Identification of potentially actionable genetic variants in epithelial ovarian cancer: a retrospective cohort study.

Ovarian cancer is the most lethal gynecologic malignancy, mainly due to late-stage diagnosis, frequent recurrences, and eventually therapy resistance. To identify potentially actionable genetic variants, sequencing data of 351 Belgian ovarian cancer patients were retrospectively captured from electronic health records. The cohort included 286 (81%) patients with high-grade serous ovarian cancer, 17 (5%) with low-grade serous ovarian cancer, and 48 (14%) with other histotypes. Firstly, an overview of the prevalence and spectrum of the BRCA1/2 variants highlighted germline variants in 4% (11/250) and somatic variants in 11% (37/348) of patients. Secondly, application of a multi-gene panel in 168 tumors revealed a total of 214 variants in 28 genes beyond BRCA1/2 with a median of 1 (IQR, 1-2) genetic variant per patient. The ten most often altered genes were (in descending order): TP53, BRCA1, PIK3CA, BRCA2, KRAS, ERBB2 (HER2), TERT promotor, RB1, PIK3R1 and PTEN. Of note, the genetic landscape vastly differed between the studied histotypes. Finally, using ESCAT the clinical evidence of utility for every genetic variant was scored. Only BRCA1/2 pathogenic variants were classified as tier-I. Nearly all patients (151/168; 90%) had an ESCAT tier-II variant, most frequently in TP53 (74%), PIK3CA (9%) and KRAS (7%). In conclusion, our findings imply that although only a small proportion of genetic variants currently have direct impact on ovarian cancer treatment decisions, other variants could help to identify novel (personalized) treatment options to address the poor prognosis of ovarian cancer, particularly in rare histotypes.

The role of community pharmacists in primary and secondary prevention of skin cancer: an evaluation of a Flemish skin cancer prevention campaign.

BACKGROUND: Skin cancer is a leading form of cancer in Belgium. Prevention of skin cancer by community pharmacists can play a role in increasing awareness and promoting sun protection. However, which persons could be reached by community pharmacists for skin cancer awareness in Belgium and whether this increased awareness is associated with increased sun protection and early detection remains unclear. METHODS: Demographics of approached persons in Flemish community pharmacies during the months of May-June 2022 and the content of the skin cancer counseling were retrieved from the pharmacy database. Sunscreen purchases and dermatologist visits were evaluated up to 180 days after the skin cancer counseling. RESULTS: Community pharmacists provided skin cancer counseling to a broad population of visitors (n = 822, 69% females, median age of 59 years Q1-Q3: 44-71 years). During the campaign, 822 visitors received a leaflet with skin cancer prevalence and sunscreen importance. On top of that, 335 visitors (41%) received additional counseling: skin type sensitivity was checked for 198 visitors (24%), typical characteristics of melanoma were discussed with 100 visitors (12%) and 37 visitors (5%) were referred to a physician for further information or concerns regarding a skin spot. Overall, one out of three visitors purchased sunscreen on the day of the counseling (33%, increasing up to 38% after 180 days). Among people under 20 years, this was even higher (51%). Additional counseling increased the likelihood of a dermatologist visit within 180 days (OR = 1.80; 95%CI: 1.12-2.88). CONCLUSIONS: By providing skin cancer counseling in Belgian community pharmacies, a broad range of citizens was reached and triggered to purchase sunscreen, often on the same day as the counseling. Notably, young people were likely to purchase sunscreen. Citizens receiving additional counseling were more likely to visit a dermatologist within 180 days.

Vaccine effectiveness against transmission of alpha, delta and omicron SARS-COV-2-infection, Belgian contact tracing, 2021-2022.

OBJECTIVES: Vaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC). METHODS: We fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022. RESULTS: For primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95-97) against Alpha, 87% (95%CI 84-88) against Delta and 31% (95%CI 25-37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86-89) against Delta and 68% (95%CI 65-70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62) respectively, 150-200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission. CONCLUSIONS: While we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.

COVID-19 surveillance in the Flemish school system: development of systematic data collection within the public health school system and descriptive analysis of cases reported between October 2020 and June 2021.

BACKGROUND: The age-specific distribution of SARS-CoV-2 cases in schools is not well described. Reported statistics reflect the intensity of community transmission while being shaped by biases from age-dependent testing regimes, as well as effective age-specific interventions. A case surveillance system was introduced within the Flemish school and health-prevention network during the 2020-2021 school year. We present epidemiological data of in-school reported cases in pre-, primary and secondary schools identified by the case surveillance system, in conjunction with test data and community cases from October 2020 to June 2021. METHODS: We describe the development of the surveillance system and provide the number of reported cases and standardized rates per grade over time. We calculated absolute and relative differences in case incidence according to school grade (primary: grades 1-6, and secondary: grades 7-12) using grades 7-8 as a comparator, relating them to non-pharmaceutical infection prevention interventions. Cumulative population incidences (IP) stratified by age, province and socioeconomic status (SES) of the school population are presented with their 95% confidence intervals (CI). RESULTS: A total of 59,996 COVID-19 cases were reported in the school surveillance system, with the highest population adjusted IP in grade 11-12 of 7.39% (95%CI 7.24-7.53) and ranging from 2.23% to 6.25% from pre-school through grade 10. Age-specific reductions in mask introduction and in-person teaching were temporally associated with decreased case incidence, while lower pupil SES was associated with an increase in cumulative cases (excess 2,739/100,000 pupils compared to highest SES tertile). Community testing volumes varied more for children compared to adults, with overall higher child test-positivity. Holidays influence capturing of cases by the system, however efficiency increased to above 75% after further automation and integration in existing structures. CONCLUSION: We demonstrate that effective integration of case surveillance within an electronic school health system is feasible, provides valuable data regarding the evolution of an epidemic among schoolchildren, and is an integral component of public health surveillance and pandemic preparedness. The relationship towards community transmission needs careful evaluation because of age-different testing regimens. In the Flemish region, case incidence within schools exhibited an age gradient that was mitigated through grade-specific interventions, though differences by SES remain.

Post COVID-19 condition and its physical, mental and social implications: protocol of a 2-year longitudinal cohort study in the Belgian adult population.

BACKGROUND: Since the onset of the COVID-19 pandemic, most research has focused on the pathophysiology and management of the acute symptoms of COVID-19, yet some people tend to experience symptoms beyond the acute phase of infection, that is, Post COVID-19 condition (PCC). However, evidence on the long-term health impacts of a COVID-19 infection are still scarce. The purpose of this paper is to describe the COVIMPACT study, which aims to set up a cohort of people who have been tested positive for COVID-19 and study the evolution of their physical, mental and social health over the medium (3 months) and long term (two years), and the factors associated with an (un)favorable evolution. METHODS: COVIMPACT is a longitudinal cohort study organised over a two-years period between April 2021 and April 2023. The eligible population is all people aged 18 years and older, living in Belgium, with a recent COVID-19 infection and contacted by the health authorities for contact tracing. Two questionnaires are used: a baseline questionnaire that aims to assess the initial health status of the participants and their status during the acute phase of the illness, and a follow-up questionnaire that is sent every three months after participants enter into the cohort. A matched non-COVID-19 control group was also selected. As of November 1, 2021, 10,708 people completed the baseline questionnaire (5% of the eligible population) and the follow-up participation rate was 79%. In total, 48% of the cohort participants appeared to fit the proposed case definition of PCC (i.e. report at least one symptom related to their COVID-19 infection three months afterwards). DISCUSSION: This study was designed to provide timely information on the short and long term impact of a COVID-19 infection, to stakeholders such as policymakers, health practitioners and people with PCC. Although the follow-up participation rate was good (79%), the participation rate of the eligible population was low (5%). Compared to other studies, this study has a large sample, of non-hospitalised and hospitalised people, who will be followed over a long period of 3 months to two years post infection, and with a global approach to their health.

Serial Intervals for SARS-CoV-2 Omicron and Delta Variants, Belgium, November 19-December 31, 2021.

We investigated the serial interval for SARS-CoV-2 Omicron BA.1 and Delta variants and observed a shorter serial interval for Omicron, suggesting faster transmission. Results indicate a relationship between empirical serial interval and vaccination status for both variants. Further assessment of the causes and extent of Omicron dominance over Delta is warranted.

Vaccine effectiveness against onward transmission of SARS-CoV2-infection by variant of concern and time since vaccination, Belgian contact tracing, 2021.

BACKGROUND: During the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-'variant of concern' (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment. METHODS: We estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event. FINDINGS: VET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0-50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72-64%) and especially of VEi (71-46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150-200 days after vaccination). We observed lower initial VEi in the age group 65-84 years (32% vs 46% in the age group 45-64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity. INTERPRETATION: VEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.

COVID-19 contact tracing in Belgium: main indicators and performance, January - September 2021.

BACKGROUND: Contact tracing is one of the main public health tools in the control of coronavirus disease 2019 (COVID-19). A centralized contact tracing system was developed in Belgium in 2020. We aim to evaluate the performance and describe the results, between January 01, 2021, and September 30, 2021. The characteristics of COVID-19 cases and the impact of COVID-19 vaccination on testing and tracing are also described. METHODS: We combined laboratory diagnostic test data (molecular and antigen test), vaccination data, and contact tracing data. A descriptive analysis was done to evaluate the performance of contact tracing and describe insights into the epidemiology of COVID-19 by contact tracing. RESULTS: Between January and September 2021, 555.181 COVID-19 cases were reported to the central contact center and 91% were contacted. The average delay between symptom onset and contact tracing initiation was around 5 days, of which 4 days corresponded to pre-testing delay. High-Risk Contacts (HRC) were reported by 49% of the contacted index cases. The mean number of reported HRC was 2.7. In total, 666.869 HRC were reported of which 91% were successfully contacted and 89% of these were tested at least once following the interview. The estimated average secondary attack rate (SAR) among the contacts of the COVID-19 cases who reported at least one contact, was 27% and was significantly higher among household HRC. The proportion of COVID-19 cases who were previously identified as HRC within the central system was 24%. CONCLUSIONS: The contact-tracing system contacted more than 90% of the reported COVID-19 cases and their HRC. This proportion remained stable between January 1 2021 and September 30 2021 despite an increase in cases in March-April 2021. We report high SAR, indicating that through contact tracing a large number of infections were prospectively detected. The system can be further improved by (1) reducing the delay between onset of illness and medical consultation (2) having more exhaustive reporting of HRC by the COVID-19 case.

COVID-19 cases, hospitalizations and deaths in Belgian nursing homes: results of a surveillance conducted between April and December 2020.

BACKGROUND: In Belgium, the first COVID-19 death was reported on 10 March 2020. Nursing home (NH) residents are particularly vulnerable for COVID-19, making it essential to follow-up the spread of COVID-19 in this setting. This manuscript describes the methodology of surveillance and epidemiology of COVID-19 cases, hospitalizations and deaths in Belgian NHs. METHODS: A COVID-19 surveillance in all Belgian NHs (n = 1542) was set up by the regional health authorities and Sciensano. Aggregated data on possible/confirmed COVID-19 cases and hospitalizations and case-based data on deaths were reported by NHs at least once a week. The study period covered April-December 2020. Weekly incidence/prevalence data were calculated per 1000 residents or staff members. RESULTS: This surveillance has been launched within 14 days after the first COVID-19 death in Belgium. Automatic data cleaning was installed using different validation rules. More than 99% of NHs participated at least once, with a median weekly participation rate of 95%. The cumulative incidence of possible/confirmed COVID-19 cases among residents was 206/1000 in the first wave and 367/1000 in the second wave. Most NHs (82%) reported cases in both waves and 74% registered ≥10 possible/confirmed cases among residents at one point in time. In 51% of NHs, at least 10% of staff was absent due to COVID-19 at one point. Between 11 March 2020 and 3 January 2021, 11,329 COVID-19 deaths among NH residents were reported, comprising 57% of all COVID-19 deaths in Belgium in that period. CONCLUSIONS: This surveillance was crucial in mapping COVID-19 in this vulnerable setting and guiding public health interventions, despite limitations of aggregated data and necessary changes in protocol over time. Belgian NHs were severely hit by COVID-19 with many fatal cases. The measure of not allowing visitors, implemented in the beginning of the pandemic, could not avoid the spread of SARS-CoV-2 in the NHs during the first wave. The virus was probably often introduced by staff. Once the virus was introduced, it was difficult to prevent healthcare-associated outbreaks. Although, in contrast to the first wave, personal protective equipment was available in the second wave, again a high number of cases were reported.

Vaccine effectiveness against infection and onwards transmission of COVID-19: Analysis of Belgian contact tracing data, January-June 2021.

In Belgium, high-risk contacts of an infected person were offered PCR-testing irrespective of their vaccination status. We estimated vaccine effectiveness (VE) against infection and onwards transmission, controlling for previous infections, household-exposure and temporal trends. We included 301,741 tests from 25 January to 24 June 2021. Full-schedule vaccination was associated with significant protection against infection. In addition, mRNA-vaccines reduced onward transmission: VE-estimates increased to >90% when index and contact were fully vaccinated. The small number of viral-vector vaccines included limited interpretability.