key: cord-0800354-jx1ur10s
authors: Gholami, Mandana; Fawad, Iman; Shadan, Sidra; Rowaiee, Rashed; Ghanem, HedaietAllah; Omer, Amar; Ho, Hassan Samuel B.
title: COVID-19 and Healthcare Workers: A Systematic Review and Metaanalysis
date: 2021-01-11
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2021.01.013
sha: 9062c9c1727a98d53d4974f7632812b30f06b99e
doc_id: 800354
cord_uid: jx1ur10s

Background The COVID-19 pandemic has focused attention on the challenges and risks faced by frontline healthcare workers (HCW). Our aim is to describe the clinical outcomes and risk factors for SARS- CoV-2 infection in HCW. Methods Three databases were surveyed identifying 328 articles. Of these, 225 articles did not meet inclusion criteria; 97 full-text article were reviewed. Finally, after further revision, 30 articles were included in the systematic review and 28 used for meta-analysis. Results A total of 28 studies were identified involving 119,883 patients. The mean age of the patients was 38.37 years (95% CI, 36.72 – 40.03) and males comprised 21.4% (95% CI, 12.4 – 34.2) of the population of health workers. The prevalence of HCW who tested positive for COVID-19 is 51.7% (95% CI, 34.7-68.2). The total prevalence of co-morbidities in 7 studies was 18.4% (95% CI, 15.5 – 21.7). The most prevalent symptoms were fever 27.5% (95% CI, 17.6-40.3), cough 26.1% (95% CI, 18.1-36).The prevalence of hospitalization of HCW was 15.1% (95% CI, 5.6-35) in 13 studies and the prevalence of death was 1.5% (95% CI, 0.5-3.9) in 12 studies. Comparisons of HCW with and without infection showed an increased relative risk for COVID-19 related to PPE, workplace setting, profession, exposure, contacts, and testing. Conclusion A significant number of HCW have been reported to be infected with COVID-19 during the first 6 months of the pandemic, with a prevalence of hospitalization of 15.1% and mortality of 1.5%. Further data is needed to track the continued risks in HCW as the pandemic evolves and health systems adapt.

could potentially contribute to exacerbating the chain of transmission in the hospital, as well as outside the health facilities, and therefore proper protection of HCW against COVID-19 through mandating protective protocol had to be prioritized (Black et al., 2020) . Along with focusing on the impact of COVID-19 on the general population, numerous studies have since been published in different parts of the world outlining the implication of this virus on healthcare systems, pertaining to the challenges and risks faced by the frontline and high-risk HCWs. The focus of these research studies range from describing clinical characteristics of HCW with COVID-19, investigating the risk factors involved in acquiring the infection, transmission dynamics among HCW, and stating the observed complications and outcomes of the infection. With this study, we aim to combine a systematic review of the published data with a meta-analysis to determine the risk and clinical outcomes of infection in HCWs, being at the frontline in diagnosing and caring for the COVID-19 infected patients. Furthermore, as part of our qualitative discussion, we aim to explore the risk factors that may have been involved in the transmission of COVID-19 to HCWs.

The protocol for this study was generated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) recommendations. The PRISMA checklist was used to guide the reporting (Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, 2015) .

J o u r n a l P r e -p r o o f PubMed, Scopus, and Google Scholar were the 3 databases surveyed starting from 1 st May up to July 9 th 2020 by 5 independent researchers. All 5 researchers independently evaluated the search result after termination of database search process. The search keywords were broadly grouped into 4 categories: "healthcare", "risk", "COVID-19" and "miscellaneous" (Supplementary Table   1 ).

Full-text, peer reviewed articles from January 1 st to July 9 th , 2020 discussing SARS-CoV-2 only amongst HCW population were included. Articles which were not in English or an English translation was not available, articles without comprehensive data, comments or viewpoints related to HCW were excluded from the analysis.

Full texts of selected articles were compared with the pre-determined inclusion and exclusion criteria after the initial search results were initially screened by title and abstract.

For all the selected papers, following variables were obtained: name of authors, year and date of publication, study design, publishing country, and total number of HCW in the study.

Regarding the quantitative part of the study, the information from the selected articles was extracted by the 5 independent researchers and thereafter, pooled together. Data pertaining to demographics (age and gender), comorbidities (DM, HTN, CVD, COPD), clinical manifestations (fever, cough, fatigue, sputum, headache, haemoptysis, sore throat, diarrhoea, nausea and vomiting), blood investigations (anemia, WBC, high creatinine, high LDH,CRP, ESR), J o u r n a l P r e -p r o o f complications (unilateral pneumonia, bilateral pneumonia, reactive airway disease, RNA anaemia, shock, hospitalization, discharge and death) was extracted to Microsoft Excel. Data was screened by a single researcher for duplicates.

For the qualitative analysis of the study, 30 articles were thoroughly reviewed by 6 independent researchers to identify risk factors contributing to HCW COVID-19 infection.

The distribution of the categorical dichotomous variables was described by calculating percentages. For continuous data, the mean and 95% confidence intervals (CI) were calculated.

Studies reporting the mean with 95% CI or the range of the data, the formula (upper limit-lower limit)/4 was used to extract the standard deviation.

Meta-Analysis using the random-effect model was performed to estimate the pooled prevalence and 95% CI. We calculated the pooled percentage, prevalence, and corresponding 95% CI in order to indicate the weighted effect size for all binary variables. We reported the measure of heterogeneity by including Cochran's Q statistics and I 2 index with the level of heterogeneity defined as poor < 25, moderate > 50, and high > 75, and the tau square (T 2 ) test. We assessed publication bias with a funnel plot and the Egger test.

Results of the search: J o u r n a l P r e -p r o o f

The total number of patients analyzed across the 28 studies was 119883. The mean age of the patients was 38.37 years (95% CI, 36.72 -40.03) and males comprised 21.4% (95% CI, 12.4 -34.2) of the population of health workers (Table 2) .

The total prevalence of co-morbidities in the 7 included studies was 18.4% (95% CI, 15.5 -21.7), the most prevalent being hypertension 2.5% (95% CI, 0.2 -27.2), CVD 2.4% (95% CI, 0.7 -7.5), COPD 2.4 (95% CI, 0.9 -6.4), and Diabetes 1.4% (95% CI, 0.1 -12.9) ( Table 2) .

Across 28 studies, the prevalence of HCW who tested positive for COVID-19 is 51.7% (95% CI, 34.7-68.2). Regarding the symptoms of COVID-19 amongst HCW, the most prevalent finding was fever 27.5% (95% CI, 17.6-40.3), followed by cough 26.1% (95% CI, 18.1-36), fatigue 23.4% (95% CI, 12.7-39), sputum 17.6% (95% CI, 10.1-28.8), headache 15.1% (95% CI, 9.0-24.1), sore throat 13.3% (95% CI, 8.2-20.9), nausea and vomiting 11.8% (95% CI, 5.8-22.6), and diarrhea 10.6% (95% CI, 5.9-18.4) ( Table 2) .

Most prevalent laboratory finding is leukocytosis 49.4% (95% CI, 10.3-89.2), followed by lymphopenia 29.1% (95% CI, 12-55.1), high creatinine 22.6% (95% CI, 7.2-52.5), high CRP 17.3% (95% CI, 5.1-45), leukopenia 13% (95% CI, 5.5-27.8), and high LDH 12.2% (95% CI, 0.4-84.3). Regarding radiological imaging, the most common pneumonia finding is bilateral pneumonia with a prevalence of 78.7% (95% CI, 43.9-94.6). Other findings included ground glass J o u r n a l P r e -p r o o f opacity with a prevalence of 67.5% (95% CI, , and unilateral pneumonia with a prevalence of 26.8% (95% CI, 19.4-35.8) ( Table 2) .

Only 2 studies reported ARDS as a complication of COVID-19 infection, with a prevalence of 12.2% (95% CI, 0-97.8). Across 13 studies, using the random-effect model to find the pooled prevalence and 95% CI, the prevalence of hospitalization of HCW was 15.1% (95% CI, 5.6-35) and across 7 studies, prevalence of discharge from the hospital was 47.5% (95% CI, 10.9-87). In 12 studies, prevalence of death was 1.5% (95% CI, 0.5-3.9) ( Table 2 ). Funnel plots of hospitalizations and deaths are indicated in Figure 2 , and these indicate a minimal risk of bias related to death rates, but more potential bias in terms of reporting of hospitalization rates.

Thirty articles were revised thoroughly by 6 independent researchers, looking for risk factors contributing to HCW COVID-19 infection. Out of 30 articles, 7 yielded information regarding the pertinent risk factors. A summary of main points regarding risk factors in the respective articles can be found in table 7. The identified risk factors have been categorized into the following 6 entities: PPE, workplace setting, profession, exposure, contacts and testing (Table 7) .

This systematic review and meta-analysis summarize the available clinical information and characteristics of HCW with COVID-19, as well as the risk factors involved in making them more J o u r n a l P r e -p r o o f susceptible to the infection. The PRISMA guidelines were followed and 30 articles were filtered in 3 online databases (Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, 2015) . In this article we have analyzed 119,883 HCW, of whom the prevalence of testing positive for COVID-19 is 51.7% from the analyzable reports. Note that many of these reports included only HCW with COVID-19 infections. The articles were primarily from China and additional countries included USA, as well as 4 European countries: Netherlands, Italy, Germany and Spain (Table 1) .

Of the HCW analyzed, a wide spectrum of symptoms, co-morbidities, and complications were observed. As a group, HCW were found to be a generally young working age population (mean age = 38.73), and the clinical characteristics of this group are likely similar to others in this age distribution. We found that the predominant symptoms in HCW with COVID-19 included fever, followed closely by cough and fatigue (Guan et al., 2020; K. Li et al., 2020; Sun et al., 2020) .

Patients with co-morbidities have shown to have a greater risk of symptomatic infection with COVID-19 with a worse prognosis, than those without (Sanyaolu et al., 2020) . In this study, 18.4% of the infected healthcare workers had pre-existing conditions. While hypertension was deemed to be the most prevalent (2.5%), CVD and COPD followed closely with a prevalence of 2.4%, and diabetes was present in only 1.4%. These findings contrast with preliminary data related to comorbidities in the general population of COVID-19 patients found in a metanalysis of reports from China, where the prevalence of these comorbidities was higher: hypertension in 15.8%, CVD in 11.7%, diabetes in 9.4%, and COPD in 1.4%. The generally lower prevalence rates of comorbidities in HCW compared with the general population is likely explained by "The Healthy J o u r n a l P r e -p r o o f Worker Effect" phenomenon which, by some, has been described as "the reduction of mortality or morbidity of occupational cohorts when compared with the general population"(Shah, 2009).

Along with co-morbidities, we additionally explored the main laboratory findings in COVID-19 infection, being leukocytosis, lymphopenia and an elevated C-reactive protein (CRP). In line with the laboratory results in this study, other studies have reported a decrease in CD4+ and CD8+ cells, attributed to lymphocyte consumption during the infection process, and an increased cytokine release, which is co-related with disease severity and mortality (Huang et al., 2020; K. Li et al., 2020; Qin et al., 2020; Ruan et al., 2020) . Bilateral pneumonia was the most observed imaging finding within our analysis for HCW, followed by ground-glass opacity. Ground glass opacity was found to be the most common finding amongst patients in the general population, whereas consolidations were seen more frequently amongst those who were deemed severely ill(K. Li et al., 2020) . No results for the presence of shock, anemia, or elevated ESR were described in the papers analyzed.

The outcomes of COVID-19 in HCW remained markedly better compared to outcomes reported from most studies from the general population. Overall, 15% required hospitalization, approximately 50% were discharged, and death was reported in 1% of HCW with COVID-19.

Factors in favor of undesirable outcomes amongst COVID-19 patients include presence of previous co-morbidities, especially CVD, secondary infection, and elevated inflammatory markers on laboratory analysis (Ruan et al., 2020) . This is in contrast with prior reports of SARS-CoV-1 and MERS amongst HCW. Between 2012 and 2018, 415 MERS-CoV positive HCW were reported to WHO amongst which, 24 (5.8%) died as a direct result of the infection (Elkholy et al., 2020) .

At that time, HCW with renal impairment were noted to be at highest risk of death (Shalhoub et al., 2018) . Due to the limited data available on SARS until 2003, with a relatively low total number of cases reported by WHO (8096 cases and 774 deaths), comparison with the current pandemic trend is difficult (WHO | Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 31 July , 2015 . Evidence of a definitive mortality rate for HCW infected with Sars-CoV-1 was not found. Xiao, et al. estimated that deaths in HCW due to SARS-CoV-1 could be up to 164 of the total 774 deaths (21%), although they stated that this number might have been exaggerated due to factors of younger age and good immunity of the front-line HCW .

The largest reported series comes from a study reaching HCW using a novel smartphone "Covid Symptom Study" application that was used by 2,035,395 individuals in the United Kingdom and the United States (Nguyen et al., 2020) . Among these were 99,795 individuals who identified themselves as HCW and reported information related to symptoms and use of PPE. Of the identified HCW there were 1922 (1.9%) that reported testing positive for Covid19, compared with 3623 (0.18%) general population subjects testing positive for Covid19. Reported rates of comorbidities in HCW were higher in this series, especially for the presence of lung disease. The methods for obtaining these novel self-reported data will need further verification, and data related to hospitalization and death were not reported.

In our review of risk factors amongst HCW who tested positive for SARS-CoV-2 infection, we found measurements of risk for the following factors: PPE, workplace setting, profession, exposure, contacts, and testing (Table 7) . Face masks were shown to be protective and having J o u r n a l P r e -p r o o f worn one at all times decreased the risk of infection Guo et al., 2020) . PPE training has been reported to be a protective factor, while lack of N95 masks, reused PPE, and suboptimal hand hygiene practices were risk factors for infection with COVID-19 (Guo et al., 2020; Long H Nguyen et al., 2020; Ran et al., 2020) Highest risk was reported to be among physicians exposed to COVID-19 positive patients when compared to nurses and general service employees.

Physicians at highest risk were those involved in interventional or surgical procedures that generate respiratory aerosols, including within the respiratory departments, infectious control departments, ICU and surgical departments. (Ran et al., 2020) . There was no association between risk of infection and length of exposure or distance with positive patients ). An overall increase risk of infection was noted in frontline HCW in all healthcare settings as compared to the general community, with a higher risk in HCW working in inpatient settings and nursing homes (Long H Nguyen et al., 2020) . Most of the extracted risk factor data has been reported from China followed by Italy, US, UK and Germany. Data reported around December-February by Guo et al., reflected PPE training as the concerned risk factor as opposed to papers published later on from March to May which reported inadequate PPE availability, work environments, and contact exposure as the primary risk factors for HCW (Guo et al., 2020) .

With the rapid spread of this novel coronavirus strain globally, it soon became evident that much research is needed to understand and contain this infection, particularly for HCW in the front lines facing the pandemic. The data encompassed by this review reflects the first 6 months after the official declaration of COVID-19 as a pandemic and reflects the early experience of the disease in HCW with a previously unknown virus. The overall global magnitude of COVID-19 in HCWs was recently documented by a survey of members of the ID-IRI (Infectious Diseases International J o u r n a l P r e -p r o o f documented 2736 HCW deaths with a mortality rate of 0-0.90 per 100,000 in the reporting countries. Further data will be needed to continue to understand the evolving implication of this pandemic on the health and well-being of health care workers internationally.

The authors declare that they do not have any known competing financial interests or personal relationships that could have reflected on the work towards reporting this paper.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Approval was not required for this study. A.

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COVID-19: the case for health-care worker screening to prevent hospital transmission. The Lancet

New York City COVID-19 resident physician exposure during exponential phase of pandemic

Community pharmacists' exposure to COVID-19

Transmission risk of SARS-CoV-2 to healthcare workers-observational results of a primary care hospital contact tracing

Characteristics of Health Care Personnel with COVID-19 -United States

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

Symptom Screening at Illness Onset of Health Care Personnel With SARS-CoV-2 Infection in King County

COVID-19 and diabetes : The why , the what and the how

MERS-CoV infection among healthcare worker and risk factors for death: Retrospectine analysis of all laboratoryconfirmed cases reported to WHO from 2012 to 2

Healthcare worker infections and deaths due to COVID-19: A survey from 37 nations and a call for WHO to post national data on their website

Impact of COVID-19 Outbreak on Healthcare Workers in Italy: Results from a National E-Survey

COVID-19 infection and diffusion among the healthcare workforce in a large university-hospital in Northwest Italy

Clinical characteristics of coronavirus disease 2019 in China

Survey of COVID-19 Disease Among Orthopaedic Surgeons in Wuhan, People's Republic of China

Transmission of COVID-19 to Health Care Personnel During Exposures to a Hospitalized Patient

Infection Among Health Care Workers and Implications for Prevention Measures in a Tertiary Hospital in Wuhan, China

Coronavirus infections and immune responses

The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia

An Outbreak of NCIP (2019-nCoV) Infection in China -Wuhan

Clinical and Transmission Characteristics of Covid-19 -A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department

Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. The Lancet Public Health

Risk of COVID-19 among frontline healthcare workers and the general community: a prospective cohort study. medRxiv : the preprint server for health sciences

A meta-analysis of 2019 novel corona virus patient clinical characteristics and comorbidities

Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China

Risk Factors of Healthcare Workers with Corona Virus Disease 2019: A Retrospective Cohort Study in a Designated Hospital of Wuhan in China

Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands

Clinical factors, preventive behaviours and temporal outcomes associated with COVID-19 infection in health professionals at a Spanish hospital

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med

Comorbidity and its Impact on Patients with COVID-19

First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit

WHO | Summary of probable SARS cases with onset of illness from 1

World Health Organisation. Coronavirus (COVID-19) events as they happen

MERS and COVID-19 among healthcare workers: A narrative review

Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China

The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19)-China, 2020. CCDC Weekly

Analysis of the infection status of the health care workers in Wuhan during the COVID-19 outbreak: A cross-sectional study

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Testing of symptomatic HCW COVID-19 adjusted OR 3.61 ( 95% CI 2.15-6.06) vs. asymptomatic, less than a half (45%) of symptomatic HCW was actually screened for COVID-19