key: cord-0885813-vx293w0l
authors: Jinadatha, Chetan; Jones, Lucas D; Choi, Hosoon; Chatterjee, Piyali; Hwang, Munok; Redmond, Sarah N; Navas, Maria E; Zabarsky, Trina F; Bhullar, Davinder; Cadnum, Jennifer L; Donskey, Curtis J
title: Transmission of SARS-CoV-2 in inpatient and outpatient settings in a Veterans Affairs healthcare system
date: 2021-06-21
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofab328
sha: 7ff60df3cc334965badfd990dd6a7487137da650
doc_id: 885813
cord_uid: vx293w0l

BACKGROUND: Healthcare personnel and patients are at risk to acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare settings, including in outpatient clinics and ancillary care areas. METHODS: Between May 1, 2020 and January 31, 2021, we identified clusters of 3 or more COVID-19 cases in which nosocomial transmission was suspected in a Veterans Affairs healthcare system. Asymptomatic employees and patients were tested for SARS-CoV-2 if they were identified as being at risk through contact tracing investigations; for 7 clusters all personnel and/or patients in a shared work area were tested regardless of exposure history. Whole genome sequencing was performed to determine the relatedness of SARS-CoV-2 samples from the clusters and from control employees and patients. RESULTS: Of 14 clusters investigated, 7 occurred in community-based outpatient clinics, 1 in the emergency department, 3 in ancillary care areas, and 3 on hospital medical/surgical wards that did not provide care for patients with known COVID-19 infection. Eighty-one of 82 (99%) symptomatic COVID-19 cases and 31 of 35 (89%) asymptomatic cases occurred in healthcare personnel. Sequencing analysis provided support for several transmission events between co-workers and in 2 cases supported transmission from healthcare personnel to patients. There were no documented transmissions from patients to personnel. CONCLUSIONS: Clusters of COVID-19 with nosocomial transmission predominantly involved healthcare personnel and often occurred in outpatient clinics and ancillary care areas. There is a need for improved measures to prevent transmission of SARS-CoV-2 by healthcare personnel in inpatient and outpatient settings.

Patients and healthcare personnel are at risk to acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare settings [1] . In hospitals, infection control measures including universal masking, use of appropriate personal protective equipment during patient care, and pre-admission and pre-procedure screening are commonly used to minimize the risk for acquisition of SARS-CoV-2 [1] [2] [3] [4] . Recent evidence suggests that these measures are effective in reducing, but not eliminating, the risk for SARS-CoV-2 transmission [4] [5] [6] [7] [8] [9] [10] [11] [12] . For example, transmission has been reported when COVID-19 cases are not recognized because admission screening results are negative or when personnel in the pre-symptomatic stage of COVID-19 provide patient care [7] [8] . Infected personnel can also transmit SARS-CoV-2 to co-workers despite universal masking [4] [5] [6] [7] [8] [9] [10] [11] [12] . Exposures to infected co-workers may occur in areas such as breakrooms or in clinical areas where personnel work without adequate physical distancing [1, [3] [4] [5] 12] .

Although nosocomial transmission of SARS-CoV-2 is often suspected, the actual source of acquisition is frequently unclear, particularly in the setting of widespread community transmission. In the VA Northeast Ohio healthcare System, a majority of personnel with COVID-19 denied higher-risk exposures to SARS-CoV-2 at work or in the community, but often worked in the same area as infected co-workers or patients with the potential for repeated brief interactions [4, 12] . In addition to clusters of COVID-19 on hospital wards, our infection control program investigated multiple clusters of cases in outpatient clinics and ancillary care areas. Such areas could potentially present a relatively high risk for transmission because acutely infected patients are often evaluated in these areas, asymptomatic patients are not routinely screened prior to visits, and personnel often share workspaces. In the current study, we performed whole genome sequencing to investigate A c c e p t e d M a n u s c r i p t 5 several clusters of suspected nosocomial transmission of SARS-CoV-2 in outpatient and inpatient settings in the VA Northeast Ohio Healthcare System.

The VA Northeast Ohio Healthcare System includes a 215-bed acute-care hospital, an adjacent long-term care facility, and 13 community-based outpatient clinics. Of 5,630 total system employees during the study, 793 (14.1%) worked in the community-based outpatient clinics, 4,597 (81.7%) worked in the hospital, and 240 (4.3%) worked in the long-term care facility. During the study period, the hospital had a dedicated 22-bed COVID-19 ward and 8beds in the intensive care unit were dedicated to COVID-19 patients. All hospital admissions as well as patients undergoing selected surgical and medical procedures were screened for COVID-19 symptoms and tested for SARS-CoV-2 by nasopharyngeal swab reverse transcriptase polymerase chain reaction (RT-PCR).

Personnel providing care for patients with suspected or known COVID-19 wore gloves, a gown, a respirator, and face shield; medical procedure facemasks and eye protection were worn during care of other patients and during interactions with co-workers. Personnel were required to wear facemasks unless in a workspace behind closed doors. It was recommended that personnel eat meals alone at their desks and not sit together during break periods. All personnel were screened for COVID-19 symptoms on entry to the healthcare facility. Compliance of personnel with control measures including physical distancing and personal protective equipment use was monitored by infection control staff and feedback was provided to individuals and supervisors. Patients were required to wear cloth facemasks when out of their room or when personnel entered. No visitors were allowed in the hospital and family members were not allowed to attend outpatient clinic visits. Testing for COVID-A c c e p t e d M a n u s c r i p t 6 19 was performed using commercial RT-PCR assays. For personnel with symptoms concerning for COVID-19 infection, including mild symptoms such as sore throat and nasal congestion, testing was available in the hospital and outpatient clinics and was recommended.

The study protocol was approved by the Cleveland VA Medical Center's Institutional Review Board with a waiver of informed consent.

The Infection Control Department conducted contact tracing in accordance with Centers for Disease Control and Prevention (CDC) recommendations [1, 13] . Higher risk exposures were defined as 15 minutes or more of continuous or cumulative contact within 6 feet without wearing both a facemask and eye protection occurring within 2 days before symptom onset through the time when the source individual met criteria for discontinuation of transmissionbased precautions [13] . Contacts that included contact within 6 feet but for less than 15 minutes or while wearing both a facemask and eye protection were classified as lower risk exposures. Personnel were questioned regarding contacts with co-workers both at work and in the community. Asymptomatic employees or patients were offered testing if they were identified as being at risk through contact tracing investigations. In clusters with large numbers of cases, surveillance nasopharyngeal swab testing was recommended for all personnel on a ward or in an outpatient clinic regardless of exposure history.

For the purposes of the study, we identified clusters of 3 or more COVID-19 cases between May 1, 2020 and January 31, 2021 in which nosocomial transmission was suspected.

The study was initiated on May 1, 2020 when testing availability increased allowing testing of contacts. Clusters in the long-term care facility were excluded. Clusters in which 3 or 

The raw sequencing data FASTQ file was uploaded to the BaseSpace sequence hub and a consensus FASTA file was generated with SARS-CoV-2 reference sequence (NC_045512. analysis. The SARS-CoV-2 plugin tool was used to analyze the SARS-CoV-2 genomic sequences. Sequences were analyzed for SNP differences relative to the NCBI reference sequence for SARS-CoV-2 (NC_045512). Sequences with <2 SNP differences were considered related if they belonged to the same clade. Sequences with 3 to 4 SNP differences were deemed to be possibly related if contact tracing indicated a plausible transmission event and the sequences were of the same clade designation. Using the advanced clustering tools, similarity matrix was calculated based on the similarity coefficient between the isolates. The results of the similarity matrix were then used as input data in the Complete linkage clustering algorithm to generate dendrograms and calculate SNP differences. Only samples that met our strict filtering criteria were used to generate the dendrograms. Table 1 shows the A c c e p t e d M a n u s c r i p t 9 location of the clusters and the numbers of personnel and patients involved including the initial cases and the number of asymptomatic individuals screened. In each of the clusters, the initial cases were employees diagnosed with COVID-19 after known or suspected community exposures, followed by suspected transmission to co-workers. Of the clusters investigated, 3 were on inpatient wards, 7 were in community-based outpatient clinics, 1 was in the emergency department, and 3 were in ancillary care areas including radiology, sleep lab, and vascular lab. In multiple areas, it was noted that computer workstations were separated by less than 6 feet and efforts were made to increase spacing between employees. with an unrelated virus. In cluster F, a physical therapist implicated as a possible source of transmission had a SARS-CoV-2 virus that was distinct from 2 subsequently infected coworkers, but the co-workers (#22 and #23) had possibly related viruses (4 SNP differences).

In cluster G, a nurse index case (#24) on a spinal cord injury unit was infected with a virus related to a second employee (#26) with a high-risk exposure; 2 employees (#3 and #25) later diagnosed on the same unit were infected with possibly related (4 SNP difference) viruses that were distinct from the index case virus. For 2 of the suspected clusters (cluster C and cluster E), there was no evidence of transmission based on sequence analysis. viruses. There were no documented transmissions from patients to personnel. Our findings are consistent with recent evidence that healthcare personnel are more likely to acquire SARS-CoV-2 from infected co-workers than from infected patients in settings with good infection control measures in place and nosocomial acquisition by patients is uncommon [4, 10, [14] [15] .

One notable finding from our study was that only 3 of the 14 clusters with suspected transmission occurred on hospital wards. Seven of the clusters occurred in community-based outpatient clinics, 1 in the emergency department, and 3 in ancillary care areas. Based on contact tracing investigations, the outpatient clinics and ancillary care areas were considered relatively high-risk for transmission among co-workers because personnel often shared work areas and break areas and had computer stations separated by less than 6 feet. Similar concerns regarding inadequate physical distancing of work and break areas were reported in a recent observational study on a general medical ward [16] . In response to the clusters, the infection control program made efforts to reinforce compliance with masking and eye protection and to increase spacing in work and break areas. For example, in areas where computer workstations were separated by less than 6 feet, new workstations were created to provide better spacing between employees.

The outpatient clinic and ancillary care settings could also present a relatively high risk for acquisition of SARS-CoV-2 from patients. In these areas, acutely infected patients with relatively high viral burden are often seen by providers and asymptomatic outpatients are not routinely screened for SARS-CoV-2. However, the contact tracing investigations and the sequencing analysis suggested that transmission from patients was uncommon.

Based on the sequencing analysis, 3 control employees with symptomatic COVID-19

were infected with viruses related to cluster A employees in the absence of known exposures.

It is possible that the SARS-CoV-2 variant associated with cluster A was widely circulating A c c e p t e d M a n u s c r i p t 13 with community acquisition by multiple personnel rather than nosocomial transmission.

Alternatively, there may have been interactions between the control and cluster A employees that were not recollected. Because employees were not routinely screened for SARS-CoV-2, it is also plausible that employees with asymptomatic shedding of the viruses may have served as intermediate sources of transmission linking the control and cluster A employees.

Previous studies with other pathogens have demonstrated that many transmissions in hospitals that are identified using highly discriminatory typing methods occur in the absence of shared ward exposure [17] [18] . For example, Eyre et al. [17] reported that 9% of Clostridioides difficile transmissions based on whole genome sequencing occurred in patients who shared time in the hospital but were never on the same ward.

The estimated mutation rate of SARS-CoV-2 is 2.5 nucleotides per month [11] .

Based on this mutation rate, genetic relatedness has typically been defined as 0 to 1 or 0 to 2 SNP differences in cases with plausible epidemiological links [5, [8] [9] [10] [11] . In the current analysis, we identified several instances where there were plausible epidemiological links between cases with 3 to 4 SNP differences. We deemed these cases to be possibly related.

However, further studies will be needed to clarify whether a cut-off of 2 SNP differences is required to define transmission events.

Our study has several limitations. We did not sequence all viruses from the clusters because some samples were not available or did not meet the stringent requirements for quality of sequencing. In addition, we only sequenced a small sample of control employee and patient samples. Thus, we cannot be certain that some of the transmission events did not represent concurrent acquisition of related viruses widely circulating in the community. In conclusion, we found that clusters of COVID-19 with suspected transmission predominantly involved healthcare personnel and often occurred in outpatient clinics.

Sequencing results provided evidence supporting multiple transmission events between coworkers and in 2 cases from healthcare personnel to patients. The findings contributed to development of improved infection control measures to limit nosocomial transmission of SARS-CoV-2, including efforts to increase spacing between co-workers. 

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