Viral Sequencing to Investigate Sources of SARS-CoV-2 Infection in US Healthcare Personnel

Abstract

Background: Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We posit that current infection control guidelines generally protect HCP from SARS-CoV-2 infection in a healthcare setting.

Methods: In this retrospective case series, we used viral genomics to investigate the likely source of SARS-CoV-2 infection in HCP at a major academic medical institution in the Upper Midwest of the United States between 25 March and 27 December 2020. We obtained limited epidemiological data through informal interviews and review of the electronic health record and combined this information with healthcare-associated viral sequences and viral sequences collected in the broader community to infer the most likely source of infection in HCP.

Results: We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or coworker (55 of 95 [57.9%]) and were genetically similar to viruses circulating concurrently in the community. We found that 10.5% of HCP infections (10 of 95) could be traced to a coworker. Strikingly, only 4.2% (4 of 95) could be traced to a patient source.

Conclusions: Infections among HCP add further strain to the healthcare system and put patients, HCP, and communities at risk. We found no evidence for healthcare-associated transmission in the majority of HCP infections evaluated. Although we cannot rule out the possibility of cryptic healthcare-associated transmission, it appears that HCP most commonly become infected with SARS-CoV-2 via community exposure. This emphasizes the ongoing importance of mask wearing, physical distancing, robust testing programs, and rapid distribution of vaccines.

Keywords: SARS-CoV-2; healthcare personnel; infection control; precision epidemiology; viral sequencing.

Figure 1.

Graphic representation of case 20. A, Viral sequences are aligned against severe acute respiratory syndrome coronavirus 2 reference sequence Wuhan-Hu-1 (MN908947.3). Vertical markers denote the location of consensus nucleotide differences between patient viruses and the reference. B, Time-resolved phylogenetic tree built using Nextstrain tools with all Wisconsin sequences available as of 15 January 2021. Viruses involved in this case are denoted with thick branches and labeled tips. Color denotes clade. Abbreviation: HCP, healthcare personnel.

Figure 2.

Graphic representation of case 16. A, Viral sequences are aligned against severe acute respiratory syndrome coronavirus 2 reference sequence Wuhan-Hu-1 (MN908947.3). Vertical markers denote the location of consensus nucleotide differences between patient viruses and the reference. Purple vertical markers indicate identical viral sequences. B, Time-resolved phylogenetic tree built using Nextstrain tools with all Wisconsin sequences available as of 15 January 2021. Viruses involved in this case are denoted with thick branches and labeled tips. Color denotes clade. Abbreviation: HCP, healthcare personnel.

Figure 3.

Graphic representation of case 10. A, Viral sequences are aligned against severe acute respiratory syndrome coronavirus 2 reference sequence Wuhan-Hu-1 (MN908947.3). Vertical markers denote the location of consensus nucleotide differences between patient viruses and the reference. Purple vertical markers indicate identical viral sequences. B, A time-resolved phylogenetic tree built using Nextstrain tools with all Wisconsin sequences available as of 15 January 2021. Viruses involved in this case are denoted with thick branches and labeled tips. Color denotes clade. Abbreviation: HCP, healthcare personnel.

Figure 4.

A time-resolved phylogenetic tree built using Nextstrain tools for all samples collected and shared in Wisconsin from March to December 2020. Healthcare-associated samples are denoted with enlarged tips and colored according to sample type. The gray tips reflect the community surveillance samples. It is likely additional healthcare personnel (HCP) and patient sequences are represented in the community data set, but we do not have access to sufficient metadata to make these designations. Laboratories responsible for obtaining and genetic sequence data included here, if not our own, are documented in Supplementary File 2.

Figure 5.

Genetic diversity among pairwise comparisons of healthcare-associated viruses (healthcare personnel [HCP] and patient samples) is generally similar to that of viruses circulating in the areas surrounding the academic medical center evaluated in this study. Gray distribution reflects 100 000 pairwise random comparisons of the community data set per month. Turquoise distribution shows n-choose-2 comparisons from the healthcare-associated data set per month, where n is the total number of HCP and patient sequences available within each month. The specific value equal to n is shown as the upper value in the turquoise parenthetical expression of n-choose-2. Dashed magenta dashed lines reflect the shared genetic diversity in healthcare-associated pairs where we have high confidence, based on epidemiological data, that these are true transmission pairs. The number of pairs represented in each magenta line is shown in magenta text to the right of each plot. Abbreviation: SNP, single-nucleotide polymorphism.