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ObjectivesTo estimate the prevalence, incidence, and longevity of antibodies against SARS-CoV-2 among primary healthcare providers (PHCPs). DesignProspective cohort study with 12 months of follow-up. SettingPrimary care in Belgium ParticipantsAny 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). InterventionsParticipants 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 measuresThe prevalence, incidence, and longevity of antibodies against SARS-CoV-2 both after natural infection and after vaccination. ResultsAmong 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. ConclusionsThis 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. RegistrationTrial registration number: NCT04779424 Strengths and limitations of this studyO_LIThis large cohort study with 12 months follow-up could provide precise estimates of the prevalence and incidence of antibodies against SARS-CoV-2 among primary health care providers (PHCPs) at national and regional level in Belgium. C_LIO_LIThe rapid serological test (RST) used targets IgM and IgG against the receptor binding domain of SARS-CoV-2 and could therefore also assess the antibody response after vaccination, and longevity of antibodies against SARS-CoV-2 both after natural infection and after vaccination, but cannot distinguish between both. C_LIO_LIThe results in PHCPs could be compared to that of the general population and other population groups, e.g. health care workers in hospitals and nursing homes. C_LIO_LIThe use of a convenience sample, missing data points and reduced RST accuracy when performed and interpreted by many different participants could limit the validity of the study results. C_LI
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In the general population, the seroconversion rate after primary vaccination with two doses of anti-SARS-CoV-2 mRNA vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here, we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. A systematic literature research was performed in Pubmed, Web of Science, and the Cochrane library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. Six studies that described the development of antibodies against receptor-binding domain (RBD) and/or S1 subunit of the spike protein were eligible for meta-analysis. Two of them also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 (45.2%; 95% confidence interval (CI) 32.5%-58.3%) than patients vaccinated with two doses of mRNA-1273 (60.4%; 95% CI 47.4%-72.7%. The relative seroconversion rate amounted 0.79 (95% CI 0.71-0.88). This systematic review and meta-analysis indicates that, in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared to BNT162b2.
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In this study of the humoral immune response after the SARS-CoV-2 mRNA vaccination, low seroconversion rates were noted in both kidney transplant recipients and dialysis patients after first dose administration. While in DP the seroconversion rate levelled up to 92.8% after a second dose of SARS-CoV-2 mRNA vaccination, KTR stayed behind with a seroconversion rate of 62.4%. Futhermore, vaccination with the mRNA-1273 vaccine (Moderna) resulted in both higher seroconversion rates and mean log-transformed antibody titer concentrations compared to BNT162b2 (Pfizer).
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IntroductionNational 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 analysisThis 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(R)) 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 disseminationEthical 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). RegistrationTrial registration number: NCT04779424 Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIThis large cohort study will provide regular, timely and precise data at national level on prevalence and incidence of antibodies against SARS-CoV-2 among primary health care providers (PHCPs) managing the vast majority of COVID-19 and other patients and therefore essential to organise health care efficiently. C_LIO_LIThis study will familiarise PHCPs with the use of serology-based point-of-care tests (POCTs) and validate the POCT in a primary care setting. C_LIO_LIMissing data points and the use of a convenience sample could limit the validity of the study results. C_LI
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Primary health care providers (PHCPs), especially general practitioners (GPs) are essential to organise health care efficiently. During the COVID-19 pandemic, they also keep the pressure off hospitals. PHCPs are assumed to be at high risk of a COVID-19 infection, as they are exposed to a large portion of the population (usually with less personal protective equipment than other frontline health care workers(HCWs)). Nevertheless, previous seroprevalence studies focussed on the general population or HCWs in hospital settings, rather than PHCPs. The aim of this study was to determine the seroprevalence of PHCPs after the first and during the second SARS-CoV-2 wave in Flanders (Belgium) and compare it to the seroprevalence in the general population (blood donors). A prospective cohort of PHCPs, mainly GPs (n=698) was screened for IgG antibodies against SARS-CoV-2 at five different time-points (June-December 2020). The dried blood spots they produced were analysed using a Luminex multiplex immunoassay. The seroprevalence of PHCPs remained stable between June and September 2020 (4.6-5.0%), but increased significantly from October to December (8.1-13.4%) 2020. The seroprevalence of PHCPs was not significantly higher than the seroprevalence of the blood donors at the end of December 2020. In conclusion, the sharp increase in seroprevalence during the second COVID-19 wave in Flanders shows that PHCPs were more at risk during the second wave compared to the first one. However, the increase was in line with the general population suggesting that PHCPs mainly got infected in their private settings.
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BACKGROUND The ongoing coronavirus disease (COVID)-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be controlled by an efficacious vaccine. Multiple vaccines are in development, but no efficacious vaccine is currently available. METHODS We designed a multi-center phase 1/2a randomized, double-blinded, placebo-controlled clinical study to assesses the safety, reactogenicity and immunogenicity of Ad26.COV2.S, a non-replicating adenovirus 26 based vector expressing the stabilized pre-fusion spike (S) protein of SARS-CoV-2. Ad26.COV2.S was administered at a dose level of 5x1010 or 1x1011 viral particles (vp) per vaccination, either as a single dose or as a two-dose schedule spaced by 56 days in healthy adults (18-55 years old; cohort 1a & 1b; n= 402 and healthy elderly >65 years old; cohort 3; n=394). Vaccine elicited S specific antibody levels were measured by ELISA and neutralizing titers were measured in a wild-type virus neutralization assay (wtVNA). CD4+ T-helper (Th)1 and Th2, and CD8+ immune responses were assessed by intracellular cytokine staining (ICS). RESULTS We here report interim analyses after the first dose of blinded safety data from cohorts 1a, 1b and 3 and group unblinded immunogenicity data from cohort 1a and 3. In cohorts 1 and 3 solicited local adverse events were observed in 58% and 27% of participants, respectively. Solicited systemic adverse events were reported in 64% and 36% of participants, respectively. Fevers occurred in both cohorts 1 and 3 in 19% (5% grade 3) and 4% (0% grade 3), respectively, were mostly mild or moderate, and resolved within 1 to 2 days after vaccination. The most frequent local adverse event (AE) was injection site pain and the most frequent solicited AEs were fatigue, headache and myalgia. After only a single dose, seroconversion rate in wtVNA (50% inhibitory concentration - IC50) at day 29 after immunization in cohort 1a already reached 92% with GMTs of 214 (95% CI: 177; 259) and 92% with GMTs of 243 (95% CI: 200; 295) for the 5x1010 and 1x1011vp dose levels, respectively. A similar immunogenicity profile was observed in the first 15 participants in cohort 3, where 100% seroconversion (6/6) (GMTs of 196 [95%CI: 69; 560]) and 83% seroconversion (5/6) (GMTs of 127 [95% CI: <58; 327]) were observed for the 5x1010 or 1x1011 vp dose level, respectively. Seroconversion for S antibodies as measured by ELISA (ELISA Units/mL) was observed in 99% of cohort 1a participants (GMTs of 528 [95% CI: 442; 630) and 695 (95% CI: 596; 810]), for the 5x1010 or 1x1011 vp dose level, respectively, and in 100% (6/6 for both dose levels) of cohort 3 with GMTs of 507 (95% CI: 181; 1418) and 248 (95% CI: 122; 506), respectively. On day 14 post immunization, Th1 cytokine producing S-specific CD4+ T cell responses were measured in 80% and 83% of a subset of participants in cohort 1a and 3, respectively, with no or very low Th2 responses, indicative of a Th1-skewed phenotype in both cohorts. CD8+ T cell responses were also robust in both cohort 1a and 3, for both dose levels. CONCLUSIONS The safety profile and immunogenicity after only a single dose are supportive for further clinical development of Ad26.COV2.S at a dose level of 5x1010 vp, as a potentially protective vaccine against COVID-19. Trial registration number: NCT04436276
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ObjectiveScrutiny of COVID-19 mortality in Belgium over the period 8 March - 9 May 2020 (Weeks 11-19), using number of deaths per million, infection fatality rates, and the relation between COVID-19 mortality and excess death rates. DataPublicly available COVID-19 mortality (2020); overall mortality (2009 - 2020) data in Belgium and demographic data on the Belgian population; data on the nursing home population; results of repeated sero-prevalence surveys in March-April 2020. Statistical methodsReweighing, missing-data handling, rate estimation, visualization. ResultsBelgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. There is a sharp excess death peak over the study period; the total number of excess deaths makes April 2020 the deadliest month of April since WWII, with excess deaths far larger than in early 2017 or 2018, even though influenza-induced January 1951 and February 1960 number of excess deaths were similar in magnitude. Using various sero-prevalence estimates, infection fatality rates (IFRs; fraction of deaths among infected cases) are estimated at 0.38 - 0.73% for males and 0.20 - 0.39% for females in the non-nursing home population (non-NHP), and at 0.79 - 1.52% for males and 0.88 - 1.31% for females in the entire population. Estimates for the NHP range from 38 to 73% for males and over 22 to 37% for females. The IFRs rise from nearly 0% under 45 years, to 4.3% and 13.2% for males in the non-NHP and the general population, respectively, and to 1.5% and 11.1% for females in the non-NHP and general population, respectively. The IFR and number of deaths per million is strongly influenced by extensive reporting and the fact that 66.0% of the deaths concerned NH residents. At 764 (our re-estimation of the figure 735, presented by "Our World in Data"), the number of COVID-19 deaths per million led the international ranking on May 9, 2020, but drops to 262 in the non-NHP. The NHP is very specific: age-related increased risk; highly prevalent comorbidities that, while non-fatal in themselves, exacerbate COVID-19; larger collective households that share inadvertent vectors such as caregivers and favor clustered outbreaks; initial lack of protective equipment, etc. High-quality health care countries have a relatively older but also more frail population [1], which is likely to contribute to this result. Thumbnail summary: What this paper addsCOVID-19 mortality and its relation to excess deaths, case fatality rates (CFRs), infection fatality rates (IFRs), and number of deaths per million are constantly being reported for a large number of countries globally. This study adds detailed insight in the Belgian situation over the period 8 March - 9 May 2020 (Week 11-Week 19). Belgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. This, combined with a high fraction of possible cases that is COVID-19 related [2] provides a basis for using all COVID-19 cases and thus not only the confirmed ones, in IFR estimation. Against each of the years from 2009 and 2019 and the average thereof, there is a strong excess death peak in 2020, which nearly entirely coincides with confirmed plus possible COVID-19 cases. The excess death/COVID-19 peak rises well above seasonal fluctuations seen in the first trimester during the most recent decade (induced in part by seasonal influenza). In the second week of April 2020, twice as many people died than in the corresponding week of the reference year. April 2020 was the deadliest month of April since WWII, although January 1951 and February 1960 saw similar figures. More recently, in the winter of 2017-2018, there was 4.6% excess mortality in Belgium (70,215 actual deaths; 3093 more than the Be-MOMO-model prediction). In the winter of 2016-2017, there was an excess of 3284 deaths (4.9% excess mortality) https://epistat.wiv-isp.be/docs/momo/Be-MOMO%20winter%202017-18%20report_FR.pdf. At 764 (our estimate), the number of COVID-19 deaths per million leads the international ranking, but drops sharply to 262 in the non-nursing home population. CFR is not a good basis for international comparison, except as a tool in estimating global infection fatality rates [2]. These authors used asymptotic models to derive IFR as a limit of CFR. CFR is strongly influenced by testing strategy, and in several studies the delay between case confirmation and deaths is not accounted for. The handling of possible cases is ambiguous at best. We do not consider it here. Bias and precision in estimation of IFR is influenced by difficulties surrounding the estimation of sero-prevalence, such as sensitivity and specificity of the tests used [3], time to IgM and in particular IgG seroconversion [4], and potential selection bias occurring in data from residual sample surveys. A sensitivity analysis is undertaken by augmenting one primary with three auxiliary estimates of sero-prevalence. Because in Belgium there is a very close agreement between excess mortality on the one hand and confirmed and possible COVID-19 cases combined on the other, and because an international study [2] suggested that a fraction as high as 0.9 of possible cases could be attributable to COVID-19 [5], it is a reasonable choice to use all COVID-19 cases in IFR estimation. This encompasses a large fraction of deaths occurring in nursing homes. The IFR values obtained align with international values [2]. Using various sero-prevalence estimates, IFRs across all ages are estimated at 0.38 - 0.73% for males and 0.20 - 0.39% for females in the non-nursing home population (non-NHP), and at 0.79 - 1.52% for males and 0.88 - 1.31% for females in the entire population. Estimates for the NHP range from 38 to 73% for males and over 22 to 37% for females. The IFRs rise from nearly 0% under 45 years, to 4.3% and 13.2% for males in the non-NHP and the general population, respectively, and to 1.5% and 11.1% for females in the non-NHP and general population, respectively. The IFR is strongly influenced by extensive death cases reporting and the fact that 66.0% of the deaths concerned NH residents. Apart from a strong age-related gradient, also for each age category, IFRs are substantially higher in males than in females Because of these dependencies, IFRs should be considered in an age, gender, and sub-population specific manner. The same proviso is made for the number of deaths per million. An important such population is the NHP because of a specific cocktail: age-related increased risk; highly prevalent comorbidities that, while non-fatal in themselves, exacerbate COVID-19; larger collective households that share inadvertent vectors such as caregivers; initial lack of protective equipment, etc. High-quality health care countries have a relatively older but also more frail population [1], which might contribute.
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To assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the national lock-down in Belgium, a nationwide seroprevalence study, stratified by age, sex and region using 3000-4000 residual samples was performed during 7 periods between 30 March and 17 October 2020. Residual sera from ambulatory patients were analyzed for IgG antibodies against S1 proteins of SARS-CoV-2 with a semi-quantitative commercial ELISA. Weighted seroprevalence (overall, by age category and sex) and seroincidence during 7 consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity. The weighted overall seroprevalence initially increased from 1.8% (95% CrI 1.0-2.6) to 5.3% (95% CrI 4.2-6.4), implying a seroincidence of 3.4% (95% CrI 2.4-4.6) between the 1st and 2nd collection period over a period of 3 weeks during the lockdown period (start lockdown mid March 2020). Thereafter, seroprevalence stabilized, however, significant decreases are observed when comparing the 3rd with the 5th and also with the 6th period resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid October 2020 a weighted overall seroprevalence of 4.2% (95% CrI 3.1-5.2). During lockdown, an initial small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.
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Although COVID-19 has been spreading throughout Belgium since February, 2020, its spatial dynamics in Belgium remain poorly understood, due to the limited testing of suspected cases. We analyse data of COVID-19 symptoms, as self-reported in a weekly online survey, which is open to all Belgian citizens. We predict symptoms incidence using binomial models for spatially discrete data, and we introduce these as a covariate in the spatial analysis of COVID-19 incidence, as reported by the Belgian government during the days following a survey round. The symptoms incidence predictions explain a significant proportion of the variation in the relative risks based on the confirmed cases, and exceedance probability maps of the symptoms incidence and the confirmed cases relative risks pinpoint the same high-risk region. We conclude that these results can be used to develop public monitoring tools in scenarios with limited lab testing capacity, and to supplement test-based information otherwise.
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Outbreaks of measles, mumps and rubella have occurred recently despite long-standing mass immunization with MMR. Antibody titres for measles, mumps and rubella of 160 students (17-23 years) with proof of at least one MMR-vaccine were studied according to the number of MMR-vaccines received. The proportion of subjects with positive antibody titres was significantly higher in those who received two vaccines against measles (77.1% versus 58.7%, p=0.05), mumps (67.5% versus 55.6%, p=0.009) and rubella (99.2% versus 71.4%, p=0.008). Comparable significant trends were seen for GMTs for measles and mumps. A similar non-significant trend was noted for rubella.
