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).

Evolution of COVID-19 mortality over time: results from the Swiss hospital surveillance system (CH-SUR) (preprint)

BackgroundWhen comparing the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons, and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors. MethodsWe investigated the trends in COVID-19 related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to May 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk. ResultsOur analysis included 16,030 episodes recorded in CH-SUR, with 2,320 reported deaths due to COVID-19 (13.0% of included episodes). We found that overall in-hospital mortality was lower during the second wave of COVID-19 compared to the first wave (HR 0.71, 95% CI 0.69 - 0.72, p-value < 0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared to the first wave (HR 1.48, 95% CI 1.42 - 1.55, p-value < 0.001), with significant changes in the course of hospitalisation between the first and the second wave. ConclusionWe found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.

Determinants of SARS-CoV-2 transmission to guide vaccination strategy in a city (preprint)

Transmission chains within cities provide an important contribution to case burden and economic impact during the ongoing COVID-19 pandemic, and should be a major focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of SARS-CoV-2 transmission in a medium-sized European city. We combined detailed epidemiological, mobility, and socioeconomic data-sets with whole genome sequencing during the first SARS-CoV-2 wave. Both phylogenetic clustering and compartmental modelling analysis were performed based on the dominating viral variant (B.1-C15324T; 60% of all cases). Here we show that transmissions on the city population level are driven by the socioeconomically weaker and highly mobile groups. Simulated vaccination scenarios showed that vaccination of a third of the population at 90% efficacy prioritising the latter groups would induce a stronger preventive effect compared to vaccinating exclusively senior population groups first. Our analysis accounts for both social interaction and mobility on the basis of molecularly related cases, thereby providing high confidence estimates of the underlying epidemic dynamics that may readily be translatable to other municipal areas.

SARS-CoV-2/COVID-19 hospitalised patients in Switzerland: a prospective cohort profile (preprint)

BackgroundSARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 43000 confirmed cases as of September 1st, 2020. AimIn cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19 in addition to their mandatory reporting system. MethodsPatients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patients admission date. ResultsAs of September 1st, 2020, 3645 patients were included. Most patients were male (2168 - 59.5%),and aged between 50 and 89 years (2778 - 76.2%), with a median age of 68 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: hypertension (1481 - 61.7%), cardiovascular diseases (948 - 39.5%), and diabetes (660 - 27.5%) being the most frequent in adults; respiratory diseases and asthma (4 -21.1%), haematological and oncological diseases (3 - 15.8%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 - 55.2% in children), renal (681 - 25.7%) and cardiac (631 - 23.8%) complication for adults. The second and third most frequent complications in children affected the digestive system and the liver (7 - 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989 - 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. 527 (14.5%) deaths were registered, all among adults. ConclusionThe surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.