A systematic outbreak investigation of SARS-CoV-2 transmission clusters in a tertiary academic care center (preprint)

Background We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020-12/2020.Methods At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of Coronavirus disease of 2019 (COVID-19), defined as polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection occurring more than five days after admission. Clusters of nosocomial infections, defined as the detection of at least two positive patients and/or healthcare workers (HCWs) within one week with an epidemiological link, were further investigated by WGS on respective strains.Results The four epidemiologic clusters included 40 patients and 60 HCWs. Sequencing data was available for 70% of all involved cases (28 patients and 42 HCWs), confirmed epidemiologically suspected in house transmission in 33 cases (47.1% of sequenced cases) and excluded transmission in the remaining 37 cases (52.9%). Among cases with identical strains, epidemiologic work-up suggested transmission mainly through a ward-based exposure (24/33, 72.7%), more commonly affecting HCWs (16/24, 66.7%) than patients (8/24, 33.3%), followed by transmission between patients (6/33, 18.2%), and among HCWs and patients (3/33, 9.1%, respectively two HCWs and one patient).Conclusions Phylogenetic analyses revealed important insights into transmission pathways supporting less than 50% of epidemiologically suspected SARS-CoV-2 transmissions. The remainder of cases most likely reflect community-acquired infection randomly detected by outbreak investigation. Notably, most transmissions occurred between HCWs, possibly indicating lower perception of the risk of infection during contacts among HCWs.

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.

SARS-CoV-2 phylogeny during the early outbreak in the Basel area, Switzerland: import and spread dominated by a single B.1 lineage variant (C15324T) (preprint)

Background: The first local case of SARS-CoV-2 in Basel, Switzerland, was detected on February 26th 2020. We present a phylogenetic cross-sectional study and explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. Methods: We sequenced SARS-CoV-2 samples from naso-oropharyngeal swabs and generated 468 high quality genomes and called variants with our COVID-19 Genome Analysis Pipeline (COVGAP). We analysed viral genetic diversity using PANGOLIN taxonomic lineages. For identification of introduction and dissemination events across the Basel area a time-calibrated phylogeny was inferred including global SARS-CoV-2 genomes. Findings: Our samples exhibit low lineage diversity compared to neighbouring countries. Lineage B.1 (82.7%), detected from March 2nd, dominated infections in Basel. A large clade within B.1 contains 69.1% of our samples, all of which carry the SNP C15324T, suggesting local transmission in spreading events. We have located the geographic origin of this mutation in our tri-national region. The remaining genomes map broadly over the global phylogenetic tree, evidencing several events of introduction from and/or dissemination to other regions of the world. Further, we have identified several transmission events within families. Interpretation: Molecular surveillance of SARS-CoV-2 by phylogenetic reconstruction in the Basel area provides important insights into local transmission (spreading events and family transmission). This phylogenetic analysis enriches epidemiological and contact tracing data, allowing connection of seemingly unconnected events and drawing conclusions, which can be used to inform public health interventions. Funding: No dedicated funding was used for this work.