Comparison of mRNA vaccine effectiveness against COVID-19-associated hospitalization by vaccination source: Immunization information systems,electronic medical records,and self-report—IVY Network,February 1–August 31, 2022

BackgroundAccurate determination of COVID-19 vaccination status is necessary to produce reliable COVID-19 vaccine effectiveness (VE) estimates. Data comparing differences in COVID-19 VE by vaccination sources (i.e., immunization information systems [IIS], electronic medical records [EMR], and self-report) are limited. We compared the number of mRNA COVID-19 vaccine doses identified by each of these sources to assess agreement as well as differences in VE estimates using vaccination data from each individual source and vaccination data adjudicated from all sources combined.MethodsAdults aged ≥18 years who were hospitalized with COVID-like illness at 21 hospitals in 18 U.S. states participating in the IVY Network during February 1–August 31, 2022, were enrolled. Numbers of COVID-19 vaccine doses identified by IIS, EMR, and self-report were compared in kappa agreement analyses. Effectiveness of mRNA COVID-19 vaccines against COVID-19-associated hospitalization was estimated using multivariable logistic regression models to compare the odds of COVID-19 vaccination between SARS-CoV-2-positive case-patients and SARS-CoV-2-negative control-patients. VE was estimated using each source of vaccination data separately and all sources combined.ResultsA total of 4499 patients were included. Patients with ≥1 mRNA COVID-19 vaccine dose were identified most frequently by self-report (n = 3570, 79 %), followed by IIS (n = 3272, 73 %) and EMR (n = 3057, 68 %). Agreement was highest between IIS and self-report for 4 doses with a kappa of 0.77 (95 % CI = 0.73–0.81). VE point estimates of 3 doses against COVID-19 hospitalization were substantially lower when using vaccination data from EMR only (VE = 31 %, 95 % CI = 16 %–43 %) than when using all sources combined (VE = 53 %, 95 % CI = 41 %–62%).ConclusionVaccination data from EMR only may substantially underestimate COVID-19 VE.     

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.     

Post-authorization surveillance of adverse events following COVID-19 vaccines in pregnant persons in the vaccine adverse event reporting system (VAERS), December 2020 – October 2021

BackgroundPregnant persons are at increased risk of severe illness from COVID-19 infection, including intensive care unit admission, mechanical ventilation, and death compared with non-pregnant persons of reproductive age. Limited data are available on the safety of COVID-19 vaccines administered during and around the time of pregnancy.ObjectiveTo evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system, in pregnant persons who received a COVID-19 vaccine to assess for potential vaccine safety problems.MethodsWe searched VAERS for US reports of adverse events (AEs) in pregnant persons who received a COVID-19 vaccine from 12/14/2020–10/31/2021. Clinicians reviewed reports and available medical records. Crude reporting rates for selected AEs were calculated, and disproportional reporting was assessed using data mining methods.ResultsVAERS received 3,462 reports of AEs in pregnant persons who received a COVID-19 vaccine; 1,831 (52.9%) after BNT162b2, 1,350 (38.9%) after mRNA-1273, and 275 (7.9%) after Ad26.COV2.S. Eight maternal deaths and 12 neonatal deaths were reported. Six-hundred twenty-one (17.9%) reports were serious. Pregnancy-specific outcomes included: 878 spontaneous abortions (<20 weeks), 101 episodes of vaginal bleeding, 76 preterm deliveries (<37 weeks), 62 stillbirths (≥20 weeks), and 33 outcomes with birth defects. Crude reporting rates for preterm deliveries and stillbirths, as well as maternal and neonatal mortality rates were below background rates from published sources. No disproportional reporting for any AE was observed.ConclusionsReview of reports to VAERS following COVID-19 vaccines in pregnant persons did not identify any concerning patterns of maternal or infant-fetal outcomes.     

Intussusception among Norwegian children: What to expect after introduction of rotavirus vaccination?

BackgroundTo reduce the risk of vaccine-associated intussusception, rotavirus vaccination in Norway was implemented under strict age limits (the first dose given by 12 weeks of age and the second dose by 16 weeks of age) in 2014. We estimated the incidence of intussusception in children <2 years old before vaccine introduction and the number of vaccine-associated cases under current and extended age limits for vaccine administration in Norway.MethodsTo estimate the baseline incidence, we validated all diagnoses in children <2 years old registered in the national hospital registry during the pre-vaccine period of 2008–2013. Using national vaccine coverage data and international estimates of intussusception risk after rotavirus vaccination, we calculated the numbers of expected vaccine-associated intussusception cases to compare with the estimated numbers of averted rotavirus cases. Uncertainty was accounted for by several scenario analyses using current and extended age limits for vaccine administration.ResultsThe pre-vaccine incidence of intussusception was 26.7 (95% CI 23.1–30.6) cases/year per 100,000 children <2 years old and 37.1 (95% CI 31.2–43.8) cases/year per 100,000 children <1 year old. In the 2016 birth cohort (approx. 60,000) vaccinated under the current age limits, 1.3 (95% CI 0.7–2.0) vaccine-associated intussusception cases were expected to occur. If age limits were extended to 16 weeks for the first vaccine dose and 24 weeks for the second dose, leading to more children vaccinated at an older age, 2.2 (95% CI 1.2–3.5) excess cases would be expected in the same cohort. Simultaneously, an estimated 1768 rotavirus hospitalizations/year in children <5 years old would be averted under current age limits, with 98 additional rotavirus hospitalizations averted under extended age limits.ConclusionsAdministering rotavirus vaccines beyond current age limits in Norway would lead to a marginal increase in the number of intussusception cases, which would be offset by the benefits of vaccination.     

An assessment of the safety of adolescent and adult tetanus–diphtheria–acellular pertussis (Tdap) vaccine,using active surveillance for adverse events in the Vaccine Safety Datalink

Using a new sequential analytic method, the safety of tetanus–diphtheria–acellular pertussis (Tdap) vaccine was monitored weekly among subjects aged 10–64 years during 2005–2008. Encephalopathy–encephalitis–meningitis, paralytic syndromes, seizures, cranial nerve disorders, and Guillain-Barré syndrome were selected as outcomes based on previous reports and biologic plausibility. The risk following Tdap was not significantly higher than the risk after Td. Statistical power was sufficient to detect a relative risk of 4–5 for Guillain-Barré syndrome and 1.5–2 for the other outcomes. This study provides reassurance that Tdap is similar in safety to Td regarding the outcomes studied and supports the viability of sequential analysis for post-licensure vaccine safety monitoring.     

Estimated COVID-19 vaccine effectiveness against seroconversion from SARS-CoV-2 Infection,March–October, 2021

BackgroundMonitoring the effectiveness of COVID-19 vaccines against SARS-CoV-2 infections remains important to inform public health responses. Estimation of vaccine effectiveness (VE) against serological evidence of SARS-CoV-2 infection might provide an alternative measure of the benefit of vaccination against infection.MethodsWe estimated mRNA COVID-19 vaccine effectiveness (VE) against development of SARS-CoV-2 anti-nucleocapsid antibodies in March–October 2021, during which the Delta variant became predominant. Participants were enrolled from four participating healthcare systems in the United States, and completed electronic surveys that included vaccination history. Dried blood spot specimens collected on a monthly basis were analyzed for anti-spike antibodies, and, if positive, anti-nucleocapsid antibodies. We used detection of new anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection, and estimated VE by comparing 154 case-participants with new detection of anti-nucleocapsid antibodies to 1,540 seronegative control-participants matched by calendar period. Using conditional logistic regression, we estimated VE ≥ 14 days after the 2nd dose of an mRNA vaccine compared with no receipt of a COVID-19 vaccine dose, adjusting for age group, healthcare worker occupation, urban/suburban/rural residence, healthcare system region, and reported contact with a person testing positive for SARS-CoV-2.ResultsAmong individuals who completed a primary series, estimated VE against seroconversion from SARS-CoV-2 infection was 88.8% (95% confidence interval [CI], 79.6%–93.9%) after any mRNA vaccine, 87.8% (95% CI, 75.9%–93.8%) after BioNTech vaccine and 91.7% (95% CI, 75.7%–97.2%) after Moderna vaccine. VE was estimated to be lower ≥ 3 months after dose 2 compared with < 3 months after dose 2, and among participants who were older or had underlying health conditions, although confidence intervals overlapped between subgroups.ConclusionsVE estimates generated using infection-induced antibodies were consistent with published estimates from clinical trials and observational studies that used virologic tests to confirm infection during the same period. Our findings support recommendations for eligible adults to remain up to date with COVID-19 vaccination.     

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.     

Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States,Vaccine Adverse Event Reporting System (VAERS), July 1, 2013−May 31, 2015

BackgroundQuadrivalent inactivated influenza vaccines (IIV4) were first available for use during 2013−14 influenza season for individuals aged ≥6 months. IIV4 is designed to protect against four different flu viruses; two influenza A viruses and two influenza B viruses.MethodsWe searched the Vaccine Adverse Event Reporting System (VAERS) for US reports after IIV4 and trivalent inactivated influenza vaccine (IIV3) from 7/1/2013–5/31/2015. Medical records were requested for non-manufacturer reports classified as serious (i.e. death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability). The review included automated data analysis, clinical review of all serious reports, reports of special interest, and empirical Bayesian data mining.ResultsVAERS received 1,838 IIV4 reports; 512 (28%) in persons aged 6 months–17 years of which 42 (8.2%) were serious reports; 1,265 (69%) in persons aged >18 years of which 84 (6.6%) were serious reports; two in children <6 months and 59 in persons of unknown age. Injection site erythema (24%), fever (14%) and injection site swelling (17%) were the most frequent adverse events among persons aged 6 months–17 years, while injection site pain (16%), pain (15%) and pain in extremity (13%) were the most frequent among persons aged 18−64 years given the vaccine alone. Among non-death serious reports, injection site reactions, constitutional symptoms, Guillain-Barré syndrome, seizures, and anaphylaxis were the most frequently reported adverse events. Data mining detected disproportional reporting for incorrect vaccine administration with no associated adverse events. Adverse events following IIV4 reported to VAERS were similar to those following IIV3.ConclusionsIn our review of VAERS reports, IIV4 had a similar safety profile to IIV3. Most of the reported AEs were non-serious. Our findings are consistent with data from pre-licensure studies of IIV4.