key: cord-0949068-sauhb9zb
authors: Baptista, Marcos C.; Burton, Wayne N.; Pawlecki, Brent; Pransky, Glenn
title: A Physician's Guide for Workers’ Return to Work During COVID-19 Pandemic
date: 2020-12-21
journal: J Occup Environ Med
DOI: 10.1097/jom.0000000000002118
sha: be6a68d0a570ad40246177952fa7816ac650df23
doc_id: 949068
cord_uid: sauhb9zb

OBJECTIVE: Higher probability of developing severe COVID-19 has been associated with health risk factors and medical conditions which are common among workers globally. For at risk workers, return to work may require additional protective policies and procedures. METHODS: A review of the medical literature was conducted on health risk factors and medical conditions associated with increased COVID-19 morbidity and mortality, standardized measures for community COVID transmission, and occupation-specific risk. RESULTS: The relative risk of acquiring and the severity of COVID-19 for workers is associated with three pillars: individual risk, workplace risk, and community risk. Matrices were developed to determine a worker's individual risk based on these three pillars. CONCLUSIONS: A practical decision tool is proposed for physicians evaluating and managing individual worker COVID-19 risk in the context of returning to work.

C oronavirus disease (COVID-19) was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. 1 Common symptoms include fever, fatigue, cough, dyspnea, sore throat, headache, anosmia, hypogeusia or ageusia, asthenia, conjunctivitis, and gastrointestinal issues (loss of appetite, diarrhea, nausea, and vomiting). Although a significant number of patients are asymptomatic or have mild clinical symptoms at presentation, a small percentage of cases can progress to uncontrolled inflammatory response with acute respiratory distress syndrome or even multiple organ failure. [2] [3] [4] [5] [6] Some individuals are at high-risk for developing severe symptoms which are associated with significant morbidity and mortality, including the elderly, certain ethnicities (eg, African Americans) and those affected by health risk factors and chronic diseases. [6] [7] [8] Specific organ damage has been described in COVID-19 patients, such as acute respiratory distress syndrome, 9 cardiovascular injuries (cardiac imbalance, coronary thrombosis, direct myocardial injury, arrhythmias, and venous thromboembolism), [10] [11] [12] [13] acute liver injury, 14, 15 acute kidney injury and kidney replacement therapy, 16, 17 and neurological complications (severe stroke, Guillain-Barre syndrome, acute encephalitis, seizures, and skeletal muscle injury) 18 that may represent a higher risk for those with pre-existing chronic health conditions.

In 2020, the global impact of COVID-19 posed unprecedented challenges to health agencies, governments, companies, healthcare systems, academia, and individuals. From the public health perspective, non-pharmaceutical interventions (NPIs) are an important strategy to mitigate the impact by slowing the epidemic spread, reducing peak healthcare demand, and protecting people at higher risk of acquiring the infection. 19 According to The Imperial College, physical distancing of people at high-risk groups is particularly effective at reducing severe outcomes. NPIs will need to be maintained until an effective COVID-19 vaccine becomes widely available. 19 Based on clinical epidemiology studies, lists of health risk factors and medical conditions that predispose individuals to severe forms of COVID-19 have been developed and published by several health agencies such as WHO, 20 CDC, 21 NHS, 22 and others. Examples of these risk factors include age, obesity, hypertension, and several health conditions such as diabetes-which are all prevalent among workers globally. 7 Using the 2017 Global Burden of Disease data, Clark et al 7 estimated that 22% of the global population (1.7 billion people) have at least one underlying condition which increases the risk of severe COVID-19 and 4% of the global population (349 million people) are at greatly elevated risk for severe disease and necessitating hospitalization if they contract For workers at increased risk who cannot work from home, return to work may expose them to COVID-19 going to and from work and at their workplaces. Strategies and guidelines are therefore needed to protect all workers, especially those at increased risk of COVID-19 complications. Governments around the world have generally not provided guidance on how to protect workers at increased risk nor assistance with decision-making about return to work for persons at heightened risk of complications and mortality from COVID-19. 23 Occupational medicine specialists in a number of countries have developed medical guidelines to protect the health of workers until an effective preventive treatment or vaccine is available for COVID-19. [24] [25] [26] Nabeel and Fischman 27 proposed a four-step approach to guide return to work of individuals with high risk which includes: (1) assess the risk of exposure in the workplace which depends on the degree of interaction with people and the nature of job tasks; (2) identify the scope of individual risk and stratify the severity or the degree of control of the disease; (3)

A review of clinical and epidemiology COVID-19 studies was conducted. The literature search on July 15, 2020 utilized medical databases (PubMed and Scielo) with MESH terms including COVID-19: ''covid19'' OR ''covid 19'' OR ''sarscov2,'' and MESH terms related to risk factors identified as associated with adverse COVID-19 outcomes: ''smoking,'' ''chronic disease,'' ''diabetes,'' ''pregnancy,'' ''immunosuppression,'' ''neurodegenerative diseases,'' ''pulmonary disease, chronic obstructive,'' ''asthma,'' ''liver diseases,'' ''obesity,'' ''hypertension,'' ''cancer,'' ''heart disease,'' ''COPD,'' and ''asthma''. In addition, a search with MESH terms including COVID-19 and ''epidemiology'' was conducted. We identified studies which described the prevalence and/or assessed the effects of sociodemographic factors, risk factors, and medical conditions associated with unfavorable COVID-19 related outcomes.

The criteria for high-risk individuals and their management from the United States, Brazil, and India were also reviewed, according to the dashboard provided by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). 29 In addition, an internet search for the three most affected countries in Europe (UK, Spain, and Italy) was conducted. The European continent became the epicenter for the pandemic following the first reported cases in China. Among the 10 countries most affected by the COVID-19 pandemic, South Africa was the only country to our knowledge to release a specific recommendation for managing employees at increased risk for COVID-19.

Recommendations from Labor and Health & Safety government agencies regarding the risk of exposure to COVID-19 at workplaces were then reviewed. The risk that a worker may be exposed to in various work settings was quantified and stratified. The third step was to review indicators which quantified the level of transmission in the community and stratify the risk of exposure of the worker in a community. In conclusion, a framework was created which included three pillars of risk based on worker health factors, workplace risk, and community level risk.

The literature review is summarized in Tables 1 and 2 . Seventythree studies were reviewed, including 66 single country studies and seven reports with data from two or more countries. Almost half, 36 of the studies, were from China, followed by the US (21), Italy (10), Spain (6) , France (4), UK and Mexico (3), South Korea (3) , and Brazil and the Netherlands (2) . The most common study methodology was cohort (33) , followed by descriptive studies (22) , meta-analysis and/ or systematic review (14) , case-control (3) , and cross-sectional (1) .

The descriptive studies examine associations between sociodemographic factors (age, male sex, non-White race/ethnicity), health risks (eg, smoking, BMI), and chronic diseases (eg, cardiovascular, hypertension, diabetes, chronic respiratory diseases, kidney diseases, cancer, immunosuppression, and rheumatic diseases), and adverse COVID-19 outcomes. Despite raising concerns about reported risk factors, descriptive studies do not confirm a causal association of these factors with severe disease and death. 103 Cohort studies are more likely to prove etiology; in these studies, significant associations with adverse COVID-19 outcomes included older age (19 studies), male gender (seven studies), non-White race (two studies), cardiovascular diseases (eight studies), hypertension (10 studies), diabetes (17 studies), BMI greater than 30 kg/m 2 (three studies), cigarette smoking (one study), chronic respiratory diseases (11 studies), chronic kidney diseases (six studies), cancer (nine studies), immunosuppression (three studies), liver diseases (three studies), pregnancy (one study), organ transplantation (three studies), stroke and other neurologic (three studies), rheumatic diseases (one study), inflammatory bowel disease (one study), obstructive sleep apnea (one study), and association or combination of more than one disease and increasing risk (six studies). Three case-control studies were reviewed and reported associations of age (two studies), hypertension (one study), diabetes (one study), and obesity (one study) with COVID-19 complications. Among the 10 meta-analyses reviewed, conclusions supported significant associations with complications for diabetes (five studies), cardiovascular diseases (three studies), chronic respiratory diseases (three studies), older age (three studies), male sex (two studies), smoking (two studies), hypertension (two studies), pregnancy, stroke, and other neurologic conditions (both one study). Table 3 presents a summary of guidelines for at-risk individuals published by several countries and legal guidelines and requirements for the management of at-risk workers. Governmental recommendations are generally in line with the published literature, based on age, health risk factors, and chronic medical conditions. However, there are several important differences. Some countries have been more specific and provided more detailed clinical criteria (UK 22,108 and South Africa 113 ) while others provide only guidelines with few details (India, 107 Spain, 109 and Brazil 105 ). Two countries created empirical risk categories: USA (increased risk and possibly at increased risk) 114 and UK (high risk or clinically extremely vulnerable and moderate risk or clinically vulnerable). 22 Legal requirements on management of high risk workers for employers differ by country, ranging from general protection measures, as Spain 110 and India 107 with no specific recommendations, to the United States 104 with general recommendation that employers must consider, to the UK 108 and Brazil 106 with more specific obligations for employers to stringent requirements in South Africa, 113 which require employers to have policies and procedures to address the needs of vulnerable employees.

The workplace in the era of the pandemic is being redesigned to reduce spread of the COVID-19 virus. A significant number of employees are working from home and are concerned about returning to work. 115, 116 Baker et al 117 estimated the number of workers in the United States who are frequently exposed to infection and disease, and therefore COVID-19, in the workplace more than once a month. Approximately 10% of US workers are exposed to disease or infection at least once per week, while 18.4% are exposed to disease or infection at least once per month. The majority of these workers are healthcare workers. Other occupations frequently exposed include police officers, correction officers, fire fighters, office and administrative support staff, educators, and community through workplace policies and procedures is important in the overall strategy to limiting the spread of the pandemic. Understanding the estimated number of workers potentially exposed is useful in developing workplace specific strategies. 118 The factors associated with the employee safely returning to the workplace in the context of COVID-19 have been categorized by Rafeemanesh et al 118 as: (1) control measures including engineering controls, (2) administrative controls, and (3) personal protective equipment. Control measures include isolation of symptomatic individuals, proper ventilation, barriers between staff and clients/ customers, using disposable tools and instruments, continuous cleaning, and disinfection. Administrative controls include preventing entry of sick workers, continuous training of staff on hygiene, reducing staff hours, and restricting staff gatherings. Personal protective equipment includes proper masks/respirators, eye protection, gloves, and special clothing.

Based on evaluation of workplace exposures, different occupations have been associated with a particular level of risk. 119 For example, by the nature of their work, healthcare workers are generally at the highest risk of COVID-19 infection whereas an outdoor agricultural worker is generally at low risk because they work independently and at a distance from coworkers (apart from risks associated with commuting and housing). 120 The US Occupational Health and Safety Administration has classified risk of occupational exposure from very high, high, medium, and lower risk. 104 Very high-risk occupations include healthcare workers performing aerosol-generating procedures and laboratory personnel and morgue workers performing autopsies. High occupational risk of exposure includes healthcare workers, medical transport workers, and mortuary workers who prepare bodies. Medium exposure risk jobs are those requiring contact within 6 ft./2 m with people who might be infected. Low risk jobs include those that do not require contact within 6 ft./2 m of the public or coworkers ( Table 4 ).

The third aspect that must be taken in consideration for managing the risk of workers is the level of community transmission of SARS-Cov-2, which reflects how prevalent the disease is in the community. 121, 122 The risk of acquiring the disease is associated with the prevalence of disease where the individual lives and works. 123 To find out the level of community transmission, the physician must be aware of the available information and data which are provided by the World Health Organization, government health agencies around the world, research centers, and other sources. WHO has defined four transmission scenarios for COVID-19 124 and provides updated information for all countries as (1) no new cases, (2) sporadic cases, (3) clusters of cases, and (4) community transmission on its website. 125 Noticeably, current experience with COVID-19 indicates that in many regions with sporadic cases, aggressive testing strategies may reveal underlying community transmission. 126 CDC classifies levels of community transmission as (1) no to minimal community transmission, (2) minimal to moderate community transmission, when there is sustained transmission and potential risk for rapid increase in cases, (3) substantial, controlled transmission, when there is large scale but controlled community transmission, and (4) substantial, uncontrolled transmission, when there is large scale, uncontrolled community transmission, including communal settings. 127 EndCoronavirus is an international volunteer coalition with over 4000 scientists, community organizers, citizens, and business owners operating since February 29, 2020. This organization offers guidelines and recommendations with the intent to help governments, communities, healthcare, institutions, families, and individuals to end the pandemic. The coalition's website 128 High risk (clinically extremely vulnerable) U Organ transplant U Chemotherapy or antibody treatment for cancer, including immunotherapy U Intense course of radiotherapy (radical radiotherapy) for lung cancer U Targeted cancer treatments that can affect the immune system (such as protein kinase inhibitors or PARP inhibitors) U Blood cancer (leukemia, lymphoma, or myeloma) U Bone marrow or stem cell transplant in the past 6 months or taking immunosuppressant medicine U Severe lung condition (cystic fibrosis, severe asthma or severe COPD) U Severe combined immunodeficiency (SCID) or sickle cell disease U High doses of steroids or immunosuppressant medicine U Serious heart condition and are pregnant Moderate risk (clinically vulnerable) U Age 70 or older U Not severe lung disease (asthma, COPD, emphysema or bronchitis) U Heart disease (such as heart failure) U Diabetes U Chronic kidney disease U Liver disease (such as hepatitis) U Neurologic diseases (Parkinson disease, motor neuron disease, multiple sclerosis, or cerebral palsy) U Use of medicine that can affect the immune system (such as low doses of steroids) U Severe obesity (BMI 40 or above) U Pregnancy Clinically extremely vulnerable workers must not return to work before specific dates. After specific dates, employees can return to work if workplace is COVID-secure. If possible, they should work from home. 1, moderate 1 to 10, high 11 to 25, and critical more than 25) and percent of positive PCR tests (low less than 3%, moderate 3% to 6%, high greater than 6% to 10%, and critical more than 10%) can be used by the physician to estimate the risk that a worker will be exposed at the community level. 129, 130 The Johns Hopkins Coronavirus Resource Center (CRC) 131 provides updated COVID-19 data and expert guidance by aggregating and analyzing data available from the United States and other countries (cases, testing, contact tracing, and vaccine efforts) to assist policymakers and healthcare professionals worldwide to respond to the pandemic. Their website includes the percentage of positive COVID-19 tests for most countries. Table 5 summarizes data the physician should consider when defining the level of transmission in a community and determining the risk for a patient. The four levels of community spread listed in Risk factors for serious complications and severe illness from COVID-19 U 60 years and older U One or more of the underlying commonly encountered chronic medical conditions (of any age) particularly if not well controlled: Chronic lung disease: moderate to severe asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, idiopathic pulmonary fibrosis, active TB and post-tuberculous lung disease (PTLD) Diabetes (poorly controlled) or with late complications Moderate/severe hypertension (poorly controlled) or with target organ damage Serious heart conditions: heart failure, coronary artery disease, cardiomyopathies, pulmonary hypertension; congenital heart disease Chronic kidney disease being treated with dialysis Chronic liver disease including cirrhosis Severe obesity (BMI of 40 or higher) Immunocompromised as a result of cancer treatment, bone marrow, or organ transplantation, immune deficiencies, poorly controlled HIV or AIDS, prolonged use of corticosteroids and other immune weakening medications >28 weeks pregnant (and especially with any comorbidity)

Employers should have a policy and procedures to address the needs of vulnerable employees. These measures need to consider the work environment and activities and include: Ensuring that potential exposure to the SARS-CoV-2 virus is eliminated or minimized If potential exposure cannot be eliminated the employer should explore other ways of temporary workplace accommodation that prevent the risk of infection. If the accommodation is not possible, consider work from home. If the above steps are not possible, adopt leave procedures according to country legislation. 

The literature review found a strong association with older age as an independent risk for severe forms and death of COVID-19. The risk for ICU admission and/or death increases exponentially with age which may be explained by immunosenescence, 132, 133 ''inflammaging,'' 132,133 and reduced mucociliary clearance. 134 Male gender has also been reported in most studies as an independent risk factor for death and severe clinical forms of COVID-19, which may be related to a higher prevalence of chronic diseases, higher health risk behaviors, occupational exposure, and sex differences in the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) which have both been implicated on virus entry on target cells. 135, 136 Race and ethnicity have been reported as independent risk factors in four studies (two cohorts and two descriptive) for higher mortality among non-white (Black, Hispanic, and Asian). However, the reason for this observation is not known at this time. Possible explanations include living conditions, health disparities, prevalence of comorbidities, and chronic stress. 137 Obesity has been reported in several studies as an independent risk factor for COVID-19 morbidity and mortality. Notably, one study found a clear dose-response gradient between increasing BMI and a greater risk of virus complications, 50 which supports a cause and effect relationship. Another study found that obesity represented 49.5% of the total effect of diabetes on COVID-19 mortality. 34 Such findings may be related to effects on immunity, occurrence of comorbidities, 138 and effects on the respiratory system. 139 A consistent finding in our literature review was that smoking is associated with unfavorable COVID-19 outcomes, which can be related to several and probably interactive effects such as structural changes in the respiratory tract, impaired cellmediated immunity in the alveolus, depletion of interleukin-1 and interleukin-6, reduced activity of natural killer (NK) cell in peripheral blood, reduced level of circulating immunoglobulins, and depressed phagocyte activity. 140 However, immunologic abnormalities are reversible and expected to resolve within 6 weeks after stopping smoking 140 so all workers must be advised and supported to quit smoking during the COVID-19 pandemic.

Pre-existing cardiovascular disease (CVD) (such as coronary artery disease, cardiomyopathy, valvular diseases, and heart failure), have consistently been reported as a risk for poor COVID-19 outcomes. Of note, a study conducted in China found a very strong association (odds ratio 21.4, P < 0.0001) 101 between coronary heart disease and in-hospital death. Hypertension has been reported as an independent risk factor for unfavorable COVID-19 outcomes. It is not clear whether this increased risk is directly related to hypertension or to other associated comorbidities (CVD, diabetes, obesity, and others) or anti-hypertensive medication treatment. 141, 142 Treatment resistant hypertension is associated with increased inflammatory biomarkers (interleukin-6, interleukin-1b, tumor necrosis factor-a, and highsensitivity C-reactive protein). 143 Hypertension might serve to enhance the systemic inflammatory response observed in patients with COVID-19. However, more research is needed to clarify the pathophysiological relation and associated risk, especially among patients with treatment resistant hypertension. 144 There has been initial concern about the safety of angiotensin-converting-enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs), related to the intensification of ACE2 receptor expression, which could be associated with an increased risk of SARS-CoV-2 infection. 145 However, ACE2 receptors may protect against acute respiratory distress syndrome (ARDS) in COVID-19 patients 145 and more recent studies suggest that the use of renin-angiotensin-aldosterone system inhibitors is not associated with increased risk of severe forms of COVID-19. 146, 147 Diabetes is an independent predictor of COVID-19 severity and mortality, which may be due to the inhibition of neutrophil chemotaxis, altered cytokine production, phagocytic cell dysfunction, impaired T cell-mediated immune responses, and ineffective microbial clearance. 148 Hyperglycemia can also be a consequence of COVID-19 infection, caused by ACE2-dependent transient damage of pancreatic islets and exocrine tissue. Hyperglycemia and diabetes development during hospital admission have been reported. 149 Hyperglycemia at admission, without history of diabetes, was reported by Sardu et al 83 as an independent risk factor for poorer outcomes. Current research highlights the importance of glycemic control during the COVID-19 pandemic and protective measures for workers with diabetes.

The respiratory diseases most studied have been COPD and asthma and one study also assessed interstitial lung diseases. COPD has consistently been identified in several studies as an independent risk factor for severe forms of COVID-19. While some studies found a significant association of asthma and poorer outcomes, others did not. Studies that reported a poorer outcome tended to combine asthma and COPD as one category (chronic respiratory diseases). Three studies which were limited to patients with asthma did not find an association with more severe COVID-19 lung involvement and poorer clinical outcomes. A large UK cohort study found a significant association of severe asthma and death of COVID-19. 91 Considering that COPD is associated with impaired local and systemic inflammatory response, reduced host immunity, microbiome imbalance, increased mucus production and structural lung damage as well as with increased risk of morbidity and mortality of respiratory infections, 150 COPD patients must be considered as high risk for complications from COVID-19. In the absence of additional research, moderate and severe asthma patients must also be considered at a higher risk. Chronic kidney disease (CKD) has consistently been associated with severe forms of COVID-19 complications in several reports, including six cohort studies. In addition, CKD has an extensively documented association with CVD, and CKD and CVD share common risk factors (diabetes mellitus, obesity, hypertension, smoking, and dyslipidemia). 151 Our study suggests that patients who are undergoing treatment for some types of cancers (hematologic cancers and locally advanced and metastatic solid tumors) have more complications and higher death rates from COVID-19. However, this may not be the case for all types of cancer. Workers with cancer must be carefully evaluated to assess their risk level.

In this review, three cohort studies found a significant association of pre-existing chronic liver diseases with more severe COVID-19. Current research suggests that workers with chronic liver disease must be carefully evaluated to determine their risk level for COVID-19 complications and death. The few published studies of patients with rheumatic diseases, have indicated no elevated risk for COVID-19 complications. According to the American College of Rheumatology, there is currently no evidence that rheumatic diseases should be considered as a risk factor for unfavorable COVID-19 outcomes. 152 Immunosuppressive treatments must not be interrupted because exacerbation of rheumatic disease may lead to a systemic inflammatory state and organ specific manifestation of the underlying condition (especially kidney and lung) which may increase the risk of COVID complications. 153 There is currently insufficient evidence to draw definitive conclusions regarding the level of risk in patients with rheumatic diseases.

Active inflammatory bowel diseases and treatment for a disease flare are associated with COVID-19 complications and death. However, it is not clear if immunosuppressive therapy is also associated with morbidity and mortality. Available research suggests a possible association with concomitant corticosteroid therapy. 35 There are few published studies of organ transplantation recipients, but the current evidences suggest that organ transplant patients are at a significantly greater risk of complications and death and must be considered at very high risk for COVID-19 unfavorable outcomes.

We found no evidence that people living with HIV with good clinical and virologic control are at increased risk for severe forms of COVID-19. However, caution is warranted for HIV patients with high viral load, low CD4 cell count, severe disease, and those not using antiretroviral therapy 71 who may be at increased risk. Three cohort studies reported a significant association of pre-existing stroke and other neurologic diseases with morbidity and death from COVID-19. Current research strongly suggests that workers with stroke and other neurologic diseases must be considered at higher risk for complications of COVID-19. We found one study which suggested that sickle-cell disease (SCD) patients are at higher risk of COVID-19 complications. 76 More studies are necessary, but workers with SCD should be considered at high risk from COVID-19 because infection is the leading cause of morbidity and mortality among SCD patients. 154 One study reported a higher risk of hospital admission of patients with obstructive sleep apnea disorder, 40 but it is not clear if it is related to other comorbidities (obesity, cardiovascular diseases, and diabetes).

Some studies reported similar risk among pregnant and nonpregnant patients and one cohort reported pregnancy among the risk factors associated with critical COVID-19 illness. Vertical transmission, and its long-term potential consequences cannot currently be excluded. At the present time, pregnancy, especially if associated comorbidities are present (obesity, hypertension, pre-eclampsia, and diabetes), should be considered at higher risk until further studies are available.

Four cohort studies reported that as the number of comorbidities increases, the risk of severe forms of COVID-19 complications also increases while two other cohort studies found that higher Charlson Comorbidity Index Scores were significantly associated with COVID-19 complications. These observations have important implications for physicians since multiple risk factors are frequently observed among workers. 155, 156 At this time, the knowledge about SARS-CoV-2 is incomplete and the literature in this area is rapidly evolving. However, based on our literature review, relevant risks that can be identified by healthcare providers to determine worker risk for COVID-19 morbidity and mortality include:

Age over 60 years old; there is generally increasing risk with age; Male sex; Cardiovascular diseases, like CAD, CHF, cardiomyopathy, and valvular diseases, especially if active and/or not well managed and compensated; Hypertension, especially if not responsive to treatment with three antihypertensive drug classes (usually a diuretic, a long-acting calcium channel blocker, and a blocker of the renin-angiotensin system) and/or with target organ damage; Diabetes types 1 and 2, with a greater risk if blood glucose is not within goal and/or with target organ damage; Obesity (BMI more than 30 kg/m 2 ), with greater risk with increasing BMI; Current smoking; Chronic respiratory diseases: COPD, interstitial lung diseases, and moderate-to-severe asthma and cystic fibrosis; Significant chronic kidney disease; Cancer, especially in cases of hematologic cancers, locally advanced and metastatic solid tumors; Significant chronic liver disease; Pregnancy, especially those with associated comorbidities; Organ transplantation recipients; HIV patients with high viral load, low CD4 cell count, severe disease, and those not using antiretroviral therapy; Neurological diseases (eg, stroke with significant functional limitation, etc) Active inflammatory bowel diseases; Sickle-cell disease. Table 6 illustrates the risk modeling we have developed to categorize workers according to individual health risks.

Although there is an association with several health risks such as cigarette smoking and BMI and elevated risk for COVID-19 complications, there is no current evidence that mitigation of these risk factors results in lower risk of the severity of COVID-19. Nevertheless, it seems prudent to advise workers to modify such risk factors with the hope of attenuating their risk.

Our explanation for differences observed in higher risk worker definitions by official health agencies may be that it is difficult for any government to establish standards and guidance in an evolving science like the COVID-19 pandemic. The different recommendations and legal requirements to manage high-risk workers may reflect the differences in country culture, labor legislation, politics, and social security regulation. Healthcare workers in all countries must comply with local laws and regulations, however, physicians must keep in mind that COVID-19 research is constantly evolving and, similarly, medical decision making, and practice guidelines are also evolving. 122 Some evidence exists that a COVID-19 case may, in some settings, be work-related. 165 The risk of exposure to SARS-CoV-2 in the healthcare workplace is based on reported estimates of 150,000 healthcare professionals infected and at least 700 who have died in the United States as of September 2020. 166 However, other factors must be considered. In addition, workers may contract the virus during travel to and from their jobs in crowded public or semiprivate transportation. 166 Protective measures adopted by the employer are effective to reduce viral dissemination in the workplace 167 and the absence of effective workplace controls has been associated with COVID-19 outbreaks in recently opened workplaces. 166 When managing a specific case of a high-risk worker, we recommend healthcare providers include an assessment of transportation used by the worker in addition to worksite control measures. Table 5 presents five definitions for the level of COVID-19 transmission in a particular country. These designations may be used by healthcare providers to determine relative risk for managing highrisk workers. The WHO transmission status is available and periodically updated on the internet for almost all countries. 125 The CDC level of community transmission is not currently published and relies on a determination by the physician. Other metrics are available on endcoronavirus.org 128 and the Johns Hopkins 131 websites. It is not currently possible to estimate the future transmission of SARS-CoV-2. Several scenarios of peaks and valleys of COVID-19 incidence have been projected for the post-pandemic period until 2025. 168 Such projections depend in part on several factors such as intensity and timing of control measures, the degree of seasonal variation in transmission, the duration of immunity, and the degree of crossimmunity between SARS-CoV-2 and other coronaviruses. 168 Precise measures of determining community activity, such as number of daily cases per 100,000 and percent of positive PCR testing should ideally be used by healthcare providers where available. We acknowledge that in several countries such data are not currently available. Table 7 summarizes four workplace options and guidelines for workers returning to work based on COVID-19 relative risk, considering individual, community, and workplace factors: (1) return to the workplace with standard recommendations, (2) return to the workplace with specific additional recommendations, (3) return to the workplace with specific work accommodation, and (4) currently stay out of the workplace. Figure 1 shows the proposed scheme, combining data on individual risk level and the OSHA classification of SARS-CoV-2 infection risk at work at the different levels of community transmission. Notably, community transmission level 3 and 4 have the same recommendations, because level 3 progresses to level 4 with more aggressive testing policies. 126 Larochelle 23 proposed a matrix for determining the risk for workers of developing severe COVID-19 infection. The matrix was a 3 Â 3 matrix with nine possible risk groups and interventions. One axis is the risk of contracting SARS-CoV-2 in the workplace rated as low, medium, and high. The other axis is the risk of death from COVID-19 as low, medium, and high. Each of the nine boxes is assigned as A, B, or C recommendation for how the healthcare professional should advise a patient based on the nine-box risk. For example, a worker who is at high risk of contracting SARS-CoV-2 in the workplace and at high risk of death because of their health risk factors should be advised to consider stopping work if working remotely is not an option. We have expanded the Larochelle matrix 23 to include job risk ranked from 1 to 4 where 1 is low risk, for example, workers who can work from home, to 4 for very high job risk for healthcare workers exposed to aerosol transmission from patients potentially infected with SARS-CoV-2. The individual employee risk of morbidity and mortality in the Larochelle model was expanded from 3 to 4 levels where 1 is relatively low risk and 4 is very high risk (see Fig. 1 ). The recommend four steps for using the proposed matrix in clinical practice is described in Fig. 2 and summarized below:

Step 1: Define community transmission level according to Table 5 . If possible, physicians must consider data at the smallest geographic area available (eg, city or state instead of country data). Precise measure of transmission such as percentage of positive tests and daily new cases per 100,000 people, if available, are preferred.

Step 2: Define individual risk level. Using Table 3 , classify each patient according to age and health risks. We suggest healthcare providers assign each worker a risk level and consider the highest level of relative risk for each worker. We acknowledge that comorbidity is common in workers who may have more than one medical conditions at level 2 and/or 3. In such situations, once research indicates that the relative risk increases as the number of comorbidities increase, the physician may assign the worker to level 4.

Step 3: Define job risk level. Use Table 4 and investigate the patient information about job exposure. Beyond the definitions provided by OSHA, we recommend physicians investigate potential exposure on transportation and protective measures implemented by the employer. If the exposure at work is not at the higher levels, if exposure may occur at transportation and/ or protective measures are not properly provided by the employer, the healthcare provider should assign the worker as exposed to a higher level. For high risk activities, if recommended PPE are not available, the physician should consider job exposure as very high.

Step 4: Provide recommendations to the worker. Once all the three risk levels (individual, job, and community) are defined, using the proposed matrix ( Fig. 1) , select the recommendation (A, B, C, or D) from the matrix box ( Fig. 1) and use the recommendations presented in Table 7 as a reference to define the medical management for each patient.

We acknowledge several limitations of this literature review and proposed framework. We have stratified three different risk levels and there is a certain lack of precision for the definition of each level, that can be counterbalanced by the individual judgment of each physician. The medical literature on COVID-19 is rapidly evolving, so healthcare providers must keep current on research and practice guidelines with new information on risks for morbidity and mortality associated with health risks and chronic conditions. The reviewed studies used to stratify individual risk have been done with the general population and not limited to employed people. Therefore, the health risks for COVID-19 morbidity and mortality may not be applicable for a working population. The metrics to determine community and workplace risk may be incomplete and not applicable to all workers. Numerous medical conditions have not been studied which may contribute to the relative risk of morbidity and mortality from COVID-19. Workplace risk may, in some instances, be better characterized by the number of unusual lapses in protection rather than the usual practices associated with a particular industry. The matrices we developed for relative risk based on community, job and individual risk are empirical and will require prospective validation.

A practice tool for healthcare providers has been developed to determine a worker's relative risk of acquiring and the severity of COVID-19 based on individual risk, workplace risk, and community risk. Recommendations for managing workers based on these three risk pillars are illustrated in three matrices.

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People Who Are at Increased Risk for Severe Illness

Who's at higher risk from coronavirus

Is it safer for me to go to work?'' Risk stratification for workers during the COVID-9 pandemic

COVID-19 return to work guide for health professionals advising patients and employers. The Society of Occupational Medicine

Safely returning America to work: part I: general guidance for employers

ANAMT practical guide on COVID-19 for Occupational Physicians

What are return to work recommendations for individuals with high risk factors or comorbidities during SARS-CoV-2 pandemic? Available at

Assessment of workers' personal vulnerability to covid-19 using 'covid-age'

Association of cardiovascular disease with coronavirus disease 2019 (COVID-19) severity: a meta-analysis

Covid-19 and kidney transplantation

A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia

High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR

Predicting mortality due to SARS-CoV-2: a mechanistic score relating obesity and diabetes to COVID-19 outcomes in mexico

Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study

Obesity and COVID-19 severity in a designated hospital in Shenzhen

The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) -China

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

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

Prevalence and characterization of asthma in hospitalized and non-hospitalized patients with COVID-19

Clinical characteristics and disease progression in early-stage COVID-19 patients in South Korea

Charlson Comorbidity index score and risk of severe outcome and death in Danish COVID-19 patients

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

Coronavirus disease 2019 during pregnancy: a systematic review of reported cases

Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterization Protocol: prospective observational cohort study

Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study

Type 1 Diabetes and COVID-19: preliminary findings from a multicenter surveillance study in the U S

Prevalence and impact of diabetes among people infected with SARS-CoV-2

Brescia Rheumatology COVID-19 Study Grou. COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and casecontrol study

Obesity is a risk factor for greater COVID-19 severity

Asthma and COPD in hospitalized COVID-19 patients

SARS-CoV-2 pneumonia in hospitalized asthmatic patients did not induce severe exacerbation

Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to icus of the Lombardy Region

Clinical characteristics of Coronavirus disease 2019 in China

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis

Factors associated with death in critically ill patients with Coronavirus Disease 2019 in the US

Severe asthma during the COVID-19 pandemic: clinical observations

COVID-19 in solid organ transplant recipients: a single-center experience

Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia -a systematic review, meta-analysis, and meta-regression

Population level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters

Impact of comorbidities in Mexican Sars-Cov-2-positive patients: a retrospective analysis in a national cohort

COVID-19 pneumonia and pregnancy; a systematic review and meta-analysis

SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis of clinical features and pregnancy outcomes

Characteristics associated with hospitalization among patients with COVID-19 -metropolitan

Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis

COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study

Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan

Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

COVID-19 among people living with HIV: a systematic review

Epidemiological and clinical characteristics of 671 COVID-19 patients in Henan Province, China

Clinical and epidemiological characteristics of patients diagnosed with COVID-19 in a tertiary care center in Mexico City: a prospective cohort study

Chronic heart diseases as the most prevalent comorbidities among deaths by COVID-19 in Brazil

Clinical characteristics of hospitalized individuals dying with COVID-19 by age group in Italy

Coronavirus disease among persons with Sickle Cell Disease

Smoking is associated with COVID-19 progression: a meta-analysis

COVID-19 in solid organ transplant recipients: initial report from the US epicenter

Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Sociodemographic, clinical and laboratory factors on admission associated with COVID-19 mortality in hospitalized patients: a retrospective observational study

Determinants of COVID-19 disease severity in patients with cancer

Outcomes in patients with hyperglycemia affected by COVID-19: can we do more on glycemic control? Diabetes Care

Clinical characteristics and risk factors for mortality of COVID-19 patients with diabetes in Wuhan, China: a twocenter, retrospective study

Coronavirus disease 2019 case surveillance -United States

Clinical characteristics and morbidity associated with coronavirus disease 2019 in a series of patients in metropolitan detroit

Risk factors for mortality in 244 older adults with COVID-19 in Wuhan, China: a retrospective study

Evaluation of incidence and risk profile for suffering Covid-19 infection by underlying conditions among middle-aged and older adults in Tarragona

Clinical Characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis

OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients

Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China

Diabetes increases the mortality of patients with COVID-19: a meta-analysis

Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study

Patients with chronic kidney disease have a poorer prognosis of coronavirus disease 2019 (COVID-19): an experience in

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Maternal and perinatal outcomes with COVID-19: a systematic review of 108 pregnancies

The clinical characteristics and prognosis factors of mild-moderate patients with COVID-19 in a mobile cabin hospital: a retrospective, single-center study

The impact of COPD and smoking history on the severity of COVID-19: a systemic review and meta-analysis

Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes

Epidemiology and clinical research design, Part 1: study types

Occupational Safety and Health Administration. Guidance on Preparing Workplaces for COVID-19

The Federative Republic of Brazil. Ministério da Saúde

The Federative Republic of Brazil

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Working safely during the coronavirus (COVID-19) outbreak. 6. Protect vulnerable workers

Ministry of Health. General Directorate of Public Health, Quality and Innovation. Scientific and technical information. Coronavirus disease, COVID-19

Guide for workplaces during COVID-19 pandemic

The Italian Republic. Ministry of Health. Covid-19 -Elderly and frail people

The shared protocol on measures to combat COVID-19 in the workplace has been integrated

Guidance on vulnerable employees and workplace accommodation in relation to COVID-19

International Labour Organization. An employer's guide on managing your workplace during COVID-19. Geneva; 2020

A blueprint for redesigning the office in the pandemic era

Estimating the burden of United States workers exposed to infection or disease: a key factor in containing risk of COVID-19 infection

A review of the strategies and studies on the prevention and control of the new coronavirus in workplaces

Italian worker at risk during the Covid-19 epidemic

Work-related COVID-19 transmission in six Asian countries/areas: a follow-up study

Thinking of risk in the era of COVID-19

Making decisions in a COVID-19 World

The Rules of Contagion: Why Things Spread and Why They Stop. Great Britain: Profile Books

The World Health Organization. Critical preparedness, readiness and response actions for COVID-19

Framework for implementation of COVID-19 community mitigation measures for lowerresource countries

The Centers for Disease Control and Prevention. implementation of mitigation strategies for communities with local COVID-19 transmission

Some are winning -some are not

Precision public health as a key tool in the COVID-19 response

Harvard Global Health Institute. Pandemic resilience: getting it done. A TTSI Technical Advice Handbook V 2.0; 2020

The Johns Hopkins Coronavirus Resource Center. How does testing in the U.S. compare to other countries? Available at

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

Immunosenescence: emerging challenges for an ageing population

The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia

Sex differences in mortality from COVID-19 pandemic: are men vulnerable and women protected?

SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor

Racial health disparities and Covid-19 -caution and context

Obesity and SARS-CoV-2: a population to safeguard

Obesity and respiratory diseases

Cigarette smoking and infection

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19

Increased arterial stiffness in resistant hypertension is associated with inflammatory biomarkers

Covid-19 and the cardiovascular system: a comprehensive review

Unauthorized reproduction of this article is prohibited ACE-inhibitors and angiotensin receptor blockers: the need to differentiate between early infection and acute lung injury

Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people

Association between Renin-Angiotensin-Aldosterone system inhibitor use and COVID-19 Hospitalization and death: a 1,4 million patient Nation-Wide registry analysis

SARS-CoV-2 and diabetes: new challenges for the disease

ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection

Chronic obstructive pulmonary disease is associated with severe coronavirus disease 2019 (COVID-19)

The link between chronic kidney disease and cardiovascular disease

American college of rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic: version 2

Care for patients with rheumatic diseases during COVID-19 pandemic: a position statement from APLAR

Immune mechanisms involved in sickle cell disease pathogenesis: current knowledge and perspectives

Multimorbidity and its impact on workers: a review of longitudinal studies

Prevalence of multimorbidity in the Brazilian adult population according to socioeconomic and demographic characteristics

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A fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents

Evaluating disease severity in idiopathic pulmonary fibrosis

Heart failure: diagnosis, management and utilization

New York Heart Association functional class predicts exercise parameters in the current era

Chronic renal disease

The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications

Is an Employee's COVID-19 Case Work-Related and Recordable? OSHA Provides Employers Clarity Through Enforcement Guidance

Occupational Safety and Health Administration (OSHA) and worker safety during the COVID-19 pandemic

Fellows of the Collegium Ramazzini. 24th Collegium Ramazzini Statement: Prevention of work-related infection in the COVID-19 pandemic

Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period

The authors wish to acknowledge Alyssa B. Schultz, PhD for her editing of this manuscript.