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.     

Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older

BackgroundMonitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public.MethodsWe evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination.FindingsFour outcomes met the threshold for a statistical signal following BNT162b2 vaccination including pulmonary embolism (PE; RR = 1.54), acute myocardial infarction (AMI; RR = 1.42), disseminated intravascular coagulation (DIC; RR = 1.91), and immune thrombocytopenia (ITP; RR = 1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the mRNA-1273 or Ad26 COV2.S vaccines.InterpretationThis early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following BNT162b2 vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.     

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.     

Risk Factors Associated With SARS-CoV-2 Breakthrough Infections in Fully mRNA-Vaccinated Individuals: Retrospective Analysis

BackgroundCOVID-19 messenger RNA (mRNA) vaccines have demonstrated efficacy and effectiveness in preventing symptomatic COVID-19, while being relatively safe in trial studies. However, vaccine breakthrough infections have been reported.ObjectiveThis study aims to identify risk factors associated with COVID-19 breakthrough infections among fully mRNA-vaccinated individuals.MethodsWe conducted a series of observational retrospective analyses using the electronic health records (EHRs) of the Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York City (NYC) adult residences with at least 1 polymerase chain reaction (PCR) record were included in this analysis. Poisson regression was performed to assess the association between the breakthrough infection rate in vaccinated individuals and multiple risk factors—including vaccine brand, demographics, and underlying conditions—while adjusting for calendar month, prior number of visits, and observational days in the EHR.ResultsThe overall estimated breakthrough infection rate was 0.16 (95% CI 0.14-0.18). Individuals who were vaccinated with Pfizer/BNT162b2 (incidence rate ratio [IRR] against Moderna/mRNA-1273=1.66, 95% CI 1.17-2.35) were male (IRR against female=1.47, 95% CI 1.11-1.94) and had compromised immune systems (IRR=1.48, 95% CI 1.09-2.00) were at the highest risk for breakthrough infections. Among all underlying conditions, those with primary immunodeficiency, a history of organ transplant, an active tumor, use of immunosuppressant medications, or Alzheimer disease were at the highest risk.ConclusionsAlthough we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Immunocompromised and male individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2 pandemic, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.     

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.     

Comparative effectiveness of four COVID-19 vaccines,BNT162b2 mRNA,mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection

BackgroundThere is limited data directly comparing the effectiveness of different COVID-19 vaccines.MethodsWe compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14–63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics.ResultsAs a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82–1.30), 1.19 (0.95–1.49), 1.70 (1.46–1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00–1.04), 1.20 (1.10–1.32), 1.39 (1.20–1.60).ConclusionsOur findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.     

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.     

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.     

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.     

Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: A prospective observational cohort study

BackgroundData on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population.MethodsWe conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals.ResultsWe included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021–12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8–58.9 %), 83.0 % (75.4–88.3 %), and 87.1 % (30.6–97.6 %), respectively.ConclusionThree doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations.     

Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults

BackgroundRisk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0–7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs.MethodsWe conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0–7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories.ResultsFollow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0–7 following dose 2 was not common among case-patients or controls.ConclusionsHistory of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.     

Safety and immunogenicity of homologous versus heterologous booster dose with AZD1222, mRNA-1273, or MVC-COV1901 SARS-CoV-2 vaccines in adults: An observer-blinded,multi-center,phase 2 randomized trial

ObjectivesTo report the safety and immunogenicity profile of a protein subunit vaccine (MVC-COV1901) compared to AZD1222 and mRNA-1273 when given as a third (booster) dose to individuals who have completed different primary vaccine regimens.MethodsIndividuals were classified according to their primary vaccine regimens, including two-dose MVC-COV1901, AZD1222, or mRNA-1273. A third dose of either half-dose MVC-COV1901, full-dose MVC-COV1901, standard-dose AZD1222, half-dose mRNA-1273 was administered in a 1:1:1:1 treatment ratio to individuals with an interval range of 84–365 days after the second dose. Endpoints included safety, humoral immunogenicity, and cell-mediated immune response on trial days 15 and 29. Exploratory endpoint included testing against variants of concern (Omicron).ResultsOverall, 803 participants were randomized and boosted − 201 received half-dose MVC-COV1901, 196 received full-dose MVC-COV1901, 203 received AZD1222, and 203 received half-dose mRNA-1273. Reactogenicity was mild to moderate, and less in the MVC-COV1901 booster group. Heterologous boosting provided the best immunogenic response. Boosting with mRNA-1273 in MVC-COV1901 primed individuals induced the highest antibody titers, even against Omicron, and cell-mediated immune response.ConclusionsOverall, MVC-COV1901 as a booster showed the best safety profiles. MVC-COV1901 as a primary series, with either homologous or heterologous booster, elicited the highest immunogenic response.ClinicalTrials.gov registration NCT05197153     

Safety of simultaneous vaccination with COVID-19 vaccines in the Vaccine Safety Datalink

IntroductionSafety data on simultaneous vaccination (SV) with primary series monovalent COVID-19 vaccines and other vaccines are limited. We describe SV with primary series COVID-19 vaccines and assess 23 pre-specified health outcomes following SV among persons aged ≥5 years in the Vaccine Safety Datalink (VSD).MethodsWe utilized VSD’s COVID-19 vaccine surveillance data from December 11, 2020-May 21, 2022. Analyses assessed frequency of SV. Rate ratios (RRs) were estimated by Poisson regression when the number of outcomes was ≥5 across both doses, comparing outcome rates between COVID-19 vaccinees receiving SV and COVID-19 vaccinees receiving no SV in the 1–21 days following COVID-19 vaccine dose 1 and 1–42 days following dose 2 by SV type received (“All SV”, “Influenza SV”, “Non-influenza SV”).ResultsSV with COVID-19 vaccines was not common practice (dose 1: 0.7 % of 8,455,037 persons, dose 2: 0.3 % of 7,787,013 persons). The most frequent simultaneous vaccines were influenza, HPV, Tdap, and meningococcal. Outcomes following SV with COVID-19 vaccines were rare (total of 56 outcomes observed after dose 1 and dose 2). Overall rate of outcomes among COVID-19 vaccinees who received SV was not statistically significantly different than the rate among those who did not receive SV (6.5 vs. 6.8 per 10,000 persons). Statistically significant elevated RRs were observed for appendicitis (2.09; 95 % CI, 1.06–4.13) and convulsions/seizures (2.78; 95 % CI, 1.10–7.06) in the “All SV” group following dose 1, and for Bell’s palsy (2.82; 95 % CI, 1.14–6.97) in the “Influenza SV” group following dose 2.ConclusionCombined pre-specified health outcomes observed among persons who received SV with COVID-19 vaccine were rare and not statistically significantly different compared to persons who did not receive SV with COVID-19 vaccine. Statistically significant adjusted rate ratios were observed for some individual outcomes, but the number of outcomes was small and there was no adjustment for multiple testing.     

Vaccine-induced seroconversion in participants in the North Carolina COVID-19 community Research Partnership

Well-regulated clinical trials have shown FDA-approved COVID-19 vaccines to be immunogenic and highly efficacious. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an mRNA COVID-19 vaccine in a cohort study of nearly 8000 adults residing in North Carolina to validate immunogenicity using a novel approach: at-home, participant administered point-of-care testing. Overall, 91.4% had documented seroconversion within 75 days of first vaccination (median: 31 days). Participants who were older and male participants were less likely to seroconvert (adults aged 41–65: adjusted hazard ratio [aHR] 0.69 [95% confidence interval (CI): 0.64, 0.73], adults aged 66–95: aHR 0.55 [95% CI: 0.50, 0.60], compared to those 18–40; males: aHR 0.92 [95% CI: 0.87, 0.98], compared to females). Participants with evidence of prior infection were more likely to seroconvert than those without (aHR 1.50 [95% CI: 1.19, 1.88]) and those receiving BNT162b2 were less likely to seroconvert compared to those receiving mRNA-1273 (aHR 0.84 [95% CI: 0.79, 0.90]). Reporting at least one new symptom after first vaccination did not affect time to seroconversion, but participants reporting at least one new symptom after second vaccination were more likely to seroconvert (aHR 1.11 [95% CI: 1.05, 1.17]). This data demonstrates the high community-level immunogenicity of COVID-19 vaccines, albeit with notable differences in older adults, and feasibility of using at-home, participant administered point-of-care testing for community cohort monitoring.Trial registration: ClinicalTrials.gov NCT04342884.     

Safety of co-administration of mRNA COVID-19 and seasonal inactivated influenza vaccines in the vaccine adverse event reporting system (VAERS) during July 1, 2021–June 30, 2022

BackgroundCOVID-19 vaccines may be co-administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines.ObjectiveTo describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of mRNA COVID-19 and seasonal influenza vaccines.MethodsWe searched the VAERS database for reports of adverse events (AEs) following co-administration of mRNA COVID-19 and seasonal influenza vaccines and following a first booster dose mRNA COVID-19 vaccine alone, during July 1, 2021–June 30, 2022. We assessed the characteristics of these reports and described the most frequently reported MedDRA preferred terms (PTs). Clinicians reviewed available medical records for serious reports and reports of adverse events of special interest (AESI) and categorized the main diagnosis by system organ class.ResultsFrom July 1, 2021 through June 30, 2022, VAERS received 2,449 reports of adverse events following co-administration of mRNA COVID-19 and seasonal influenza vaccines. Median age of vaccinees was 48 years (IQR: 31, 66); 387 (15.8%) were classified as serious. Most reports (1,713; 69.3%) described co-administration of a first booster dose of an mRNA COVID-19 vaccine with seasonal influenza vaccine. The most common AEs among non-serious reports were injection site reactions (193; 14.5%), headache (181; 13.6%), and pain (171; 12.8%). The most common AEs among reports classified as serious were dyspnea (38; 14.9%), COVID-19 infection (32; 12.6%), and chest pain (27; 10.6%).DiscussionThis review of reports to VAERS following co-administration of mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19 disease) was expected. CDC will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines, including co-administration involving bivalent mRNA COVID-19 booster vaccines that have been recommended for people ages ≥ 6 months in the United States.     

A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report

IntroductionThe mRNA vaccine, mRNA-1273/TAK-919, encodes the prefusion-stabilised spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report interim results of the first study evaluating safety and immunogenicity of mRNA-1273 in healthy Japanese participants.MethodsThis phase 1/2, randomised, observer-blind, placebo-controlled trial, conducted in Japan (two sites), enrolled healthy adults aged ≥ 20 years with no prior exposure to investigational coronavirus vaccines/treatments, and no known history/risk of SARS-CoV-2 infection. Participants were stratified by age (< 65/≥ 65 years) and randomised to receive two doses of 100 μg mRNA-1273 or placebo administered as intramuscular injections 28 days apart. Primary outcomes were safety and immunogenicity assessed by anti-SARS-CoV-2-spike protein-binding antibody level (bAb). A secondary outcome was SARS-CoV-2 neutralising antibody (nAb) response.ResultsParticipants were enrolled between 21 January and 3 February 2021, and 200 were randomised: mRNA-1273, n = 150 (< 65 years, n = 100; ≥ 65 years, n = 50); placebo, n = 50 (< 65 years, n = 40; ≥ 65 years, n = 10). Solicited adverse events (AEs) through 7 days after each vaccination occurred in 144/150 (96%) and 19/50 (38%) participants in the mRNA-1273 and placebo arms, respectively. In the mRNA-1273 arm, injection-site pain, myalgia and fatigue were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with mRNA-1273 (n = 147) with a bAb geometric mean fold rise (95% confidence interval [CI]) from baseline of 1009 (865, 1177) and a nAb of 21.7 (19.8, 23.8) at day 57. Seroconversion rates (95% CI) for bAb and nAb were both 100% (97.5, 100) at day 57. No such response occurred with placebo (n = 49).ConclusionTwo doses of 100 μg mRNA-1273 given 28 days apart demonstrated an acceptable safety profile and induced significant anti-SARS-CoV-2 immune responses in a Japanese population aged ≥ 20 years. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov: NCT04677660.     

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.     

Factors associated with receipt of mRNA-1273 vaccine at a United States national retail pharmacy during the COVID-19 pandemic

IntroductionThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted accelerated vaccine development of novel messenger RNA (mRNA)-based vaccines by Moderna and Pfizer, which received FDA Emergency Use Authorization in December 2020. The purpose of this study was to examine trends in primary series administration and multi-dose completion rates with Moderna’s mRNA-1273 vaccine administered at a United States retail pharmacy.MethodsWalgreens pharmacy data were joined to publicly available data sets to examine trends in mRNA-1273 primary series and multi-dose completion across patient race/ethnicity, age, gender, distance to first vaccination, and community characteristics. Eligible patients received their first dose of mRNA-1273 administered by Walgreens between December 18, 2020 and February 28, 2022. Variables significantly associated with on-time second dose (all patients) and third dose (immunocompromised patients) in univariate analyses were included in linear regression models. A subset of patients in selected states were studied to identify differences in early and late vaccine adoption.ResultsPatients (N = 4,870,915) who received ≥ 1 dose of mRNA-1273 were 57.0% White, 52.6% female, and averaged 49.4 years old. Approximately 85% of patients received a second dose during the study period. Factors associated with on-time second dose administration included older age, race/ethnicity, traveling ≤ 10 miles for the first dose, higher community-level health insurance, and residing in areas with low social vulnerability. Only 51.0% of immunocompromised patients received the third dose as recommended. Factors associated with third dose administration included older age, race/ethnicity, and small-town residence. Early adopters accounted for 60.6% of patients. Factors associated with early adoption included older age, race/ethnicity, and metropolitan residence.ConclusionOver 80% of patients received their on-time second dose of mRNA-1273 vaccine per CDC recommendations. Patient demographics and community characteristics were associated with vaccine receipt and series completion. Novel approaches to facilitate series completion during a pandemic should be further studied.     

Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years

BackgroundActive monitoring of safety outcomes following COVID-19 vaccination is critical to understand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure trials. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals.MethodsWe evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12–64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively. We conducted biweekly or monthly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination.FindingsAmong 17 outcomes evaluated, 15 did not meet the threshold for statistical signal in any of the three databases. Myocarditis/pericarditis met the statistical threshold for a signal following BNT162b2 in two of three databases (RRs: 1.83–2.47). Anaphylaxis met the statistical threshold for a signal in all three databases following BNT162b2 vaccination (RRs: 4.48–10.86) and mRNA-1273 vaccination (RRs: 7.64–12.40).DiscussionConsistent with published literature, our near-real time monitoring of 17 adverse outcomes following COVID-19 vaccinations identified signals for myocarditis/pericarditis and anaphylaxis following mRNA COVID-19 vaccinations. The method is intended for early detection of safety signals, and results do not imply a causal effect. Results of this study should be interpreted in the context of the method’s utility and limitations, and the validity of detected signals must be evaluated in fully adjusted epidemiologic studies.