Developing a Video Game as an Awareness and Research Tool Based on SARS-CoV-2 Epidemiological Dynamics and Motivational Perspectives

In mid-2020, the University of Liège (ULiège, Belgium) commissioned the ULiège Video Game Research Laboratory (Liège Game Lab) and the AR/VR Lab of the HEC-Management School of ULiège to create a serious game to raise awareness of preventive measures for its university community. This project has its origins in two objectives of the institutional policy of ULiège in response to the crisis caused by SARS-CoV-2 to raise awareness among community members of various preventive actions that can reduce the spread of the virus and to inform about the emergence and progression of a pandemic. After almost two years of design, the project resulted in the creation of SARS Wars, a decision-making management game for browsers and smartphones. This article presents the creative process of the game, specifically the integration of an adapted SEIR (susceptible-exposed-infectious-recovered) model, as well as the modeling of intercompartmental circulation dynamics in the game's algorithm, and the various limitations observed regarding the game's original missions and possibilities for future work. The SARS-CoV-2 video game project may be considered an innovative way to translate epidemiology into a language that can be used in the scope of citizen sciences. On the one hand, it provides an engaging tool and encourages active participation of the audience. On the other hand, it allows us to have a better understanding of the dynamic changes of a pandemic or an epidemic (crisis preparedness, monitoring, and control) and to anticipate potential consequences in the given parameters at set time (emerging risk identification), while offering insights for impact on some parameters on motivation (social science aspect).

Systematic Review of the Key Factors Influencing the Indoor Airborne Spread of SARS-CoV-2.

The COVID-19 pandemic due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been plaguing the world since late 2019/early 2020 and has changed the way we function as a society, halting both economic and social activities worldwide. Classrooms, offices, restaurants, public transport, and other enclosed spaces that typically gather large groups of people indoors, and are considered focal points for the spread of the virus. For society to be able to go "back to normal", it is crucial to keep these places open and functioning. An understanding of the transmission modes occurring in these contexts is essential to set up effective infection control strategies. This understanding was made using a systematic review, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) 2020 guidelines. We analyze the different parameters influencing airborne transmission indoors, the mathematical models proposed to understand it, and discuss how we can act on these parameters. Methods to judge infection risks through the analysis of the indoor air quality are described. Various mitigation measures are listed, and their efficiency, feasibility, and acceptability are ranked by a panel of experts in the field. Thus, effective ventilation procedures controlled by CO2-monitoring, continued mask wearing, and a strategic control of room occupancy, among other measures, are put forth to enable a safe return to these essential places.

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.

Compliance with Barrier Gestures during COVID-19 Pandemic as a Function of the Context: A Longitudinal Observational Survey at the University of Liège.

During the COVID-19 pandemic, barrier gestures such as mask wearing, physical distancing, greetings without contact, one-way circulation flow, and hand sanitization were major strategies to prevent the spread of SARS-CoV-2, but they were only useful if consistently applied. This survey was a follow-up of the first survey performed in 2020 at the University of Liège. We aim to evaluate the compliance with these gestures on campuses and examine differences in the extent of the compliance observed in different educational activities and contexts. During 3.5 months, the counting of compliant and non-compliant behaviors was performed each week in randomly selected rooms. Using data collected during both surveys (2020 and 2021), binomial negative regression models of compliance depending on periods (teaching periods and exam sessions), type of rooms, and campuses were conducted to evaluate prevalence ratios of compliance. The percentage of compliance in this second survey was the highest for mask wearing and physical distancing during educational activities (90% and 88%, respectively) and lowest for physical distancing outside educational activities and hand sanitization (45% and 52%, respectively). Multivariate analyses revealed that the compliance with most gestures was significantly higher in teaching rooms than in hallways and restaurants and during exam sessions. The compliance with physical distancing was significantly higher (from 66%) in auditoriums, where students had to remain seated, than during practical works that allowed or required free movement. Therefore, the compliance with barrier gestures was associated with contextual settings, which should be considered when communicating and managing barrier gestures. Further studies should specify and confirm the determining contextual characteristics regarding the compliance with barrier gestures in times of pandemic.

Nationwide Harmonization Effort for Semi-Quantitative Reporting of SARS-CoV-2 PCR Test Results in Belgium.

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.

Factors influencing the adoption and participation rate of nursing homes staff in a saliva testing screening programme for COVID-19.

Testing strategies are crucial to prevent and control the spread of covid-19 but suffer from a lack of investment in understanding the human factors that influence their implementation. The aim of this study was to understand the factors that encourage participation and the level of engagement of nursing homes staff in a routine saliva testing programme for COVID-19 In December 2020, nursing homes (n = 571) in Wallonia (Belgium) were invited to participate in a saliva testing programme for their staff. The directors were questioned by telephone at the end of a 3-week pilot phase. 445 nursing homes took part in the evaluation questionnaire, of which 36(8%) answered that they chose not to participate in the testing programme. The average participation rate of nursing staff was 49(±25)%. Perception of the justification of the efforts required for testing and perception of practicability of the procedure were significantly associated with the adoption of the system by the nursing homes directors (OR(95%CI): 5.96(1.97-18.0), p = 0.0016); OR(95%CI): 5.64(1.94-16.4), p = 0.0015 respectively). Staff support, incentives and meetings increased the level of engagement in testing (p<0.05). While the adoption of the programme confirmed the acceptability of salivary testing as a means of screening, the participation rate confirmed the need for studies to understand the factors that encourage health care staff to take part. The results suggested rethinking strategies to consider staff engagement from a health promotion perspective.

Kinetics and Persistence of the Cellular and Humoral Immune Responses to BNT162b2 mRNA Vaccine in SARS-CoV-2-Naive and -Experienced Subjects: Impact of Booster Dose and Breakthrough Infections.

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the cellular and humoral immune response in healthcare workers up to 12 months after the initial vaccination, with one additional boosting dose between 6 and 12 months. Methods: This prospective study enrolled 208 healthcare workers (HCWs) from the Liège University Hospital (CHU) of Liège in Belgium. Participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2) and a booster dose 6-12 months later. Fifty participants were SARS-CoV-2 experienced and 158 were naïve before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3), 6 months (T4) and 12 months (T5) after the second dose. Between T4 and T5, participants also got the third boosting vaccine dose. A total of 1145 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies, using the DiaSorin LIAISON SARS-CoV-2 Trimeric S IgG assay, and for anti-Nucleocapsid antibodies, using Elecsys anti-SARS-CoV-2 assay​​. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization assay. Cell-mediated immune response was evaluated at T4 and T5 on 80 and 55 participants, respectively, by measuring the secretion of IFN-γ on peripheral blood lymphocytes using the QuantiFERON Human IFN-γ SARS-CoV-2, from Qiagen. We analyzed separately the naïve and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced HCWs compared to naïve HCWs at all time points analyzed except the one after boosting dose. Cellular immune response was also higher in experienced HCWs six months following vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative association between age and persistence of humoral response. The booster dose induced an increase in humoral and cellular immune responses, particularly in naive individuals. Breakthrough infections resulted in higher cellular and humoral responses after the booster dose. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. The benefit of the booster dose was greater in naive individuals. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses.

A 2-month field cohort study of SARS-CoV-2 in saliva of BNT162b2 vaccinated nursing home workers.

Background: Nursing home (NH) residents have been severely affected during the COVID-19 pandemic because of their age and underlying comorbidities. Infection and outbreaks in NHs are most likely triggered by infected workers. Screening for asymptomatic NH workers can prevent risky contact and viral transmission to the residents. This study examined the effect of the BNT162b2 mRNA COVID­19 (Comirnaty®; BioNTech and Pfizer) vaccination on the saliva excretion of SARS-CoV-2 among NH workers, through weekly saliva RT-qPCR testing. Methods: A 2-month cohort study was conducted among 99 NHs in the Walloon region (Belgium), at the start of February 2021. Three groups of workers, i.e., non-vaccinated (n = 1618), one-dosed vaccinated (n = 1454), and two-dosed vaccinated (n = 2379) of BNT162b2 mRNA COVID­19 vaccine, were followed-up weekly. Their saliva samples were used to monitor the shedding of SARS-CoV-2. All positive samples were sequenced and genotyped to identify the circulating wild-type virus or variants of concern. Results: The protection fraction against the excretion of the SARS-CoV-2 in the saliva samples of the workers after the second dose is estimated at 0.90 (95% CI: 0.18; 0.99) at 1 week and 0.83 (95% CI: 0.54; 0.95) at 8 weeks. We observe more circulating SARS-CoV-2 and a greater variability of viral loads in the unvaccinated group compared to those of the vaccinated group. Conclusions: This field cohort study advances our knowledge of the efficacy of the mRNA BNT162b2 COVID-19 vaccine on the viral shedding in the saliva specimens of vaccinated NH workers, contributing to better decision-making in public health interventions and management.

Decision-based interactive model to determine re-opening conditions of a large university campus in Belgium during the first COVID-19 wave.

BACKGROUND: The role played by large-scale repetitive SARS-CoV-2 screening programs within university populations interacting continuously with an urban environment, is unknown. Our objective was to develop a model capable of predicting the dispersion of viral contamination among university populations dividing their time between social and academic environments. METHODS: Data was collected through real, large-scale testing developed at the University of Liège, Belgium, during the period Sept. 28th-Oct. 29th 2020. The screening, offered to students and staff (n = 30,000), began 2 weeks after the re-opening of the campus but had to be halted after 5 weeks due to an imposed general lockdown. The data was then used to feed a two-population model (University + surrounding environment) implementing a generalized susceptible-exposed-infected-removed compartmental modeling framework. RESULTS: The considered two-population model was sufficiently versatile to capture the known dynamics of the pandemic. The reproduction number was estimated to be significantly larger on campus than in the urban population, with a net difference of 0.5 in the most severe conditions. The low adhesion rate for screening (22.6% on average) and the large reproduction number meant the pandemic could not be contained. However, the weekly screening could have prevented 1393 cases (i.e. 4.6% of the university population; 95% CI: 4.4-4.8%) compared to a modeled situation without testing. CONCLUSION: In a real life setting in a University campus, periodic screening could contribute to limiting the SARS-CoV-2 pandemic cycle but is highly dependent on its environment.

Acceptability of Community Saliva Testing in Controlling the COVID-19 Pandemic: Lessons Learned from Two Case Studies in Nursing Homes and Schools.

Current public health debate centers on COVID-19 testing methods and strategies. In some communities, high transmission risk may justify routine testing, and this requires test methods that are safe and efficient for both patients and the administrative or health-care workers administering them. Saliva testing appears to satisfy those criteria. There is, however, little documentation on the acceptability of this method among beneficiaries. This article presents the lessons learned from a pilot study on the use of saliva testing for routine screening of nursing home and secondary school personnel in Wallonia (the French-speaking part of Belgium), conducted in December 2020 to April 2021, respectively. Administrators at the facilities in question seemed to think highly of saliva testing and wished to continue it after the pilot study was over. This result reinforces the criteria (the noninvasive aspect, in particular) supporting a key role for saliva testing in monitoring community spread of the virus. Nevertheless, wider-scale deployment of this particular method will only be possible if the testing strategy as a whole takes a health promotion approach.

Reliable and Scalable SARS-CoV-2 qPCR Testing at a High Sample Throughput: Lessons Learned from the Belgian Initiative.

We present our approach to rapidly establishing a standardized, multi-site, nation-wide COVID-19 screening program in Belgium. Under auspices of a federal government Task Force responsible for upscaling the country's testing capacity, we were able to set up a national testing initiative with readily available resources, putting in place a robust, validated, high-throughput, and decentralized qPCR molecular testing platform with embedded proficiency testing. We demonstrate how during an acute scarcity of equipment, kits, reagents, personnel, protective equipment, and sterile plastic supplies, we introduced an approach to rapidly build a reliable, validated, high-volume, high-confidence workflow based on heterogeneous instrumentation and diverse assays, assay components, and protocols. The workflow was set up with continuous quality control monitoring, tied together through a clinical-grade information management platform for automated data analysis, real-time result reporting across different participating sites, qc monitoring, and making result data available to the requesting physician and the patient. In this overview, we address challenges in optimizing high-throughput cross-laboratory workflows with minimal manual intervention through software, instrument and assay validation and standardization, and a process for harmonized result reporting and nation-level infection statistics monitoring across the disparate testing methodologies and workflows, necessitated by a rapid scale-up as a response to the pandemic.

In-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2.

The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the sensitivity of tests for various sample specimens. Seventy-five participants with confirmed COVID-19 were included in the study. Nasopharyngeal swabs, oropharyngeal swabs, Oracol-collected saliva, throat washes and rectal specimens were collected along with pooled swabs. Participants were asked to complete a questionnaire to correlate specific clinical symptoms and the symptom duration with the sensitivity of detecting COVID-19 in various sample specimens. Sampling was repeated after 7 to 10 days (T2), then after 14 to 20 days (T3) to perform a longitudinal analysis of sample specimen sensitivity. At the first time point, the highest percentages of SARS-CoV-2-positive samples were observed for nasopharyngeal samples (84.3%), while 74%, 68.2%, 58.8% and 3.5% of throat washing, Oracol-collected saliva, oropharyngeal and rectal samples tested positive, respectively. The sensitivity of all sampling methods except throat wash samples decreased rapidly at later time points compared to the first collection. The throat washing method exhibited better performance than the gold standard nasopharyngeal swab at the second and third time points after the first positive test date. Nasopharyngeal swabs were the most sensitive specimens for early detection after symptom onset. Throat washing is a sensitive alternative method. It was found that SARS-CoV-2 persists longer in the throat and saliva than in the nasopharynx.

The First Random Observational Survey of Barrier Gestures against COVID-19.

In the context of COVID-19 in Belgium, face-to-face teaching activities were allowed in Belgian universities at the beginning of the 2020-2021 academic year. Nevertheless, several control measures were established to control COVID-19 transmission on the campuses. To ensure compliance with these measures, a random observational survey, based on five barrier gestures, was implemented at the University of Liege (greetings without contact, hand sanitisation, following a one-way traffic flow, wearing a mask and physical distancing). Each barrier gesture was weighted, based on experts' elicitation, and a scoring system was developed. The results were presented as a diagram (to identify the margin of improvement for each barrier gesture) and a risk management barometer. In total, 526 h of observations were performed. The study revealed that some possible improvements could be made in the management of facilities, in terms of room allocation, the functionality of hydro-alcoholic gel dispensers, floor markings and one-way traffic flow. Compliance with the barrier gestures reached an overall weighted score of 68.2 (between 0 and 100). Three barrier gestures presented a lower implementation rate and should be addressed: the use of hydro-alcoholic gel (particularly when exiting buildings), compliance with the traffic flow and the maintenance of a 1.5 m physical distance outside of the auditoriums. The methodology and tool developed in the present study can easily be applied to other settings. They were proven to be useful in managing COVID-19, as the barometer that was developed and the outcomes of this survey enabled an improved risk assessment on campuses, and identified the critical points to be addressed in any further public health communication or education messages.

Repetitive saliva-based mass screening as a tool for controlling SARS-CoV-2 transmission in nursing homes.

Nursing home (NH) residents and staff have been severely affected by the COVID-19 pandemic. The aim of this study was to examine the use of weekly saliva RT-qPCR testing for SARS-CoV-2 detection among NH workers as a strategy to control disease transmission within NHs in Belgium. From 16 November to 27 December 2020, a voluntary and anonymous weekly screening was implemented in a cohort of 50,000 workers across 572 NHs in the Walloon region of Belgium to detect asymptomatic cases of SARS-CoV-2 via saliva RT-qPCR testing and using the Diagenode saliva sample collection device. Positive workers were isolated to avoid subsequent infections in residents and other staff. RT-qPCR testing was based on pooled saliva sampling techniques from three workers, followed by individual testing of each positive or inconclusive pool. The majority of NHs (85%) and 55% of their workers participated. Pooling did not affect sensitivity as it only induced a very decrease in sensitivity estimated as 0.33%. Significant decreases in the prevalence (34.4-13.4%) and incidence of NHs with either single (13.8-2%) or multiple positive workers (3.7-0%) were observed over time. In addition, deaths among NH residents and NH worker absences decreased significantly over time. Weekly saliva RT-qPCR testing for SARS-CoV-2 demonstrated large-scale feasibility and efficacy in disrupting the chain of transmission. Implementation of this testing strategy in NHs could also be extended to other settings with the aim to control viral transmission for maintaining essential activities.