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From the COCCI Syndemic to the COVID-19 Pandemic Scholars Insight Publishers Journal of Epidemiology and Global Health Research Research Article Open Access From the COCCI Syndemic to the COVID-19 Pandemic: A Cautionary Tale Interaction of Metabolic Syndrome, Obesity, Particulate Matter (PM), SARS-CoV-2 and the inflammatory response Clearfield M*, Gayer G, Wagner A, Stevenson T, Shubrook J and Gugliucci A Touro University College of Osteopathic Medicine, California, USA Corresponding Author: Dr. Clearfield M, Touro University Abstract College of Osteopathic Medicine, California, USA. A narrative review of the literature was conducted to determine E-mail id: [email protected] associations between cardiovascular (CV) risk factors associated with the COCCI syndemic (Cardiovascular disease as a result of the Received Date: March 15, 2021; interactions between obesity, climate change and inflammation) and Accepted Date: May 19, 2021; COVID-19. Published Date: May 21, 2021; The COCCI syndemic consists of two health conditions Publisher: Scholars Insight Online Publishers (dysmetabolic obesity and air pollution) that interact via biologic Citation: Clearfield M*, Gayer G, Wagner A, Stevenson T, pathways admixed with social, economic and ecologic drivers Shubrook J and Gugliucci A “From the COCCI Syndemic to augmenting adverse clinical outcomes in excess of either of these the COVID-19 Pandemic: A Cautionary Tale Interaction of health conditions individually. Metabolic Syndrome, Obesity, Particulate Matter (PM), SARS- The comorbidities noted with COVID-19 are in large part aligned CoV-2 and the inflammatory response”. J Epidemiol Glob Health with those traditional risk factors associated with CVD. In addition, Res. 2021; 1:102 when the traditional CV comorbidities are combined with the Copyright: ©2021 Clearfield M. This work is licensed under a emerging CV risk factors found in the COCCI syndemic there is Creative Commons Attribution 4.0 International License, which an increasing likelihood for the development of COVID-19 and for permits unre stricted se, distribution, and reproduction in any increasing the morbidity and mortality associated with COVID-19, medium, provided the original work is properly cited. especially as a result of cardiovascular complications. Background: The severe acute respiratory syndrome coronavirus-2 the world exhibiting some common trends, characteristics and (SARS-CoV-2), the causal agent of the Corona Virus Disease-2019 comorbidities associated with both disease prevalence and severity. (COVID-19) was first identified in December 2019 in Wuhan China From the onset, COVID-19 prevalence and severity was associated and within a few months spread around the world creating a global with comorbidities and risk factors associated with Cardiovascular pandemic [1]. Disease (CVD) such as older age, male sex, hypertension, diabetes and the presence of CVD itself [4-6]. In addition to the traditional Methods: A narrative review of the literature was conducted to CV risk factors, several residual or emerging CVD risk factors determine associations between the cardiovascular (CV) risk factors including obesity, metabolic syndrome and air pollution have also associated with the COCCI syndemic (obesity with associated been investigated as potential risk factors for COVID-19 [7-10]. metabolic disorders, climate change and air pollution, and inflammation) and COVID-19 [1,2]. Conclusion: The comorbidities noted with COVID-19 are in large part the same as those traditional risk factors associated with CVD. Findings: From a global perspective, since the onset of COVID-19 In addition, the traditional CV comorbidities when combined through January 1, 2021, there have been 82,707,976 cases and with the emerging CV risk factors noted in the COCCI syndemic 1,805,002 deaths, attributed to coronavirus-2 with 19,654,998 cases consisting of obesity, metabolic syndrome and air pollution share and 340,679 deaths in the United States alone [3]. COVID-19 has an increasing likelihood for the development of COVID-19 and the created an unprecedented response in the medical literature with a associated morbidity and mortality, especially as a result of cardiac PubMed search for COVID-19 resulting in 86,000 articles published complications [11,12]. through January 1, 2021 with hundreds of new articles appearing daily. Over the first few months of the pandemic the trajectory of Keywords: Metabolic syndrome; Obesity; Particulate matter (PM); disease moved from China to Europe to the United States and to SARS-CoV-2 and the inflammatory response. 1 Journal of Epidemiology and Global Health Research Scholars Insight Publishers Introduction Cardiovascular disease as a result of traditional and residual risk factors Cardiovascular disease has remained the number one cause of mortality for the past century. It has maintained its status despite the many groundbreaking advances in the treatment of the primary risk factors causing CVD, as well as advanced interventional measures treating the disease itself [9]. The Behavioral Risk Factor Surveillance System measured five traditional CV risk factors: total blood cholesterol ≥240 mg/ dL, hypertension, BMI ≥30 kg/m2, hemoglobin A1c ≥6.5% and Figure 1: PM and obesity can symbiotically augment and enhance current smoker which accounted for approximately half of CV atherosclerosis [13]. events in 2009-2010 [13]. The other half of CV events are, in part represented by the residual risk associated with metabolic, and O3 and all-cause mortality, while cardiovascular, respiratory thrombotic, and inflammatory pathways [7-9]. Of note, as with and cerebrovascular mortality remained positively associated with traditional CV risk factors, many of the residual CV risk categories PM10 and PM2.5 [25]. Long term exposure to PM2.5 across the also augment the chances of a poor prognosis from COVID-19 [7- United States has been associated with increased CVD, especially 9,15-19]. in areas where the prevalence of obesity was greater throughout the population [26]. The residual risk for CVD has been explored previously with a particular focus on the metabolic syndrome associated, or not, Subclinical inflammation is one factor connecting obesity and with obesity and its related risk factors of elevated triglyceride, PM where both inflamed adipocytes and PM2.5 can induce an decreased HDL-C, increased blood pressure, blood glucose inflammatory response resulting in macrophage release of IL-1α, and waist circumference [20]. As an emerging residual risk, the IL-1β, Il-18 and IL-33 signaling pathways activating an immune metabolic syndrome was found to double the risk for CVD [21]. system response through the NOD-Like Receptor Family Pyrin Expanding the residual CV risk secondary to obesity and metabolic domain containing 3 (NLRP3) inflammasome [7-29]. A mechanistic syndrome to also include the projected synergistic effects from aberrant pathway activating the NLRP3 inflammasome proposes air pollution, specifically particulate matter less than 2.5 micron both central adipose tissue and PM2.5 induce oxidative stress and (PM2.5), introduces the possibility of augmenting risk even beyond inflammation which contributes to acute, sub-acute and chronic those ascribed to an additive affect from each of the individual responses promoting atherosclerosis and subsequent CV events residual risk factors [10]. [30-32,46]. COCCI Syndemic and CVD Three recent trials using two different anti-inflammatory The concept of a syndemic consists of two or more health medications (canakinumab, colchicine) demonstrated significant conditions or contributors to health conditions that interact via reductions in CV events which appear to be dependent on their biologic pathways admixed with social, economic and/or ecologic ability to influence the NLRP3 inflammasome [33-37]. The drivers that augment the adverse clinical outcomes in excess of CANTOS trial (Canakinumab Anti-inflammatory Thrombosis the health conditions individually [22]. The combining of obesity Outcomes Study) utilizes a monoclonal antibody that binds IL- and associated metabolic risk factors with air pollution and climate 1β, significantly reduced major CV events by 15% [34]. The change sets the foundational context for a syndemic [13,23]. The COLCOT trial (Colchicine Cardiovascular Disease Outcome unfavorable adverse outcomes previously explored by combining Trial) and the LoDoCo2 trial (Low Dose Colchicine Trial-2) obesity, specifically central obesity associated with metabolic both utilize colchicine, which interferes with the assembly of abnormalities, and air pollution/climate change, contributes to the inflammasome and the release of IL-1β. Both COLCOT and sustaining and augmenting CV morbidity and mortality [13,21,24]. LoDoCo2 also demonstrated significant reduction in CV events, 23% and 31% respectively [35,36]. The COCCI syndemic (CVD as a result of Obesity, Climate Change and Inflammation) proposes that central adiposity when Several recent trials have also reported on the efficacy associated with an underlying dysmetabolic state, is highly of Interleukin-6 receptor (IL-6) antagonists (tocilizumab and vulnerable to the pro-inflammatory effects from particulate matter sarilumab) in hospitalized patients with COVID-19 [38,39]. The less than 2.5 micron (PM2.5) [13]. (Figure 1) A systematic review results were mixed with no significant benefit noted in reducing and meta-analysis of 196 articles found evidence of a positive intubation or mortality with tocilizumab in the BACC Bay trial association between short-term exposure
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