Vaccine hesitancy: current and future challenges.

Vaccine hesitancy, defined by the WHO as reluctance or refusal to vaccinate, despite the availability of vaccines, threatens to undermine progress in tackling vaccine-preventable disease. In this Immunology Futures article, I explore my experiences of combating vaccine hesitancy, and how research in this area can help. The graphic was made with assets from Freepik.com.

Impact of coronavirus disease 2019 (COVID-19) vaccination on menstrual bleeding quantity: An observational cohort study.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) vaccination impacts menstrual bleeding quantity. DESIGN: Retrospective cohort. SETTING: Five global regions. POPULATION: Vaccinated and unvaccinated individuals with regular menstrual cycles using the digital fertility-awareness application Natural Cycles°. METHODS: We used prospectively collected menstrual cycle data, multivariable longitudinal Poisson generalised estimating equation (GEE) models and multivariable multinomial logistic regression models to calculate the adjusted difference between vaccination groups. All regression models were adjusted for confounding factors. MAIN OUTCOME MEASURES: The mean number of heavy bleeding days (fewer, no change or more) and changes in bleeding quantity (less, no change or more) at three time points (first dose, second dose and post-exposure menses). RESULTS: We included 9555 individuals (7401 vaccinated and 2154 unvaccinated). About two-thirds of individuals reported no change in the number of heavy bleeding days, regardless of vaccination status. After adjusting for confounding factors, there were no significant differences in the number of heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced an increase in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; adjusted difference 4.0%, 99.2% CI 0.7%-7.2%). This translates to an estimated 40 additional people per 1000 individuals with normal menstrual cycles who experience a greater total bleeding quantity following the first vaccine dose' suffice. Differences resolved in the cycle post-exposure. CONCLUSIONS: A small increase in the probability of greater total bleeding quantity occurred following the first COVID-19 vaccine dose, which resolved in the cycle after the post-vaccination cycle. The total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transient.

COVID-19 vaccination and menstruation.

COVID-19 vaccination causes small changes to menstruation that quickly resolve.

Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data.

OBJECTIVES: To identify whether covid-19 vaccines are associated with menstrual changes in order to address concerns about menstrual cycle disruptions after covid-19 vaccination. DESIGN: Global, retrospective cohort study of prospectively collected data. SETTING: International users of the menstrual cycle tracking application, Natural Cycles. PARTICIPANTS: 19 622 individuals aged 18-45 years with cycle lengths of 24-38 days and consecutive data for at least three cycles before and one cycle after covid (vaccinated group; n=14 936), and those with at least four consecutive cycles over a similar time period (unvaccinated group; n=4686). MAIN OUTCOME MEASURES: The mean change within individuals was assessed by vaccination group for cycle and menses length (mean of three cycles before vaccination to the cycles after first and second dose of vaccine and the subsequent cycle). Mixed effects models were used to estimate the adjusted difference in change in cycle and menses length between the vaccinated and unvaccinated. RESULTS: Most people (n=15 713; 80.08%) were younger than 35 years, from the UK (n=6222; 31.71%), US and Canada (28.59%), or Europe (33.55%). Two thirds (9929 (66.48%) of 14 936) of the vaccinated cohort received the Pfizer-BioNTech (BNT162b2) covid-19 vaccine, 17.46% (n=2608) received Moderna (mRNA-1273), 9.06% (n=1353) received Oxford-AstraZeneca (ChAdOx1 nCoV-19), and 1.89% (n=283) received Johnson & Johnson (Ad26.COV2.S). Individuals who were vaccinated had a less than one day adjusted increase in the length of their first and second vaccine cycles, compared with individuals who were not vaccinated (0.71 day increase (99.3% confidence interval 0.47 to 0.96) for first dose; 0.56 day increase (0.28 to 0.84) for second dose). The adjusted difference was larger in people who received two doses in a cycle (3.70 days increase (2.98 to 4.42)). One cycle after vaccination, cycle length was similar to before the vaccine in individuals who received one dose per cycle (0.02 day change (99.3% confidence interval -0.10 to 0.14), but not yet for individuals who received two doses per cycle (0.85 day change (99.3% confidence interval 0.24 to 1.46)) compared with unvaccinated individuals. Changes in cycle length did not differ by the vaccine's mechanism of action (mRNA, adenovirus vector, or inactivated virus). Menses length was unaffected by vaccination. CONCLUSIONS: Covid-19 vaccination is associated with a small and likely to be temporary change in menstrual cycle length but no change in menses length.

Effect of COVID-19 vaccination on the timing and flow of menstrual periods in two cohorts.

COVID-19 vaccination protects against the potentially serious consequences of SARS-CoV-2 infection, but some people have been hesitant to receive the vaccine because of reports that it could affect menstrual bleeding. To determine whether this occurs we prospectively recruited a cohort of 79 individuals, each of whom recorded details of at least three consecutive menstrual cycles, during which time they each received at least one dose of COVID-19 vaccine. In spontaneously cycling participants, COVID-19 vaccination was associated with a delay to the next period, but this change reversed in subsequent unvaccinated cycles. No delay was detected in those taking hormonal contraception. To explore hypotheses about the mechanism by which these menstrual changes occur, we retrospectively recruited a larger cohort, of 1,273 people who had kept a record of their menstrual cycle and vaccination dates. In this cohort, we found a trend toward use of combined hormonal contraception being protective against reporting a delayed period, suggesting that menstrual changes following vaccination may be mediated by perturbations to ovarian hormones. However, we were unable to detect a clear association between the timing of vaccination within the menstrual cycle and reports of menstrual changes. Our findings suggest that COVID-19 vaccination can lengthen the menstrual cycle and that this effect may be mediated by ovarian hormones. Importantly, we find that the menstrual cycle returns to its pre-vaccination length in unvaccinated cycles.

SARS-CoV-2 infection and COVID-19 vaccination in pregnancy.

SARS-CoV-2 infection poses increased risks of poor outcomes during pregnancy, including preterm birth and stillbirth. There is also developing concern over the effects of SARS-CoV-2 infection on the placenta, and these effects seem to vary between different viral variants. Despite these risks, many pregnant individuals have been reluctant to be vaccinated against the virus owing to safety concerns. We now have extensive data confirming the safety and effectiveness of COVID-19 vaccination during pregnancy, although it will also be necessary to determine the effectiveness of these vaccines specifically against newly emerging viral variants, including Omicron. In this Progress article, I cover recent developments in our understanding of the risks of SARS-CoV-2 infection in pregnancy, and how vaccination can reduce these.

COVID-19 vaccines: what do we know so far?

When the novel coronavirus was described in late 2019, it could not have been imagined that within a year, more than 100 vaccine candidates would be in preclinical development and several would be in clinical trials and even approved for use. The scale of the COVID-19 outbreak pushed the scientific community, working in collaboration with pharmaceutical companies, public health bodies, policymakers, funders and governments, to develop vaccines against SARS-CoV-2 at record-breaking speed. As well as driving major amendments to the usual timeframe for bringing a vaccine to fruition, the pandemic has accelerated the development of next-generation technologies for vaccinology, giving rise to two frontrunner RNA vaccines. Although none of the critical safety and efficacy steps have been skipped within the compressed schedules, and the technologies underpinning the novel vaccines have been refined by scientists over many years, a significant proportion of the global population is sceptical of the benefits of COVID-19 vaccines and wary of potential risks. In this interview-based article, we give an overview of how the vaccines were developed and how they work to generate a robust immune response against COVID-19, as well as addressing common questions relating to safety and efficacy.