Predictors of moderate-to-severe side-effects following COVID-19 mRNA booster vaccination: A prospective cohort study among primary health care providers in Belgium. (preprint)

Background COVID-19 vaccine effectiveness declines months after vaccination. Therefore, it is likely that during the next few years, people may be repeatedly offered a booster vaccine to enhance humoral immunity levels. A growing number of people are questioning whether the benefits of a booster vaccine outweigh the side-effects.Objective This study aims (1) to identify the most frequently reported side-effects after different doses of COVID-19 mRNA vaccines, (2) and the longest lasting symptoms; and (3) to predict the likelihood of having moderate-to-severe side-effects after a booster COVID-19 mRNA vaccine given individual- and vaccine-specific characteristics.Design, setting, and participants : Secondary analysis of a prospective cohort study in primary health care providers (PHCPs) in Belgium conducted between December 2020 and December 2021, and in February-March 2023.Methods In nine subsequent surveys over a period of 2 years vaccine dose-number and side-effects after COVID-19 vaccines were collected. A Generalized Estimation Equations approach on the data of the first and second booster dose was used to investigate the probability of having moderate-to-severe side-effects after mRNA booster vaccination. Predictive performance of a binary classifier was assessed by looking at discrimination (i.e., quantified in terms of the area under the receiver operating characteristic curve). The final prediction model was validated using data with regard to the third booster by assessing misclassification rate, sensitivity and specificity.Results In total, 11% of the PHCPs had moderate-to-severe side-effects after their booster COVID-19 mRNA vaccine. The most common side-effects of COVID-19 mRNA doses included fatigue, local pain at the injection site, general pains, and headache. These side-effects typically lasted for a median of 1 to 2 days. The final model included five predictors: sex, alcohol consumption, history of moderate-to-severe side-effects after any previous dose, recent COVID-19 infection, and the booster dose-number (first, second). Having experienced moderate-to-severe side-effects after any previous dose was the strongest predictor of moderate-to-severe side-effects following an mRNA vaccine booster, with an odds ratio (OR) of 3.64 (95% CI: 2.80–4.75). The OR for female sex was 1.49 (95% CI: 1.21–1.84) implying that females have a higher odds of moderate-to-severe side-effects following booster vaccination. The differences in effect for booster dose-number, alcohol consumption and recent COVID-19 infection was not significant.Conclusion and Relevance: COVID-19 mRNA booster vaccination implies a low prevalence of moderate-to-severe side-effects among PHCPs, with a short median duration of symptoms if any. The strongest predictors are a history of moderate-to-severe side-effects after any previous dose and being female. These reassuring findings can help addressing concerns about booster vaccination and encourage their uptake.Trial Registration: NCT04779424

The prevalence, incidence and longevity of antibodies against SARS-CoV-2 among primary healthcare providers in Belgium: a prospective cohort study with 12 months of follow-up (preprint)

Objectives: To estimate the prevalence, incidence, and longevity of antibodies against SARS-CoV-2 among primary healthcare providers (PHCPs). Design: Prospective cohort study with 12 months of follow-up. Setting: Primary care in Belgium Participants: Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages (examines, tests, treats) patients were eligible. A convenience sample of 3,648 eligible PHCPs from 2,001 GP practices registered for this study (3,044 and 604 to start in December 2020 and January 2021, respectively). 3,390 PHCPs (92,9%) participated in their first testing timepoint (2,820 and 565, respectively) and 2,557 PHCPs (70,1%) in the last testing timepoint (December 2021). Interventions: Participants were asked to perform a rapid serological test (RST) targeting IgM and IgG against the receptor binding domain (RBD) of SARS-CoV-2 and to complete an online questionnaire at each of maximum 8 testing timepoints. Primary and secondary outcome measures: The prevalence, incidence, and longevity of antibodies against SARS-CoV-2 both after natural infection and after vaccination. Results: Among all participants, 67% were women and 77% GPs. Median age was 43 years. The seroprevalence in December 2020 (before vaccination availability) was 15.1% (95% CI: 13.5% to 16.6%), increased to 84.2% (95% CI: 82.9% to 85.5%) in March 2021 (after vaccination availability) and reached 93.9% (95% CI: 92.9% to 94.9%) in December 2021 (during booster vaccination availability and fourth (delta variant dominant) covid wave). Among not (yet) vaccinated participants the first monthly incidence of antibodies against SARS-CoV-2 was estimated to be 2.91% (95% CI: 1.80% to 4.01%). The longevity of antibodies is higher in PHCPs with self-reported COVID-19 infection. Conclusions: This study confirms that occupational health measures provided sufficient protection when managing patients. High uptake of vaccination resulted in high seroprevalence of SARS-CoV-2 antibodies in PHCPs in Belgium. Longevity of antibodies was supported by booster vaccination and virus circulation. Registration: Trial registration number: NCT04779424

PREVALENCE AND INCIDENCE OF ANTIBODIES AGAINST SARS-COV-2 AMONG PRIMARY HEALTHCARE PROVIDERS IN BELGIUM DURING ONE YEAR OF THE COVID-19 EPIDEMIC: PROSPECTIVE COHORT STUDY PROTOCOL (preprint)

Introduction National severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence data provides essential information about population exposure to the virus and helps predict the future course of the epidemic. Early cohort studies have suggested declines in levels of antibodies in individuals, associated with, for example, illness severity, age and co-morbidities. This protocol focuses on the seroprevalence among primary health care providers (PHCPs) in Belgium. They manage the vast majority of COVID-19 patients in addition to other patients and therefore play an essential role in the efficient organisation of health care. Currently, evidence is lacking on 1. how many PHCPs get infected with SARS-CoV-2 in Belgium, 2. the rate at which this happens, 3. their clinical spectrum, 4. their risk factors, 5. the effectiveness of the measures to prevent infection and 6. the accuracy of the serology-based point-of-care test in a primary care setting. Methods and analysis This study will be set up as a prospective cohort study. General practitioners (GPs) and other PHCPs (working in a GP practice) will be recruited via professional networks and professional media outlets to register online to participate. Registered GPs and other PHCPs will be asked at each testing point (n=9) to perform a capillary blood sample antibody point-of-care test (OrientGene) and complete an online questionnaire. The primary outcomes are the prevalence and incidence of antibodies against SARS-CoV-2 in PHCPs during a 12-month follow-up period. Secondary outcomes include the longevity of antibodies against SARS-CoV-2. Ethics and dissemination: Ethical approval has been granted by the Ethics Committee of the University Hospital Antwerp/University of Antwerp (Belgian registration number: 3002020000237). Alongside journal publications, dissemination activities include the publication of monthly reports to be shared with the participants and the general population through the publicly available website of the Belgian health authorities (Sciensano).