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.

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.

Incidence and Risk Factors of COVID-19 Vaccine Breakthrough Infections: A Prospective Cohort Study in Belgium.

The objective of this study was to investigate the incidence and risk factors associated with COVID-19 vaccine breakthrough infections. We included all persons ≥18 years that had been fully vaccinated against COVID-19 for ≥14 days, between 1 February 2021 and 5 December 2021, in Belgium. The incidence of breakthrough infections (laboratory confirmed SARS-CoV-2-infections) was determined. Factors associated with breakthrough infections were analyzed using COX proportional hazard models. Among 8,062,600 fully vaccinated adults, we identified 373,070 breakthrough infections with an incidence of 11.2 (95%CI 11.2-11.3)/100 person years. Vaccination with Ad26.COV2.S (HR1.54, 95%CI 1.52-1.56) or ChAdOx1 (HR1.68, 95%CI 1.66-1.69) was associated with a higher risk of a breakthrough infection compared to BNT162b2, while mRNA-1273 was associated with a lower risk (HR0.68, 95%CI 0.67-0.69). A prior COVID-19-infection was protective against a breakthrough infection (HR0.23, 95%CI 0.23-0.24), as was an mRNA booster (HR0.44, 95%CI 0.43-0.45). During a breakthrough infection, those who had a prior COVID-19 infection were less likely to have COVID-19 symptoms of almost all types than naïve persons. We identified risk factors associated with breakthrough infections, such as vaccination with adenoviral-vector vaccines, which could help inform future decisions on booster vaccination strategies. A prior COVID-19 infection lowered the risk of breakthrough infections and of having symptoms, highlighting the protective effect of hybrid immunity.

Conceptual causal framework to assess the effect of SARS-CoV-2 variants on COVID-19 disease severity among hospitalized patients.

BACKGROUND: SARS-CoV-2 strains evolve continuously and accumulate mutations in their genomes over the course of the pandemic. The severity of a SARS-CoV-2 infection could partly depend on these viral genetic characteristics. Here, we present a general conceptual framework that allows to study the effect of SARS-CoV-2 variants on COVID-19 disease severity among hospitalized patients. METHODS: A causal model is defined and visualized using a Directed Acyclic Graph (DAG), in which assumptions on the relationship between (confounding) variables are made explicit. Various DAGs are presented to explore specific study design options and the risk for selection bias. Next, the data infrastructure specific to the COVID-19 surveillance in Belgium is described, along with its strengths and weaknesses for the study of clinical impact of variants. DISCUSSION: A well-established framework that provides a complete view on COVID-19 disease severity among hospitalized patients by combining information from different sources on host factors, viral factors, and healthcare-related factors, will enable to assess the clinical impact of emerging SARS-CoV-2 variants and answer questions that will be raised in the future. The framework shows the complexity related to causal research, the corresponding data requirements, and it underlines important limitations, such as unmeasured confounders or selection bias, inherent to repurposing existing routine COVID-19 data registries. TRIAL REGISTRATION: Each individual research project within the current conceptual framework will be prospectively registered in Open Science Framework (OSF identifier: https://doi.org/10.17605/OSF.IO/UEF29 ). OSF project created on 18 May 2021.

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.

Rapid establishment of a national surveillance of COVID-19 hospitalizations in Belgium.

BACKGROUND: In response to the COVID-19 epidemic, caused by a novel coronavirus, it was of great importance to rapidly collect as much accurate information as possible in order to characterize the public health threat and support the health authorities in its management. Hospital-based surveillance is paramount to monitor the severity of a disease in the population. METHODS: Two separate surveillance systems, a Surge Capacity survey and a Clinical survey, were set up to collect complementary data on COVID-19 from Belgium's hospitals. The Surge Capacity survey collects aggregated data to monitor the hospital capacity through occupancy rates of beds and medical devices, and to follow a set of key epidemiological indicators over time. Participation is mandatory and the daily data collection includes prevalence and incidence figures on the number of COVID-19 patients in the hospital. The Clinical survey is strongly recommended by health authorities, focusses on specific patient characteristics and relies on individual patient data provided by the hospitals at admission and discharge. CONCLUSIONS: This national double-level hospital surveillance was implemented very rapidly after the first COVID-19 patients were hospitalized and revealed to be crucial to monitor hospital capacity over time and to better understand the disease in terms of risk groups and outcomes. The two approaches are complementary and serve different needs.

Impact of solid cancer on in-hospital mortality overall and among different subgroups of patients with COVID-19: a nationwide, population-based analysis.

BACKGROUND: Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer. METHODS: We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis). RESULTS: A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (<60 years) and 2.27 (95% CI 1.41 to 3.64) among patients without other comorbidities. Severe event occurrence was similar in both groups (36.7% vs 28.8%; aOR 1.10; 95% CI 0.95 to 1.29). CONCLUSIONS: This population-based analysis demonstrates that solid cancer is an independent adverse prognostic factor for in-hospital mortality among patients with COVID-19. This adverse effect was more pronounced among younger patients and those without other comorbidities. Patients with solid cancer should be prioritised in vaccination campaigns and in tailored containment measurements.

Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants.

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617-0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617-0.796) and aHR = 0.647 (95% CI 0.525-0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.