Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink

BackgroundThe Centers for Disease Control and Prevention’s Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study’s objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines.MethodsVSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters.ResultsMore than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10–15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1–10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination.ConclusionsIn this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days.     

Incidence of myopericarditis after mRNA COVID-19 vaccination: A meta-analysis with focus on adolescents aged 12–17 years

BackgroundThe incidence of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12–17 years remains unknown. Therefore, we conducted a study to pool the incidence of myopericarditis following COVID-19 vaccination in this age group.MethodsWe did a meta-analysis by searching 4 electronic databases until February 6, 2023. The following main keywords were used: “COVID-19”, “vaccines”, “myocarditis”, “pericarditis”, and “myopericarditis”. Observational studies reporting on adolescents aged 12–17 years who had myopericarditis in temporal relation to receiving mRNA COVID-19 vaccines were included. The pooled incidence of myopericarditis and 95 % confidence interval (CI) were calculated using a single-group meta-analysis.ResultsFifteen studies were included. The pooled incidences of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12–17 years were 43.5 (95 % CI, 30.8–61.6) cases per million vaccine doses for both BNT162b2 and mRNA-1273 (39 628 242 doses; 14 studies), and 41.8 (29.4–59.4) cases for BNT162b2 alone (38 756 553 doses; 13 studies). Myopericarditis was more common among males (66.0 [40.5–107.7] cases) than females (10.1 [6.0–17.0] cases) and among those receiving the second dose (60.4 [37.6–96.9] cases) than those receiving the first dose (16.6 [8.7–31.9] cases). The incidences of myopericarditis did not differ significantly when grouped by age, type of myopericarditis, country, and World Health Organization region. None of the incidences of myopericarditis pooled in the current study were higher than those after smallpox vaccinations and non-COVID-19 vaccinations, and all of them were significantly lower than those in adolescents aged 12–17 years after COVID-19 infection.ConclusionsThe incidences of myopericarditis after mRNA COVID-19 vaccination among adolescents aged 12–17 years were very rare; they were not higher than other important reference incidences. These findings provide an important context for health policy makers and parents with vaccination hesitancy to weight the risks and benefits of mRNA COVID-19 vaccination among adolescents aged 12–17 years.     

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.     

Evaluation of mortality risk after COVID-19 vaccination,Utah 2021

IntroductionIn order to evaluate trends in death after COVID-19 vaccination we analyzed the timing of death relative to vaccination date and the causes of death in vaccinated Utahns in 2021.MethodsWe matched people in the Utah immunization registry with documented COVID-19 vaccinations between December 18, 2020 and December 31, 2021 to Utah’s 2021 vital statistics death records. Vaccinated people were categorized as having one, two, or ≥ three COVID-19 vaccine doses in a time-updated metric. We examined crude mortality rates by dosing groups in two-week intervals for all deaths, and by COVID-19 versus non-COVID-19 causes, within the 44 weeks following receipt of the most recent vaccine.ResultsWe identified 2,072,908 individuals who received at least one dose of COVID-19 vaccine of whom 10,997 died in 2021. Only 17.5 % of the total vaccinated population was age 65+, while 80.9 % of those who died were over 65. In the four weeks following the first or second vaccination, all-cause mortality was low and then stabilized for the remainder of the evaluation period at a bi-weekly average of 33.0 and 39.0 deaths/100,000 people for one and two doses, respectively. Typical seasonal variation in death was observed among those with two doses. Small sample size precluded analysis of those with ≥ three doses, but trends were similar.ConclusionsMortality rates in the 44 weeks following the COVID-19 vaccination did not show trends suggesting an increase in mortality related to COVID-19 vaccination, reinforcing the safety of COVID-19 vaccines. This represents an accessible approach for local evaluation.     

A post-marketing safety assessment of COVID-19 mRNA vaccination for serious adverse outcomes using administrative claims data linked with vaccination registry in a city of Japan

IntroductionThe safety profiles of COVID-19 vaccines are incompletely evaluated in Japan.ObjectivesTo examine the risk of serious adverse effects after COVID-19 mRNA vaccination (BNT162b2 and mRNA-1273) in cohort studies and self-controlled case series (SCCS).MethodsUsing an administrative claims database linked with the COVID-19 vaccination registry in a city in Japan between September 2020 and September 2021, we identified health insurance enrolees aged ≥ 18 years. We evaluated the risk of acute myocardial infarction, appendicitis, Bell’s palsy, convulsions/seizures, disseminated intravascular coagulation, immune thrombocytopenia, pulmonary embolism, haemorrhagic or ischemic stroke, venous thromboembolism, and all-cause mortality, 21 days following any COVID-19 mRNA vaccination, compared with non-vaccination periods. For the cohort studies, we estimated incidence rate ratios (IRRs) by Poisson regression and rate differences (IRDs) by weighted least-squares regression, adjusting for sex, age, and Charlson comorbidity index. We applied a modified SCCS design to appropriately treat outcome-dependent exposures. For the modified SCCS, we estimated within-subject IRRs by weighted conditional Poisson regression. Subgroup analyses stratified by sex and age were also conducted.ResultsWe identified 184,491 enrolees [male: 87,218; mean (standard deviation) age: 64.2 (19.5) years] with 136,667 first and 127,322 s dose vaccinations. The risks of any outcomes did not increase in any analyses, except for the fact that the modified SCCS indicated an increased risk of pulmonary embolism after the first dose in women (within-subject IRR [95%CI]: 3.97 [1.18–13.32]).ConclusionThe findings suggested that the COVID-19 mRNA vaccine was generally safe, whilst a signal of pulmonary embolism following the first dose of the COVID-19 mRNA vaccine was observed.     

Vasovagal reactions after COVID-19 vaccination in Japan

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10–19 years and 20–29 years, respectively. In individuals aged 10–29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.     

COVID-19 vaccination coverage in patients with chronic obstructive pulmonary disease – A cross-sectional study in Hungary

IntroductionCoronavirus infection is a particular risk for patients with chronic obstructive pulmonary disease (COPD), because they are much more likely to become severely ill due to oxygen supply problems. Primary prevention, including COVID-19 vaccination is of paramount importance in this disease group. The aim of our study was to assess COVID-19 vaccination coverage in COPD patients during the first vaccination campaign of the COVID-19 pandemic.MethodsA cross-sectional observational study (CHANCE) has been conducted in COPD patients in the eastern, western and central regions of Hungary from 15th November 2021. The anthropometric, respiratory function test results and vaccination status of 1,511 randomly selected patients were recorded who were aged 35 years and older.ResultsThe median age was 67 (61–72) years, for men: 67 (62–73) and for women: 66 (60–72) years, with 47.98 % men and 52.02 % women in our sample. The prevalence of vaccination coverage for the first COVID-19 vaccine dose was 88.62 %, whereas 86.57 % of the patients received the second vaccine dose. When unvaccinated (n = 172) and double vaccinated (n = 1308) patients were compared, the difference was significant both in quality of life (CAT: 17 (12–23) vs 14 (10–19); p < 0.001) and severity of dyspnea (mMRC: 2 (2–2) vs 2 (1–2); p = 0.048). The COVID-19 infection rate between double vaccinated and unvaccinated patients was 1.61 % vs 22.67 %; p < 0.001 six months after vaccination. The difference between unvaccinated and vaccinated patients was significant (8.14 % vs 0.08 %; p < 0.001) among those with acute COVID-19 infection hospitalized. In terms of post-COVID symptoms, single or double vaccinated patients had significantly fewer outpatient hospital admissions than unvaccinated patients (7.56 vs 0 %; p < 0.001).ConclusionThe COVID-19 vaccination coverage was satisfactory in our sample. The uptake of COVID-19 vaccines by patients with COPD is of utmost importance because they are much more likely to develop severe complications.     

Reactions following Pfizer-BioNTech COVID-19 mRNA vaccination and related healthcare encounters among 7,077 children aged 5-11 years within an integrated healthcare system

BackgroundStudies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety.MethodsWe conducted an observational study using data from a digital survey and EHR of children aged 5–11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope).ResultsThe study recruited 7,077 participants aged 5–11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising <0.5 % of children. No encounters were related to myocarditis.ConclusionWhile post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5–11 years, our data showed that in most cases they were transient and did not require medical care.     

Neutralization of Omicron subvariants BA.1 and BA.5 by a booster dose of COVID-19 mRNA vaccine in a Japanese nursing home cohort

The sustained epidemic of Omicron subvariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide concern, and older adults are at high risk. We conducted a prospective cohort study to assess the immunogenicity of COVID-19 mRNA vaccines (BNT162b2 or mRNA-1273) in nursing home residents and staff between May 2021 and December 2022. A total of 335 SARS-CoV-2 naïve individuals, including 141 residents (median age: 88 years) and 194 staff (median age: 44 years) participated. Receptor-binding domain (RBD) and nucleocapsid (N) protein IgG and neutralizing titer (NT) against the Wuhan strain, Alpha and Delta variants, and Omicron BA.1 and BA.5 subvariants were measured in serum samples drawn from participants after the second and third doses of mRNA vaccine using SARS-CoV-2 pseudotyped virus. Breakthrough infection (BTI) was confirmed by a notification of COVID-19 or a positive anti-N IgG result in serum after mRNA vaccination. Fifty-one participants experienced SARS-CoV-2 BTI during the study period. The RBD IgG and NTs against Omicron BA.1 and BA.5 were markedly increased in SARS CoV-2 naïve participants 2 months after the third dose of mRNA vaccine, compared to those 5 months after the second dose, and declined 5 months after the third dose. The decline in RBD IgG and NT against Omicron BA.1 and BA.5 in SARS-CoV-2 naïve participants after the second and the third dose was particularly marked in those aged ≥ 80 years. BTIs during the BA.5 epidemic period, which occurred between 2 and 5 months after the third dose, induced a robust NT against BA.5 even five months after the booster dose vaccination. Further studies are required to assess the sustainability of NTs elicited by Omicron-containing bivalent mRNA booster vaccine in older adults.     

Frequency and temporal evolution of COVID-19 vaccination rate among oncological patients undergoing 18F-FDG-PET

PurposeTo evaluate the temporal evolution of vaccination against COVID-19 in a Swiss oncological cohort.MethodsHistory of complete vaccination (i.e. at least two vaccine doses) against COVID-19 of patients undergoing oncological 18F-FDG PET/CT between February and September 2021 (n = 2613) was taken. Vaccination rate was compared with age-matched national data from the Swiss Federal Office of Public Health. Subgroup differences in temporal evolution of vaccination rate were analyzed by fitting a generalized linear model and determined by significant interaction between, sex, oncological diagnosis, and month of examination.ResultsRate of complete vaccination against COVID-19 steadily increased and reached 81 % in September 2021. The fraction of vaccinated patients in the oncological cohort was higher in the beginning and approached the fraction in the age-matched general Swiss population at the end of the study period. Month of exam (p < 0.001) was the only significant predictor of the vaccination rate.ConclusionVaccination rate against COVID-19 in a Swiss oncological cohort increased steadily from February to September 2021. Compared to the age-matched general population it was higher in the beginning and similar by the end of the study period.Ethics approval: Trial registration: BASEC 2021-00444, Ethikkommission Zürich (Cantonal Ethics Committee Zurich), Switzerland, registered February 24th 2021.     

Efficacy and safety of the BNT162b2 mRNA COVID-19 vaccine in participants with a history of cancer: subgroup analysis of a global phase 3 randomized clinical trial

IntroductionIndividuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or benign/unknown) and up to 6 months’ follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine.Patients and methodsBetween July 2020–January 2021, 46,429 participants aged ≥ 12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate; those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥ 16 years for safety and ≥ 12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up.ResultsAt baseline, 3813 participants had a history of neoplasm; most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2; vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months’ follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4 (BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported.ConclusionIn participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer.Clinical trial number: NCT04368728.     

Assessing the long-stand antibody response induced by COVID-19 vaccines: A study in an educational cohort in San Luis,Argentina

BackgroundAlthough there has developed an increased interest in the vaccines BNT1622b2 (Pfizer/BioNTech), mRNA-1273 (Moderna/NIAID), and ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford), there are still few reports describing the immune response induced by different vaccine platforms in real-world settings of low-income countries. Here, we proposed to analyse the humoral immune response elicited by the primary vaccines used in Argentina from July-December 2021.MethodsAnti-SARS-CoV-2-Spike-RBD IgG and neutralising antibodies were assayed by ELISA in a total of 871 serum samples obtained from 376 volunteers from an educational staff. The individuals were vaccinated with BBIBP-CorV (Sinopharm), ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford, AZ), Gam-COVID-Vac (Sputnik V, SpV) or combined vaccines (mostly SpV and mRNA-1273, Moderna). The antibody response was analysed several days after the initial vaccination (20, 40, 120 and 180 days).ResultsAfter receiving at least one dose of the COVID-19 vaccine, we detected 93.34% of seroprevalence. Previously SARS-CoV-2 infected showed higher antibody concentrations compared with naïve vaccinees. Six months after the initial vaccination, combined vaccination induced higher anti-SARS-CoV-2 antibody levels than the other vaccines in naïve volunteers. However, we did not find differences in the neutralising responses after any vaccine from naïve vaccines or between the naïve and previously infected volunteers on day 120 after vaccination.ConclusionsOur long-term analysis of volunteers from the educational system provides data in a real-world context, showing the benefits of a boost dose still in previously infected volunteers, and suggesting the advantages of a heterologous prime-boost schedule.     

Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting

BackgroundIt is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups.MethodsWe conducted a retrospective study in patients ≥12 years who underwent testing for SARS-CoV-2 virus from April 14 through October 25, 2021, at urgent care centers in the New York metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n = 474,805), partially vaccinated (n = 87,834), and unvaccinated (n = 369,333) patients, adjusted for demographic factors and calendar time.ResultsVE against symptomatic infection after 2 doses of mRNA vaccine was 96% (95% Confidence Interval: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12–15-year-olds (85%; [95% CI: 81%, 88%]) was higher compared to older age groups (<65% for all other age groups). VE estimates did not differ by sex and race/ethnicity. VE against symptomatic infection was the highest for individuals with a prior infection followed by full vaccination. VE against symptomatic infection after the 2-dose mRNA-1273 vaccine (82% [95% CI: 80%, 84%]) was higher compared to the BNT162b2 vaccine (76% [95% CI: 74%, 78%]) in the delta period. VE after 1-dose of the Ad26.COV2.S vaccine was the lowest compared to other vaccines (19% [95% CI: 15%, 23%]) in the delta period.ConclusionsVE against infection after two doses of the mRNA vaccines was high initially, but significantly reduced against the delta variant for both FDA-approved vaccines.     

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.     

A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink

BackgroundExcept for spontaneous reporting systems, vaccine safety monitoring generally involves pre-specifying health outcomes and post-vaccination risk windows of concern. Instead, we used tree-based data-mining to look more broadly for possible adverse events after Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccination.MethodsVaccine Safety Datalink enrollees receiving ≥1 dose of COVID-19 vaccine in 2020–2021 were followed for 70 days after Pfizer-BioNTech or Moderna and 56 days after Janssen vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the post-vaccination follow-up period. We used the self-controlled tree-temporal scan statistic and TreeScan software. Monte Carlo simulation was used to estimate p-values; p = 0.01 was the pre-specified cut-off for statistical significance of a cluster.ResultsThere were 4.1, 2.6, and 0.4 million Pfizer-BioNTech, Moderna, and Janssen vaccinees, respectively. Clusters after Pfizer-BioNTech vaccination included: (1) unspecified adverse effects, (2) common vaccine reactions, such as fever, myalgia, and headache, (3) myocarditis/pericarditis, and (4) less specific cardiac or respiratory symptoms, all with the strongest clusters generally after Dose 2; and (5) COVID-19/viral pneumonia/sepsis/respiratory failure in the first 3 weeks after Dose 1. Moderna results were similar but without a significant myocarditis/pericarditis cluster. Further investigation suggested the fifth signal group was a manifestation of mRNA vaccine effectiveness after the first 3 weeks. Janssen vaccinees had clusters of unspecified or common vaccine reactions, gait/mobility abnormalities, and muscle weakness. The latter two were deemed to have arisen from confounding related to practices at one site.ConclusionsWe detected post-vaccination clusters of unspecified adverse effects, common vaccine reactions, and, for the mRNA vaccines, chest pain and palpitations, as well as myocarditis/pericarditis after Pfizer-BioNTech Dose 2. Unique advantages of this data mining are its untargeted nature and its inherent adjustment for the multiplicity of diagnoses and risk intervals scanned.     

Factors associated with COVID-19 vaccination during June–October 2021: A multi-site prospective study

IntroductionVaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership.MethodsIn June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analyses assessed predictors of subsequent vaccination among those initially unvaccinated.ResultsIn June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9 %) became vaccinated by October 31, 2021. In June, unvaccinated participants were less likely to feel “very concerned” about getting COVID-19 than vaccinated participants (10.6 % vs. 43.3 %, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5 % reported vaccination before study end. Two latent factors predicted subsequent vaccination—being ‘more receptive’ was derived from motivation to protect one’s own or others’ health and resume usual activities; being ‘less receptive’ was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention.ConclusionThis study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions.     

Antibody titers among healthcare workers for coronavirus disease 2019 at 6 months after BNT162b2 vaccination

BackgroundAntibody levels decrease substantially at 6 months after the BNT162b2 vaccine. The factors influencing titer of antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among healthcare workers for coronavirus disease 2019 (COVID-19) is unclear.MethodsWe conducted a 6-month longitudinal prospective study in Japanese healthcare workers in a tertiary care hospital for COVID-19. Participants in the study were tested for the presence of anti-spike protein (SP) IgG antibodies before and at 1 and 6 months after the last vaccination dose.ResultsAmong 1076 healthcare workers, 794 received the vaccine, and 469 entered the study. Five were infected with SARS-CoV-2 (none among COVID-19 section workers) by the end of the study and 451 participants were finally analyzed (mean age, 42.5 years; 27.3 % male; 18.8 % COVID-19 section workers). Median SP IgG index values were 0.0, 44.4, and 5.5 before and at 1 and 6 months after the last dose, respectively. Regression analysis revealed a negative correlation of SP IgG antibody levels with age (P < 0.0001), and higher levels in COVID-19 section workers (P = 0.0185) and in females (P = 0.0201).ConclusionIn healthcare workers at a COVID-19 hospital, IgG antibody titer was substantially lower at 6 months after receipt of the last dose of the BNT162b2 vaccine compared with that 1 month after the last dose, but was better preserved among younger participants, COVID-19 section workers and females.     

Short-term mortality following COVID-19 vaccination in Bologna,Italy: a one-year study

The main objective of the study is to assess whether there is an increased risk of mortality in the days following the administration of COVID-19 vaccines in Bologna Health Authority in the first year of COVID-19 vaccination campaign. A secondary objective was to describe causes of deaths occurred in the days after vaccination. We conducted a retrospective observational study on all residents of Bologna Health Authority who received at least one COVID-19 vaccination dose from December 27, 2020 to December 31, 2021 and compared mortality in the 3, 7, 14 30 days after vaccination (risk interval) with the mortality in the period of the same length (3, 7, 14 and 30 days) beyond the 30th day after the last dose of vaccination (control interval). The cohort included 717,538 people. The mortality rate was 2.24 per 100 person-years during the 30 days risk interval vs 2.72 in the control interval with an adjusted incidence rate ratio equal to 0.76 (95% CI: 0.70–0.83, p < 0.001). The risk of mortality is significantly lower (p < 0.001) also in the 3, 7, 14 days risk intervals than in the control intervals. This study shows that there is no increase in mortality in the short-term period after COVID-19 vaccines.     

The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. A Swedish nationwide study (COVID19-REUMA)

ObjectivesTo elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).MethodsAntibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2–12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins.ResultsPatients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21–40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2–12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001).ConclusionsOlder individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.     

BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was severe. Following first dose, systemic reactions were significantly more frequent among HCWs with past infection than in infection-naïve individuals, and among HCWs with pre-existing cellular immunity than in those without it. The rate of systemic reactions after second dose was 1.7 and 2.0-times higher than after first dose among infection-naïve HCWs and those without pre-existing cellular immunity, respectively. Levels of SARS-CoV-2-specific T-cells before vaccination were higher in HCWs with systemic reactions after the first dose than in those without them. BNT162b2 vaccine reactogenicity after first dose is attributable to pre-existing cellular immunity elicited by prior COVID-19 or cross-reactivity. Reactogenicity following second dose suggests an immunity-boosting effect. Overall, these data may reduce negative attitudes towards COVID-19 vaccines.Study Registration.The study was registered on clinicaltrials.gov, NCT04402827.