Unraveling a Nosocomial Outbreak of COVID-19: The Role of Whole-Genome Sequence Analysis

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component, and there is accumulating evidence that whole-genome sequencing of the virus may provide more objective insight.

Methods: We report a large nosocomial outbreak in 1 of the medicine departments in our institution. Following intensive epidemiological investigation, we discovered that 1 of the patients involved was suffering from persistent COVID-19 while initially thought to be a recovering patient. She was therefore deemed to be the most likely source of the outbreak. We then performed whole-genome sequencing of the virus of 14 infected individuals involved in the outbreak.

Results: Surprisingly, the results of whole-genome sequencing refuted our initial hypothesis. A phylogenetic tree of the samples showed multiple introductions of the virus into the ward, 1 of which led to a cluster of 10 of the infected individuals. Importantly, the results pointed in the direction of a specific index patient that was different from the 1 that arose from our initial investigation.

Conclusions: These results underscore the important added value of using whole-genome sequencing in epidemiological investigations as it may reveal unexpected connections between cases and aid in understanding transmission dynamics, especially in the setting of a pandemic where multiple possible index cases exist simultaneously.

Keywords: COVID-19; epidemiology; nosocomial; outbreak; sequencing.

Figure 1.

Floor scheme of the medicine department involved in the outbreak, with a map of the patients who tested positive for SARS-CoV-2. Yellow circle, immobile patient. Abbreviations: P, infected patient; P1 (red), originally assumed index patient; P5 (blue), index patient as suggested by sequencing; S, infected staff; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Schematic overview of hospital stay, onset of symptoms, and diagnosis of COVID-19 of patients involved in the outbreak. Top row, dates of stay in the month of September 2020. Purple, hospital stay in the described medicine department. Blue, hospital stay in another department in the hospital. Patient 1 (red), initially assumed index case. Patient 5 (blue), index case as suggested by sequencing. ○, SARS-CoV-2 PCR negative. ●, SARS-CoV-2 PCR positive. Abbreviations: COVID-19, coronavirus disease 2019; S, onset of symptoms; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Phylogenetic tree of SARS-CoV-2 sequences obtained in the epidemiological investigation. Samples from the investigation are in color; each of the 5 clades colored differently indicates a separate introduction into the ward. Sequences in gray are unrelated samples from Israel from a similar time point. Bootstrap values are shown on branches (n = 1000). Abbreviations: P, patient; P1, originally assumed index patient; P5, index patient as suggested by sequencing; S, staff member; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.