COVID-19: a new occupational disease
Unless claims by the Trump administration turn out to have an evidence base the current pandemic most likely started as an occupational disease cluster with zoonotic origin. A sentinel study published in Nature [2020:579;270–73] analysed samples from seven patients, all suffering severe pneumonia within an intensive care unit in Wuhan, China. Six of these patients were sellers or delivery men from a seafood market. A novel coronavirus (2019-nCoV) whose genome had 96% homology with a bat coronavirus was found in five of these patients. The same paper in Nature also demonstrated that, as a means of entering human cells in order to hijack the intracellular machinery required to replicate, the virion particles of 2019-nCoV utilise the same cell surface protein as did SARS-CoV, the coronavirus responsible for the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. This cell surface protein, also used for cell entry by another coronavirus, NL63, is Angiotensin Converting Enzyme 2 (ACE2). ACE2 is part of a key metabolic pathway for human blood pressure regulation — the Renin-Angiotensin-Aldosterone system. It converts angiotensin II, a vasoconstrictor that raises blood pressure, into smaller peptides.
At the same time as the new 2019 coronavirus (subsequently named SARS-CoV2) and its portal of entry into human cells were being characterised at a molecular level it was becoming apparent that human to human transmission was occurring — at a fast rate. Even before the pandemic was declared commentators suggested that its relative transmissibility and pathogenicity would determine its extent of spread. A virus with high pathogenicity is less likely to transmit exponentially than one which causes minimal human disease. The ‘selfish genes’ of a virus will only prosper if their host remains well enough to interact with others.
Munster et al [NEJM 2020:382;692–94] illustrate this concept well by comparing two previous outbreaks caused by viruses within the Coronoviridae family: NL63 and SARS-CoV. Although NL63 was identified in 2004 as a cause of bronchiolitis in children in Holland, the vast majority of infected people only develop mild upper respiratory tract symptoms. As a result NL63 has become endemic in the global population without really dominating the headlines. SARS-CoV, on the other hand, was high profile headline news because it induced severe lower respiratory tract disease (SARS) with a case fatality rate of 11%. However, because it was most infectious in severe stages of the illness, generally the second week after infection, containment was possible. SARS-CoV2, the cause of COronaVIrus Disease 19 (COVID-19), has pathogenicity characteristics somewhere in between these two family members. Its infection rate (‘R’) is thought to be close to 3 in unchecked UK society, and most person to person transmission occurs in the first few days of an individual becoming infected — a time when they are usually either asymptomatic or only have mild symptoms that would not (in normal circumstances) preclude them from interacting with others. The proportion of people infected with SARS-CoV2 who go on to develop severe disease is much lower than for SARS-CoV, but too much higher than for NL63 for governments to allow transmission to go unchecked.
The COVID-19 respiratory illness that may lead to hospital admission is usually associated with fever, cough and/or shortness of breath. This can either quickly resolve or develop, sometimes after initial apparent recovery, into severe pneumonia with radiological changes, respiratory distress or ‘happy hypoxia’. Myocardial injury can also occur. Sadly, as we are made aware on a daily basis, this severe form of COVID-19 is all too often fatal. Milder presentations (the vast majority of cases) are characterised by varying combinations of anatomically dispersed symptoms including; sore throat or runny nose, alterations in taste or smell, gastrointestinal symptoms such as diarrhoea and ocular symptoms such as conjunctival hyperaemia [BMJ 2020;369:m1470]. What we do not know is the proportions of populations who have been infected with SARS-CoV2 asymptomatically yet develop immunity.
What determines the variability in symptomatic presentation of COVID-19?
One theoretical explanation is that the cell surface protein (enzyme) ACE2, on which SARS-CoV2 is dependent for cell entry, varies in anatomical distribution and extent of expression. High expression of ACE2 has been demonstrated not only on type II alveolar cells (the focal site for COVID-19 pneumonia) but also in the myocardium, ileum, upper respiratory tract and kidney [Front. Med. http://journal.hep.com.cn/fmd/EN/ 10.1007/s11684–020–0754–0 (2020)]. High interindividual variation in distribution is recognised. Interestingly ACE2 expression has been demonstrated throughout the oral mucosa, with the highest enrichment being found on the tongue [Int J Oral Sci (2020) 12:8]; a possible explanation for the frequently reported COVID-19 symptom of impaired taste?
In addition to there being correlations between distribution of cell surface ACE2 and anatomical location of COVID-19 symptoms, there is also evidence that the severity of disease caused by such individual coronavirus strains varies with receptor affinity. The spike proteins (the ‘key’) on the surface of NL63 interact with ACE2 (the ‘lock’) with much lower affinity than do the equivalent surface proteins of SARS-CoV, perhaps explaining the lower pathogenicity of NL63 relative to SARS-CoV. [The Open Virology Journal, 2010;4:76–84].
Six months since the first cases were identified in Wuhan important signals of increased risk of severe COVID-19 are emerging [New Scientist [Health 6 May 2020: Why is coronavirus deadly for some but harmless for others?] Reported associations with severe COVID-19 include: age (high), gender (male), ethnicity (BAME), BMI (high), hypertension, diabetes and cancer. These 7 signals are unlikely to be independent determinants of severe COVID-19 and dissecting out the complex confounding factors will be necessary before robust evidence based guidance on assessing individual risk can be developed. For example obesity is often associated with hypertension and diabetes and certain ethnic groups have a higher prevalence of hypertension and diabetes. Cancer can be associated with obesity. Possible underlying determinants that could link these signals might potentially include socioeconomic factors such as crowded living (predisposing to a high SARS-CoV2 infection dose), smoking or general health parameters, particularly relating to immune function. At a genetic level HLA type could play a part in independently determining severity of COVID-19 and other signals. But perhaps one of the most important confounders might be variation in the expression and distribution of ACE2. Variations in the renin-angiotensin-aldosterone system activity are observed in hypertension, diabetes, obesity, certain ethnic groups and age groups. Perhaps the SARS-CoV2 ‘lock’ is the key to understanding interindividual predisposition to severe COVID-19. However the viral exposure dose causing infection is likely to be the most important exogenous determinant of disease severity. Therefore certain occupational groups might potentially be more at risk of severe COVID-19.
So what are the occupational risks of COVID-19?
Given that we currently have no way of knowing with certainty that any individual human does not present a SARS-CoV2 infection hazard [with the possible exception of someone just out of 14 day quarantine ] every fellow human currently needs to be considered as having potential to cause harm from COVID-19. Thus lone home working is the only completely safe way of ensuring no exposure to this new workplace hazard. As UK workers that have so far been deemed non-essential tip toe back to the workplace after lockdown, risk assessments by employers will be closely regulated both generically, in terms of basic self distancing and hygiene principles, and more specifically for certain occupational groups. The UK Office for National Statistics (ONS) have published within the last few days the earliest age-standardised COVID-19 related mortality data that looks at occupational groups. Important occupational signals appear to include men in lower skilled jobs. Interestingly a subanalysis of mortality amongst road transport drivers appears to show a correlation between mortality and likelihood of close proximity with others. These subgroups of drivers in descending order of mortality rates were: taxi and cab drivers and chauffeurs; bus and coach drivers; van drivers; large goods vehicle drivers. However, these data have not yet been adjusted for confounders other than age.
One of the main roles for occupational health professionals will be to integrate knowledge of an individual’s personal risk factors with risks from occupation specific exposures to advise on appropriate risk management. Already there have been significant challenges in this area, notably in the health and care sector. Other than strict hygiene practice, risk management tools for those required to provide direct care for patients potentially infectious for SARS-CoV2 have so far been limited to restrictions for workers who have individual risk factors, and PPE (where available). ONS has also recently published data on which occupations have the highest potential exposure to the coronavirus that causes COVID-19: https://www.ons.gov.uk/releases/whichoccupationshavethehighestpotentialexposuretothecoronaviruscovid19
Many questions need answering in occupational health areas relating to quantification of exposure risk and determinants of individual risk, the efficacy of PPE and other risk management strategies. Indirect risks, for example as a result of increased home working or mental health issues caused by the pandemic also pose important research questions.
The Centre for Occupational and Environmental Health (COEH) at the University of Manchester provides post graduate training in occupational medicine and hygiene, which are two professions providing important input in work place risk assessment and management. In addition, the COEH and colleagues within the Epidemiology and Public Health Group and others within the University are working on a range of research projects that aim to understand the determinants of developing disease in different occupational groups, the route of exposures in various occupational settings and how to assess and manage risk. If you are interesting in learning more about our teaching please contact:
Dr Melanie Carder, Occupational Medicine (Melanie.Carder@manchester.ac.uk)
or Dr Anne Clayson, Occupational Hygiene (Anne.Clayson@manchester.ac.uk)
If you would like to learn more about our research into how health is affected by work during the COVID19 epidemic, please contact Martie van Tongeren (Martie.j.van-tongeren@manchester.ac.uk).
About the author
Martin Seed is a consultant in occupational medicine working within the NHS and a clinical senior lecturer at the University of Manchester. His doctorate research was on chemical structure and respiratory sensitisation.
