Prenatal maternal COVID-19 vaccination and pregnancy outcomes

BackgroundPrenatal maternal physiological changes may cause severe COVID-19 among pregnant women. The Pfizer-BioNTech COVID-19 vaccine (BNT162b2 mRNA) has been shown to be highly effective and it is recommended for individuals aged ≥16 years, including pregnant women, although the vaccine has not been tested on the latter.ObjectiveTo study the association between prenatal Pfizer-BioNTech COVID-19 vaccination, pregnancy course and outcomes.Study designA retrospective cohort study was performed, including all women who delivered between January and June 2021 at Soroka University Medical Center, the largest birth center in Israel. Excluded were women diagnosed with COVID-19 in the past, multiple gestations or unknown vaccination status. Pregnancy, delivery and newborn complications were compared between women who received 1 or 2-dose vaccines during pregnancy and unvaccinated women. Multivariable models were used to adjust for background characteristics.ResultsA total of 4,399 women participated in this study, 913 (20.8%) of which were vaccinated during pregnancy. All vaccinations occurred during second or third trimesters. As compared to the unvaccinated women, vaccinated women were older, more likely to conceive following fertility treatments, to have sufficient prenatal care, and of higher socioeconomic position. In both crude and multivariable analyses, no differences were found between the groups in pregnancy, delivery and newborn complications, including gestational age at delivery, incidence of small for gestational age and newborn respiratory complications.ConclusionsPrenatal maternal COVID-19 vaccine has no adverse effects on pregnancy course and outcomes. These findings may help pregnant women and health care providers to make informed decision regarding vaccination.     

Early exploration of COVID-19 vaccination safety and effectiveness during pregnancy: interim descriptive data from a prospective observational study

ObjectiveDuring December 2020, a massive vaccination program was introduced in our country. The Pfizer-BioNTech, BNT162b2 vaccine was first offered exclusively to high-risk population, such as medical personnel (including pregnant women). In this study we compare short term outcomes in vaccinated vs. non-vaccinated pregnant women.MethodsIn this prospective observational cohort study, vaccinated and non-vaccinated pregnant women were recruited using an online Google forms questionnaire targeting medical groups on Facebook and WhatsApp. A second questionnaire was sent one month after the first one for interim analysis. Our primary outcome was composite complications in vaccinated and non-vaccinated groups, considered any of the following: vaginal bleeding, pregnancy loss, hypertension, gestational diabetes, and preterm birth. Secondary outcomes included: vaccine side effects, diagnosis of COVID-19 since the last questionnaire, prevalence of vaccinated participants, and reasons for refusal to be vaccinated.ResultsOverall, 432 women answered the first questionnaire, of which 326 responses were received to the second questionnaire. Vaccination rate increased from 25.5% to 62% within a month. Maternal age, gestational age at enrollment, nulliparity and number of children were similar in both groups. The rate of composite pregnancy complications was similar between vaccinated and non-vaccinated group (15.8% vs 20.1%, p = 0.37), respectively. The risk for COVID-19 infection was significantly lower in the vaccinated group (1.5% vs 6.5%, p = 0.024, Odds Ratio: 4.5, 95% confidence interval 1.19–17.6).ConclusionsmRNA vaccine during pregnancy does not seem to increase the rate of pregnancy complications and is effective in prevention of COVID-19 infection.     

Relationship between pre-existing allergies and anaphylactic reactions post mRNA COVID-19 vaccine administration

Two mRNA vaccines for COVID-19, Pfizer-BioNTech and Moderna, are approved for emergency use in the United States. After their approval and dosing in millions of recipients, reports of anaphylaxis began to appear in the Vaccine Adverse Reporting System (VAERS). Here we provide an analysis of the relationship between prior history of allergy and/or anaphylaxis and anaphylaxis rates following the administration of mRNA COVID-19 vaccines. Overall reported incidence of anaphylaxis was estimated to be rare at 4.2 cases per million doses. It appeared that the relative incidence of anaphylaxis following administration of these COVID-19 vaccines was two and seven times higher for recipients with a prior history of allergies and/or anaphylaxis, respectively. This report provides valuable metrics to make evidence-based decisions for subjects with pre-existing allergic conditions receiving a COVID-19 mRNA vaccine.     

Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BackgroundOur near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations.MethodsWe conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell’s Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri).ResultsThe primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies’ results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP.ConclusionWe did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.     

Reducing the rates of household transmission: The impact of COVID-19 vaccination in healthcare workers with a known household exposure

ObjectiveTo determine the impact of COVID-19 vaccination on infection rates in healthcare workers (HCWs) with a household exposure.MethodsRetrospective cohort study 8410 HCWs (400 fully vaccinated, 1645 partially vaccinated, 6365 unvaccinated), employed by a large integrated healthcare system in the southeastern United States, tested for SARS-CoV-2 between January 1 and February 26, 2021.ResultsBenefit of vaccination persisted even with household exposure, with unvaccinated HCWs being 3.7 to 7.7 times more likely to be infected than partially or fully vaccinated HCW with positive household contacts respectively (partial OR = 3.73, 95% CI 2.17 – 6.47; full OR = 7.67, CI 2.75 – 21.35). Whereas 89.4% of unvaccinated COVID-positive HCWs with known household exposures were symptomatic, 50% of fully vaccinated HCWs had symptoms, reducing risk of secondary spread from and between HCWs.ConclusionsCOVID-19 vaccination provided protection against infection even amongst healthcare workers with close household contact, and after adjusting for community prevalence.     

Guidance for design and analysis of observational studies of fetal and newborn outcomes following COVID-19 vaccination during pregnancy

COVID-19 vaccines are now being deployed as essential tools in the public health response to the global SARS-CoV-2 pandemic. Pregnant individuals are a unique subgroup of the population with distinctive considerations regarding risk and benefit that extend beyond themselves to their fetus/newborn. As a complement to traditional pharmacovigilance and clinical studies, evidence to comprehensively assess COVID-19 vaccine safety in pregnancy will need to be generated through observational epidemiologic studies in large populations. However, there are several unique methodological challenges that face observational assessments of vaccination during pregnancy, some of which may be more pronounced for COVID-19 studies. In this contribution, we discuss the most critical study design, data collection, and analytical issues likely to arise. We offer brief guidance to optimize the quality of such studies to ensure their maximum value for informing public health decision-making.     

The impact of COVID-19 vaccination delay: A data-driven modeling analysis for Chicago and New York City

BackgroundBy the beginning of December 2020, some vaccines against COVID-19 already presented efficacy and security, which qualify them to be used in mass vaccination campaigns. Thus, setting up strategies of vaccination became crucial to control the COVID-19 pandemic.MethodsWe use daily COVID-19 reports from Chicago and New York City (NYC) from 01-Mar2020 to 28-Nov-2020 to estimate the parameters of an SEIR-like epidemiological model that accounts for different severity levels. To achieve data adherent predictions, we let the model parameters to be time-dependent. The model is used to forecast different vaccination scenarios, where the campaign starts at different dates, from 01-Oct-2020 to 01-Apr-2021. To generate realistic scenarios, disease control strategies are implemented whenever the number of predicted daily hospitalizations reaches a preset threshold.ResultsThe model reproduces the empirical data with remarkable accuracy. Delaying the vaccination severely affects the mortality, hospitalization, and recovery projections. In Chicago, the disease spread was under control, reducing the mortality increment as the start of the vaccination was postponed. In NYC, the number of cases was increasing, thus, the estimated model predicted a much larger impact, despite the implementation of contention measures.The earlier the vaccination campaign begins, the larger is its potential impact in reducing the COVID-19 cases, as well as in the hospitalizations and deaths. Moreover, the rate at which cases, hospitalizations and deaths increase with the delay in the vaccination beginning strongly depends on the shape of the incidence of infection in each city.     

Impact of COVID-19 vaccination in post-COVID cardiac complications

BackgroundAfter the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms. Methods: All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis. Results: From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17–0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40–0.69, p<0.001). Conclusion: Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population.     

COVID-19 vaccination and menstrual cycle characteristics: A prospective cohort study

We prospectively examined the association between COVID-19 vaccination and menstrual cycle characteristics in an internet-based prospective cohort study. We included a sample of 1,137 participants who enrolled in Pregnancy Study Online (PRESTO), a preconception cohort study of couples trying to conceive, during January 2021-August 2022. Eligible participants were aged 21–45 years, United States or Canadian residents, and trying to conceive without fertility treatment. At baseline and every 8 weeks for up to 12 months, participants completed questionnaires on which they provided information on COVID-19 vaccination and menstrual cycle characteristics, including cycle regularity, cycle length, bleed length, heaviness of bleed, and menstrual pain. We fit generalized estimating equation (GEE) models with a log link function and Poisson distribution to estimate the adjusted risk ratio (RR) for irregular cycles associated with COVID-19 vaccination. We used linear regression with GEE to estimate adjusted mean differences in menstrual cycle length associated with COVID-19 vaccination. We adjusted for sociodemographic, lifestyle, medical and reproductive factors. Participants had 1.1 day longer menstrual cycles after receiving the first dose of COVID-19 vaccine (95 % CI: 0.4, 1.9) and 1.3 day longer cycles after receiving the second dose (95 % CI: 0.2, 2.5). Associations were attenuated at the second cycle post-vaccination. We did not observe strong associations between COVID-19 vaccination and cycle regularity, bleed length, heaviness of bleed, or menstrual pain. In conclusion, COVID-19 vaccination was associated with a ∼1 day temporary increase in menstrual cycle length, but was not appreciably associated with other menstrual cycle characteristics.     

SIRVA (Shoulder Injury Related to Vaccine Administration) following mRNA COVID-19 Vaccination: Case discussion and literature review

Shoulder injury related to vaccine administration (SIRVA) is an increasingly recognised complication after vaccination and presents with significant shoulder pain and stiffness. SIRVA is thought to occur as a result of improper administration of vaccine into the subdeltoid bursa or shoulder joint. This results in an inflammatory cascade that damages the structures in the shoulder region. The incidence of SIRVA is relatively higher for influenza vaccination due its widespread administration. We present a reported case of SIRVA following a mRNA COVID-19 vaccination and review the current literature. As we embark on a worldwide scale of COVID-19 vaccination, it is of utmost important that we use proper vaccination techniques and screen patients at risk of SIRVA. This would improve the efficacy of the vaccine and improve the outcomes of the vaccination programme.     

Safety,immunogenicity, and immune persistence of two inactivated COVID-19 vaccines replacement vaccination in China: An observational cohort study

BackgroundTo mitigate a national shortage of WIBP-CorV COVID-19 vaccine, China’s regulator approved administering BBIBP-CorV after WIBP-CorV for completion of a primary series. In a pragmatic observational study, we compared immunogenicity and safety of a primary series of WIBP-CorV followed by BBIBP-CorV with a primary series of two doses of BBIBP-CorV.MethodsWe invited healthy 18–59-years-old adults who had already received either WIBP-CorV or BBIBP-CorV as their first dose in a primary series to participate in this observational cohort study. Subjects who had received WIBP-CorV as their first dose became the observation group; subjects who had received BBIBP-CorV as their first dose became the control group. All participants received BBIBP-CorV as their second dose. We obtained sera 1, 2, and 6 months after second doses for nAb titer measurement by micro-neutralization cytopathic effect assay with SARS-CoV-2 strain HB01, standardized with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Safety was assessed for the 7 days after administration of second doses.ResultsBetween March and December 2021, 275 subjects were included in the observation group and 133 in the control group. Neutralizing seropositivity (≥1:4) rates were 98.91 % and 99.25 % at 1 month and 53.16 % and 70.69 % at 6 months. One-month geometric mean titers (GMTs) were 21.33 and 22.45; one-month geometric mean concentrations (GMCs) were 227.71 IU/mL and 273.27 IU/mL. One to two months after vaccination, observation group seropositivity rates and titers were not significantly different to the control group’s. Adverse reaction rates were 11.27 % and 18.80 %, all mild or moderate in severity.ConclusionsBoth primary series were immunogenic; immunogenicity of WIBP-CorV followed by BBIBP-CorV was not different than immunogenicity following two doses of BBIBP-CorV for two months after vaccination; safety profiles were acceptable for both regimens. BBIBP-CorV can be used to complete a primary series that started with WIBP-CorV.     

COVID-19 mRNA vaccines as hypothetical epigenetic players: Results from an in silico analysis,considerations and perspectives

ObjectivesTo investigate in silico the occurrence of epigenetic crosstalk by nucleotide sequence complementarity between the BNT162b2 mRNA vaccine and whole human genome, including coding and noncoding (nc)RNA genes. To correlate these results with those obtained with the original spike (S) gene of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2).MethodsThe publicly available FASTA sequence of the BNT162b2 mRNA vaccine and the SARS-CoV-2 isolate Wuhan-Hu-1 S gene (NC_045512.2) were used separately as key input to the Ensembl.org library to evaluate base pair match to human GRCh38 genome. Human coding and noncoding genes harboring hits were assessed for functional activity and health effects using bioinformatics tools and GWAS databases.ResultsThe BLAT analysis against the human GRCh38 genome revealed a total of 37 hits for BNT162b2 mRNA and no hits for the SARS-CoV-2 S gene. More specifically, BNT162b2 mRNA matched 19 human genes whose protein products are variously involved in enzyme reactions, nucleotide or cation binding, signaling, and carrier functions.In BLASTN analysis of ncRNA genes, BNT162b2 mRNA and SARS-CoV-2 S gene matched 17 and 24 different human genomic regions, respectively. Overall, characterization of the matched noncoding sequences revealed stronger interference with epigenetic pathways for BNT162b2 mRNA compared with the original S gene.ConclusionThis pivotal in silico analysis shows that SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. Although they do not share the same complementarity pattern, both may disrupt epigenetic mechanisms in target cells, potentially leading to long-term complications.     

全球新冠疫苗研发与接种策略进展

WHO于2023年5月5日宣布新型冠状病毒感染(corona virus disease 2019,COVID-19)疫情不再构成国际关注的突发公共卫生事件。全球疫情相对稳定,但是各国仍不能放松对COVID-19的警惕。接种新冠疫苗仍是有效的预防手段。本文主要围绕当前全球新冠疫苗研发进展、不同国家疫苗接种策略调整情况等进行对比分析,并结合WHO推荐对新冠疫苗接种策略的最新指导意见,分析探讨全球新冠疫苗研发及各国疫苗接种策略对我国的启示,提出适合我国国情的针对性疫苗接种建议。     

The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study

BackgroundSymptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC.MethodsRECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression.FindingsOf 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46–5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183–324) and 181 (147–230) among participants with PASC, and 170 (125–252) and 144 (113–196) among those without PASC, respectively.InterpretationOur study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC.     

Perceptions of the COVID-19 vaccine and willingness to receive vaccination among health workers in Nigeria

ObjectivesThe study aimed to examine health workers’ perceptions of the coronavirus disease 2019 vaccine in Nigeria and their willingness to receive the vaccine when it becomes available.Methods This multi-center cross-sectional study used non-probability convenience sampling to enroll 1,470 hospital workers aged 18 and above from 4 specialized hospitals. A structured and validated self-administered questionnaire was used for data collection. Data entry and analysis were conducted using IBM SPSS ver. 22.0.Results The mean age of respondents was 40±6 years. Only 53.5% of the health workers had positive perceptions of the COVID-19 vaccine, and only slightly more than half (55.5%) were willing to receive vaccination. Predictors of willingness to receive the COVID-19 vaccine included having a positive perception of the vaccine (adjusted odds ratio [AOR], 4.55; 95% confidence interval [CI], 3.50−5.69), perceiving a risk of contracting COVID-19 (AOR, 1.50; 95% CI, 1.25–3.98), having received tertiary education (AOR, 3.50; 95% CI, 1.40−6.86), and being a clinical health worker (AOR, 1.25; 95% CI, 1.01−1.68).Conclusion Perceptions of the COVID-19 vaccine and willingness to receive the vaccine were sub-optimal among this group. Educational interventions to improve health workers'' perceptions and attitudes toward the COVID-19 vaccine are needed.     

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.     

COVID-19 vaccination in pregnant women in Sweden and Norway

Vaccines against SARS-CoV-2 are highly effective in preventing severe disease and mortality. Although pregnant women are at increased risk of severe COVID-19, vaccination uptake among pregnant women varies. We used the Swedish and Norwegian population-based health registries to identify pregnant women and to investigate background characteristics associated with not being vaccinated. In this study of 164 560 women giving birth between May 2021 and May 2022, 78% in Sweden and 87% in Norway have been vaccinated with at least one dose at delivery. Not being vaccinated while being pregnant was associated with age below 30 years, low education and income level, birth region other than Scandinavia, smoking during pregnancy, not living with a partner, and gestational diabetes. These results can assist health authorities develop targeted vaccination information to diminish vaccination inequality and prevent severe disease in vulnerable groups.