Homologous and Heterologous Prime-Boost Vaccination: Impact on Clinical Severity of SARS-CoV-2 Omicron Infection among Hospitalized COVID-19 Patients in Belgium.

We investigated effectiveness of (1) mRNA booster vaccination versus primary vaccination only and (2) heterologous (viral vector-mRNA) versus homologous (mRNA-mRNA) prime-boost vaccination against severe outcomes of BA.1, BA.2, BA.4 or BA.5 Omicron infection (confirmed by whole genome sequencing) among hospitalized COVID-19 patients using observational data from national COVID-19 registries. In addition, it was investigated whether the difference between the heterologous and homologous prime-boost vaccination was homogenous across Omicron sub-lineages. Regression standardization (parametric g-formula) was used to estimate counterfactual risks for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality under exposure to different vaccination schedules. The estimated risk for severe COVID-19 and in-hospital mortality was significantly lower with an mRNA booster vaccination as compared to only a primary vaccination schedule (RR = 0.59 [0.33; 0.85] and RR = 0.47 [0.15; 0.79], respectively). No significance difference was observed in the estimated risk for severe COVID-19, ICU admission and in-hospital mortality with a heterologous compared to a homologous prime-boost vaccination schedule, and this difference was not significantly modified by the Omicron sub-lineage. Our results support evidence that mRNA booster vaccination reduced the risk of severe COVID-19 disease during the Omicron-predominant period.

Evaluating methodological approaches to assess the severity of infection with SARS-CoV-2 variants: scoping review and applications on Belgian COVID-19 data.

BACKGROUND: Differences in the genetic material of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in altered virulence characteristics. Assessing the disease severity caused by newly emerging variants is essential to estimate their impact on public health. However, causally inferring the intrinsic severity of infection with variants using observational data is a challenging process on which guidance is still limited. We describe potential limitations and biases that researchers are confronted with and evaluate different methodological approaches to study the severity of infection with SARS-CoV-2 variants. METHODS: We reviewed the literature to identify limitations and potential biases in methods used to study the severity of infection with a particular variant. The impact of different methodological choices is illustrated by using real-world data of Belgian hospitalized COVID-19 patients. RESULTS: We observed different ways of defining coronavirus disease 2019 (COVID-19) disease severity (e.g., admission to the hospital or intensive care unit versus the occurrence of severe complications or death) and exposure to a variant (e.g., linkage of the sequencing or genotyping result with the patient data through a unique identifier versus categorization of patients based on time periods). Different potential selection biases (e.g., overcontrol bias, endogenous selection bias, sample truncation bias) and factors fluctuating over time (e.g., medical expertise and therapeutic strategies, vaccination coverage and natural immunity, pressure on the healthcare system, affected population groups) according to the successive waves of COVID-19, dominated by different variants, were identified. Using data of Belgian hospitalized COVID-19 patients, we were able to document (i) the robustness of the analyses when using different variant exposure ascertainment methods, (ii) indications of the presence of selection bias and (iii) how important confounding variables are fluctuating over time. CONCLUSIONS: When estimating the unbiased marginal effect of SARS-CoV-2 variants on the severity of infection, different strategies can be used and different assumptions can be made, potentially leading to different conclusions. We propose four best practices to identify and reduce potential bias introduced by the study design, the data analysis approach, and the features of the underlying surveillance strategies and data infrastructure.

SARS-CoV-2 Transmission in Belgian French-Speaking Primary Schools: An Epidemiological Pilot Study.

Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.

Effects of surgical facemasks on perceived exertion during submaximal exercise test in healthy children.

Only a few data associated to wearability of facemask during exercise are available in children. The aim of the study was to evaluate the effect of wearing a facemask on perceived exertion (primary aim), dyspnea, physical performance, and cardiorespiratory response during a submaximal exercise test in children aged between 8 and 12 years. This study was performed in 2021 in healthy volunteer children from 8 to 12 years. They performed prospectively two 1-min sit-to-stand tests (STST), with or without a surgical facemask. The perceived exertion (modified Borg scale), dyspnea (Dalhousie scale), heart rate, and pulsed oxygen saturation were recorded before and after STST. The STST measured the submaximal performance. Thirty-eight healthy children were recruited (8-9 years: n = 19 and 10-11 years: n = 19). After the STST, the perceived exertion increased with or without a facemask (8-9 years group: + 1 [0.6; 1.4] and + 1.6 [1.0; 2.1] - 10-11 years group: + 1.3 [0.7; 1.8] and + 1.9 [1.3; 2.6]) and it was higher with the facemask. The difference between the two conditions in perceived exertion was not clinically relevant in any group (mBorgf: 0.56 pts and 0.68 pts, respectively). The different domains of dyspnea assessed with Dalhousie scale were not influenced by the facemask. The submaximal performance measured by the STST was not changed by the mask whatever the age group. The cardio-respiratory demand was not clinically modified.Conclusion: The surgical facemask had no impact on dyspnea, cardiorespiratory parameters, and exercise performance during a short submaximal exercise in healthy children.

Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients.

BACKGROUND: SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor. The resulting endothelial injury induces widespread thrombosis and microangiopathy. Nevertheless, early specific markers of endothelial dysfunction and vascular redox status in COVID-19 patients are currently missing. METHODS: Observational study including ICU and non-ICU adult COVID-19 patients admitted in hospital for acute respiratory failure, compared with control subjects matched for cardiovascular risk factors similar to ICU COVID-19 patients, and ICU septic shock patients unrelated to COVID-19. FINDINGS: Early SARS-CoV-2 infection was associated with an imbalance between an exacerbated oxidative stress (plasma peroxides levels in ICU patients vs. controls: 1456.0 ± 400.2 vs 436 ± 272.1 mmol/L; P < 0.05) and a reduced nitric oxide bioavailability proportional to disease severity (5-α-nitrosyl-hemoglobin, HbNO in ICU patients vs. controls: 116.1 ± 62.1 vs. 163.3 ± 46.7 nmol/L; P < 0.05). HbNO levels correlated with oxygenation parameters (PaO2/FiO2 ratio) in COVID-19 patients (R2 = 0.13; P < 0.05). Plasma levels of angiotensin II, aldosterone, renin or serum level of TREM-1 ruled out any hyper-activation of the renin-angiotensin-aldosterone system or leucocyte respiratory burst in ICU COVID-19 patients, contrary to septic patients. INTERPRETATION: Endothelial oxidative stress with ensuing decreased NO bioavailability appears as a likely pathogenic factor of endothelial dysfunction in ICU COVID-19 patients. A correlation between NO bioavailability and oxygenation parameters is observed in hospitalized COVID-19 patients. These results highlight an urgent need for oriented research leading to a better understanding of the specific endothelial oxidative stress that occurs during SARS-CoV-2. FUNDING: Stated in the acknowledgments section.

A systematic review and meta-analysis of host genetic factors associated with influenza severity.

BACKGROUND: The severity of influenza disease can range from mild symptoms to severe respiratory failure and can partly be explained by host genetic factors that predisposes the host to severe influenza. Here, we aimed to summarize the current state of evidence that host genetic variants play a role in the susceptibility to severe influenza infection by conducting a systematic review and performing a meta-analysis for all markers with at least three or more data entries. RESULTS: A total of 34 primary human genetic association studies were identified that investigated a total of 20 different genes. The only significant pooled ORs were retrieved for the rs12252 polymorphism: an overall OR of 1.52 (95% CI [1.06-2.17]) for the rs12252-C allele compared to the rs12252-T allele. A stratified analysis by ethnicity revealed opposite effects in different populations. CONCLUSION: With exception for the rs12252 polymorphism, we could not identify specific genetic polymorphisms to be associated with severe influenza infection in a pooled meta-analysis. This advocates for the use of large, hypothesis-free, genome-wide association studies that account for the polygenic nature and the interactions with other host, pathogen and environmental factors.

Seroprevalence of SARS-CoV-2 infection in health care workers of a teaching hospital in Belgium: self-reported occupational and household risk factors for seropositivity.

This study aims to evaluate SARS-CoV-2 seroprevalence among health care workers (HCWs) and to assess self-reported risk factors for seropositivity. A total of 3255 HCWs were included and the overall seroprevalence was 7.8%. The likelihood of seropositivity was higher in participants reporting any COVID-19 symptoms within the last 4 months (OR 8.32, 95% CI 5.83-11.88, P < 0.001). Being a female HCW (OR 1.32, 95% CI 1.11-2.32, P < 0.01), having a cohabitant who was infected with SARS-CoV-2 (OR 2.55, 95% CI 1.78-3.66 P < 0.001) or a cohabitant who was a nursing home caregiver (OR 3.71, 95% CI 1.59-8.65, P = 0.002) were independently associated with an increased risk of seropositivity. Working in a COVID-19 unit (OR 1.64, 95% CI 1.21-2.23, P < 0.001) and being exposed to a SARS-CoV-2 infected co-worker (OR 1.30,95% CI 0.97-1.74, P = 0.016) resulted in higher seropositivity rate. Even if in-hospital exposure may play a significant role, increased infection risk is most likely attributable to household contact.

Surgical mask on top of high-flow nasal cannula improves oxygenation in critically ill COVID-19 patients with hypoxemic respiratory failure.

OBJECTIVE: Critically ill patients admitted in ICU because of COVID-19 infection display severe hypoxemic respiratory failure. The Surviving Sepsis Campaign recommends oxygenation through high-flow nasal cannula over non-invasive ventilation. The primary outcome of our study was to evaluate the effect of the addition of a surgical mask on a high-flow nasal cannula system on oxygenation parameters in hypoxemic COVID-19 patients admitted in ICU who do not require urgent intubation. The secondary outcomes were relevant changes in PaCO2 associated with clinical modifications and patient's feelings. DESIGN: We prospectively assessed 21 patients admitted in our mixed Intensive Care Unit of the Cliniques Universitaires Saint Luc. MAIN RESULTS: While FiO2 was unchanged, we demonstrate a significant increase of PaO2 (from 59 (± 6), to 79 mmHg (± 16), p < 0.001), PaO2/FiO2 from 83 (± 22), to 111 (± 38), p < 0.001) and SaO2 (from 91% (± 1.5), to 94% (± 1.6), p < 0.001), while the patients were under the surgical mask. The SpO2 returned to pre-treatment values when the surgical mask was removed confirming the effect of the device rather than a spontaneous positive evolution. CONCLUSION: A surgical mask placed on patient's face already treated by a High-flow nasal cannula device improves COVID-19 patient's oxygenation admitted in Intensive Care Unit for severe hypoxemic respiratory failure without any clinically relevant side.

A meta-analysis of potential biomarkers associated with severity of coronavirus disease 2019 (COVID-19).

BACKGROUND: Prognostic factors for the Coronavirus disease 2019 (COVID1-9) are not well established. This study aimed to summarize the available data on the association between the severity of COVID-19 and common hematological, inflammatory and biochemical parameters. METHODS: EMBASE, MEDLINE, Web of sciences were searched to identify all published studies providing relevant data. Random-effects meta-analysis was used to pool effect sizes. RESULTS: The bibliographic search yielded 287 citations, 31 of which were finally retained. Meta-analysis of standardized mean difference (SMD) between severe and non-severe COVID-19 cases showed that CK-MB (SMD = 0.68,95%CI: 0.48;0.87; P-value:< 0.001), troponin I (SMD = 0.71, 95%CI:0.42;1.00; P-value:< 0.001), D-dimer (SMD = 0.54,95%CI:0.31;0.77; P-value:< 0.001), prothrombin time (SMD = 0.48, 95%CI:0.23;0.73; P-value: < 0.001), procalcitonin (SMD = 0.72, 95%CI: 0.34;1,11; P-value:< 0.001), interleukin-6 (SMD = 0.93, 95%CI: 0.25;1.61;P-value: 0.007),C-reactive protein (CRP) (SMD = 1.34, 95%CI:0.83;1.86; P-value:< 0.001), ALAT (SMD = 0.53, 95%CI: 0.34;0,71; P-value:< 0.001), ASAT (SMD = 0.96, 95%CI: 0.58;1.34; P-value: < 0.001), LDH (SMD = 1.36, 95%CI: 0.75;1.98; P-value:< 0.001), CK (SMD = 0.48, 95%CI: 0.10;0.87; P-value:0.01), total bilirubin (SMD = 0.32, 95%CI: 0.18;0.47;P-value: < 0.001), γ-GT (SMD = 1.03, 95%CI: 0.83;1.22; P-value: < 0.001), myoglobin (SMD = 1.14, 95%CI: 0.81;1.47; P-value:< 0.001), blood urea nitrogen (SMD = 0.32, 95%CI: 0.18;0.47;P-value:< 0.001) and Creatininemia (SMD = 0.18, 95%CI: 0.01;0.35; P-value:0.04) were significantly more elevated in severe cases, in opposition to lymphocyte count (SMD = -0.57, 95%CI:-0.71; - 0.42; P-value: < 0.001) and proportion of lymphocytes (SMD = -0.81, 95%CI: - 1.12; - 0.49; P-value:< 0.001) which were found to be significantly lower in severe patients with other biomarker such as thrombocytes (SMD = -0.26, 95%CI: - 0.48; - 0.04; P-value:0.02), eosinophils (SMD = - 0.28, 95%CI:-0.50; - 0.06; P-value:0.01), haemoglobin (SMD = -0.20, 95%CI: - 0.37,-0.03; P-value:0.02), albuminemia (SMD-1.67,95%CI -2.40; - 0.94; P-value:< 0.001), which were also lower. Furthermore, severe COVID-19 cases had a higher risk to have lymphopenia (RR =1.66, 95%CI: 1.26;2.20; P-value:0.002), thrombocytopenia (RR = 1.86, 95%CI: 1.59;2.17; P-value: < 0.001), elevated procalcitonin level (RR = 2.94, 95%CI: 2.09-4.15; P-value:< 0.001), CRP (RR =1.41,95%CI: 1.17-1.70; P-value:0.003), ASAT(RR =2.27, 95%CI: 1.76;2.94; P-value:< 0.001), CK(RR = 2.61, 95%CI: 1.35;5.05; P-value: 0.01), Creatininemia (RR = 3.66, 95%CI: 1.53;8.81; P-value: 0.02) and LDH blood level (RR = 2.03, 95%CI: 1.42;290; P-value: 0.003). CONCLUSION: Some inflammatory (procalcitonin, CRP), haematologic (lymphocyte, Thrombocytes), and biochemical (CK-MB, Troponin I, D-dimer, ASAT, ALAT, LDH, γ-GT) biomarkers are significantly associated with severe COVID-19. These biomarkers might help in prognostic risk stratification of patients with COVID-19.