Nosocomial outbreak of SARS-CoV-2 in a “non-COVID-19” hospital ward: virus genome sequencing as a key tool to understand cryptic transmission

Abstract

Background. Dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions affects both patients and health-care workers (HCW), as well as the institutional capacity to provide essential health services. Methods. We conducted an investigation of a cluster of SARS-CoV-2 positive cases detected in a 'non-COVID-19' hospital ward during Summer 2020. The magnitude of the nosocomial outbreak was disclosed by massive testing, challenging the retrospective reconstruction of the introduction and transmission events. An in-depth contact tracing investigation was carried out to identify the contacts network during the 15-day period before the screening. In parallel, positive SARS-CoV-2 RNA samples were subjected to virus genome sequencing. Results. Of the 245 tested individuals, 48 (21 patients and 27 HCWs) tested positive for SARS-CoV-2. HCWs were mostly asymptomatic, but the mortality among the vulnerable patient group reached 57.1% (12/21). Phylogenetic reconstruction revealed that all cases were part of the same transmission chain, thus confirming a single origin behind this nosocomial outbreak. By combining vast epidemiological and genomic data, including analysis of emerging minor variants, we unveiled a scenario of silent SARS-CoV-2 dissemination within the hospital ward, mostly driven by the close contact within the HCWs group and between HCWs and patients. This investigation triggered enhanced prevention and control measures, leading to a more timely detection and containment of novel nosocomial outbreaks. Conclusions. The present study shows the benefit of combining genomic and epidemiological data for the investigation of complex nosocomial outbreaks, and provides valuable data to minimize the risk of transmission of COVID-19 in healthcare facilities.

Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals: a systematic review

“…Of the 18 included studies, 7 were done in the USA [19][20][21][22][23][24][25], 7 in Europe [26][27][28], of which 4 were in UK [29][30][31][32], two in Canada [33,34], one in Japan (cruise ship) [35] and one in Australia (flight) [36]. Most studies were completed in 2020, with 11 in the first half of the year [19,22,25,27,28,30,31,[33][34][35][36], and four in the second half [23,24,26,29]; two studies were done between December and January 2021 [20,21].…”

“…Four studies were done in long-term care facilities [19,24,28,30], and one among patients in a hospital [26]. Three studies were based in schools with or without associated J o u r n a l P r e -p r o o f households [20,21,29].…”

“…Sixteen studies reported carrying GS for phylogenetic assessment to assess possible alternative sources of infection [19][20][21][22][25][26][27][28][29][30][31][32][33][34][35][36].…”

Epidemiological data and genome sequencing reveals that nosocomial transmission of SARS-CoV-2 is underestimated and mostly mediated by a small number of highly infectious individuals

“…The sensitivity and specificity of this SNP threshold for defining linkage varies according to the point during the pandemic at which it is being applied, both in terms of time since the start of the pandemic (greater overall viral diversity afforded by later time points in the pandemic), and the current rate of transmission (locally reduced diversity during exponential periods of spread, such as was observed with the emergence of the alpha variant in the winter of 2020). Improvements in sensitivity and specificity to detect transmission might also be gained from considering patterns of intra-host variation [ 35 , 36 ]. Generally, however, joint epidemiologic and genomic analysis enable the limitations of one method to be compensated for by the strengths of the other, acknowledging both approaches are limited by undiagnosed cases.…”

Complementation of contact tracing by mass testing for successful containment of beta COVID-19 variant (SARS-CoV-2 VOC B.1.351) epidemic in Hong Kong

“…In a modelling study, optimizing testing and tracing coverage, and minimizing tracing delays could enhance contact tracing effectiveness with the potential of preventing up to 80% of all transmissions. 35 Timely use of whole genome sequencing can greatly facilitate outbreak investigation, not only to understand the cryptic chain of transmission, 36 but also to explore the possible mode of transmission. 37 The source of SARS-CoV-2 VOC B.1.351 acquisition for the index case remains to be resolved.…”