Combined epidemiological and genomic analysis of nosocomial SARS-CoV-2 transmission identifies community social distancing as the dominant intervention reducing outbreaks

Abstract

Many healthcare facilities report SARS-CoV-2 outbreaks but transmission analysis is complicated by the high prevalence of infection and limited viral genetic diversity. The contribution of different vectors to nosocomial infection or the effectiveness of interventions is therefore currently unclear. Detailed epidemiological and viral nanopore sequence data were analysed from 574 consecutive patients with a PCR positive SARS-CoV-2 test between March 13th and March 31st, when the pandemic first impacted on a large, multisite healthcare institution in London. During this time the first major preventative interventions were introduced, including progressive community social distancing (CSD) policies leading to mandatory national lockdown, exclusion of hospital visitors, and introduction of universal surgical facemask-use by healthcare-workers (HCW). Incidence of nosocomial cases, community SARS-CoV-2 cases and infection in a cohort of 228 HCWs followed the same dynamic course, decreasing shortly after introduction of CSD measures and prior to the main hospital-based interventions. We investigated clusters involving nosocomial cases based on overlapping ward-stays during the 14-day incubation period and SARS-CoV-2 genome sequence similarity. Our method placed 63 (79%) of 80 sequenced probable and definite nosocomial cases into 14 clusters containing a median of 4 patients (min 2, max 19) No genetic support was found for the majority of epidemiological clusters (31/44, 70%) and genomics revealed multiple contemporaneous outbreaks within single epidemiological clusters. We included a measure of hospital enrichment compared to community cases to increase confidence in our clusters, which were 1-14 fold enriched. Applying genomics, we could provide a robust estimate of the incubation period for nosocomial transmission, with a median lower bound and upper bound of 6 and 9 days respectively. Six (43%) clusters spanned multiple wards, with evidence of cryptic transmission, and community-onset cases could not be identified in more than half the clusters, particularly on the elective hospital site, implicating HCW as vectors of transmission. Taken together these findings suggest that CSD had the dominant impact on reducing nosocomial transmission by reducing HCW infection.

Enhancing epidemiological investigation of nosocomial SARS-CoV-2 infection with whole genome sequencing: A retrospective cohort study across four hospitals in the UK

“…This study demonstrates that retrospective analyses of genomic data is useful in some circumstances to guide future IPC practice, with results consistent with similar studies in the UK [7][8][9][10]. It remains to be seen whether the additional costs of generating and analysing this genomic data near real-time (<48hrs from sample to dissemination of results) are justified by additional IPC gains, or whether the rapid and rigorous application of gold standard epidemiological methods in response to fast accumulation of nosocomial PCR-based diagnoses is the key intervention.…”

First and second SARS-CoV-2 waves in inner London: A comparison of admission characteristics and the impact of the B.1.1.7 variant

“…In contrast, current UK public health policy recommends surgical facemasks for patient interactions unless performing aerosol generating procedures [34]. This incidence of nosocomial infection is a major challenge for UK healthcare institutions, with associated crude mortality at around 30% during the first wave [35,36]. For this reason it will be important to further investigate the factors involved in nosocomial acquisition in both waves.…”

A systematic review and meta-analysis of inpatient mortality associated with nosocomial and community COVID-19 exposes the vulnerability of immunosuppressed adults

“…A further 48 studies were excluded as they did not report mortality within both community and nosocomial-acquired COVID-19 patient groups. This left 21 studies for primary meta-analysis (9)(10)(11)(12)(13)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46), summarised in…”

“…As shown in Table 1, a range of case definitions were employed to distinguish community-acquired and nosocomial COVID-19. A fixed interval between admission and diagnosis was employed in 14/21 (62%) ranging from >2 days (45) to >14 days (12), supplemented by additional patient-level clinical data (41) and viral whole genome sequencing (32). Seven studies primarily employed epidemiological nosocomial definitions, for instance a history of close contact with positive cases (n=3, (31,39,43)), or the absence of symptoms on admission with subsequent positive test (n=2, (10,35)).…”

“…In order to support the generalisability of our findings, we included studies with implicit and explicit definitions of nosocomial COVID-19. Accordingly, we catalogued a wide spectrum of case definitions, including combined epidemiological and genomic viral sequencing (32). We controlled for this variation in case definitions within our sensitivity analyses, for instance utilising outcomes meeting consensus international criteria for definite nosocomial infection wherever available.…”