Firefighters and COVID-19: An Occupational Health Perspective

Abstract

Diagnoses of coronavirus disease 2019 (COVID-19) from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were first reported in December 2019. Since its emergence from the Chinese province of Wuhan, the World Health Organization (WHO) has announced 162 million confirmed cases of the SARS-CoV-2 infection worldwide, and reported roughly 3.3 million deaths as of May 16, 2021.1 Stratified by country, the United States leads with nearly 33 million confirmed COVID-19 cases, followed by India, Brazil, France, Turkey, and Russia.2 Structural firefighters perform essential public safety work and have continued that work despite the challenges of COVID-19. Career firefighters typically have long work schedules (24 or 48 hours on duty followed by multiple days off) and eat and sleep at the station as part of a team/shift. Firefighters respond to multiple hazards which include fires and rescues. In many localities, firefighters are dual trained as emergency medical service (EMS) personnel and provide emergency medical care. Because of their close living quarters and contact with the public, including rendering patient care and transporting patients, it is likely that firefighters are at an increased risk of infection with SARS-CoV-2. The fire service is aware of the risk of infection and has quickly adopted the increased use of personal protective equipment (PPE) and modified policies and procedures aimed at reducing the risk to firefighters.3,4 However, very little attention has been paid to occupational risks that may increase the severity of COVID-19 or to the potential long-term consequences of COVID-19 that may pose specific concerns for firefighters. The purpose of this review is to 1) outline the pathogeneses of COVID-19, 2) explore clinical and mechanistic links between COVID-19 and cardiovascular disease, 3) review known risk factors for COVID-19 complications and their prevalence among firefighters, and 4) consider steps that can be taken to better understand the long-term consequences of COVID-19 in the fire service. The review is limited to occupational factors for structural firefighters and does not cover wildland firefighters, although we acknowledge that COVID-19 may also present special concerns for wildland firefighters. PATHOGENESIS OF COVID-19 The SARS-CoV-2 virus enters the body predominantly via the lungs, and often results in pronounced respiratory symptoms. Thus COVID-19 was initially described as a respiratory disease. Indeed, respiratory failure from acute respiratory distress syndrome has been shown to be leading cause of COVID-19 induced mortality.5 A study by Guan et al6 reported that the majority of COVID-19 related consequences feature pneumonia and acute respiratory distress, which is consistent with other analyses suggesting that about 40% of COVID-19 patients develop acute respiratory distress syndrome, and 20% of these syndromes are severe.7 Wang et al8 showed that 61% of the individuals that required intensive care due to COVID-19 developed acute respiratory distress syndrome. COVID-19 not only lead to respiratory symptoms, but also underlying respiratory conditions increase the likelihood of experiencing severe symptoms. Meta-analyses revealed that the odds of severe COVID-19 infection were 5.69 times higher if individuals who have a history of chronic obstructive pulmonary disease.9 The virus requires the cooperation of two key proteins, TMPRSS2, and angiotensinogen converting enzyme 2 (ACE2) to infiltrate the body via the lung pneumocytes. TMPRSS2 is a key cellular regulator of coronavirus spike protein (S protein), with the S1 domain of the S protein responsible for receptor binding and the S2 domain controlling membrane fusion. Thus, coronavirus requires the binding of the S1 region to a cell surface receptor followed by the S2 subunit mediated fusion of the viral and cellular membranes in order to enter its host.10 This process requires S protein priming, or cleavage, by host proteases at the S1and S2 domains of the virus. This process has been described as a principle step for the cellular entry of SARS-CoV-2.11 Following S protein cleavage, Sars-CoV-2 binds to and enters lung cells via the enzyme ACE2, which is highly expressed in alveolar type 2 cells.12 Dissimilar to the original SARS-CoV, it has been suggested that SARS-CoV-2 may have a higher affinity to ACE2 positive cells in the upper respiratory tract, exacerbating its potent and detrimental effects.11 ACE2 is a membranous protein and importantly, an inactivator of angiotensin II (AngII). The binding of SARS-CoV-2 to ACE2 in lung cells promotes the endocytosis of the ACE2-SARS-CoV-2 complex, resulting in a reduction of membrane ACE2 abundance and an increase in serum AngII.12 Thus, SARS-CoV-2's affinity for ACE2 could explain its downstream effects on vascular parameters, including alterations in systolic and diastolic blood pressures, as elevated plasma AngII can increase blood pressure via aldosterone-mediated vasoconstriction and sodium and water retention on the kidneys.13 Furthermore, increased plasma AngII is associated with increased risks of myocardial infarction and left ventricular hypertrophy.13 In addition, SARS-CoV-2 promotes inflammation via the AT1R.12 The AngII-AT1R axis activates pro-inflammatory transcription factors NF-kB and STAT3, upregulating pro-inflammatory cytokines such as TNFa and IL-6 family cytokines,12,14 possibly leading to vascular inflammation and disease. Furthermore, recent studies suggest that the Sars-CoV-2 protein ORF3a encourages an aggressive inflammatory response via NF-κB activation, chemokine secretion, Golgi fragmentation, ER stress, and cell death.15 ORF3a can also inhibit type I interferon (type I IFN) signaling, downregulate major histocompatibility complex (MHC) class I expression, and reduce CD8+ cytotoxic T cell activity. Specifically, Siu et al15 demonstrated that ORF3a encourages the binding of TRAF3 to cytoplasmic portions of TNF receptors, promoting ubiquitination, and processing of p105 to p50. P50 is generated by TRAF3 ubiquitin-ligase ubiquitination of p150 and 26S proteasome-mediated removal of p105C terminal sequences. P50 then binds to RelA, RelB, or C-Rel subunits to produce functional NF-κB, a transcription factor essential for pro-IL-1β expression. The prevalence of pro-IL-1β transcripts is a requirement for NLRP3 inflammasome activation. Therefore, ORF3a-mediated p105 processing into p50 can help activate the NLRP3 inflammasome and lead to a robust inflammatory response.15 Siu et al further demonstrated ORF3a's ability to induce ASC polyubiquitination via a TRAF3 ubiquitin-ligase.15 ASC is the adapter complex of the NLRP3 inflammasome, and polyubiquitination of ASC provides a nondegradative signal necessary for ASC activation, caspase-1 activation, and mature IL-1β protein formation.15 Ultimately, the studies mentioned above illustrate how COVID-19 can target the cardiovascular system through its mode of entry and lead to vascular inflammation and dysfunction via upregulation of pro-inflammatory signaling. COVID-19 AND CARDIOVASCULAR DISEASE Although SARS-CoV-2 was first described as a respiratory disease, cardiac tissue and blood vessels express ACE2 receptors and appear to be particularly prone to COVID-19 infection.14 The heart, an ACE2 expressing tissue, was studied during the Toronto SARS outbreak (SARS-CoV), and investigators found evidence of SARS-CoV RNA in 35% of autopsied hearts.16 COVID-19 acts in a similar manner to the previous SARS-CoV, indicating that individuals with cardiovascular disease (CVD) are more prone to severe complications of SARS-CoV-2 compared to healthy individuals. Initial research on CVD-induced complications of COVID-19 was conducted in China. Wang et al investigated the association between biomarkers of CVD and the exacerbation of COVID-19 in hospitalized patients and found that cardiac injury, defined as either elevated high-sensitivity cardiac troponin I (hs-cTnI) or ECG/echocardiographic abnormalities, was present in 7.2% of the patients.8,17,19 The study also found that 22% of COVID-19 patients in ICU had biomarkers of cardiac injury.8,17 Zhou et al reported that hs-cTnI levels were at or greater than the 99th percentile upper reference limit in 46% of non-survivors, compared to only 1% of survivors who had levels this high.17,18 Thus, it has become apparent that COVID-19 can have severe cardiovascular consequences. Ultimately, it is also becoming clear that the presence of CVD, or CVD risk factors, can increase the likelihood of severe complications of COVID-19. The observational study by Zhou et al described above, also reported that 8% of patients (13% of non-survivors) had been diagnosed with CVD and 38% (48% of non-survivors) had been diagnosed with hypertension.17,18 Furthermore, Wang et al found that comorbidity of COVID-19 and CVD was prevalent in 15% (25% requiring ICU care) of patients analyzed, and Guan et al reported that 2.5% (9% among those with intubation or death) of COVID-19 patients also suffered from coronary artery disease.10,11,14 Chen et al demonstrated that in a cohort of 99 COVID-19 infected individuals at the Wuhan Jinyintan Hospital, 40% had some manifestation of cardiovascular or cerebrovascular disease.19 Other researchers have also reported on the higher prevalence of hypertension among COVID-19 patients; one study that although reports 15% of COVID patients had hypertension, 36% of those who needed intubation or suffered death had hypertension. 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