SARS-CoV-2 in schools: genome analysis shows that concurrent cases in the second and third wave were often unconnected (preprint)

Background. The risk of SARS-CoV-2 (SCoV2) infection in schools and student households is typically assessed using classical epidemiology whereby transmission is based on time of symptom onset and contact tracing data. Using such methodologies may be imprecise regarding transmission events of different, simultaneous SCoV2 variants spreading with different rates and directions in a given population. We analysed with high resolution the transmission among different communities, social networks, and educational institutions and the extent of outbreaks using whole genome sequencing (WGS). Methods and Findings. We combined WGS and contact tracing spanning two pandemic waves from October 2020 to May 2021 in the Canton of Basel-City, Switzerland and performed an in-depth analysis of 235 cases relating to 22 educational institutions. We describe the caseload in educational institutions and the public health measures taken and delineate the WGS-supported outbreak surveillance. During the study period, 1,573 of 24,557 (6.4%) children and 410 of 3,726 (11%) staff members from educational institutions were reported SCoV2 positive. Thereof, WGS data from 83 children, 35 adult staff in 22 educational institutions and their 117 contacts (social network, families) was available and analysed. 353 contextual sequences from residents of the Canton of Basel-City sequenced through surveillance were identified to be related to cases in the educational institutions. In total, we identified 55 clusters and found that coinciding SCoV2-cases in individual educational institutions were mostly introduced from different sources such as social networks or the larger community. More transmission chains started in the community and were brought into the educational institutions than vice versa (31 vs. 13). Adolescents (12-19 years old) had the highest case prevalence over both waves compared to younger children or adults, especially for the emerging Alpha variant. Conclusions. Introduction of SCoV2 into schools accounts for most events and reflects transmission closely related to social activity, whereby teenagers and young adults contribute to significant parallel activity. Combining WGS with contact tracing is pivotal to properly inform authorities about SCoV2 infection clusters and transmission directions in educational settings and the effectiveness of enacted public health measures. The gathered data showing more clusters to seed in the community than vice versa as well as few subsequent in-school transmissions indicate that the agilely employed health measures for educational institutions helped to prevent outbreaks among staff and children. The clinical trial accession number is NCT04351503 (clinicaltrials.gov).

SARS-CoV-2 vaccine Alpha and Delta variant breakthrough infections are rare and mild, but happen relative early after vaccination (preprint)

IntroductionCOVID-19 vaccines significantly reduce SARS-CoV-2 (SCoV2)-related hospitalization and mortality in randomized controlled clinical trials, as well as in real-world effectiveness against different circulating SCoV2-lineages. However, some vaccine recipients show breakthrough infection and it remains unknown, which host and viral factors contribute to this risk and how many resulted in severe outcomes. Our aim was to identify demographic and clinical risk factors for SCoV2 breakthrough infections and severe disease in fully vaccinated individuals and to compare patient characteristics in breakthrough infections caused by SCoV2 Alpha or Delta variant. MethodsWe conducted an exploratory retrospective case-control study from 28th of December to 25th of October 2021 dominated by the Delta SCoV2 variant. All cases of infection had to be reported by law to the local health authorities. Vaccine recipients data was anonymously available from the national Vaccination Monitoring Data Lake and the main local vaccine center. We compared anonymized patients characteristics of breakthrough infection (n=492) to two overlapping control groups including all vaccine recipients from the Canton of Basel-City (group 1 n=126586 and group 2 n=109382). We also compared patients with breakthrough infection caused by the Alpha to Delta variant. We used different multivariate generalized linear models (GLM). ResultsWe found only 492/126586 (0.39%) vaccine recipients with a breakthrough infection after vaccination during the 10 months observational period. Most cases were asymptomatic or mild (478/492 97.2%) and only very few required hospitalization (14/492, 2.8%). The time to a positive SCoV2 test shows that most breakthrough infections occurred between a few days to about 170 days after full vaccination, with a median of 78 days (interquartile range, IQR 47-124 days). Factors associated with a lower odds for breakthrough infection were: age (OR 0.987, 95%CI 0.983-0.992), previous COVID-19 infection prior to vaccination (OR 0.296, 95%CI 0.117-0.606), and (self-declared) serious side-effects from previous vaccines (OR 0.289, 95%CI 0.033-1.035). Factors associated with a higher odds for breakthrough infection were: vaccination with the Pfizer/BioNTech vaccine (OR 1.459, 95%CI 1.238-1.612), chronic disease as vaccine indication (OR 2.109, 95%CI 1.692-2.620), and healthcare workers (OR 1.404, 95%CI 1.042-1.860). We did not observe a significantly increased risk for immunosuppressed patients (OR 1.248, 95% CI 0.806-1.849). ConclusionsOur study shows that breakthrough infections are rare and show mild illness, but that it occurs early after vaccination with more than 50% of cases within 70 to 80 days post-full vaccination. This clearly implies that boost vaccination should be much earlier initiated compared to the currently communicated 180-day threshold. This has important implications especially for risk groups associated with more frequent breakthrough infections such as healthcare workers, and people in high-risk care facilities. Due to changes in the epidemiological dynamic with new variants emerging, continuous monitoring of breakthrough infections is helpful to provide evidence on booster vaccines and patient groups at risk for potential complications.