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. 2020 Dec 28;15(12):e0244477. doi: 10.1371/journal.pone.0244477

Epidemiology, clinical characteristics, household transmission, and lethality of severe acute respiratory syndrome coronavirus-2 infection among healthcare workers in Ontario, Canada

Kevin L Schwartz 1,2,3,*, Camille Achonu 1, Sarah A Buchan 1,2, Kevin A Brown 1,2, Brenda Lee 1, Michael Whelan 1, Julie HC Wu 1, Gary Garber 1,4
Editor: Lamberto Manzoli5
PMCID: PMC7769426  PMID: 33370384

Abstract

Introduction

Protecting healthcare workers (HCWs) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a priority to maintain a safe and functioning healthcare system. Our objective was to describe and compare the epidemiology, clinical characteristics, and lethality of SARS-CoV-2 infections among HCWs compared to non-HCWs.

Methods

Using reportable disease data at Public Health Ontario, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with SARS-CoV-2 infections as of 30 September 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. We evaluated the risk of death using a multivariable logistic regression model adjusting for age, sex, comorbidities, symptoms, and long-term care home exposure.

Results

There were 7,050 (12.5%) HCW SARS-CoV-2 infections in Ontario, Canada, of whom 24.9% were nurses, 2.3% were physicians, and the remaining 72.8% other specialties, including personal support workers. Overall HCWs had an infection rate of 1,276 per 100,000 compared to non-HCWs of 346 per 100,000 (3.7 times higher). This difference decreased from a 7 times higher rate in April to no difference in September 2020. Twenty-six percent of HCWs had a household member with SARS-CoV-2 infection; 6.8% were probable acquisitions, 12.3% secondary transmissions, and 6.9% unknown direction of transmission. Death among HCWs was 0.2% compared to 6.1% of non-HCWs. The risk of death in HCWs remained significantly lower than non-HCWs after adjustment (adjusted odds ratio 0.09; 95%CI 0.05–0.17).

Conclusion

HCWs represent a disproportionate number of diagnosed SARS-CoV-2 infections in Ontario, however this discrepancy is at least partially explained by limitations in testing earlier in the pandemic for non-HCWs. We observed a low risk of death in HCWs which could not be completely explained by other factors.

Introduction

We are in the midst of a global pandemic from Coronavirus disease of 2019 (COVID-19), caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). COVID-19 is impacting healthcare systems globally which are coping with outbreaks in congregate living facilities and the rapid influx of critically ill patients requiring care in intensive care units [1]. Preventing healthcare worker (HCW) infections is critical to maintaining a functioning healthcare system, and they have been a priority group for testing throughout the pandemic [2].

The proportion of SARS-CoV-2 infections affecting HCWs reported from a single centre has ranged from 0 to 29% [35]. In China approximately 4% of all SARS-CoV-2 infections were in HCWs, with an infection rate three times higher in HCWs compared to the general population [68]. Seroprevalence estimates among HCWs have varied between 4% and 19% depending on the jurisdiction [9, 10]. HCWs may be exposed to SARS-CoV-2 in the community, at work from patients as well as fellow HCWs, and may pose a risk to others around them if infected. The World Health Organization (WHO) has identified research priorities related to the burden and risk factors for HCW SARS-CoV-2 infections as well as risk factors for household transmission from HCWs [11]. Our objectives were to describe demographic, exposure, and clinical differences between HCW and non-HCW SARS-CoV-2 infections across all of Ontario, Canada. We further evaluated the risk of death from SARS-CoV-2 between HCWs and non-HCWs, as well as the frequency of HCW household members with SARS-CoV-2 infection.

Methods

Design and setting

We conducted a cross-sectional study comparing HCW and non-HCW SARS-CoV-2 infections. Data collection began with the first COVID-19 diagnosed patient in Ontario, Canada on 21 January 2020 until 30 September 2020. We obtained the data from reportable surveillance infectious disease data at Public Health Ontario (PHO). The activities described in this manuscript were conducted in fulfillment of PHO’s legislated mandate to provide scientific and technical advice and operational support in an emergency or outbreak situation (Ontario Agency for Health Protection and Promotion Act, SO 2007, c 10). Research ethics committee approval was sought from PHO’s Ethics Review Board and determined to be not required because the activities described are considered public health practice and not research. Data were fully anonymized and informed consent was not required.

Data source

We obtained the data from the integrated Public Health Information System (iPHIS), the Toronto Public Health Coronavirus Rapid Entry System (CORES), the Ottawa Public Health COVID-19 Ottawa Database (The COD), Middlesex-London COVID-19 Case and Contact Management tool (CCMtool), and the Public Health Case and Contact Management Solution (CCM) accessed on 14 October 2020 (but only including cases up to 30 September 2020 to account for a delay in reporting). These databases are web-based information systems for the reporting and surveillance of diseases of public health significance in Ontario. PHO is a government corporation dedicated to protecting and promoting the health of all Ontarians and reducing inequities in health. All confirmed SARS-CoV-2 infections are entered by local public health units.

Definitions and variables

A HCW was defined as an individual who self-reported to have an occupation involving caring for patients including (but not limited to) doctors, nurses, dentists, dental hygienists, midwives, other medical technicians, personal support workers, respiratory therapists, and first responders. The database has additional fields for doctor and nurse, however all other HCWs were recorded as “other” with the opportunity for free text. Data quality was evaluated and HCW cases were excluded if they were <15 or >80 years of age (n = 27). All other individuals with diagnosed SARS-CoV-2 infections were classified as non-HCWs. Demographic information available included gender, age, and comorbidities (anemia, asthma, cancer, cardiovascular condition, chronic liver disease, chronic obstructive pulmonary disease (COPD), diabetes, immunocompromised, neurologic disorder, obesity, pregnancy or 6 weeks post-partum, renal condition, tuberculosis, and other chronic medical condition). Exposures were classified by the local public health unit contact investigation as outbreak associated or close contact to a confirmed or probable SARS-CoV-2 infection, community transmission with no epidemiological link, travel to an endemic area for SARS-CoV-2 outside of Ontario within the incubation period of 14 days, or missing exposure information. A separate variable to identify nosocomial cases was added 3 April 2020. Analysis with the nosocomial variable was limited to this time frame. Clinical symptoms were classified as asymptomatic, presymptomatic (defined as having a testing date prior to symptoms onset date), typical with fever and/or cough, other symptoms, or missing. Clinical outcomes were classified in descending order as died, requiring a ventilator in the intensive care unit, intensive care unit without a ventilator, hospitalized, or not hospitalized.

Onset of illness was defined as symptom onset date, which was available for 69.2% of the cohort. For those missing symptom onset date we calculated the weekly median number of days from test date to symptom onset date where the data was available and performed a deterministic imputation base on the week of testing. If test date was not available we used the weekly median time from symptoms onset to date reported to the local public health unit. Onset date in asymptomatic individuals was the testing date or reporting date if not available.

We defined household spread using a natural language processing algorithm to link confirmed HCWs with SARS-CoV-2 infections to other confirmed household contacts with SARS-CoV-2 infection by residential address. The algorithm used Python’s sklearn library. Address text was broken down into short segments (N-grams) with a term-frequency inverse document frequency matrix. The closest proximity match within the matrix was returned and validated using checks for numerical portions of the address field, including suite number if available. The algorithm matched those within the same household or apartment unit, and not to neighbours. If symptom onset dates in the non-HCWs were two or more days earlier than the HCWs then these were defined as a probable HCW acquisition. If household cases symptom onset dates were two or more days following a HCWs’ then this was defined as a probable transmission. Infections that were -1, 0, or +1 days apart were classified as unknown direction of transmission. As a sensitivity analysis we used ±4 days for greater confidence in the direction of transmission.

Statistical analysis

Variables were compared between HCWs and non-HCWs by chi-squared tests, t-tests, or non-parametric tests as appropriate in bivariable analyses with two-side p-values <0.05 as statistically significant. Rates of infection in non-HCWs were determined using population denominators from Statistics Canada. HCW denominators were calculated from publicly available sources at the Canadian Institute for Health Information and Statistics Canada [12, 13]. A multivariable logistic regression model was built to evaluate the association between status of HCW (independent variable) and death (dependent variable). Covariates in the model were selected a priori based on their clinical relevance. We included sex (male versus female), age (<30 years, 30–44 years, 60–74 years, or ≥75 years, compared to 45–59 years), comorbidities (asthma, COPD, renal disease, cardiac disease, diabetes, immune compromised or cancer, obesity, or other comorbidities, compared to no comorbidities), working or residing in a long-term care home (yes versus no), and symptoms (fever and/or cough, other symptoms, or missing symptoms compared to asymptomatic). Where necessary missing data was included as its own covariate.

Results

There are an estimated 552,560 HCWs and 14,311,868 non-HCWs in Ontario. As of 30 September 2020 there were 56,606 confirmed SARS-CoV-2 infections in Ontario, including 7,050 (12.5%) HCWs. There was geographical variability in the proportion of HCW SARS-CoV-2 infections ranging from 2–26% across Ontario’s 34 public health units. In general, the regions with the largest numbers of cases did not overlap with those with the highest proportions (Fig 1). For instance, Toronto and Peel regions had the highest numbers of cases (2,211 and 1,148), but were in the lowest quartile of regions by the proportion of cases that were HCWs (11.1% and 11.5%).

Fig 1. Geographical variability by Ontario public health unit until 30 September 2020.

Fig 1

Left map shows the percent of total SARS-CoV-2 infections in each region that are healthcare workers. Right map shows the cumulative number of healthcare worker SARS-CoV-2 infections.

HCWs with SARS-CoV-2 infection were more likely to be female and were more commonly between the ages of 30–60 years compared to non-HCWs. There were 11 (0.2%) HCWs ≥75 years of age compared to 8,079 (16.3%) non-HCWs. Approximately 30% of both HCW and non-HCWs had one or more comorbidities, most commonly cardiovascular conditions, diabetes, and asthma (Table 1).

Table 1. Clinical, demographic and exposure comparison between healthcare workers and non-healthcare workers with SARS-CoV-2 infection (n = 56,606).

Variable Healthcare workers, n (%) Non-healthcare workers, n (%) p-valuea
Doctor Nurse Otherb Total
Total (% of all SARS-CoV-2 infections) 161 (0.3) 1756 (3.1) 5133 (9.1) 7050 (12.5) 49556 (87.5)
Female gender 65 (40.4) 1516 (86.3) 4142 (80.7) 5723 (81.2) 23479 (47.4) <0.001
Age <0.001
    <30 25 (15.5) 443 (25.2) 890 (17.3) 1358 (19.3) 15107 (30.5)
    30–44 68 (42.2) 630 (35.9) 1603 (31.2) 2301(32.6) 10153(20.5)
    45–59 36 (22.4) 557 (31.7) 2057 (40.1) 2650 (37.6) 9581 (19.3)
    60–74 29 (18.0) 125 (7.1) 576 11.2) 730 (10.4) 6630 (13.4)
    75+ 3 (1.9) 1 (0.1) 7 (0.1) 11 (0.2) 8079 (16.3)
    Unknown 0 0 0 0 6 (<0.1)
One or more comorbiditiesc 36 (22.4) 537 (30.6) 1482 (28.9) 2055 (29.1) 14073 (28.4) 0.19
    Asthma 8 (5.0) 123 (7.0) 327 (6.4) 458 (6.5) 2197 (4.4)
    COPD 0 7 (0.4) 8 (0.2) 15 (0.2) 669 (1.3)
    Renal conditions 1 (0.6) 9 (0.5) 39 (0.8) 49 (0.7) 1020 (2.1)
    Cardiovascular conditions 13 (8.1) 163 (9.3) 457 (8.9) 633 (9.0) 6012 (12.1)
    Diabetes 5 (3.1) 108 (6.2) 364 (7.1) 477 (6.8) 3988 (8.0)
    Immune compromised or cancer 3 (1.9) 45 (2.6) 132 (2.6) 180 (2.6) 1693 (3.4)
    Obesity 1 (0.6) 43 (2.4) 89 (1.7) 133 (1.9) 589 (1.2)
    Other medical conditions 13 (8.1) 249 (14.2) 578 (11.3) 840 (11.9) 6274 (12.7)
Clinical presentation
    Presymptomatic 1 (0.6) 30 (1.7) 77 (1.5) 108 (1.5) 601 (1.2) 0.02
    Presenting symptoms <0.001
        Asymptomatic 19 (11.8) 177 (10.1) 951 (18.5) 1147 (16.3) 8680 (17.5)
        Fever and/or cough 90 (55.9) 981 (55.9) 2578 (50.2) 3802 (53.9) 23165 (46.7)
        Other symptoms 32 (19.9) 427 (24.3) 1359 (26.5) 1906 (27.0) 12918 (26.1)
        Missing symptom data 4 (2.5) 40 (2.3) 220 (4.3) 195 (2.8) 4793 (9.7)
Outcomes <0.001
        Not hospitalized 150(93.2) 1687 (96.1) 4966 (96.7) 6803 (96.5) 42713 (86.2)
        Hospitalized 7 (4.3) 51 (2.9) 121 (2.4) 179 (2.5) 3128 (6.3)
        Intensive care unit—not on ventilator 1 (0.6) 10 (0.6) 30 (0.6) 41 (0.6) 500 (1.0)
        Intensive care unit–on a ventilator 3 (1.9) 7 (0.4) 5 (0.1) 15 (0.2) 211 (0.4)
        Died 0 1 (0.1) 11 (0.2) 12 (0.2) 3004 (6.1)
Resolved 161 (100.0) 1752 (99.8) 5109 (99.5) 7022 (99.6) 45737 (92.3) <0.001
Exposure history <0.001
        Outbreak-associated or close contact of a confirmed case 67 (41.6) 1347 (76.7) 3956 (77.1) 5370 (76.2) 31268 (63.1)
        No known epidemiological link 57 (35.4) 291 (16.6) 835 (16.3) 1183 (16.8) 8281 (16.7)
        Travel-Related 28 (17.4) 77 (4.4) 152 (3.0) 257 (3.6) 1997 (4.0)
        Information missing 9 (5.6) 41 (2.3) 190 (3.7) 240 (3.4) 8010 (16.2)
Exposed to long-term care home 6 (3.7) 586 (33.4) 2334 (45.5) 2926 (41.5) 6926 (14.0)
Nosocomial transmissiond <0.001
        Yes 1 (0.9) 80 (5.1) 106 (2.3) 187 (3.0) 410 (0.9)
        No 33 (30.3) 301 (19.0) 820 (18.0) 1154 (18.4) 6523 (14.1)
        Unknown or missing 75 (68.8) 1201 (75.9) 3642 (79.7) 4918 (78.6) 39490 (85.1)

a Statistical comparison between total healthcare workers and non-healthcare workers

b 2154 (30.6%) were personal support workers identified through free text searching.

c Comorbidities include; anemia or hemoglobinopathy, asthma, cancer, cardiovascular disease, chronic liver disease, chronic obstructive pulmonary disease (COPD), diabetes, immunocompromised, neurological disorder, obesity, pregnant or post-partum, renal conditions, tuberculosis, other chronic medical condition.

d Nosocomial variable added on April 3, 2020, therefore the denominators used were 6259 healthcare workers (109 doctors, 1582 nurses, and 4568 other) and 46423 non-healthcare workers.

HCWs were identified as cases at a rate 3.7 times higher than non-HCWs with rates of 1,276 per 100,000 compared to 346 per 100,000. There were 161 physicians infected, comprising 2.3% of HCW infections, with an infection rate 1.4 times the general population. There were 1,756 nurses (24.9% of HCWs) who comprised 3.1% of all Ontario infections with an infection rate 3.3 times higher than the general population. There were 5,133 (72.8% of HCWs) other HCWs, including 2,154 personal support workers (PSWs). These HCWs had an infection rate 4.1 times that of the general population (Table 2).

Table 2. Rate of new SARS-CoV-2 infections in healthcare workers and non-healthcare workers.

Healthcare workers Non-healthcare workers
Number (%) Rate per 100,000 Number (%) Rate per 100,000
Total 7050 1275.9 49556 346.3
    Physicians 161 (2.3) 475.3 NA NA
    Nurses 1756 (24.9) 1128.8 NA NA
    Other 5133 (72.8) 1413.6 NA NA
Average daily new infections
February 15–29 3 (<0.1) 0.5 28 (0.1) 0.2
March 1–14 82 (1.2) 14.8 645 (1.3) 4.5
March 15–31 1001 (14.2) 181.2 3840 (7.8) 26.8
April 1–14 1456 (20.7) 263.5 5338 (10.8) 37.3
April 15–30 1720 (24.4) 311.3 6070 (12.3) 42.4
May 1–14 783 (11.1) 141.7 3827 (7.7) 26.7
May 15–31 593 (8.4) 107.3 5178 (10.5) 36.2
June 1–14 260 (3.7) 47.1 2497 (5.0) 17.4
June 15–30 228 (3.2) 41.3 2376 (4.8) 16.6
July 1–14 118 (1.7) 21.4 1694 (3.4) 11.8
July 15–31 111 (1.6) 20.1 1923 (3.9) 13.4
August 1–14 68 (1.0) 12.3 1208 (2.4) 8.4
August 15–31 106 (1.5) 19.2 1936 (3.9) 13.5
September 1–14 149 (2.1) 27.0 3602 (7.3) 25.2
September 15–30 372 (5.3) 67.3 9381 (18.9) 65.5

NA = not applicable.

The difference in daily new infection rates varied between 1–7 fold throughout the epidemic. Capacity to test non-hospitalized, non-HCWs, was extremely limited until June 2020 [14]. As testing capacity improved in Ontario the difference in detection rates equilibrated and remained similar through the rise in cases in September 2020 (Fig 2).

Fig 2.

Fig 2

Epidemic curve by symptom onset date showing daily new case numbers until 30 September 2020 (left axis) and 14-day moving average of daily rate of new SARS-CoV-2 infections by symptom onset date (right axis) for healthcare workers and non-healthcare workers.

There were 1,746 (26.0%) HCW household SARS-CoV-2 infections; of these the median number of cases was 1 with a range of 1–10. We observed that 829 (12.3%) of HCWs probably transmitted SARS-CoV-2 to a household member; of these, 20.1% were to children <19 years, 63.7% to those 19–59 years and 16.2% to those ≥60 years. We observed 454 (6.8%) instances where the HCW probably acquired the infection from a household contact; of these, 7.5% were from children <19 years, 72.9% from adults 19–59 years and 19.6% from adults ≥60 years. In 463 (6.9%) contacts the direction of transmission could not be determined (Table 3). In the sensitivity analysis using ±4 days, instead of ±2 days, there were 541 (8.1%) transmissions and 281 (4.2%) acquisitions.

Table 3. Healthcare worker within household SARS-CoV-2 acquisitions and transmissions (n = 6,716 healthcare workers).

Number (%) Age group of household contact, n (row %)
<19 years 19–59 years ≥60 years
HCW acquired from household contact 454 (6.8) 34 (7.5) 331 (72.9) 89 (19.6)
HCW transmitted to household contact 829 (12.3) 167 (20.1) 528 (63.7) 134 (16.2)
Household infection with unknown direction of transmission 463 (6.9) 74 (16.0) 315 (68.0) 74 (24.9)
Total household transmissions involving HCWs 1746 (26.0) 275 (15.8) 1174 (67.2) 297 (17.0)

HCW = healthcare worker; 334 HCWs were missing a home address or were linked to a congregate setting and excluded from this analysis.

We observed 12 (0.2%) deaths in HCWs; 0 physicians, 1 nurse, 6 PSWs, and 5 unknown, compared to 3,004 (6.1%) in non-HCWs (p<0.001). In the multivariable model HCW status remained strongly associated with a lower risk of death after adjusting for multiple possible confounders including age, sex, comorbidities, long-term care home exposure, and symptoms (adjusted odds ratio (aOR) 0.09; 95%CI 0.05–0.17, p<0.001). Age was strongly associated with death. Comorbidities associated with an increased risk of death were obesity, renal conditions, COPD, immunocompromised state or cancer, and diabetes (p<0.05). Asthma and cardiovascular conditions were not significantly associated with death (Table 4).

Table 4. Multivariable logistic regression model evaluating risk of death subsequent to SARS-CoV-2 infection.

Variable Adjusted Odds Ratio 95% Confidence Intervals p-value
Healthcare worker
    Yes 0.09 0.05–0.165 <0.001
    No Reference - -
Age
    <30 years 0.03 0.01–0.08 <0.001
    30–44 years 0.132 0.08–0.23 <0.001
    45–59 years Reference - -
    60–75 years 5.47 4.44–6.72 <0.001
    ≥75 years 20.41 16.68–24.97 <0.001
Comorbidities
    Asthma 0.85 0.66–1.09 0.198
    COPD 1.39 1.14–1.70 0.001
    Renal conditions 1.61 1.35–1.92 <0.001
    Cardiovascular conditions 1.10 0.99–1.22 0.078
    Diabetes 1.13 1.01–1.28 0.042
    Immune compromise or cancer 1.48 1.27–1.74 <0.001
    Obesity 1.66 1.19–2.30 0.003
    Other medical conditions 1.18 1.06–1.31 0.003
    None Reference - -
Exposed to long-term care home
    Yes 3.04 2.75–3.37 <0.001
    No Reference - -
Symptoms
    Fever and/or cough 3.95 3.42–4.57 <0.001
    Other symptoms 3.60 3.06–4.23 <0.001
    Missing 3.53 2.98–4.18 <0.001
    Asymptomatic Reference - -

COPD = chronic obstructive pulmonary disease.

Interpretation

HCWs have comprised 12.5% of the 56,606 confirmed SARS-CoV-2 infections in Ontario, Canada as of 30 September, 2020. The rate of new infections per day varied between one and seven times the general population over time and by type of HCW with physicians being lower risk than nurses, who were lower risk than other specialties combined, which includes PSWs. Interestingly, during the period of time without restrictions in access to testing (June to September 2020) for non-HCWs there were small to no differences between the rate of HCW and non-HCW SARS-CoV-2 infections.

Data from China suggest that approximately 4% of all SARS-CoV-2 infections were in HCWs [7, 8]. In the United States 6% of hospitalized SARS-CoV-2 infections were HCWs [15]. There has been wide variation in single centre reports of HCW COVID-19 infections. Early in the pandemic one report from Wuhan observed that 29% of 138 hospitalized SARS-CoV-2 infections were in HCWs, with at least 10 of those related to a possible super-spreader event [5]. However, other centres have reported no SARS-CoV-2 infections despite significant exposures [3, 16]. In a long term care facility outbreak in Washington state, HCWs comprised 26% of infections, however the clinical course was substantially less severe in HCWs compared to residents and visitors [4]. Seropositivity studies have demonstrated wide variability from 4% to 19% of HCWs have detectable SARS-CoV-2 IgG antibodies [9, 10, 17]. This variability is likely related to differences in community transmission rates and personal protective equipment (PPE) availability. Some studies have demonstrated similar infection prevalence among clinical and non-clinical facing staff suggesting that a substantial proportion of HCW infections were likely acquired from the community or co-workers [1820].

The Center for Disease Control and Prevention in the United States reported on over 9,000 infected HCWs. Compared to our study they observed higher percent of hospitalizations (10% versus 2.5% in our study) but similar rate of death (0.3% versus 0.2%) [21]. In a study from Mexico, 13.1% of all SARS-CoV-2 infections were HCWs, and the risk of death was lower (9.9% in non-HCWs compared to 1.9% in HCWs) which persisted after multivariable adjustment for age, sex, and comorbidities (OR 0.53; 95%CI 0.46–0.61) [22]. In Mexico, there were 116 physician deaths among the 4,609 infections (2.5%), which was significantly higher compared to the 33 deaths among 6,240 nurses (0.5%, p<0.001). In our study we observed no physician deaths and 1 nurse death among 161 (0%) and 1,752 (0.05%) cases, respectively.

Studies from China and the Netherlands reported that approximately 1% of HCWs within hospitals were infected with SARS-CoV-2 earlier in the pandemic [18, 23]. In our study, 1.3% of all HCWs and 0.3% of non-HCWs in Ontario have been diagnosed with SARS-CoV-2 infection, including 0.5% of doctors and 1.1% of nurses. A report from Alberta, Canada identified that 0.1% of all HCWs had SARS-CoV-2 infections (including 0.3% of doctors) compared to 0.1% of the general population [24]. Alberta has similar IPAC guidance on PPE to Ontario which includes surgical masks, eye protection, gloves, and gowns for suspected or confirmed COVID-19 patients and N95 respirators for aerosol generating medical procedures. Our study was not able to evaluate the adequacy of PPE used by HCWs, however it is unlikely to explain the differences between Ontario and Alberta. Ontario likely has substantially more undiagnosed cases in the general population as well as more long-term care home outbreaks. The most important risk factors previously reported for HCW SARS-CoV-2 infections are community (i.e. restaurants, bars, and public transportation) and household exposures [25]. Further study is needed to better understand the nosocomial risk for SARS-CoV-2 infection among HCWs.

We observed a 10-fold lower odds of death among HCWs compared to non-HCWs even after adjustment for important confounders of age, sex, symptoms, and comorbidities. Testing bias, particularly earlier in the pandemic, likely contributed to the discrepancy in HCW and non-HCW rates which is supported by our epidemic curve in Fig 2. Improved access to PPE and adherence to infection prevention and control guidance is also possible. HCWs have been a priority population for testing throughout the pandemic, even during times of limited capacity. Between June and September 2020 mobility restrictions were gradually lifted in the province and there was substantially improved access to testing [14]. This finding suggests there were substantial underestimates of true population disease burden, which may actually be closer to the rate we observed in HCWs. In a report from Lombardy, Italy that performed serological studies on HCWs and non-HCWs, they identified that 23% of HCWs sampled were positive for COVID-19 antibodies compared to 62% of the general population [26].

HCWs may be a potential source of SARS-COV-2 transmission to both patients and household contacts. In particular since presymptomatic cases comprise a substantial portion of transmissions [27]. Transmitting to household members has been a source of stress for HCWs[28] and has been identified as a knowledge gap by the WHO [11]. We observed that 12.3% of infected HCWs likely transmitted SARS-CoV-2 to a household contact. Using a stricter definition of 4 days, we observed a transmission rate of 8.1%. Interestingly, children were relatively infrequently the source of infection compared to becoming secondary household cases (7.5% versus 20.1%). This finding may be due to the lower risk of SARS-CoV-2 infections in children earlier in the pandemic or children may be inefficient transmitters of SARS-CoV-2 [29].

This study has some limitations. The data quality is dependent on entry by 34 public health units across Ontario. Data completeness and quality may vary and it is possible some HCWs were misclassified. The variable for nosocomial transmission was added later in the study period and largely incomplete even after restricting to the later time period, therefore limited inference can be drawn. This may be in part due to the challenge of assigning causality of infections without a clear exposure history or multiple potential exposures. The general population, doctor, and nurse denominators used to calculate infection rates are accurate and current, however there is no complete data source for other HCWs in Ontario. We used various sources to arrive at an overall estimated HCW denominator which may impact the ability to compare rates. We lacked granularity in the type of HCW beyond physician or nurse. We searched the free text for PSW, however as a result we likely under captured this group. We quantified household transmissions using a natural language processing algorithm, however we do not have data on the denominator of household contacts to estimate attack rates. Finally, while HCWs were priority groups for testing throughout the pandemic, testing criteria and capacity varied substantially. Case identification was substantially better throughout for HCWs and as a result general population cases are undoubtedly underestimates.

In conclusion, 1.3% of HCWs in Ontario have been diagnosed with SARS-CoV-2 compared to 0.3% of non-HCWs after the first 8 months of the COVID-19 pandemic. Substantial under diagnosis of non-HCWs earlier in the pandemic at least partially explains this discrepancy. We observed only 12 HCW deaths, and HCW lethality remained significantly lower compared to non-HCWs after multivariable adjustment.

Acknowledgments

We would like to thank James Johnson for developing the natural language processing algorithm linking household cases, as well as Brendan Smith and Christine Warren for their help determining total numbers of healthcare workers in Ontario.

Data Availability

Public Health Ontario (PHO) cannot disclose the underlying data. Doing so would compromise individual privacy contrary to PHO’s ethical and legal obligations. Restricted access to the data may be available under conditions prescribed by the Ontario Personal Health Information Protection Act, 2004, the Ontario Freedom of Information and Protection of Privacy Act, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2 (2018)), and PHO privacy and ethics policies. Data are available for researchers who meet PHO’s criteria for access to confidential data. Information about PHO’s data access request process is available on-line at https://www.publichealthontario.ca/en/data-and-analysis/using-data/data-requests.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Lamberto Manzoli

7 Aug 2020

PONE-D-20-18932

COVID-19 infections among Healthcare Workers and Transmission within Households

PLOS ONE

Dear Dr. Schwartz,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

In addition to the minor issues raised by the reviewer, there are several major issues that need to be addressed.

1.

Throughout the manuscript, COVID-19 cases (disease) have been confused with SARS-CoV-2 infections. This is clear because also the asymptomatic subjects have been included among the "cases". This is plain wrong, misleading for the reader, and definitely requires to be corrected everywhere.

2.

In the methodology, it is written that all COVID-19 cases (which is referred to SARS-CoV-2 infections) have been captured by Public Health Ontario. Later in the manuscript, it is written repeatedly that many infections have likely been lost. Consistently, the authors should refer to their sample as "all the SARS-CoV-2 infections that have been diagnosed".

3.

No details have been provided on the "natural language processing" algorithm, that has been used to identify the household transmission (an essential part of the study). Was the household referred solely to those residing in the same house, or also to the neighbours? This clearly needs to be clarified.

4.

Mortality has been sometimes confused with lethality. Please correct it everywhere.

5.

Insufficient details have been provided on the definition of healthcare workers. It is only written that they are "caring for patients". Does this definition include also cohabiting caregivers who are not employees of the National healthcare system? If so, how many? Given that only 22.6% of the healthcare workers were physicians or nurses, more information on the remaining 77.4% is definitively needed. In the manuscript, the only detail is given in the footnote b of Table 1, where it is written that "at least 708 (21.6%) were personal support workers identified through free text searching". First, what does "at least mean? Second, what about the remaining 1968? Who are they? This is an essential information that is needed to understand the adopted definition of healthcare worker.

6.

A number of comorbidities have been listed as available, but these data have not been reported and, even more importantly, they have not been used to perform multivariate analyses, which are essential to make any meaningful comparison between the risk of death of healthcare workers and the rest of the population. This point needs to be clarified and data, if really available, provided for both healthcare workers and the rest of the population. Also, if these data are available, a multivariate analysis predicting the risk of death of healthcare workers versus others should be performed and would be the most interesting part of the study (for the limitations that will be mentioned later).

7.

The information on nosocomial transmission is missing for 76.9% of the healthcare workers, and 87.5% of the population. Despite this clear, huge bias, the authors extensively discuss these data, just briefly mentioning the missing data issue. With such a large amount of missing data, any discussion of the result should be avoided. The risk of bias of these data is too large to be meaningful in any way, and they can also be misleading. All analyses on nosocomial infections can be shown but briefly mentioned in the Results as merely indicative. Do not mention them in the Discussion (if not in the limitations), Conclusions or Abstract.

8.

Both the Results and the Discussion need to be improved. In the Results there some confusion, the most important data, those on the comparisons of the infection and mortality rates, have been reported after some trivial data (as the difference in the proportion of asymptomatic cases, a clear example of a statistically significant yet meaningless finding - 8.1% versus 7.0%).

The Discussion is redundant, and does not follow a clear reasoning. There also are some speculations (page 8, lines 177-178 on Ontario), some sentences that are to placed into an Introduction (page 10, lines 212-215) and, most importantly, it is totally unclear how the conclusions of the authors "we feel that data highlight the importance of community and household risk for HCWs, maintaining physicial distancing from colleagues and utilizing addition PPI..."

First, all the conclusions were known before the study. Second, and most importantly, it is not explained why the results of the study lead the authors to "feel" this way. In this study, nosocomial infections (with all the limitations above reported) were as low as 3.6%, and household transmissions were also relatively low (9.8%; lower than many other non-cited studies). It is unclear why these findings should bring us to "emphasize the protection policies of healthcare workers". This definitively needs explanation.

Also, as briefly mentioned before, the discussion on the potential explanations for the observed difference in lethality (not mortality) should be based upon multivariate analyses. Otherwise, it is speculative.

9.

Page 10, lines 217-220: how many children were there to be infected? This point needs clarification.

10.

Limitations need to be expanded, including the absence of a multivariate analysis, the huge missing data (not only for nosocomial infections, but also the symptoms were missing for almost 40% of the population), and the unavoidable underestimation of the SARS-CoV-2 infection in the total population.

11.

The abstract is the weakest part of the manuscript and needs to be extensively revised. First, the comparison is not stated, it is repeatedly stated that "HCWs were more likely...", but it is not clear "than who?".

12.

No definition of acquisition is provided, nosocomial infections need to be cut, mortality is lethality, COVID-19 is SARS-CoV-2 infection, it is not clear whether the 9.8% of probable secondary household transmissions are cases or episodes, low numbers are low percentages, the conclusion is unsubstantiated, and other issues as above.

Minor issues

13.

References 4-6 could be updated.

14.

Page 3, lines 47-48: it is unclear whether this point is related to the aim of the study.

Please submit your revised manuscript by Sep 21 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Kind regards,

Lamberto Manzoli, M.D., M.P.H.

Academic Editor

PLOS ONE

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Reviewer #1: Yes

**********

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Reviewer #1: Yes

**********

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Reviewer #1: Yes

**********

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Reviewer #1: Yes

**********

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Reviewer #1: I have only a few minor suggestions:

p. 2 line 29 Given that the majority of HCW are ‘other’, it would be helpful to include at least the example of the largest group in the abstract. If these are personal support workers, I think this is important to put in the abstract.

p. 3 line 49 suggest revising to read “reported from a single centre has ranged”

p. 4 line 75. Many people will not know what a Crown corporation is. Can you use a more descriptive or generic term?

p. 4 line 81 insert ‘and’ before comorbidities

p. 5 line 100. Is there any way or sense of how multiple occupancy addresses (apartment buildings were included and how they were handled in the data analysis?

p. 7 and other pages. Can you clarify if you are defining nosocomial and acquired in a hospital or acquired in the place the HCW works/from a patient. As most infections are in personal support workers, I found this confusing and the discuss about this on p.8 line 178 to the end of the paragraph took me several readings to understand and I am still not sure I am following correctly. Is all of this discussion about the fact that it is hard to be sure how HCWs were infected, or is it more complex?

**********

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Reviewer #1: Yes: Annette M. Totten

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PLoS One. 2020 Dec 28;15(12):e0244477. doi: 10.1371/journal.pone.0244477.r002

Author response to Decision Letter 0


26 Nov 2020

1.

Throughout the manuscript, COVID-19 cases (disease) have been confused with SARS-CoV-2 infections. This is clear because also the asymptomatic subjects have been included among the "cases". This is plain wrong, misleading for the reader, and definitely requires to be corrected everywhere.

Response: This has been corrected throughout.

2.

In the methodology, it is written that all COVID-19 cases (which is referred to SARS-CoV-2 infections) have been captured by Public Health Ontario. Later in the manuscript, it is written repeatedly that many infections have likely been lost. Consistently, the authors should refer to their sample as "all the SARS-CoV-2 infections that have been diagnosed".

Response: This has been corrected in the methods and throughout.

3.

No details have been provided on the "natural language processing" algorithm, that has been used to identify the household transmission (an essential part of the study). Was the household referred solely to those residing in the same house, or also to the neighbours? This clearly needs to be clarified.

Response: Further details of the NLP algorithm added (page 6-7 line 127-131): “The algorithm used Python’s sklearn library. Address text was broken down into short segments (N-grams) with a term-frequency inverse document frequency matrix. The closest proximity match within the matrix was returned and validated using checks for numerical portions of the address field, including suite number if available. The algorithm matched those within the same household or apartment unit, and not to neighbours.”

4.

Mortality has been sometimes confused with lethality. Please correct it everywhere.

Response: The term “mortality” has been changed to “death” or “lethality” throughout.

5.

Insufficient details have been provided on the definition of healthcare workers. It is only written that they are "caring for patients". Does this definition include also cohabiting caregivers who are not employees of the National healthcare system? If so, how many? Given that only 22.6% of the healthcare workers were physicians or nurses, more information on the remaining 77.4% is definitively needed. In the manuscript, the only detail is given in the footnote b of Table 1, where it is written that "at least 708 (21.6%) were personal support workers identified through free text searching". First, what does "at least mean? Second, what about the remaining 1968? Who are they? This is an essential information that is needed to understand the adopted definition of healthcare worker.

Response: Additional details on the definition of HCW has been added (Page 5 line 100-104). “A HCW was defined as an individual who self-reported to have an occupation involving caring for patients including (but not limited to) doctors, nurses, dentists, dental hygienists, midwives, other medical technicians, personal support workers, respiratory therapists, and first responders. The database has fields for doctor and nurse, however all other HCWs were recorded as “other” with the opportunity for free text.”

6.

A number of comorbidities have been listed as available, but these data have not been reported and, even more importantly, they have not been used to perform multivariate analyses, which are essential to make any meaningful comparison between the risk of death of healthcare workers and the rest of the population. This point needs to be clarified and data, if really available, provided for both healthcare workers and the rest of the population. Also, if these data are available, a multivariate analysis predicting the risk of death of healthcare workers versus others should be performed and would be the most interesting part of the study (for the limitations that will be mentioned later).

Response: A multivariable model evaluating the risk of death between HCWs and non-HCWs has now been added as suggested (Table 4). In addition, the comorbidity data has been expanded and utilized for this analysis as suggested.

7.

The information on nosocomial transmission is missing for 76.9% of the healthcare workers, and 87.5% of the population. Despite this clear, huge bias, the authors extensively discuss these data, just briefly mentioning the missing data issue. With such a large amount of missing data, any discussion of the result should be avoided. The risk of bias of these data is too large to be meaningful in any way, and they can also be misleading. All analyses on nosocomial infections can be shown but briefly mentioned in the Results as merely indicative. Do not mention them in the Discussion (if not in the limitations), Conclusions or Abstract.

Response: Reference to the nosocomial data in discussion, conclusion, and abstract has been removed (aside from the noted limitation on line 300).

8.

Both the Results and the Discussion need to be improved. In the Results there some confusion, the most important data, those on the comparisons of the infection and mortality rates, have been reported after some trivial data (as the difference in the proportion of asymptomatic cases, a clear example of a statistically significant yet meaningless finding - 8.1% versus 7.0%).

The Discussion is redundant, and does not follow a clear reasoning. There also are some speculations (page 8, lines 177-178 on Ontario), some sentences that are to placed into an Introduction (page 10, lines 212-215) and, most importantly, it is totally unclear how the conclusions of the authors "we feel that data highlight the importance of community and household risk for HCWs, maintaining physicial distancing from colleagues and utilizing addition PPI..."

First, all the conclusions were known before the study. Second, and most importantly, it is not explained why the results of the study lead the authors to "feel" this way. In this study, nosocomial infections (with all the limitations above reported) were as low as 3.6%, and household transmissions were also relatively low (9.8%; lower than many other non-cited studies). It is unclear why these findings should bring us to "emphasize the protection policies of healthcare workers". This definitively needs explanation.

Also, as briefly mentioned before, the discussion on the potential explanations for the observed difference in lethality (not mortality) should be based upon multivariate analyses. Otherwise, it is speculative.

Response: The results and discussion has been updated with the new results and substantially re-written with sections removed and/or revised as suggested. We have added the multivariable model with death as the outcome (table 4) and added discussion on this. We hope you will find the discussion more organized and supported by the data presented.

9.

Page 10, lines 217-220: how many children were there to be infected? This point needs clarification.

Response: Denominator for household contacts are not known. As stated in the methods this data is only positive cases with SARS-CoV-2 infection. This has been added to the limitations (line 308)

10.

Limitations need to be expanded, including the absence of a multivariate analysis, the huge missing data (not only for nosocomial infections, but also the symptoms were missing for almost 40% of the population), and the unavoidable underestimation of the SARS-CoV-2 infection in the total population.

Response: A multivariable model was added and reference to nosocomial data removed due to the large amount of missing data. With updating the results missing symptom data has been greatly reduced. The missing data has been retained in the multivariable model as its own covariate. Further discussion throughout the manuscript has been added related to the underestimation of general population cases.

11.

The abstract is the weakest part of the manuscript and needs to be extensively revised. First, the comparison is not stated, it is repeatedly stated that "HCWs were more likely...", but it is not clear "than who?".

Response: The abstract has been re-written and updated with the new results.

12.

No definition of acquisition is provided, nosocomial infections need to be cut, mortality is lethality, COVID-19 is SARS-CoV-2 infection, it is not clear whether the 9.8% of probable secondary household transmissions are cases or episodes, low numbers are low percentages, the conclusion is unsubstantiated, and other issues as above.

Response: Acquisition definition is provided in the methods lines 131-135 (household case with symptom onset data 2+ days prior to the HCW). As a sensitivity analysis we used +/-4 days. Reference to nosocomial variable has been removed from the results text and discussion (aside from the limitations). Mortality has been changed to death or lethality throughout as suggested. COVID-19 has been changed to SARS-CoV-2 infection as suggested throughout. The household transmission data represents new infections (see methods lines 131-135). The results have been substantially revised to not discuss less important findings. The discussion and conclusion (including in the abstract) have been substantially revised and re-written based on the feedback provided and updated results.

Minor issues

13.

References 4-6 could be updated.

Response: Newer references have been added in addition to these from earlier in the pandemic.

14.

Page 3, lines 47-48: it is unclear whether this point is related to the aim of the study.

Response: This line has been removed.

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________________________________________

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Reviewer #1: I have only a few minor suggestions:

p. 2 line 29 Given that the majority of HCW are ‘other’, it would be helpful to include at least the example of the largest group in the abstract. If these are personal support workers, I think this is important to put in the abstract.

Response: We have further explained the definition and data available to describe the type of HCW (page 5 line 100-104): “A HCW was defined as an individual who self-reported to have an occupation involving caring for patients including (but not limited to) doctor, nurse, dentist, dental hygienist, midwife, other medical technicians, personal support worker, respiratory therapist, and first responder. The database has fields for doctor and nurse, however all other HCWs were recorded as “other” with the opportunity for free text.” From the data we cannot be certain on the precise numbers within the “other” category. We performed free text searching for PSW to attempt to delineate this further but we prefer not to emphasize this since it is possible we are missing PSWs since it relies on free text entry.

p. 3 line 49 suggest revising to read “reported from a single centre has ranged”

Response: corrected as suggested.

p. 4 line 75. Many people will not know what a Crown corporation is. Can you use a more descriptive or generic term?

Response: Changed crown to government

p. 4 line 81 insert ‘and’ before comorbidities

Response: Added

p. 5 line 100. Is there any way or sense of how multiple occupancy addresses (apartment buildings were included and how they were handled in the data analysis?

Response: Further details on the NLP algorithm was added including the incorporation of apartment suite numbers (page 6 line 126-131): “The NLP algorithm used Python’s sklearn library. Address text was broken down into short segments with a term-frequency inverse document frequency matrix (TF-IDF). The closest proximity match within the TF-IDF matrix was returned and validated using checks for numerical portions of the address field, including suite number if available.”

p. 7 and other pages. Can you clarify if you are defining nosocomial and acquired in a hospital or acquired in the place the HCW works/from a patient. As most infections are in personal support workers, I found this confusing and the discuss about this on p.8 line 178 to the end of the paragraph took me several readings to understand and I am still not sure I am following correctly. Is all of this discussion about the fact that it is hard to be sure how HCWs were infected, or is it more complex?

Response: Based on the editors comments discussion of this variable has been substantially de-emphasized based on the degree of missing data.

________________________________________

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Reviewer #1: Yes: Annette M. Totten

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Attachment

Submitted filename: Response to reviewers_NOV26_2020.docx

Decision Letter 1

Lamberto Manzoli

11 Dec 2020

Epidemiology, Clinical Characteristics, Household Transmission, and Lethality of Severe Acute Respiratory Syndrome Coronavirus-2 Infection among Healthcare Workers in Ontario, Canada

PONE-D-20-18932R1

Dear Dr. Schwartz,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Lamberto Manzoli, M.D., M.P.H.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Lamberto Manzoli

15 Dec 2020

PONE-D-20-18932R1

Epidemiology, Clinical Characteristics, Household Transmission, and Lethality of Severe Acute Respiratory Syndrome Coronavirus-2 Infection among Healthcare Workers in Ontario, Canada

Dear Dr. Schwartz:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Lamberto Manzoli

Academic Editor

PLOS ONE

Associated Data

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    Submitted filename: Response to reviewers_NOV26_2020.docx

    Data Availability Statement

    Public Health Ontario (PHO) cannot disclose the underlying data. Doing so would compromise individual privacy contrary to PHO’s ethical and legal obligations. Restricted access to the data may be available under conditions prescribed by the Ontario Personal Health Information Protection Act, 2004, the Ontario Freedom of Information and Protection of Privacy Act, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2 (2018)), and PHO privacy and ethics policies. Data are available for researchers who meet PHO’s criteria for access to confidential data. Information about PHO’s data access request process is available on-line at https://www.publichealthontario.ca/en/data-and-analysis/using-data/data-requests.


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