COVID-19 Nosocomial Transmission Dynamics, a Retrospective Cohort Study of Two Healthcare Associated Clusters in a District Hospital in England during March and April 2020

Summary Objective: To understand the transmission dynamics of SARS-CoV-2 in a hospital outbreak to inform infection control actions. Design: Retrospective cohort study. Setting: General medical and elderly inpatient wards in a hospital in England. Methods: COVID-19 patients were classified as community or healthcare-associated by time from admission to onset/positivity using European Centre for Disease Prevention and Control definitions. COVID-19 symptoms were classified as asymptomatic, non-respiratory or respiratory. Infectiousness was calculated from 2 days prior to 14 days post symptom onset or positive test. Cases were defined as healthcare-associated COVID-19 patients where infection was acquired from the wards under investigation. COVID-19 exposures were calculated based on symptoms and bed proximity to an infectious patient. Risk ratios and adjusted odds ratios (aOR) were calculated from univariable and multivariable logistic regression. Results: Of 153 patients: 65 were COVID-19 patients (45 healthcare-associated). Exposure to a COVID-19 patient with respiratory symptoms was associated with healthcare-associated infection irrespective of proximity (aOR 3.81; 95%CI 1.6.3-8.87), non-respiratory exposure was only significant within 2.5m (aOR 5.21; 95%CI 1.15-23.48). A small increase in risk ratio was observed for exposure to a respiratory patient for >1 day compared to 1 day from 2.04 (95%CI 0.99-4.22) to 2.36 (95%CI 1.44-3.88) Discussion: Respiratory exposure anywhere within a 4-bedded bay was a risk whereas non-respiratory exposure required bed distance ≤2.5m. Standard Infection control measures required beds to be >2m apart; our study suggests this may be insufficient to stop SARS-CoV-2 spread. We recommend improving cohorting and further studies into bed distance and transmission factors.

Analysis of the diagnostic accuracy of rapid antigenic tests for detection of SARS-CoV-2 in hospital outbreak situation

The reverse transcriptase polymerase chain reaction (RT-PCR) continues to be the reference diagnostic method for the confirmation of COVID-19 cases; however, rapid antigen detection tests (RADT) have recently been developed. The purpose of the study is to assess the performance of rapid antigen-based COVID-19 testing in the context of hospital outbreaks. This was an observational, cross-sectional study. The study period was from October 2020 to January 2021. The “Panbio COVID-19 AG” RADT (Abbott) was performed and TaqPath COVID-19 test RT-PCR. The samples were obtained from hospitalised patients in suspected outbreak situations at the Ramón y Cajal Hospital. A hospital outbreak was defined as the presence of 3 or more epidemiologically linked cases. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the RADT were calculated using RT-PCR as a reference. A total of 17 hospital outbreaks were detected in 11 hospital units during the study period, in which 34 RT-PCR and RADT screenings were performed. We obtained 541 samples, which were analysed with RT-PCR and a further 541 analysed with RADT. Six RADT tests gave conflicting results with the RT-PCR, 5 of them with a negative RADT and positive RT-PCR and one with positive RADT and a negative RT-PCR. The sensitivity of the RADT was 83.3% (65.3–94.4%) and the specificity was 99.8% (98.9–100%). The PPV was 96.2% (80.4–99.9%) and the NPV was 99% (97.7–99.7%). The RADT shows good diagnostic performance in patients on non-COVID-19 hospital wards, in the context of an outbreak.

Clonal Spread and Intra- and Inter-Species Plasmid Dissemination Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales During a Hospital Outbreak in Barcelona, Spain

Objectives: The study aimed to characterize the clonal spread of resistant bacteria and dissemination of resistance plasmids among carbapenem-resistant Enterobacterales at a tertiary hospital in Catalonia, Spain.Methods: Isolates were recovered from surveillance rectal swabs and diagnostic samples. Species identification was by matrix-assisted laser desorption ionization-time time of flight mass spectrometry (MALDI-TOF MS). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Antimicrobial susceptibility was assessed by gradient-diffusion and carriage of bla genes was detected by PCR. Plasmid typing, conjugation assays, S1-PFGE studies and long-read sequencing were used to characterize resistance plasmids.Results: From July 2018 to February 2019, 125 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were recovered from 101 inpatients from surveillance (74.4%) or clinical samples (25.6%), in a tertiary hospital in Barcelona. Clonality studies identified a major clone of Klebsiella pneumoniae belonging to sequence type ST15 and additional isolates of K. pneumoniae, Escherichia coli and Enterobacter sp. from different STs. All isolates but one carried the blaKPC–2 allelic variant. The blaKPC–2 gene was located in an IncFIIk plasmid of circa 106 Kb in a non-classical Tn4401 element designated NTEKPC-pMC-2-1. Whole-genome sequencing revealed different rearrangements of the 106 Kb plasmid while the NTEKPC-pMC-2-1 module was highly conserved.Conclusion: We report a hospital outbreak caused by the clonal dissemination of KPC-producing ST15 K. pneumoniae but also the intra- and inter-species transmission of the blaKPC–2 gene associated with plasmid conjugation and/or transposon dissemination. To our knowledge, this is the first report of an outbreak caused by KPC-producing Enterobacterales isolated from human patients in Catalonia and highlights the relevance of surveillance studies in the early detection and control of antibiotic resistant high-risk clones.

Hospital Outbreak of the SARS-CoV-2 Delta Variant in Partially and Fully Vaccinated Patients and Healthcare Workers in Toronto, Canada

The SARS-CoV-2 Delta variant is highly transmissible and current vaccines may have reduced effectiveness in preventing symptomatic infection. Using epidemiological and genomic analysis, we investigated an outbreak of the variant in an acute care setting amongst partially and fully vaccinated individuals. Effective outbreak control was achieved using standard measures.

How well does SARS-CoV-2 spread in hospitals?

Covid-19 poses significant risk of nosocomial transmission, and preventing this requires good estimates of the basic reproduction number R0 in hospitals and care facilities, but these are currently lacking. Such estimates are challenging due to small population sizes in these facilities and inconsistent testing practices.We estimate the patient-to-patient R0 and daily transmission rate of SARS-CoV-2 using data from a closely monitored hospital outbreak in Paris 2020 during the first wave. We use a realistic epidemic model which accounts for progressive stages of infection, stochastic effects and a large proportion of asymptomatic infections. Innovatively, we explicitly include changes in testing capacity over time, as well as the evolving sensitivity of PCR testing at different stages of infection. We conduct rigorous statistical inference using iterative particle filtering to fit the model to the observed patient data and validate this methodology using simulation.We provide estimates for R0 across the entire hospital (2.6) and in individual wards (from 3 to 15), possibly reflecting heterogeneity in contact patterns or control measures. An obligatory mask-wearing policy introduced during the outbreak is likely to have changed the R0, and we estimate values before (8.7) and after (1.3) its introduction, corresponding to a policy efficacy of 85%.

Multiple Occurrences of a 168-Nucleotide Deletion in SARS-CoV-2 ORF8, Unnoticed by Standard Amplicon Sequencing and Variant Calling Pipelines

Genomic surveillance of the SARS-CoV-2 pandemic is crucial and mainly achieved by amplicon sequencing protocols. Overlapping tiled-amplicons are generated to establish contiguous SARS-CoV-2 genome sequences, which enable the precise resolution of infection chains and outbreaks. We investigated a SARS-CoV-2 outbreak in a local hospital and used nanopore sequencing with a modified ARTIC protocol employing 1200 bp long amplicons. We detected a long deletion of 168 nucleotides in the ORF8 gene in 76 samples from the hospital outbreak. This deletion is difficult to identify with the classical amplicon sequencing procedures since it removes two amplicon primer-binding sites. We analyzed public SARS-CoV-2 sequences and sequencing read data from ENA and identified the same deletion in over 100 genomes belonging to different lineages of SARS-CoV-2, pointing to a mutation hotspot or to positive selection. In almost all cases, the deletion was not represented in the virus genome sequence after consensus building. Additionally, further database searches point to other deletions in the ORF8 coding region that have never been reported by the standard data analysis pipelines. These findings and the fact that ORF8 is especially prone to deletions, make a clear case for the urgent necessity of public availability of the raw data for this and other large deletions that might change the physiology of the virus towards endemism.