Unexpected details regarding nosocomial transmission revealed by whole-genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2)

Abstract

Objective: Effective infection prevention and control (IPC) measures are key for protecting patients from nosocomial infections and require knowledge of transmission mechanisms in different settings. We performed a detailed outbreak analysis of the transmission and outcome of coronavirus disease 2019 (COVID-19) in a geriatric ward by combining whole-genome sequencing (WGS) with epidemiological data.

Design: Retrospective cohort study.

Setting: Tertiary-care hospital.

Participants: Patients and healthcare workers (HCWs) from the ward with a nasopharyngeal sample (NPS) positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA during the outbreak period.

Methods: Patient data regarding clinical characteristics, exposure and outcome were collected retrospectively from medical records. Stored NPSs from 32 patients and 15 HCWs were selected for WGS and phylogenetic analysis.

Results: The median patient age was 84 years and 17 (53%) of 32 were male. Also, 14 patients (44%) died within 30 days of sampling. Viral loads were significantly higher among the deceased. WGS was successful in 28 (88%) of 32 patient samples and 14 (93%) of 15 HCW samples. Moreover, 3 separate viral clades were identified: 1 clade and 2 subclades among both patient and HCW samples. Integrated epidemiological and genetic analyses revealed 6 probable transmission events between patients and supported hospital-acquired COVID-19 among 25 of 32 patients.

Conclusions: WGS provided an insight into the outbreak dynamics and true extent of nosocomial COVID-19. The extensive transmission between patients and HCWs indicated that current IPC measures were insufficient. We recommend increased use of WGS in outbreak investigations to identify otherwise unknown transmission links and to evaluate IPC measures.

Fig. 1.

Epidemic curve of COVID-19 cases in a hospital ward outbreak. Day of positive SARS-CoV-2 nasopharyngeal samples from 32 patients (above x-axis) and 15 healthcare workers (HCW; below x-axis) are displayed according to timeline throughout the outbreak period. Individual case numbers are shown for patients and HCWs separately. Colors indicate viral clades and arrows the implementation of outbreak control measures.

Fig. 2.

Patient–patient transmission of SARS-CoV-2 in a hospital ward outbreak. The panel display 22 patient cases defined as close contacts due to sharing a room with another case. Individual case numbers and letters indicating shared room are seen on the y-axis, and timeline of the outbreak period (days) seen on the x-axis. Bars show day of admission until discharge from the affected ward. Colors represent duration of shared room with another case and viral clade. Dots indicate time point for sampling and stars represent symptom onset. A patient–patient transmission event was probable if: sequence differences did not exclude a genetic relationship, and day of sampling or symptom onset for 2 close contacts occurred within 2–14 days of each other.