020 without active infection or symptoms of COVID-19 completed a self-questionnaire and had a blood test at inclusion, at 3 and 12 months. Positive serological status of SARS-CoV-2 infection was defined by anti-nucleocapsid antibodies and/or IgG anti-spike antibodies, except at 12 months due to vaccine. Half of the HWs were included (N = 517) and 89% were followed for three months (N = 500) and one year (N = 462). Seroprevalence of SARS-CoV-2 infection was 3.5% (95% CI: 1.9-5.1), 6.2% (95% CI: 4.1-8.3), and 10% (95% CI: 7.2-12.7) on June-September 2020, September 2020-January 2021, and June-October 2021, respectively. At 12 months, 93.3% had detectable antibodies with 80% vaccinated in the first three months of vaccine availability. The COVID-19-free policy of the institution, respect for barrier gestures, high and early vaccination of HWs, and low prevalence of SARS-CoV-2 in NA may explain the low rate of seropositivity among the HWs of the Institut Bergonié.

Validation of dried blood spot sampling for detecting SARS-CoV-2 antibodies and total immunoglobulins in a large cohort of asymptomatic young adults

BackgroundDetecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. MethodsWe compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. ResultsBaseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. ConclusionsThis is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.