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Viruses
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SARS-CoV-2 Research in Belgium
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SARS-CoV-2 Research in Belgium

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 71821

Special Issue Editors

Dr. Guy Baele

E-Mail Website
Guest Editor
Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, 3000 Leuven, Belgium
Interests: phylogenetic inference; phylogeographic inference; pathogen phylodynamics; molecular evolution; SARS-CoV-2 lineage analysis
Dr. Emmanuel André

E-Mail Website
Guest Editor
KU Leuven, Laboratory of Clinical Bacteriology and Mycology, campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
Interests: COVID-19 testing; contact tracing; SARS-CoV-2 diagnostics; clinical virology; epidemiology

Special Issue Information

Dear Colleagues,

Following the initial detection of the first COVID-19 infection in Belgium on February 3, 2020, many Belgian research groups initiated a wide panel of research initiatives targeting different aspects of the SARS-CoV-2 pandemic. In this Special Issue, we aim to collect and synergise this wide variety of high-quality research efforts on SARS-CoV-2 in Belgium. Because the pandemic and its consequences on the health system and society in general outpaces the traditional scope of virology research, we aim to stimulate outstanding virology research, but also research papers which have taken a multidisciplinary approach to complex problems. Manuscripts covering the analysis of the different waves of the pandemic that hit Belgium and localised outbreaks in nursing homes, hospitals, the work sector and schools will be analysed with a great deal of attention, together with studies on phylogenetic and phylodynamic inference, outbreak and transmission chain analysis, clinical studies assessing the impact of novel diagnostic or treatment approaches, next-generation sequencing efforts, mathematical and epidemiological model development, vaccine efficacy, and intervention strategies.

Dr. Guy Baele
Dr. Emmanuel André
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • COVID-19
  • Outbreak analysis
  • Transmission chain analysis
  • Pathogen phylodynamics
  • Next-generation sequencing
  • Vaccine efficacy
  • Demographic analysis
  • Epidemiological models
  • Diagnostics

Published Papers (27 papers)

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Research

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11 pages, 1574 KiB  
Article
Surfing the Waves: Differences in Hospitalised COVID-19 Patients across 4 Variant Waves in a Belgian University Hospital
by Lucie Seyler, Els Van Nedervelde, Diederik De Cock, Claudia Mann, Karen Pien, Sabine D. Allard and Thomas Demuyser
Viruses 2023, 15(3), 618; https://0-doi-org.brum.beds.ac.uk/10.3390/v15030618 - 23 Feb 2023
Cited by 7 | Viewed by 1404
Abstract
The unprecedented COVID-19 pandemic took the form of successive variant waves, spreading across the globe. We wanted to investigate any shift in hospitalised patients’ profiles throughout the pandemic. For this study, we used a registry that collected data automatically from electronic patient health [...] Read more.
The unprecedented COVID-19 pandemic took the form of successive variant waves, spreading across the globe. We wanted to investigate any shift in hospitalised patients’ profiles throughout the pandemic. For this study, we used a registry that collected data automatically from electronic patient health records. We compared clinical data and severity scores, using the National Institute of Health (NIH) severity scores, from all patients admitted for COVID-19 during four SARS-CoV-2 variant waves. Our study concluded that patients hospitalised for COVID-19 showed very different profiles across the four variant waves in Belgium. Patients were younger during the Alpha and Delta waves and frailer during the Omicron period. ‘Critical’ patients according to the NIH criteria formed the largest fraction among the Alpha wave patients (47.7%), while ‘severe’ patients formed the largest fraction among Omicron patients (61.6%). We discussed host factors, vaccination status, and other confounders to put this into perspective. High-quality real-life data remain crucial to inform stakeholders and policymakers that shifts in patients’ clinical profiles have an impact on clinical practice. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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10 pages, 988 KiB  
Article
Declining Prevalence of SARS-CoV-2 Antibodies among Vaccinated Nursing Home Residents and Staff Six Months after the Primary BNT162b2 Vaccination Campaign in Belgium: A Prospective Cohort Study
by Eline Meyers, Ellen Deschepper, Els Duysburgh, Liselore De Rop, Tine De Burghgraeve, Pauline Van Ngoc, Marina Digregorio, Simon Delogne, Anja Coen, Nele De Clercq, Laëtitia Buret, Samuel Coenen, An De Sutter, Beatrice Scholtes, Jan Y Verbakel, Piet Cools and Stefan Heytens
Viruses 2022, 14(11), 2361; https://0-doi-org.brum.beds.ac.uk/10.3390/v14112361 - 26 Oct 2022
Cited by 3 | Viewed by 1315
Abstract
In the SCOPE study, we monitored SARS-CoV-2 antibodies in a national sample of residents and staff from Belgian nursing homes. Here, we report the seroprevalence among infected and infection-naive residents and staff after the primary COVID-19 vaccination campaign. Among 1554 vaccinated nursing home [...] Read more.
In the SCOPE study, we monitored SARS-CoV-2 antibodies in a national sample of residents and staff from Belgian nursing homes. Here, we report the seroprevalence among infected and infection-naive residents and staff after the primary COVID-19 vaccination campaign. Among 1554 vaccinated nursing home residents and 1082 vaccinated staff from 69 nursing homes in Belgium, we assessed the proportion having SARS-CoV-2 antibodies approximately two (April 2021), four (June 2021), and six months (August 2021) after a two-dose regimen of the BNT162b2 vaccine. We measured the seroprevalence using SARS-CoV-2 antibody rapid tests and collected socio-demographic and COVID-19 medical data using an online questionnaire. Two months after vaccination (baseline), we found a seroprevalence of 91% (95% CI: 89–93) among vaccinated residents and 99% (95% CI: 98–99) among vaccinated staff. Six months after vaccination, the seroprevalence significantly decreased to 68% (95% CI: 64–72) among residents and to 89% (95% CI; 86–91) among staff (p < 0.001). The seroprevalence was more likely to decrease among infection-naive residents, older residents, or residents with a high care dependency level. These findings emphasize the need for close monitoring of nursing home residents, as a substantial part of this population fails to mount a persistent antibody response after BNT162b2 vaccination. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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10 pages, 1491 KiB  
Article
Healthcare-Associated COVID-19 across Five Pandemic Waves: Prediction Models and Genomic Analyses
by Thomas Demuyser, Lucie Seyler, Rhea Buttiens, Oriane Soetens, Els Van Nedervelde, Ben Caljon, Jessy Praet, Thomas Seyler, Joost Boeckmans, Jessy Meert, Robin Vanstokstraeten, Helena Martini, Florence Crombé, Denis Piérard, Sabine D. Allard and Ingrid Wybo
Viruses 2022, 14(10), 2292; https://0-doi-org.brum.beds.ac.uk/10.3390/v14102292 - 18 Oct 2022
Cited by 1 | Viewed by 1462
Abstract
Background: Healthcare-associated SARS-CoV-2 infections need to be explored further. Our study is an analysis of hospital-acquired infections (HAIs) and ambulatory healthcare workers (aHCWs) with SARS-CoV-2 across the pandemic in a Belgian university hospital. Methods: We compared HAIs with community-associated infections (CAIs) to identify [...] Read more.
Background: Healthcare-associated SARS-CoV-2 infections need to be explored further. Our study is an analysis of hospital-acquired infections (HAIs) and ambulatory healthcare workers (aHCWs) with SARS-CoV-2 across the pandemic in a Belgian university hospital. Methods: We compared HAIs with community-associated infections (CAIs) to identify the factors associated with having an HAI. We then performed a genomic cluster analysis of HAIs and aHCWs. We used this alongside the European Centre for Disease Control (ECDC) case source classifications of an HAI. Results: Between March 2020 and March 2022, 269 patients had an HAI. A lower BMI, a worse frailty index, lower C-reactive protein (CRP), and a higher thrombocyte count as well as death and length of stay were significantly associated with having an HAI. Using those variables to predict HAIs versus CAIs, we obtained a positive predictive value (PPV) of 83.6% and a negative predictive value (NPV) of 82.2%; the area under the ROC was 0.89. Genomic cluster analyses and representations on epicurves and minimal spanning trees delivered further insights into HAI dynamics across different pandemic waves. The genomic data were also compared with the clinical ECDC definitions for HAIs; we found that 90.0% of the ‘definite’, 87.8% of the ‘probable’, and 70.3% of the ‘indeterminate’ HAIs belonged to one of the twenty-two COVID-19 genomic clusters we identified. Conclusions: We propose a novel prediction model for HAIs. In addition, we show that the management of nosocomial outbreaks will benefit from genome sequencing analyses. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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15 pages, 3768 KiB  
Article
SARS-CoV-2 Transmission in Belgian French-Speaking Primary Schools: An Epidemiological Pilot Study
by Julie Frère, Olga Chatzis, Kelly Cremer, Joanna Merckx, Mathilde De Keukeleire, Florence Renard, Nathalie Ribesse, Frédéric Minner, Jean Ruelle, Benoit Kabamba, Hector Rodriguez-Villalobos, Bertrand Bearzatto, Marie-Luce Delforge, Coralie Henin, Fabrice Bureau, Laurent Gillet, Annie Robert and Dimitri Van der Linden
Viruses 2022, 14(10), 2199; https://0-doi-org.brum.beds.ac.uk/10.3390/v14102199 - 06 Oct 2022
Viewed by 1525
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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24 pages, 706 KiB  
Article
Follow-Up of a Cohort of Patients with Post-Acute COVID-19 Syndrome in a Belgian Family Practice
by Marc Jamoulle, Gisele Kazeneza-Mugisha and Ayoub Zayane
Viruses 2022, 14(9), 2000; https://0-doi-org.brum.beds.ac.uk/10.3390/v14092000 - 09 Sep 2022
Cited by 4 | Viewed by 4053
Abstract
Fifty-five patients who suffered from COVID-19, who were still very ill after several months, with extreme fatigue, effort exhaustion, brain fog, anomia, memory disorder, anosmia, dysgeusia, and other multi-systemic health problems have been followed in a family practice setting between May 2021 and [...] Read more.
Fifty-five patients who suffered from COVID-19, who were still very ill after several months, with extreme fatigue, effort exhaustion, brain fog, anomia, memory disorder, anosmia, dysgeusia, and other multi-systemic health problems have been followed in a family practice setting between May 2021 and July 2022. Data extracted from the medical records of the 55 patients (40 women), mean age 42.4 (12 to 79 years), and a qualitative study of 6 of them using a semi-open-ended questionnaire allowed to highlight the clinical picture described by WHO as post-acute COVID-19 syndrome (PACS) also known as long COVID. We used brain single-photon emission computed tomography (SPECT-CT) in thirty-two patients with a high severity index and a highly impaired functional status, demonstrating vascular encephalopathy in twenty nine patients and supporting the hypothesis of a persistent cerebral vascular flow disorder in post COVID-19 condition. The patients will benefit from the consortium COVID Human Genetic Effort (covidhge.com) to explore the genetic and immunological basis of their problem, as 23/55 cases don’t have immunological certainty of a COVID-19 infection. There is no known verified treatment. Analyzing the data from the first 52 patients, three categories of patients emerged over time: 16 patients made a full recovery after 6–8 months, 15 patients were able to return to life and work after 12–18 months with some sequelae, both groups being considered cured. In the third group, 21 patients are still very ill and unable to resume their work and life after 18 months. The biopsychosocial consequences on patients’ lives are severe and family doctors are left out in the cold. It is necessary to test the reproducibility of this description, conducted on a small number of patients. Nevertheless, identifying, monitoring and supporting these patients is a necessity in family medicine. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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13 pages, 910 KiB  
Article
SARS-CoV-2 Surveillance in Belgian Wastewaters
by Raphael Janssens, Sven Hanoteaux, Hadrien Maloux, Sofieke Klamer, Valeska Laisnez, Bavo Verhaegen, Catherine Linard, Lies Lahousse, Peter Delputte, Matthieu Terwagne, Jonathan Marescaux, Rosalie Pype, Christian Didy, Katelijne Dierick, Koenraad Van Hoorde and Marie Lesenfants
Viruses 2022, 14(9), 1950; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091950 - 02 Sep 2022
Cited by 6 | Viewed by 2164
Abstract
Wastewater-based surveillance was conducted by the national public health authority to monitor SARS-CoV-2 circulation in the Belgian population. Over 5 million inhabitants representing 45% of the Belgian population were monitored throughout 42 wastewater treatment plants for 15 months comprising three major virus waves. [...] Read more.
Wastewater-based surveillance was conducted by the national public health authority to monitor SARS-CoV-2 circulation in the Belgian population. Over 5 million inhabitants representing 45% of the Belgian population were monitored throughout 42 wastewater treatment plants for 15 months comprising three major virus waves. During the entire period, a high correlation was observed between the daily new COVID-19 cases and the SARS-CoV-2 concentration in wastewater corrected for rain impact and covered population size. Three alerting indicators were included in the weekly epidemiological assessment: High Circulation, Fast Increase, and Increasing Trend. These indicators were computed on normalized concentrations per individual treatment plant to allow for a comparison with a reference period as well as between analyses performed by distinct laboratories. When the indicators were not corrected for rain impact, rainy events caused an underestimation of the indicators. Despite this negative impact, the indicators permitted us to effectively monitor the evolution of the fourth virus wave and were considered complementary and valuable information to conventional epidemiological indicators in the weekly wastewater reports communicated to the National Risk Assessment Group. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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9 pages, 1183 KiB  
Article
Evaluation of Saliva as a Matrix for RT-PCR Analysis and Two Rapid Antigen Tests for the Detection of SARS-CoV-2
by Julie De Meyer, Hanne Goris, Olivier Mortelé, An Spiessens, Guy Hans, Hilde Jansens, Herman Goossens, Veerle Matheeussen and Sarah Vandamme
Viruses 2022, 14(9), 1931; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091931 - 30 Aug 2022
Cited by 4 | Viewed by 2378
Abstract
The use of saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sparks debate due to presumed lower sensitivity and lack of standardization. Our aim was to evaluate the performance characteristics of (i) saliva collected by the ORAcollectTM device [...] Read more.
The use of saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sparks debate due to presumed lower sensitivity and lack of standardization. Our aim was to evaluate the performance characteristics of (i) saliva collected by the ORAcollectTM device as a matrix for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR), and (ii) 2 saliva rapid antigen tests (AgRDT). From 342 ambulatory individuals, both a nasopharyngeal swab and saliva sample via ORAcollectTM were obtained for a SARS-CoV-2 RT-PCR test. Furthermore, 54 and 123 additionally performed the V-ChekTM or WhistlingTM saliva AgRDT. In total, 35% of individuals screened positive for SARS-CoV-2 via nasopharyngeal swab. Saliva, as a matrix for the RT-PCR, had a specificity of 96.5% and a negative predictive value (NPV) of 91.3%. Interestingly, 6 out of 8 patients thought to be false positive in saliva re-tested positive by nasopharyngeal sampling after 2 to 9 days. Both V-ChekTM and WhistlingTM AgRDT had a lack of sensitivity, resulting in an NPV of 66.9 and 67.3%, respectively. Saliva proved to be a sensitive and specific matrix for SARS-CoV-2 detection by the RT-PCR. In this setting, saliva might have an earlier window of detection than the nasopharyngeal swab. By contrast, both AgRDT showed an unacceptably low sensitivity and NPV. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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13 pages, 1900 KiB  
Article
Serum SARS-CoV-2 Antigens for the Determination of COVID-19 Severity
by Julien Favresse, Jean-Louis Bayart, Clara David, Constant Gillot, Grégoire Wieërs, Gatien Roussel, Guillaume Sondag, Marc Elsen, Christine Eucher, Jean-Michel Dogné and Jonathan Douxfils
Viruses 2022, 14(8), 1653; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081653 - 28 Jul 2022
Cited by 12 | Viewed by 2060
Abstract
The diagnostic of SARS-CoV-2 infection relies on reverse transcriptase polymerase chain reactions (RT-PCRs) performed on nasopharyngeal (NP) swabs. Nevertheless, false-negative results can be obtained with inadequate sampling procedures, making the use of other biological matrices worthy of investigation. This study aims to evaluate [...] Read more.
The diagnostic of SARS-CoV-2 infection relies on reverse transcriptase polymerase chain reactions (RT-PCRs) performed on nasopharyngeal (NP) swabs. Nevertheless, false-negative results can be obtained with inadequate sampling procedures, making the use of other biological matrices worthy of investigation. This study aims to evaluate the kinetics of serum N antigens in severe and non-severe patients and compare the clinical performance of serum antigenic assays with NP RT-PCR. Ninety patients were included in the study and monitored for several days. Disease severity was determined according to the WHO clinical progression scale. Serum N antigen levels were measured with a chemiluminescent assay (CLIA) and the Single Molecular Array (Simoa) assay. Viremia thresholds for severity were determined and proposed. In severe patients, the peak antigen response was observed 7 days after the onset of symptoms, followed by a decline. No real peak response was observed in non-severe patients. Severity thresholds for the Simoa and the CLIA provided positive likelihood ratios of 30.0 and 10.9 for the timeframe between day 2 and day 14, respectively. Sensitive detection of N antigens in serum may thus provide a valuable new marker for COVID-19 diagnosis and evaluation of disease severity. When assessed during the first 2 weeks since the onset of symptoms, it may help in identifying patients at risk of developing severe COVID-19 to optimize better intensive care utilization. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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11 pages, 264 KiB  
Article
SARS-CoV-2 Seroprevalence among Healthcare Workers after the First and Second Pandemic Waves
by Nathalie de Visscher, Xavier Holemans, Aline Gillain, Anne Kornreich, Raphael Lagasse, Philippe Piette, Manfredi Ventura and Frédéric Thys
Viruses 2022, 14(7), 1535; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071535 - 14 Jul 2022
Cited by 2 | Viewed by 1445
Abstract
Background: The Grand Hôpital de Charleroi is a large non-academic Belgian hospital that treated a large number of COVID-19 inpatients. In the context of this pandemic, all professions-combined healthcare workers (HCWs), and not only direct caregivers, are a frontline workforce in contact with [...] Read more.
Background: The Grand Hôpital de Charleroi is a large non-academic Belgian hospital that treated a large number of COVID-19 inpatients. In the context of this pandemic, all professions-combined healthcare workers (HCWs), and not only direct caregivers, are a frontline workforce in contact with suspected and confirmed COVID-19 cases and seem to be a high-risk group for exposure. The aim of our study was to estimate the prevalence of anti-SARS-CoV-2 antibodies in HCWs in our hospital after the first and second pandemic waves and to characterize the distribution of this seroprevalence in relation to various criteria. Methods: At the end of the two recruitment periods, a total of 4008 serological tests were performed in this single-center cross-sectional study. After completing a questionnaire including demographic and personal data, possible previous COVID-19 diagnostic test results and/or the presence of symptoms potentially related to COVID-19, the study participants underwent blood sampling and serological testing using DiaSorin’s LIAISON® SARS-CoV-2 S1/S2 IgG test for the first phase and LIAISON® SARS-CoV-2 TrimericS IgG test for the second phase of this study. Results: In total, 302 study participants (10.72%) in the first round of the study and 404 (33.92%) in the second round were positive for SARS-CoV-2-IgG antibodies. The prevalence of seropositivity observed after the second wave was 3.16 times higher than after the first wave. We confirmed that direct, prolonged, and repeated contact with patients or their environment was a predominant seroconversion factor, but more unexpectedly, that this was the case for all HCWs and not only caregivers. Finally, the notion of high-risk contact seemed more readily identifiable in one’s workplace than in one’s private life. Conclusions: Our study confirmed that HCWs are at a significantly higher risk of contracting COVID-19 than the general population, and suggests that repeated contacts with at-risk patients, regardless of the HCWs’ professions, represents the most important risk factor for seroconversion (Clinicaltrials.gov number, NCT04723290). Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
11 pages, 1475 KiB  
Article
Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19—BNT162b2 mRNA Vaccination
by Emilie Catry, Julien Favresse, Constant Gillot, Jean-Louis Bayart, Damien Frérotte, Michel Dumonceaux, Patrick Evrard, François Mullier, Jonathan Douxfils, François M. Carlier and Mélanie Closset
Viruses 2022, 14(7), 1470; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071470 - 02 Jul 2022
Cited by 4 | Viewed by 1900
Abstract
(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 [...] Read more.
(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0–491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0–159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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17 pages, 1315 KiB  
Communication
HYGIEIA: HYpothesizing the Genesis of Infectious Diseases and Epidemics through an Integrated Systems Biology Approach
by Bradley Ward, Jean Cyr Yombi, Jean-Luc Balligand, Patrice D. Cani, Jean-François Collet, Julien de Greef, Joseph P. Dewulf, Laurent Gatto, Vincent Haufroid, Sébastien Jodogne, Benoît Kabamba, Sébastien Pyr dit Ruys, Didier Vertommen, Laure Elens and Leïla Belkhir
Viruses 2022, 14(7), 1373; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071373 - 23 Jun 2022
Cited by 1 | Viewed by 2547
Abstract
More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic [...] Read more.
More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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16 pages, 1853 KiB  
Article
Evaluation of Screening Program and Phylogenetic Analysis of SARS-CoV-2 Infections among Hospital Healthcare Workers in Liège, Belgium
by Majdouline El Moussaoui, Nathalie Maes, Samuel L. Hong, Nicolas Lambert, Stéphanie Gofflot, Patricia Dellot, Yasmine Belhadj, Pascale Huynen, Marie-Pierre Hayette, Cécile Meex, Sébastien Bontems, Justine Defêche, Lode Godderis, Geert Molenberghs, Christelle Meuris, Maria Artesi, Keith Durkin, Souad Rahmouni, Céline Grégoire, Yves Beguin, Michel Moutschen, Simon Dellicour and Gilles Darcisadd Show full author list remove Hide full author list
Viruses 2022, 14(6), 1302; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061302 - 14 Jun 2022
Cited by 3 | Viewed by 2088
Abstract
Healthcare workers (HCWs) are known to be at higher risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections although whether these risks are equal across all occupational roles is uncertain. Identifying these risk factors and understand SARS-CoV-2 transmission pathways in healthcare [...] Read more.
Healthcare workers (HCWs) are known to be at higher risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections although whether these risks are equal across all occupational roles is uncertain. Identifying these risk factors and understand SARS-CoV-2 transmission pathways in healthcare settings are of high importance to achieve optimal protection measures. We aimed to investigate the implementation of a voluntary screening program for SARS-CoV-2 infections among hospital HCWs and to elucidate potential transmission pathways though phylogenetic analysis before the vaccination era. HCWs of the University Hospital of Liège, Belgium, were invited to participate in voluntary reverse transcriptase-polymerase chain reaction (RT-PCR) assays performed every week from April to December 2020. Phylogenetic analysis of SARS-CoV-2 genomes were performed for a subgroup of 45 HCWs. 5095 samples were collected from 703 HCWs. 212 test results were positive, 15 were indeterminate, and 4868 returned negative. 156 HCWs (22.2%) tested positive at least once during the study period. All SARS-CoV-2 test results returned negative for 547 HCWs (77.8%). Nurses (p < 0.05), paramedics (p < 0.05), and laboratory staff handling respiratory samples (p < 0.01) were at higher risk for being infected compared to the control non-patient facing group. Our phylogenetic analysis revealed that most positive samples corresponded to independent introduction events into the hospital. Our findings add to the growing evidence of differential risks of being infected among HCWs and support the need to implement appropriate protection measures based on each individual’s risk profile to guarantee the protection of both HCWs and patients. Furthermore, our phylogenetic investigations highlight that most positive samples correspond to distinct introduction events into the hospital. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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16 pages, 785 KiB  
Article
Clinical Severity of SARS-CoV-2 Omicron Variant Compared with Delta among Hospitalized COVID-19 Patients in Belgium during Autumn and Winter Season 2021–2022
by Nina Van Goethem, Pui Yan Jenny Chung, Marjan Meurisse, Mathil Vandromme, Laurane De Mot, Ruben Brondeel, Veerle Stouten, Sofieke Klamer, Lize Cuypers, Toon Braeye, Lucy Catteau, Louis Nevejan, Joris A. F. van Loenhout and Koen Blot
Viruses 2022, 14(6), 1297; https://doi.org/10.3390/v14061297 - 14 Jun 2022
Cited by 39 | Viewed by 3665
Abstract
This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with the Omicron variant compared to when infected with the Delta variant. The study [...] Read more.
This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with the Omicron variant compared to when infected with the Delta variant. The study is based on a causal framework using individually-linked data from national COVID-19 registries. The study population consisted of 954 COVID-19 patients (of which, 445 were infected with Omicron) above 18 years old admitted to a Belgian hospital during the autumn and winter season 2021–2022, and with available viral genomic data. Patients were matched based on the hospital, whereas other possible confounders (demographics, comorbidities, vaccination status, socio-economic status, and ICU occupancy) were adjusted for by using a multivariable logistic regression analysis. The estimated standardized risk for severe COVID-19 and ICU admission in hospitalized patients was significantly lower (RR = 0.63; 95% CI (0.30; 0.97) and RR = 0.56; 95% CI (0.14; 0.99), respectively) when infected with the Omicron variant, whereas in-hospital mortality was not significantly different according to the SARS-CoV-2 variant (RR = 0.78, 95% CI (0.28–1.29)). This study demonstrates the added value of integrated genomic and clinical surveillance to recognize the multifactorial nature of COVID-19 pathogenesis. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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17 pages, 551 KiB  
Article
Nationwide Harmonization Effort for Semi-Quantitative Reporting of SARS-CoV-2 PCR Test Results in Belgium
by Lize Cuypers, Jannes Bode, Kurt Beuselinck, Lies Laenen, Klaas Dewaele, Reile Janssen, Arnaud Capron, Yves Lafort, Henry Paridaens, Bertrand Bearzatto, Mathieu Cauchie, Aline Huwart, Jonathan Degosserie, Olivier Fagnart, Yarah Overmeire, Arlette Rouffiange, Ilse Vandecandelaere, Marine Deffontaine, Thomas Pilate, Nicolas Yin, Isabel Micalessi, Sandrine Roisin, Veronique Moons, Marijke Reynders, Sophia Steyaert, Coralie Henin, Elena Lazarova, Dagmar Obbels, François E. Dufrasne, Hendri Pirenne, Raf Schepers, Anaëlle Collin, Bruno Verhasselt, Laurent Gillet, Stijn Jonckheere, Philippe Van Lint, Bea Van den Poel, Yolien Van der Beken, Violeta Stojkovic, Maria-Grazia Garrino, Hannah Segers, Kevin Vos, Maaike Godefroid, Valerie Pede, Friedel Nollet, Vincent Claes, Inge Verschraegen, Pierre Bogaerts, Marjan Van Gysel, Judith Leurs, Veroniek Saegeman, Oriane Soetens, Merijn Vanhee, Gilberte Schiettekatte, Evelyne Huyghe, Steven Martens, Ann Lemmens, Heleen Nailis, Kim Laffineur, Deborah Steensels, Elke Vanlaere, Jérémie Gras, Gatien Roussel, Koenraad Gijbels, Michael Boudewijns, Catherine Sion, Wim Achtergael, Wim Maurissen, Luc Iliano, Marianne Chantrenne, Geert Vanheule, Reinoud Flies, Nicolas Hougardy, Mario Berth, Vanessa Verbeke, Robin Morent, Anne Vankeerberghen, Sébastien Bontems, Kaat Kehoe, Anneleen Schallier, Giang Ho, Kristof Bafort, Marijke Raymaekers, Yolande Pypen, Amelie Heinrichs, Wim Schuermans, Dominique Cuigniez, Salah Eddine Lali, Stefanie Drieghe, Dieter Ory, Marie Le Mercier, Kristel Van Laethem, Inge Thoelen, Sarah Vandamme, Iqbal Mansoor, Carl Vael, Maxime De Sloovere, Katrien Declerck, Elisabeth Dequeker, Stefanie Desmet, Piet Maes, Katrien Lagrou and Emmanuel Andréadd Show full author list remove Hide full author list
Viruses 2022, 14(6), 1294; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061294 - 14 Jun 2022
Cited by 13 | Viewed by 2862
Abstract
From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand [...] Read more.
From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand to report cycle threshold (Ct) values rapidly emerged. As Ct values can be affected by a number of factors, we considered that harmonization of semi-quantitative PCR results across laboratories would avoid potential divergent interpretations, particularly in the absence of clinical or serological information. A proposal to harmonize reporting of test results was drafted by the National Reference Centre (NRC) UZ/KU Leuven, distinguishing four categories of positivity based on RNA copies/mL. Pre-quantified control material was shipped to 124 laboratories with instructions to setup a standard curve to define thresholds per assay. For each assay, the mean Ct value and corresponding standard deviation was calculated per target gene, for the three concentrations (107, 105 and 103 copies/mL) that determine the classification. The results of 17 assays are summarized. This harmonization effort allowed to ensure that all Belgian laboratories would report positive PCR results in the same semi-quantitative manner to clinicians and to the national database which feeds contact tracing interventions. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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22 pages, 2115 KiB  
Article
High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium
by Bas Calcoen, Nico Callewaert, Aline Vandenbulcke, Winnie Kerstens, Maya Imbrechts, Thomas Vercruysse, Kai Dallmeier, Johan Van Weyenbergh, Piet Maes, Xavier Bossuyt, Dorinja Zapf, Kersten Dieckmann, Kim Callebaut, Hendrik Jan Thibaut, Karen Vanhoorelbeke, Simon F. De Meyer, Wim Maes and Nick Geukens
Viruses 2022, 14(6), 1257; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061257 - 09 Jun 2022
Cited by 6 | Viewed by 3202
Abstract
To mitigate the massive COVID-19 burden caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccination campaigns were initiated. We performed a single-center observational trial to monitor the mid- (3 months) and long-term (10 months) adaptive immune response and to document breakthrough [...] Read more.
To mitigate the massive COVID-19 burden caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccination campaigns were initiated. We performed a single-center observational trial to monitor the mid- (3 months) and long-term (10 months) adaptive immune response and to document breakthrough infections (BTI) in healthcare workers (n = 84) upon BNT162b2 vaccination in a real-world setting. Firstly, serology was determined through immunoassays. Secondly, antibody functionality was analyzed via in vitro binding inhibition and pseudovirus neutralization and circulating receptor-binding domain (RBD)-specific B cells were assessed. Moreover, the induction of SARS-CoV-2-specific T cells was investigated by an interferon-γ release assay combined with flowcytometric profiling of activated CD4+ and CD8+ T cells. Within individuals that did not experience BTI (n = 62), vaccine-induced humoral and cellular immune responses were not correlated. Interestingly, waning over time was more pronounced within humoral compared to cellular immunity. In particular, 45 of these 62 subjects no longer displayed functional neutralization against the delta variant of concern (VoC) at long-term follow-up. Noteworthily, we reported a high incidence of symptomatic BTI cases (17.11%) caused by alpha and delta VoCs, although vaccine-induced immunity was only slightly reduced compared to subjects without BTI at mid-term follow-up. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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10 pages, 1407 KiB  
Article
Two Separate Clusters of SARS-CoV-2 Delta Variant Infections in a Group of 41 Students Travelling from India: An Illustration of the Need for Rigorous Testing and Quarantine
by Jan Van Elslande, Femke Kerckhofs, Lize Cuypers, Elke Wollants, Barney Potter, Anne Vankeerberghen, Lien Cattoir, Astrid Holderbeke, Sylvie Behillil, Sarah Gorissen, Mandy Bloemen, Jef Arnout, Marc Van Ranst, Johan Van Weyenbergh, Piet Maes, Guy Baele, Pieter Vermeersch, Emmanuel André and on behalf of the COG-Belgium Consortium
Viruses 2022, 14(6), 1198; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061198 - 31 May 2022
Cited by 4 | Viewed by 2221
Abstract
We report two clusters of SARS-CoV-2 B.1.617.2 (Delta variant) infections in a group of 41 Indian nursing students who travelled from New Delhi, India, to Belgium via Paris, France. All students tested negative before departure and had a second negative antigen test upon [...] Read more.
We report two clusters of SARS-CoV-2 B.1.617.2 (Delta variant) infections in a group of 41 Indian nursing students who travelled from New Delhi, India, to Belgium via Paris, France. All students tested negative before departure and had a second negative antigen test upon arrival in Paris. Upon arrival in Belgium, the students were quarantined in eight different houses. Four houses remained COVID-free during the 24 days of follow-up, while all 27 residents of the other four houses developed an infection during quarantine, including the four residents who were fully vaccinated and the two residents who were partially vaccinated. Genome sequencing revealed two distinct clusters affecting one and three houses, respectively. In this group of students, vaccination status did not seem to prevent infection nor decrease the viral load. No severe symptoms were reported. Extensive contact tracing and 3 months of nationwide genomic surveillance confirmed that these outbreaks were successfully contained and did not contribute to secondary community transmission in Belgium. These clusters highlight the importance of repeated testing and quarantine measures among travelers coming from countries experiencing a surge of infections, as all infections were detected 6 days or more after arrival. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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14 pages, 3041 KiB  
Article
SARS-CoV-2 Virion Infectivity and Cytokine Production in Primary Human Airway Epithelial Cells
by Thuc Nguyen Dan Do, Sandra Claes, Dominique Schols, Johan Neyts and Dirk Jochmans
Viruses 2022, 14(5), 951; https://0-doi-org.brum.beds.ac.uk/10.3390/v14050951 - 02 May 2022
Cited by 6 | Viewed by 2647
Abstract
The emergence of new SARS-CoV-2 variants and the replacement of preceding isolates have been observed through B.1.1.7, B.1.351, B.1.617.2, and B.1.1.529 lineages (corresponding to alpha, beta, delta, and omicron variants of concern (VoC), respectively). However, there is still a lack of biological evidence [...] Read more.
The emergence of new SARS-CoV-2 variants and the replacement of preceding isolates have been observed through B.1.1.7, B.1.351, B.1.617.2, and B.1.1.529 lineages (corresponding to alpha, beta, delta, and omicron variants of concern (VoC), respectively). However, there is still a lack of biological evidence to which extent those VoC differ from the ancestral lineages. By exploiting human airway epithelial cell (HAEC) cultures, which closely resemble the human airway architecture and physiology, we report distinctive SARS-CoV-2 tropism in different respiratory tissues. In general, SARS-CoV-2 VoC predominantly infect and replicate in HAEC better than the progenitor USA-WA1 isolate or the BavPat1 isolate, which contains the D614G mutation, even though there is little to no difference between variants regarding their infectivity (i.e., virion-per-vRNA copy ratio). We also observe differential tissue-specific innate immunity activation between the upper and lower respiratory tissues in the presence of the virus. Our study provides better comprehension of the behavior of the different VoC in this physiologically relevant ex vivo model. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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16 pages, 1445 KiB  
Article
Prevalence of Anti-SARS-CoV-2 Antibodies and Potential Determinants among the Belgian Adult Population: Baseline Results of a Prospective Cohort Study
by Victoria Leclercq, Nayema Van den Houte, Lydia Gisle, Inge Roukaerts, Cyril Barbezange, Isabelle Desombere, Els Duysburgh and Johan Van der Heyden
Viruses 2022, 14(5), 920; https://0-doi-org.brum.beds.ac.uk/10.3390/v14050920 - 28 Apr 2022
Cited by 6 | Viewed by 1867
Abstract
The prevalence of anti-SARS-CoV-2 antibodies and potential determinants were assessed in a random sample representative of the Belgian adult population. In total, 14,201 individuals (≥18 years) were invited by mail to provide saliva via an Oracol® swab. Survey weights were applied, and [...] Read more.
The prevalence of anti-SARS-CoV-2 antibodies and potential determinants were assessed in a random sample representative of the Belgian adult population. In total, 14,201 individuals (≥18 years) were invited by mail to provide saliva via an Oracol® swab. Survey weights were applied, and potential determinants were estimated using multivariable logistic regressions. Between March and August 2021, 2767 individuals participated in the first data collection. During this period, which coincided with the onset of the vaccination campaign, the seroprevalence in the population increased from 25.2% in March/April to 78.1% in July. Among the vaccinated there was an increase from 74,2% to 98.8%; among the unvaccinated, the seroprevalence remained stable (around 17%). Among the vaccinated, factors significantly associated with the presence of antibodies were: having at least one chronic disease (ORa 0.22 (95% CI 0.08–0.62)), having received an mRNA-type vaccine (ORa 5.38 (95% CI 1.72–16.80)), and having received an influenza vaccine in 2020–2021 (ORa 3.79 (95% CI 1.30–11.07)). Among the unvaccinated, having a non-O blood type (ORa 2.00 (95% CI 1.09–3.67)) and having one or more positive COVID-19 tests (ORa 11.04 (95% CI 4.69–26.02)) were significantly associated. This study provides a better understanding of vaccine- and/or natural-induced presence of anti-SARS-CoV-2 antibodies and factors that are associated with this presence. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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14 pages, 1675 KiB  
Article
Incidence and Risk Factors of COVID-19 Vaccine Breakthrough Infections: A Prospective Cohort Study in Belgium
by Veerle Stouten, Pierre Hubin, Freek Haarhuis, Joris A. F. van Loenhout, Matthieu Billuart, Ruben Brondeel, Toon Braeye, Herman Van Oyen, Chloé Wyndham-Thomas and Lucy Catteau
Viruses 2022, 14(4), 802; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040802 - 13 Apr 2022
Cited by 26 | Viewed by 4708
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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9 pages, 545 KiB  
Communication
Analytical Sensitivity of Six SARS-CoV-2 Rapid Antigen Tests for Omicron versus Delta Variant
by Jean-Louis Bayart, Jonathan Degosserie, Julien Favresse, Constant Gillot, Marie Didembourg, Happy Phanio Djokoto, Valérie Verbelen, Gatien Roussel, Céline Maschietto, François Mullier, Jean-Michel Dogné and Jonathan Douxfils
Viruses 2022, 14(4), 654; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040654 - 22 Mar 2022
Cited by 34 | Viewed by 5714
Abstract
Rapid antigen detection (RAD) tests are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC), presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. [...] Read more.
Rapid antigen detection (RAD) tests are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC), presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One hundred and twenty samples were selected and tested with both RT-qPCR and six commercial RAD tests that are commonly sold in Belgian pharmacies. Of these, direct whole-genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron (BA.1 and BA.1.1 sub-lineages, respectively). The sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) ranged from 70.0% to 92.9% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct > 25, corresponding to <4.9 log10 copies/mL), only the Roche RAD test showed acceptable performances for the Delta strains (80.0%), while poor performances were observed for the other RAD tests (20.0% to 40.0%). All the tested devices had poor performances for the Omicron samples with a low viral load (0.0% to 23.1%). The poor performances observed with low viral loads, particularly for the Omicron strain, is an important limitation of RAD tests, which is not sufficiently highlighted in the instructions for use of these devices. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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17 pages, 1840 KiB  
Article
Optimization and Application of a Multiplex Digital PCR Assay for the Detection of SARS-CoV-2 Variants of Concern in Belgian Influent Wastewater
by Tim Boogaerts, Siel Van den Bogaert, Laura A. E. Van Poelvoorde, Diala El Masri, Naomi De Roeck, Nancy H. C. Roosens, Marie Lesenfants, Lies Lahousse, Koenraad Van Hoorde, Alexander L. N. van Nuijs and Peter Delputte
Viruses 2022, 14(3), 610; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030610 - 15 Mar 2022
Cited by 12 | Viewed by 3563
Abstract
Since the beginning of the COVID-19 pandemic, the wastewater-based epidemiology (WBE) of SARS-CoV-2 has been used as a complementary indicator to follow up on the trends in the COVID-19 spread in Belgium and in many other countries. To further develop the use of [...] Read more.
Since the beginning of the COVID-19 pandemic, the wastewater-based epidemiology (WBE) of SARS-CoV-2 has been used as a complementary indicator to follow up on the trends in the COVID-19 spread in Belgium and in many other countries. To further develop the use of WBE, a multiplex digital polymerase chain reaction (dPCR) assay was optimized, validated and applied for the measurement of emerging SARS-CoV-2 variants of concern (VOC) in influent wastewater (IWW) samples. Key mutations were targeted in the different VOC strains, including SΔ69/70 deletion, N501Y, SΔ241 and SΔ157. The presented bioanalytical method was able to distinguish between SARS-CoV-2 RNA originating from the wild-type and B.1.1.7, B.1.351 and B.1.617.2 variants. The dPCR assay proved to be sensitive enough to detect low concentrations of SARS-CoV-2 RNA in IWW since the limit of detection of the different targets ranged between 0.3 and 2.9 copies/µL. This developed WBE approach was applied to IWW samples originating from different Belgian locations and was able to monitor spatio-temporal changes in the presence of targeted VOC strains in the investigated communities. The present dPCR assay developments were realized to bring added-value to the current national WBE of COVID-19 by also having the spatio-temporal proportions of the VoC in presence in the wastewaters. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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Review

Jump to: Research, Other

19 pages, 2746 KiB  
Review
Two Years of Genomic Surveillance in Belgium during the SARS-CoV-2 Pandemic to Attain Country-Wide Coverage and Monitor the Introduction and Spread of Emerging Variants
by Lize Cuypers, Simon Dellicour, Samuel L. Hong, Barney I. Potter, Bruno Verhasselt, Nick Vereecke, Laurens Lambrechts, Keith Durkin, Vincent Bours, Sofieke Klamer, Guillaume Bayon-Vicente, Carl Vael, Kevin K. Ariën, Ricardo De Mendonca, Oriane Soetens, Charlotte Michel, Bertrand Bearzatto, Reinout Naesens, Jeremie Gras, Anne Vankeerberghen, Veerle Matheeussen, Geert Martens, Dagmar Obbels, Ann Lemmens, Bea Van den Poel, Ellen Van Even, Klara De Rauw, Luc Waumans, Marijke Reynders, Jonathan Degosserie, Piet Maes, Emmanuel André and Guy Baeleadd Show full author list remove Hide full author list
Viruses 2022, 14(10), 2301; https://doi.org/10.3390/v14102301 - 20 Oct 2022
Cited by 6 | Viewed by 2970
Abstract
An adequate SARS-CoV-2 genomic surveillance strategy has proven to be essential for countries to obtain a thorough understanding of the variants and lineages being imported and successfully established within their borders. During 2020, genomic surveillance in Belgium was not structurally implemented but performed [...] Read more.
An adequate SARS-CoV-2 genomic surveillance strategy has proven to be essential for countries to obtain a thorough understanding of the variants and lineages being imported and successfully established within their borders. During 2020, genomic surveillance in Belgium was not structurally implemented but performed by individual research laboratories that had to acquire the necessary funds themselves to perform this important task. At the start of 2021, a nationwide genomic surveillance consortium was established in Belgium to markedly increase the country’s genomic sequencing efforts (both in terms of intensity and representativeness), to perform quality control among participating laboratories, and to enable coordination and collaboration of research projects and publications. We here discuss the genomic surveillance efforts in Belgium before and after the establishment of its genomic sequencing consortium, provide an overview of the specifics of the consortium, and explore more details regarding the scientific studies that have been published as a result of the increased number of Belgian SARS-CoV-2 genomes that have become available. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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12 pages, 242 KiB  
Review
Pharmacological Studies in Hospitalized COVID-19 Patients in Belgium: We Could Do Better
by Maya Hites and Jean-Louis Vincent
Viruses 2022, 14(7), 1427; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071427 - 29 Jun 2022
Cited by 1 | Viewed by 2408
Abstract
Belgium has actively participated in clinical research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the beginning of the pandemic to help identify effective and safe treatments for COVID-19. The objective of this review is to provide a picture of the clinical [...] Read more.
Belgium has actively participated in clinical research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the beginning of the pandemic to help identify effective and safe treatments for COVID-19. The objective of this review is to provide a picture of the clinical studies carried out in hospitalized patients with COVID-19 in Belgium. We collected data on all randomized, interventional trials in patients with COVID-19 that were registered on two recognized clinical trial registers, started enrollment before 31 December 2021, and included at least one patient in a Belgian center. Data were collected concerning the therapies investigated and the nature of the trials performed. Thirty-three hospitals (32% of all Belgian hospitals) participated in at least one of 28 trials (13 sponsored by the industry and 15 by academic centers) on therapeutics for COVID-19 in hospitalized patients: 7 (25%) evaluated antivirals, 17 (61%) immunomodulators, 2 (7%) anti-coagulants, and 1 (3%) nitric oxide to improve respiratory function. Nineteen (68%) were phase II trials. Only three (11%) of the trials were international platform trials. Despite numerous trials, less than 3% of all Belgian patients hospitalized with COVID-19 participated in a clinical trial on therapeutics. As in many other countries, more efforts could have been made to avoid running small, under-powered, mono- or bicenter trials, to create better collaboration between the different Belgian hospitals, and to participate in more international clinical trials, and more specifically in adaptive, platform trials. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)

Other

Jump to: Research, Review

11 pages, 2158 KiB  
Case Report
Healthcare-Associated SARS-CoV-2 Reinfection after 3 Months with a Phylogenetically Distinct Omicron Variant: A Case Report
by Kim Callebaut, Anke Stoefs, Dimitri Stylemans, Oriane Soetens, Florence Crombé, Ellen Vancutsem, Hideo Imamura, Ingrid Wybo, Deborah De Geyter, Denis Piérard, Astrid Muyldermans and Thomas Demuyser
Viruses 2022, 14(9), 1852; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091852 - 23 Aug 2022
Cited by 2 | Viewed by 1523
Abstract
This case report describes a 60-year-old female patient suffering from systemic sclerosis, for which she received immunomodulatory drugs. Her first SARS-CoV-2-positive nasopharyngeal sample was obtained in the emergency department, on 31 January 2022. Whole genome sequencing confirmed infection with Omicron BA.1.1. Her hospital [...] Read more.
This case report describes a 60-year-old female patient suffering from systemic sclerosis, for which she received immunomodulatory drugs. Her first SARS-CoV-2-positive nasopharyngeal sample was obtained in the emergency department, on 31 January 2022. Whole genome sequencing confirmed infection with Omicron BA.1.1. Her hospital stay was long and punctuated by many complications, including admission to the intensive care unit. At the beginning of April 2022, she started complaining of increased coughing, for which another SARS-CoV-2 RT-qPCR test was performed. The latter nasopharyngeal swab showed a strongly positive result. To support the theory of healthcare-associated reinfection, whole genome sequencing was performed and confirmed reinfection with Omicron BA.2. Since this patient was one of ten positive cases in this particular ward, a hospital outbreak investigation was performed. Whole genome sequencing data were available for five of these ten patients and showed a cluster of four patients with ≤2 small nucleotide polymorphisms difference. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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7 pages, 948 KiB  
Brief Report
Effect of COVID-19 Vaccination Campaign in Belgian Nursing Homes on COVID-19 Cases, Hospital Admissions, and Deaths among Residents
by Sara Dequeker, Milena Callies, Catharina Vernemmen, Katrien Latour, Laura Int Panis, Romain Mahieu, Lennert Noppe, Muhammet Savsin and Els Duysburgh
Viruses 2022, 14(7), 1359; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071359 - 22 Jun 2022
Cited by 4 | Viewed by 1598
Abstract
In view of the grave situation during the first two waves of SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), nursing homes (NHs) were prioritised for vaccination once vaccines became available in Belgium. The aim of this study was to assess the effect of [...] Read more.
In view of the grave situation during the first two waves of SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), nursing homes (NHs) were prioritised for vaccination once vaccines became available in Belgium. The aim of this study was to assess the effect of the COVID-19 (Coronavirus Disease 2019) vaccination campaign on COVID-19 cases, hospital admissions, and deaths among residents living in Belgian NHs. All 1545 Belgian NHs were invited to participate in a COVID-19 surveillance program. In Belgium, before vaccination, COVID-19 morbidity and mortality rates were driven by the situation in the NHs. Shortly after the COVID-19 vaccination campaign, and later the booster campaign, the number of hospital admissions and deaths among NH residents dropped, while clear peaks could be observed among the general population. The impact of vaccination on virus circulation was less effective than expected. However, due to the high vaccination coverage, NH residents remain well protected against hospital admission and death due to COVID-19 more than one year after being vaccinated. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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8 pages, 437 KiB  
Brief Report
Investigating COVID-19 Vaccine Impact on the Risk of Hospitalisation through the Analysis of National Surveillance Data Collected in Belgium
by Diana Erazo, Maria F. Vincenti-Gonzalez, Joris A. F. van Loenhout, Pierre Hubin, Mathil Vandromme, Piet Maes, Maxime Taquet, Johan Van Weyenbergh, Lucy Catteau and Simon Dellicour
Viruses 2022, 14(6), 1315; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061315 - 16 Jun 2022
Viewed by 2272
Abstract
The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from [...] Read more.
The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status. For each period, vaccination status, and age group, we estimated risk ratios (RR) corresponding to the ratio between the probability of being hospitalised following SARS-CoV-2 infection if belonging to the vaccinated population and the same probability if belonging to the unvaccinated population. In October 2021, a relatively high RR was estimated for vaccinated people > 75 years old, possibly reflecting waning immunity within this group, which was vaccinated early in 2021 and invited to receive the booster vaccination at that time. In January 2022, a RR increase was observed in all age categories coinciding with the dominance of the Omicron variant. Despite the absence of control for factors like comorbidities, previous infections, or time since the last administered vaccine, we showed that such real-time aggregated data make it possible to approximate trends in vaccine impact over time. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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Case Report
Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab
by Nathalie Van der Moeren, Philippe Selhorst, My Ha, Laura Heireman, Pieter-Jan Van Gaal, Dimitri Breems, Pieter Meysman, Kris Laukens, Walter Verstrepen, Natasja Van Gasse, Benson Ogunjimi, Kevin K. Arien and Reinout Naesens
Viruses 2022, 14(4), 752; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040752 - 03 Apr 2022
Cited by 8 | Viewed by 3019
Abstract
Background. Prolonged shedding of SARS-CoV-2 in immunocompromised patients has been described. Furthermore, an accumulation of mutations of the SARS-CoV-2 genome in these patients has been observed. Methods. We describe the viral evolution, immunologic response and clinical course of a patient with a lymphoma [...] Read more.
Background. Prolonged shedding of SARS-CoV-2 in immunocompromised patients has been described. Furthermore, an accumulation of mutations of the SARS-CoV-2 genome in these patients has been observed. Methods. We describe the viral evolution, immunologic response and clinical course of a patient with a lymphoma in complete remission who had received therapy with rituximab and remained SARS-CoV-2 RT-qPCR positive for 161 days. Results. The patient remained hospitalised for 10 days, after which he fully recovered and remained asymptomatic. A progressive increase in Ct-value, coinciding with a progressive rise in lymphocyte count, was seen from day 137 onward. Culture of a nasopharyngeal swab on day 67 showed growth of SARS-CoV-2. Whole genome sequencing (WGS) demonstrated that the virus belonged to the wildtype SARS-CoV-2 clade 20B/GR, but rapidly accumulated a high number of mutations as well as deletions in the N-terminal domain of its spike protein. Conclusion. SARS-CoV-2 persistence in immunocompromised individuals has important clinical implications, but halting immunosuppressive therapy might result in a favourable clinical course. The long-term shedding of viable virus necessitates customized infection prevention measures in these individuals. The observed accelerated accumulation of mutations of the SARS-CoV-2 genome in these patients might facilitate the origin of new VOCs that might subsequently spread in the general community. Full article
(This article belongs to the Special Issue SARS-CoV-2 Research in Belgium)
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