Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination

BackgroundEvidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population.MethodsMembers 18–39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0–7 days post-vaccination.ResultsFrom December 14, 2020 – January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0–7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5–34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7–64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0–7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02–2.54).ConclusionsBoth vaccines were associated with increased risk of myocarditis and pericarditis in 18–39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.     

Reactogenicity within 2 weeks after mRNA COVID-19 vaccines: Findings from the CDC v-safe surveillance system

BackgroundPost-authorization monitoring of mRNA-based COVID-19 vaccines is needed to better characterize their reactogenicity. We assessed reactions reported during the 2 weeks after receipt of BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) vaccines.MethodsWe monitored persons who enrolled in v-safe after vaccination health checker^SM, a U.S. smartphone-based vaccine monitoring system, after receiving BNT162b2 or mRNA-1273. V-safe participants received text message prompts to complete web-based surveys. We analyzed responses from persons who received BNT162b2 or mRNA-1273 from December 14, 2020 through March 14, 2021 and completed at least one survey by March 28, 2021. We measured the proportion of participants reporting local and systemic reactions solicited in surveys completed days 0 through 7 post-vaccination. For day 14 surveys, participants described new or worsening symptoms in a free-text response. We assessed the proportion of participants reporting new or worsening local and systemic reactions.ResultsOne-third of participants were aged <45 years, two-thirds were female, and approximately half received BNT162b2 vaccine. A total of 4,717,908 participants reported during the 7 days after dose 1 and 2,906,377 reported during the 7 days after dose 2. Most reported at least one injection-site reaction (68.5% after dose 1; 72.9% after dose 2) or at least one systemic reaction (50.6% after dose 1; 69.5% after dose 2). Reactogenicity was greater after dose 2 and among mRNA-1273 recipients, persons aged <45 years, and females. New or worsening local and systemic reactions were uncommon during week 2 after either dose; the most frequent were local reactions for dose 1 mRNA-1273 recipients (2.6%). These reactions were reported more often among females after dose 1 mRNA-1273 (3.6%).ConclusionsDuring post-authorization monitoring among >4 million vaccinees, local and systemic reactions were commonly reported following mRNA-based vaccines. Reactions were most common during the first week following dose 2 and among persons aged <45 years, females, and mRNA-1273 recipients.     

Humoral immune response characterization of heterologous prime-boost vaccination with CoronaVac and BNT162b2

BackgroundVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven to be a successful strategy for prevent severe infections. CoronaVac and BNT162b2 are the most used vaccines worldwide, but their use in heterologous vaccination schedules is still subjected to evaluation.MethodsFifty healthy individuals who received heterologous prime-boost vaccination with CoronaVac and BNT162b2 were enrolled in a post-vaccination serological follow-up longitudinal prospective study. We evaluated specific serum anti-receptor binding domain (RBD) IgG antibody levels, and their capacity to block RBD-ACE2 interaction with a surrogate neutralization assay. In 20 participants, we assessed antibody binding kinetics by surface plasmon resonance, and Fc-mediated functions by ADCC and ADCP reporter assays.ResultsOur baseline seronegative cohort, displayed seroconversion after two doses of CoronaVac and an important decrease in serum anti-RBD IgG antibodies levels 80 days post-second dose. These levels increased significantly early after the third dose with BNT162b2, but 73 days after the booster we found a new fall. Immunoglobulin functionalities showed a similar behavior.ConclusionsThe heterologous prime-boost vaccination with CoronaVac and BNT162b2 generated an impressive increase in serum anti-RBD specific antibody levels followed by a drop. Nevertheless, these titers remained well above those found in individuals only vaccinated with CoronaVac in the same elapsed time. Serum IgG levels showed high correlation with antibody binding analysis, their capacity to block RBD-ACE2 interaction, and Fc-effectors mechanisms. Our work sheds light on the humoral immune response to heterologous vaccination with CoronaVac and BNT162b2, to define a post-vaccination correlate of protection against SARS-CoV-2 infection and to discuss the scheduling of future vaccine boosters in general population.     

Myocarditis and/or pericarditis risk after mRNA COVID-19 vaccination: A Canadian head to head comparison of BNT162b2 and mRNA-1273 vaccines

BackgroundCanadian and international data suggest the risk of myocarditis and/or pericarditis is elevated during the week after mRNA COVID-19 vaccination, particularly in younger age groups, in males, and after second doses.ObjectivesThis article examines whether there is a product-specific difference in the risk for myocarditis and/or pericarditis between the two mRNA vaccines administered in Canada: BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax).Materials and methodsReporting rates of myocarditis and/or pericarditis were calculated from reports received by the Canadian Adverse Events Following Immunization Surveillance System from December 2020-March 2022. Excess cases and attributable incidence among individuals aged 18–39 were estimated for each vaccine in comparison with background rates from 2015 to 2019. Head-to-head comparisons used Poisson regression, conditioned on week of vaccine administration, to estimate rate ratios for the week after mRNA-1273 vaccination versus the week after BNT162b2, by age and sex as well as overall. Analyses were restricted to May 30–March 13, 2021, when heightened media awareness was unlikely to have affected reporting rates for the two products differentially.ResultsIn 18–29 year-old males who received a second dose of mRNA COVID-19 vaccine, attributable risk of myocarditis and/or pericarditis was found to be 5.69 (95% CI: 4.07 – 7.95; p < 0.001) times higher among mRNA-1273 recipients (n = 106) as compared to BNT162b2 recipients (n = 33). In the same group, Poisson regression modelling estimated that the risk of myocarditis and/or pericarditis was 4.72 (p-value = <0.001) times higher after mRNA-1723 compared to BNT162b2 vaccination.ConclusionsThe risk of myocarditis and/or pericarditis is higher after mRNA-1723 vaccination than BNT162b2 vaccination in those aged 18–39 years, especially in males aged 18–29 years, where the risk is several times higher.     

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

BackgroundAlthough several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays.MethodsThis prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20–64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays.ResultsAmong the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively.ConclusionsTwo BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.     

COVID-19 mRNA BNT162b2 vaccine immunogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS)

We conducted a prospective cohort study of 20 patients with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS group, median age seven years, 70% male) and 34 healthy controls without such a history (CONTROL group, median age eight years, 38% male) aged 5–12 years, to assess the immunogenicity of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®). Patients received two doses of COVID-19 mRNA BNT162b2 vaccine (10 ug/dose) 21 days apart. Pre-vaccine anti-S SARS-CoV-2 IgG antibodies were measured on the day of the first dose and at the median of 23 days after the second dose. The study was conducted during the COVID-19 wave dominated by the Omicron variant of the virus. Anti-NCP SARS-CoV-2 IgG antibodies were measured twice to evaluate incidents of infection during the study period. Pre-vaccine quantification of both types of antibodies allowed us to differentiate patients into COVID-19 naive and previously infected in order to compare hybrid immunity with vaccine-induced immunity.Before vaccination, anti-S IgG serum geometric mean concentration (GMC) was 61.17 BAU/ml in the PIMS group and 24.97 in the CONTROL group, while post-vaccination GMC was 3879.14 BAU/ml and 3704.87 BAU/ml, respectively, and did not significantly differ between the groups. Hybrid immunity (regardless of PIMS history) resulted in a higher concentration of SARS-CoV-2 anti-S antibodies after vaccination. Four (20%) of the children in the PIMS group and 11 (32%) in the CONTROL group got infected with SARS-CoV-2 during the study period, yet all of them asymptomatically, and this event has not significantly altered post-vaccination anti-S titers.In conclusion, COVID-19 vaccination was highly immunogenic in children, including those with a history of PIMS-TS; hybrid immunity overperforms vaccine-induced immunity in terms of serological response in children. However, vaccination effectiveness in preventing SARS-CoV-2 infections in children should be further evaluated.     

Vaccine effectiveness against onward transmission of SARS-CoV2-infection by variant of concern and time since vaccination,Belgian contact tracing, 2021

BackgroundDuring the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-‘variant of concern’ (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment.MethodsWe estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event.FindingsVET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0–50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72–64%) and especially of VEi (71–46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150–200 days after vaccination). We observed lower initial VEi in the age group 65–84 years (32% vs 46% in the age group 45–64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity.InterpretationVEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.     

A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine

BackgroundVaccines are urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the safety and immunogenicity of vaccine candidate mRNA-1273, encoding the prefusion-stabilized spike protein of SARS-CoV-2.MethodsThis phase 2, randomized, observer-blind, placebo-controlled trial was conducted at 8 sites in the USA, in healthy adults aged ≥18 years with no known history or risk of SARS-CoV-2 infection, and had not previously received an investigational CoV vaccine or treatment. Participants were stratified into two age cohorts (≥18-<55 and ≥55) and were randomly assigned (1:1:1) to either 50 or 100 µg of mRNA-1273, or placebo administered as two intramuscular injections 28 days apart. The primary outcomes were safety, reactogenicity, and immunogenicity assessed by anti-SARS-CoV-2-spike binding antibody level (bAb). Secondary outcome was immunogenicity assessed by SARS-CoV-2 neutralizing antibody (nAb) response.ResultsBetween 29 May and 8 July 2020, 600 participants were randomized, 300 per age cohort. The most common solicited adverse reactions were pain at injection site, headache, and fatigue following each vaccination in both age cohorts. One serious adverse event deemed unrelated by the site investigator occurred 33 days post-vaccination one. mRNA-1273 induced bAb and nAb by 28 days post-vaccination one that were higher at the 100 µg dose relative to the 50 µg dose; this difference was less apparent post-vaccination two. Binding antibodies and nAb increased substantially by 14 days following the second vaccination (day 43) to levels exceeding those of convalescent sera and remained elevated through day 57.ConclusionsVaccination with mRNA-1273 resulted in significant immune responses to SARS-CoV-2 in participants 18 years and older, with an acceptable safety profile, confirming the safety and immunogenicity of 50 and 100 µg mRNA-1273 given as a 2 dose-regimen.ClinicalTrials.gov; NCT04405076.     

mRNA-1273 but not BNT162b2 induces antibodies against polyethylene glycol (PEG) contained in mRNA-based vaccine formulations

Two messenger RNA (mRNA)-based vaccines are widely used globally to prevent coronavirus disease 2019 (COVID-19). Both vaccine formulations contain PEGylated lipids in their composition, in the form of polyethylene glycol [PEG] 2000 dimyristoyl glycerol for mRNA-1273, and 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide for BNT162b2. It is known that some PEGylated drugs and products for human use which contain PEG are capable of eliciting immune responses that lead to to detectable PEG-specific antibodies in serum. In this study, we determined if any of the components of mRNA-1273 or BNT162b2 formulations elicited PEG-specific antibody responses in serum by enzyme linked immunosorbent assay (ELISA). We detected an increase in the reactivity to mRNA vaccine formulations in mRNA-1273 but not BNT162b2 vaccinees’ sera in a prime-boost dependent manner. Furthermore, we observed the same pattern of reactivity against irrelevant lipid nanoparticles from an influenza virus mRNA formulation and found that the reactivity of such antibodies correlated well with antibody levels against high and low molecular weight PEG. Using sera from participants selected based on the vaccine-associated side effects experienced after vaccination, including delayed onset, injection site or severe allergic reactions, we found no obvious association between PEG antibodies and adverse reactions. Overall, our data shows a differential induction of anti-PEG antibodies by mRNA-1273 and BNT162b2. The clinical relevance of PEG reactive antibodies induced by administration of the mRNA-1273 vaccine, and the potential interaction of these antibodies with other PEGylated drugs remains to be explored.     

Real-world comparative effectiveness of mRNA-1273 and BNT162b2 vaccines among immunocompromised adults identified in administrative claims data in the United States

IntroductionHead-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences.MethodsThis observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated.ResultsOverall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53 % were female, and baseline immunodeficiencies included prior blood transplant (8%–9%), prior organ transplant (7%), active cancer (12%–13%), primary immunodeficiency (5–6%), HIV (20%–21%), and immunosuppressive therapy use (60%–61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83–27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75–0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67–0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96–4.51) for mRNA-1273 and 4.68 (3.91–5.59) for BNT162b2 (HR, 0.78; 0.59–1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57–0.92) and 0.66 (0.58–0.76), respectively.ConclusionsAmong immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only.Study registrationNCT05366322.     

Immunological responses and adverse reactions of the heterologous second booster dose of BNT162b2 after two-dose CoronaVac for COVID-19 vaccination in healthcare workers of Faculty of Medicine,Naresuan University

BackgroundThe first COVID-19 vaccination campaign in Thailand began in April 2020, with healthcare workers receiving two doses of inactivated COVID-19 vaccine (CoronaVac). However, the emergence of the delta and omicron variants raised concerns about vaccine effectiveness. The Thai Ministry of Public Health provided the first booster dose (third dose) and second booster dose (fourth dose) of the mRNA vaccine (BNT162b2) for healthcare workers. This study investigated the immunity and adverse reactions elicited by a heterologous second booster dose of BNT162b2 after a two-dose CoronaVac vaccination for COVID-19 in healthcare workers of the Faculty of Medicine, Naresuan University.MethodsIgG titres against the SARS-CoV-2-spike protein were measured four and 24 weeks after the second booster dose of BNT162b2 in the study participants. Adverse reactions were recorded during the first three days, four weeks and 24 weeks after the second booster dose of BNT162b2.ResultsIgG against the SARS-CoV-2-spike protein was positive (>10 U/ml) in 246 of 247 participants (99.6 %) at both four and 24 weeks after the second booster dose of BNT162b2. The median specific IgG titres at four and 24 weeks after the second booster dose of BNT162b2 were 299 U/ml (min: 2, max: 29,161) and 104 U/ml (min: 1, max: 17,920), respectively. The median IgG level declined significantly 24 weeks after the second booster dose of the BNT162b2 vaccine. Of the 247 participants, 179 (72.5 %) experienced adverse reactions in the first three days after the second booster dose of BNT162b2. Myalgia, fever, headache, injection site pain and fatigue were the most common adverse reactions.ConclusionThis study demonstrated that a heterologous second booster dose of BNT162b2 after two doses of CoronaVac induced elevated IgG against the SARS-CoV-2-spike protein and caused minor adverse reactions in healthcare workers of the Faculty of Medicine, Naresuan University.This study was registered as Thailand Clinical Trials No. TCTR20221112001.     

Delay between COVID-19 complete vaccination and SARS-CoV-2 infection among healthcare workers

ObjectivesHealthcare workers (HCWs), at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccination, which became mandatory for them on September 15th, 2021 in France. In November they were confronted to the fifth COVID-19 wave despite excellent vaccine coverage. We aimed to estimate the incidence of SARS-CoV-2 infection after complete vaccination among HCWs with different vaccination schemes, and its determinants.MethodsWe enrolled all HCWs in the university hospital of Rennes, France who had received complete vaccination (two doses of COVID-19 vaccine). The delay from last vaccination dose to SARS-CoV-2 infection was computed. Fitted mixed Cox survival model with a random effect applied to exposure risk periods to account for epidemic variation was used to estimate the determinants of SARS-CoV-2 infection after complete vaccination.ResultsOf the 6674 (82%) HCWs who received complete vaccination (36% BNT162b2, 29% mRNA-1273, and 34% mixed with ChAdOx1 nCoV-19) and were prospectively followed-up for a median of 7.0 [6.3–8.0] months, 160 (2.4%) tested positive for SARS-CoV-2 by RT-PCR. Incidence density of SARS-CoV-2 infection after complete vaccination was 3.39 [2.89–3.96] infections per 1000 person-month. Median time from vaccine completion to SARS-CoV-2 infection was 5.5 [3.2–6.6] months. Using fitted mixed Cox regression with the delay as a time-dependent variable and random effect applied to exposure risk periods, age (P < 0.001) was independently associated with the incidence of SARS-CoV-2 infection. Vaccine schemes were not associated with SARS-CoV-2 infection (P = 0.068). A period effect was significantly associated with the incidence of SARS-CoV-2 infection (P < 0.001).ConclusionsIn this real-world study, incidence of SARS-CoV-2 infection increases with time in fully vaccinated HCWs with no differences according to the vaccination scheme. The short delay between complete vaccination and incident SARS-CoV-2 infection highlights the need for sustained barrier measures even in fully vaccinated HCWs.     

Anaphylaxis rates following mRNA COVID-19 vaccination in children and adolescents: Analysis of data reported to EudraVigilance

AimThe present study aimed to estimate the anaphylaxis rates following mRNA COVID-19 vaccination in children and adolescents in Europe.MethodsWe retrieved data on 371 anaphylaxis cases following mRNA COVID-19 vaccination in children ≤ 17 years old notified to EudraVigilance as of October 8, 2022. Overall, 27,120,512 doses of BNT162b2 vaccine and 1,400,300 doses of mRNA-1273 vaccine have been delivered to children during the study period.ResultsThe overall mean anaphylaxis rate was 12.81 [95% confidence interval (CI): 11.49–14.12] per 10⁶ mRNA vaccine doses [12.14 (95% CI: 6.37–17.91) per 10⁶ doses for mRNA-1273 and 12.84 (95% CI: 11.49–14.19) per 10⁶ doses for BNT162b2]. Children 12–17 years old accounted for 317 anaphylaxis cases, followed by 48 cases in children 3–11 years old, and 6 cases in children 0–2 years old. Children 10–17 years old had a mean anaphylaxis rate of 13.52 (95% CI: 12.03–15.00) cases per 10⁶ mRNA vaccine doses and children 5–9 years old had a mean anaphylaxis rate of 9.51 (95% CI: 6.82–12.20) cases per 10⁶ mRNA vaccine doses. There were two fatalities, both in the 12–17 years age group. The fatal anaphylaxis rate was 0.07 cases per 10⁶ mRNA vaccine doses.ConclusionsAnaphylaxis is a rare adverse event after receiving an mRNA COVID-19 vaccine in children. Continuous surveillance of serious adverse events is needed to guide vaccination policies as we move towards SARS-CoV-2 endemicity. Larger real-world studies on COVID-19 vaccination in children, using clinical case confirmation, are imperative.     

Dynamic of anti-spike receptor binding domain (RBD) levels and short-term adverse events following a heterologous booster dose of BNT162b2 after two doses of CoronaVac in Thai health care workers

BackgroundCoronaVac was administered as the primary COVID-19 vaccine for Thai health care workers (HCWs) in early 2021 in response to the epidemic of new variants. This study aimed to evaluate the dynamic of humoral immune response as well as the short-term side effects resulting from the booster dose of BNT162b2 following completion of a CoronaVac double-dose in Thai HCWs.MethodsThis study was conducted at a teaching hospital in Northern Thailand during August and September 2021. The participants were 50 HCWs who were vaccinated with 2 doses of CoronaVac and were scheduled to receive a booster dose of BNT162b2. Anti-SARS-CoV-2 IgG antibodies levels and short-term side effects were assessed. The anti-RBD level was determined using Architect SARS-CoV-2 IgG II Quant (Abbott).ResultOf the 50 participants, 37 were female. The median age was 33.0 years old. The average time between the second CoronaVac shot and the BNT162b2 booster shot was 81.7 days (SD = 25.0). The median anti-SARS-CoV-2 IgG antibody level on booster vaccination date, as well as day 14, and day 28 after the booster were 335.5 AU/ml, 31,613.5 AU/ml, and 20,311.9 AU/ml, respectively. Fourteen days after the booster, 94% of participants had anti-SARS-CoV-2 IgG antibody levels higher than 50.0 AU/ml. Being female, higher log anti-SARS-CoV-2 IgG antibodies prior to booster vaccination, and longer interval between the second shot and the booster shot were found to be significantly associated with higher levels of anti-SARS-CoV-2 IgG antibodies at both day 14 and day 28 after the booster. There were no reports of serious adverse events.ConclusionA booster dose of BNT162B2 promoted a high level of anti-SARS-CoV-2 IgG antibodies among HCWs who received 2 doses of CoronaVac. The time between the second CoronaVac shot and the booster shot should be at least three months. There were no severe adverse effects observed.     

Vaccine-induced humoral response against SARS-CoV-2 dramatically declined but cellular immunity possibly remained at 6 months post BNT162b2 vaccination

To evaluate vaccine-induced humoral and cell-mediated immunity at 6 months after completion of two doses of BNT162b2 vaccination, immunoglobulin G against SARS-CoV-2 spike protein (SP IgG), 50% neutralizing antibody (NT₅₀), and spot-forming cell (SFC) counts were evaluated by interferon-γ releasing ELISpot assay of 98 healthy subjects (median age, 43 years). The geometric mean titers of SP IgG and NT₅₀ decreased from 95.2 (95% confidence interval (CI) 79.8–113.4) to 5.7 (95% CI 4.9–6.7) and from 680.4 (588.0–787.2) to 130.4 (95% CI 104.2–163.1), respectively, at 3 weeks and 6 months after the vaccination. SP IgG titer was negatively correlated with age and alcohol consumption. Spot-forming cell counts at 6 months did not correlate with age, gender, and other parameters of the patients. SP IgG, NT_50, and SFC titers were elevated in the breakthrough infected subjects. Although the levels of vaccine-induced antibodies dramatically declined at 6 months after vaccination, a certain degree of cellular immunity was observed irrespective of the age.     

A heterologous AZD1222 priming and BNT162b2 boosting regimen more efficiently elicits neutralizing antibodies,but not memory T cells,than the homologous BNT162b2 regimen

BackgroundComparative analyses of SARS-CoV-2-specific immune responses elicited by diverse prime-boost regimens are required to establish efficient regimens for the control of COVID-19.MethodIn this prospective observational cohort study, spike-specific immunoglobulin G (IgG) and neutralizing antibodies (nAbs) alongside spike-specific T-cell responses in age-matched groups of homologous BNT162b2/BNT162b2 or AZD1222/AZD1222 vaccination, heterologous AZD1222/BNT162b2 vaccination, and prior wild-type SARS-CoV-2 infection/vaccination were evaluated.ResultsPeak immune responses were achieved after the second vaccine dose in the naïve vaccinated groups and after the first dose in the prior infection/vaccination group. Peak titers of anti-spike IgG and nAb were significantly higher in the AZD1222/BNT162b2 vaccination and prior infection/vaccination groups than in the BNT162b2/BNT162b2 or AZD1222/AZD1222 groups. However, the frequency of interferon-γ-producing CD4⁺ T cells was highest in the BNT162b2/BNT162b2 vaccination group. Similar results were observed in the analysis of polyfunctional T cells. When nAb and CD4⁺ T-cell responses against the Delta variant were analyzed, the prior infection/vaccination group exhibited higher responses than the groups of other homologous or heterologous vaccination regimens.ConclusionnAbs are efficiently elicited by heterologous AZD1222/BNT162b2 vaccination, as well as prior infection/vaccination, whereas spike-specific CD4⁺ T-cell responses are efficiently elicited by homologous BNT162b2 vaccination. Variant-recognizing immunity is more efficiently generated by prior infection/vaccination than the other homologous or heterologous vaccination regimens.     

Protection from Omicron Infection in Residents of Nursing and Retirement Homes in Ontario,Canada

ObjectivesTo identify factors that contribute to protection from infection with the Omicron variant of SARS-CoV-2 in older adults in nursing and retirement homes.DesignLongitudinal cohort study with retrospective analysis of infection risk.Setting and Participants997 residents of nursing and retirement homes from Ontario, Canada, in the COVID in LTC study.MethodsResidents with 3 messenger RNA (mRNA) dose vaccinations were included in the study. SARS-CoV-2 infection was determined by positive nasopharyngeal polymerase chain reaction test and/or circulating antinucleocapsid IgG antibodies. Cumulative probability of Omicron infection after recent COVID-19 was assessed by log-rank test of Kaplan-Meier curves. Cox regression was used to assess risk of Omicron infection by age, sex, mRNA vaccine combination, whether individuals received a fourth dose, as well as recent COVID-19.ResultsIn total, 171 residents (17.2%) had a presumed Omicron variant SARS-CoV-2 infection between December 15, 2021 (local start of the first Omicron wave) and May 3, 2022. Risk of Omicron infection was not different by age [hazard ratio (95% confidence interval) 1.01 (0.99‒1.02)], or in women compared with men [0.97 (0.70‒1.34)], but infection risk decreased 47% with 3 vaccine doses of mRNA-1273 (Moderna) compared with BNT162b2 (Pfizer) [0.53 (0.31-0.90)], 81% with any fourth mRNA vaccine dose [0.19 (0.12‒0.30)], and 48% with SARS-CoV-2 infection in the 3 months prior to beginning of the Omicron wave [0.52, (0.27‒0.99)].Conclusions and ImplicationsVaccine type (ie, mRNA-1273/Spikevax vs BNT162b2/Cominarty), any fourth vaccine dose, and hybrid immunity from recent COVID-19, were protective against infection with the Omicron variant. These data emphasize the importance of vaccine type, and number of vaccine doses, in maintenance of protective immunity and reduction of risk of Omicron variant breakthrough infection. These findings promote continued public health efforts to support vaccination programs and monitor vaccine immunogenicity in older adults.     

T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents

ObjectivesNursing home (NH) residents have been significantly affected by the coronavirus disease 2019 (COVID-19) pandemic. Studies addressing the immune responses induced by COVID-19 vaccines in NH residents have documented a good postvaccination antibody response and the beneficial effect of a third booster vaccine dose. Less is known about vaccine-induced activation of cell-mediated immune response in frail older individuals in the long term. The aim of the present study is to monitor messenger RNA SARS-CoV-2 vaccine-induced T-cell responses in a sample of Italian NH residents who received primary vaccine series and a third booster dose and to assess the interaction between T-cell responses and humoral immunity.DesignLongitudinal cohort study.Setting and ParticipantsThirty-four residents vaccinated with BNT162b2 messenger RNA SARS-CoV-2 vaccine between February and April 2021 and who received a third BNT162b2 booster dose between October and November 2021 were assessed for vaccine-induced immunity 6 (prebooster) and 12 (postbooster) months after the first BNT162b2 vaccine dose.MethodsPre- and postbooster cell-mediated immunity was assessed by intracellular cytokine staining of peripheral blood mononuclear cells stimulated in vitro with peptides covering the immunodominant sequence of SARS-CoV-2 spike protein. The simultaneous production of interferon-γ, tumor necrosis factor-α, and interleukin-2 was measured. Humoral immunity was assessed in parallel by measuring serum concentration of antitrimeric spike IgG antibodies.ResultsBefore the booster vaccination, 31 out of 34 NH residents had a positive cell-mediated immunity response to spike. Postbooster, 28 out of 34 had a positive response. Residents without a previous history of SARS-CoV-2 infection, who had a lower response prior the booster administration, showed a greater increase of T-cell responses after the vaccine booster dose. Humoral and cell-mediated immunity were, in part, correlated but only before booster vaccine administration.Conclusions and ImplicationsThe administration of the booster vaccine dose restored spike-specific T-cell responses in SARS-CoV-2 naïve residents who responded poorly to the first immunization, while a previous SARS-CoV-2 infection had an impact on the magnitude of vaccine-induced cell-mediated immunity at earlier time points. Our findings imply the need for a continuous monitoring of the immune status of frail NH residents to adapt future SARS-CoV-2 vaccination strategies.     

Humoral response to different SARS-CoV-2 vaccines in orthotopic liver transplant recipients

BackgroundThe safety and efficacy data of the different types of available vaccines is still needed. The goal of the present analysis was to evaluate the humoral response to the COVID-19 vaccines in orthotopic liver transplant (OLT) recipients.MethodsParticipants were included from February to September 2021. No prioritized vaccination roll call applied for OLT patients. Controls were otherwise healthy people. Blood samples were drawn after 15 days of the complete vaccine doses. The samples were analyzed according to the manufacturer's instructions using the Liaison XL platform from DiaSorin (DiaSorin S.p.A., Italy), and SARS-COV-2 IgG II Quant (Abbott Diagnostics, IL, USA).ResultsA total of 187 participants (133 OLT, 54 controls, median age: 60 years, 58.8% women) were included for the analysis; 74.3% had at least one comorbidity. The serologic response in OLT patients was lower than in controls (median 549 AU/mL vs. 3450 AU/mL, respectively; p = 0.001). A positive humoral response was found in 133 OLT individuals: 89.2% with BNT162b2 (Pfizer-BioNTech), 60% ChAdOx1 nCOV-19 (Oxford-AstraZeneca), 76.9% with CoronaVac (Sinovac, Life Sciences, China), 55.6% Ad5-nCov (Cansino, Biologics), 68.2% Gam-COVID-Vac (Sputnik V) and 100% with mRNA-1273. In controls the serological response was 100%, except for Cansino (75%). In a multivariable model, personal history of COVID-19 and BNT162b2 inoculation were associated with the serologic response, while the use of prednisone (vs. other immunosuppressants) reduced this response.ConclusionThe serologic response to COVID-19 vaccines in OLT patients is lower than in healthy controls. The BNT162b2 vaccine was associated with a higher serologic response.