Individual level analysis of digital proximity tracing for COVID-19 in Belgium highlights major bottlenecks (preprint)

To complement labour-intensive conventional contact tracing, digital proximity tracing was implemented widely during the COVID-19 pandemic. However, the privacy-centred design of the dominant Google-Apple exposure notification framework has hindered assessment of its effectiveness. Between October 2021 and January 2022, we systematically collected app use and notification receipt data within a test and trace programme for university students in Leuven, Belgium. Due to low success rates in each studied step of the digital notification cascade, only 4.3% of exposed contacts (CI: 2.8-6.1%) received such notifications, resulting in 10 times more cases detected through conventional contact tracing. Moreover, the infection risk of digitally traced contacts (5.0%; CI: 3.0-7.7%) was lower than that of conventionally traced non-app users (9.8%; CI: 8.8-10.7%; p=0.002). Contrary to common perception as near instantaneous, there was a 1.2-day delay (CI: 0.6-2.2) between case PCR result and digital contact notifications. These results highlight major limitations of the dominant digital proximity tracing framework.

Unravelling the effect of winter holiday celebrations on SARS-CoV-2 transmission (preprint)

Public holidays have been associated with SARS-CoV-2 incidence surges, although a firm causal link remains to be established. This association is sometimes attributed to events where transmissions occur at a disproportionately high rate, known as superspreading events. Here, we describe a sudden surge in new cases with the Omicron BA.1 strain amongst higher education students in Belgium. Contact tracers classed most of these cases as likely or possibly infected on New Year's Eve, indicating a direct trigger by New Year celebrations. Using a combination of contact tracing and phylogenetic data, we show the limited role of superspreading events in this surge. Finally, the numerous simultaneous transmissions allowed a unique opportunity to determine the distribution of incubation periods of the Omicron strain. Overall, our results indicate that, even under social restrictions, a surge in transmissibility of SARS-CoV-2 can occur when holiday celebrations result in small social gatherings attended simultaneously and communitywide.

Natural ventilation, low CO2 and air filtration are associated with reduced indoor air respiratory pathogens (preprint)

Currently, the real-life impact of indoor climate, human behavior, ventilation and air filtration on respiratory pathogen detection and concentration are poorly understood. This hinders the interpretability of bioaerosol quantification in indoor air to surveil respiratory pathogens and transmission risk. We tested 341 indoor air samples from 21 community settings for 29 respiratory pathogens using qPCR. On average, 3.9 pathogens were positive per sample and 85.3% of samples tested positive for at least one. The number of detected pathogens and their respective concentrations varied significantly by pathogen, month, and age group in generalized linear (mixed) models and generalized estimating equations. High CO2 and low natural ventilation were independent risk factors for detection. CO2 concentration and air filtration were independently associated with their concentration. Occupancy, sampling time, mask wearing, vocalization, temperature, humidity and mechanical ventilation were not significant. Our results support the importance of ventilation and air filtration to reduce transmission.

Risk factors for SARS-CoV-2 transmission in student residences: a case-ascertained study in Leuven, Belgium from October 2020 until May 2021 (preprint)

Background Student residences are at high risk for rapid COVID-transmission due to crowding and frequent close contact. Aim We aimed to investigate the overall secondary attack rates (SAR) in student residences and to discern risk factors for higher transmission in order to improve the evidence base for screening efforts and preventive measures. Methods In this retrospective case-ascertained study, we analysed data from student residences screened in Leuven, Belgium between October 2020 and May 2021, following detection of a COVID-19 case in the residence. We investigated the impact on the SAR in the living units screened of delay-time until follow-up, shared use of kitchen or sanitary facilities, presence of an external infection source and occurrence of social gatherings attended by the index case. Results We included 200 residence units, representing 2326 screened residents, of which 68 units showed secondary transmission. The overall SAR was estimated at 0.0813 (95%CI 0.0705-0.0936). Both sharing sanitary facilities (p=0.04) and social gatherings attended by the index case (p=0.033) significantly impacted SAR, which increased from 3% to 13% when both risk factors were present compared to absent. Conclusions We identify risk factors which should be considered when selecting students for screening during an outbreak of COVID-19 in student residences to improve comprehensiveness and proportionality of testing. The identified risk factors improve the evidence base for preventive measures aimed at limiting social gatherings and improving ventilation of shared spaces in outbreak-prone settings. Lastly, they should be considered when designing student accommodation and other shared households.

Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization (preprint)

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa 1,2 . It has in the meantime spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the Spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development 3 , and to antibodies present in 90 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.

Integrated PCR testing and extended window contact tracing system for COVID-19 to improve comprehensiveness and speed (preprint)

Testing and contact tracing are standard tools for controlling the spread of COVID-19 1 . Their effectiveness hinges on a sequence of processes encompassing testing coverage and timeliness, testing quality and speed of reporting, contact tracing speed and comprehensiveness and compliance with advice given 2–6 . We optimized this sequence of processes in the context of a public health program targeting around 33,000 higher education students through a combination of low barrier PCR testing with rapid turn-around-time, close integration of testing and tracing teams and IT infrastructure, community engagement and the implementation of bidirectional contact tracing by extending the contact tracing window from 2 to 7 days before symptom onset or test of the index case. We anticipate this combined intervention to help improve epidemic control.

Empirical evidence on the efficiency of backward contact tracing in COVID-19 (preprint)

Standard contact tracing practice for COVID-19 is to identify persons exposed to an infected person during the contagious period, assumed to start two days before symptom onset or diagnosis. In the first large cohort study on backward contact tracing for COVID-19, we extended the contact tracing window by 5 days, aiming to identify the source of the infection and persons infected by the same source. The risk of infection amongst these additional contacts was similar to contacts exposed during the standard tracing window and significantly higher than symptomatic individuals in a control group, leading to 42% more cases identified through contact tracing. Compared to standard practice, backward traced contacts required fewer tests and shorter quarantine, but if infected they were identified later in their infectious cycle. Our results support implementing backward contact tracing when rigorous suppression of viral transmission is warranted.