Abstract
Background
Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited.
Methods
From ...a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription–polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models.
Results
Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766–1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596–4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186–6926) compared with BNT162b2 vaccine (GMT, 2309; 1825–2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766–31 756) after mRNA vaccine dose 1, without further increase after dose 2.
Conclusions
A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product.
One dose of mRNA COVID-19 vaccine after previous SARS-CoV-2 infection produced the highest neutralizing antibody titers; among those without history of infection, 2 doses of mRNA vaccine produced the most robust response.
In a cohort of frontline health care workers, a third dose of an mRNA vaccine provided 91% protection against SARS-CoV-2 infection with the delta variant and 60% against the omicron variant.
Abstract
Background
Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare ...personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history.
Methods
Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model.
Results
Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval CI = 2.2–3.0) in group 2 and 2.9-fold (95% CI = 2.6–3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days interquartile range, 213–246 after dose 2) did not increase significantly after dose 3.
Conclusions
A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.
Among frontline workers, a third dose of messenger RNA vaccine typically elicited a robust humoral immune response. Those with infection <3 months before dose 3 did not have a significant boost in antibody concentrations.
IMPORTANCE: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, ...2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. OBJECTIVE: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. EXPOSURE: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. MAIN OUTCOME AND MEASURES: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase–polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. RESULTS: Of the 2959 participants (47.8% were female; median age, 10.6 years IQR, 8.0-13.2 years; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. CONCLUSION AND RELEVANCE: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the ...relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.
•Effect of serum PFAS on immune response to COVID-19 examined here.•Found relationship between serum PFAS and post-SARS-CoV-2 infection immune response.•High serum PFAS concentration may dampen response to SARS-CoV-2 infection.
Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary ...SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. Methods: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021–August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14–59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. Results: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). Conclusions: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.
Respiratory specimen collection materials shortages hampers severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We compared specimen alternatives and evaluated SARS-CoV-2 RNA ...stability under simulated shipping conditions. We compared concordance of RT-PCR detection of SARS-CoV-2 from flocked midturbinate swabs (MTS) in viral transport media (VTM), foam MTS without VTM, and saliva. Specimens were collected between August 2020 and April 2021 from three prospective cohorts. We compared RT-PCR cycle quantification (
) for Spike (S), Nucleocapsid (N), and the Open Reading Frame 1ab (ORF) genes for flocked MTS and saliva specimens tested before and after exposure to a range of storage temperatures (4-30°C) and times (2, 3, and 7 days). Of 1,900 illnesses with ≥2 specimen types tested, 335 (18%) had SARS-CoV-2 detected in ≥1 specimen; 304 (91%) were concordant across specimen types. Among illnesses with SARS-CoV-2 detection, 97% (95% confidence interval CI: 94-98%) were positive on flocked MTS, 99% (95% CI: 97-100%) on saliva, and 89% (95% CI: 84-93%) on foam MTS. SARS-CoV-2 RNA was detected in flocked MTS and saliva stored up to 30°C for 7 days. All specimen types provided highly concordant SARS-CoV-2 results. These findings support a range of viable options for specimen types, collection, and transport methods that may facilitate SARS-CoV-2 testing during supply and personnel shortages.
Findings from this analysis indicate that (1) self-collection of flocked and foam MTS and saliva samples is feasible in both adults and children, (2) foam MTS with VTM and saliva are both viable and reasonable alternatives to traditional flocked MTS in VTM for SARS-CoV-2 detection, and (3) these sample types may be stored and transported at ambient temperatures for up to 7 days without compromising sample quality. These findings support methods of sample collection for SARS-CoV-2 detection that may facilitate widespread community testing in the setting of supply and personnel shortages during the current pandemic.
Background
We sought to evaluate the impact of changes in estimates of COVID‐19 vaccine effectiveness on the incidence of laboratory‐confirmed infection among frontline workers at high risk for ...SARS‐CoV‐2.
Methods
We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID‐19 by month as well as the association of COVID‐19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self‐collected mid‐turbinate nasal swabs and reported symptoms.
Results
Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory‐confirmed SARS‐CoV‐2 infection in January 2021 was 13.9 (95% confidence interval CI: 10.4–17.4), declining to 0.5 (95% CI ‐0.4‐1.4) per 1000 person‐weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8–19.4) per 1000 person‐weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9–3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID‐19 and vaccinated participants during hours in the community.
Conclusions
COVID‐19 vaccination was significantly associated with a lower risk of SARS‐CoV‐2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.
There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (SARS-CoV-2 infection or COVID-19 vaccination). From a cohort of health care personnel, ...first responders, and other frontline workers in six US states, we examined heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels.
Exposures included event-count (sum of infections and vaccine doses) and event-order, categorized into seven permutations of vaccination and/or infection. Outcome was level of serum binding antibodies against receptor binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding Ig), measured by enzyme-linked immunosorbent assay. Mean antibody levels were examined up to 365 days after each of the 1st-7th events.
Analysis included 5,793 participants measured from August 7, 2020 to April 15, 2023. Hybrid immunity from infection before one or two vaccine doses elicited modestly superior antibody responses after the 2nd and 3rd events (compared to infections or vaccine-doses alone). This superiority was not evident after the 4th and 5th events (additional doses). Among adults infected before vaccination, adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were 1.23 (1.14-1.33), 1.09 (1.03-1.14), 0.87 (0.81-0.94), and 0.99 (0.85-1.15) after the 2nd-5th events, respectively. Post-vaccination infections elicited superior responses: adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated-only) were: 0.93 (0.75-1.17), 1.11 (1.06-1.16), 1.17 (1.11-1.24), and 1.20 (1.07-1.34) after the 2nd-5th events, respectively.
Findings reflecting heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy.
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