1. Introduction

2. Coronary Artery Calcium Score and COVID-19 Prognosis

CAC scoring can be defined by multiple methods [1]: Agatston scoring, volume score, mass score, and visualization score (V-CACS). The clinical application of CAC scoring allows delineation and risk stratification of patients with increased atherosclerotic risk ^[1][2][1,7]. CAC score can be obtained by a non-contrast computed tomography of the chest, which may be obtained at the time of COVID-19 diagnosis ^[3][8]. Although standardized cutoff values for CAC have previously been studied ^[1][2][1,7], the actual utilized scoring and cutoffs for coronary studies seem user- and institution-dependent. Given the variability in the study methods, this analysis aimed to establish a systematic approach to comparison of CAC scores to synthesize and aggregate data. Few studies utilized V-CACS to separate the patients into absent, mild, moderate, and severe categories ^[4][5][9,10]. Other studies reported scores in Agatston format ^{[6][7][8][9][10]}[5,11,12,13,14]. One study reported as “high CAC” and “low CAC” groups [15]. Based on the provided ^[11]data, the reviewers classified those data into low CAC and high CAC group. There may be subjected to observer bias. Objective data on the presence or absence of CAC were analyzed to minimize the risk of observer bias. These two parameters were used to assess risk of three clinical outcomes: death, mechanical ventilation, and ICU admission.

A history of coronary atherosclerotic disease (CAD) is known to be associated with a 10% increased mortality risk in hospitalized patients with COVID-19 ^[12][16]. Other studies have reported similar findings. Additionally, COVID-19 has been associated with various cardiovascular complications ^[13][14][17,18]. Hyperinflammation, cytokine storm, lymphohistiocytosis, coronary microvascular thrombosis, and endotheliitis have been proposed to be possible mechanisms of acute myocardial injury in COVID-19 ^[15][19]. Slipczuk et al. (2021) measured the epicardial adipose tissue (EAT) and deemed it to be an independent risk factor for mortality in patients with COVID-19. Given the increased oxygen demand as well as cardiovascular strain and stress, patients with a history of CAD are at increased risk for worse clinical outcomes compared with their healthy counterparts. A single-center cohort study showed that there was a lower prevalence of myocardial injury if CAC was absent in patients with COVID-19 ^[16][20]. Absence of CAC had a high negative predictive value for major adverse cardiac events in patients hospitalized with COVID-19 even in the presence of other cardiac risk factors ^[17][21]. Based on the analysis, the presence of CAC alone increased the mortality rate for hospitalized patients with COVID-19 (Figure 2B). It may be safe to presume that patients with no known history of CAD may benefit from CAC scoring as a prognostic indicator for death during hospitalization.

COVID-19 is a primary respiratory disorder that can lead to acute respiratory distress syndrome (ARDS), which for many patients may require mechanical ventilation ^[18][22]. ARDS is defined by noncardiogenic pulmonary edema that can lead to life threatening hypoxia from a lack of proper oxygen exchange within the lung parenchyma ^[19][23]. The therapy for ARDS in COVID-19 is multidisciplinary, but the mainstay for critically ill patients is low tidal volume mechanical ventilation ^[19][23]. The risk of being mechanically ventilated is based on a multitude of factors such as age, obesity, cardiovascular disease, and socioeconomic background ^[20][24]. In a single-center cohort study of 5279 patients, the strongest risk factor for development to severe illness and possible intubation, in addition to age, was heart failure, with an odds ratio of 1.9 ^[20][24]. This analysis looked to assess whether CAC was a possible risk factor for intubation and mechanical ventilation. Of the studies reviewed, Luo et al. (2021) noted an increased risk for mechanical ventilation with high CAC scores; however, the aggregate data were not consistent with this finding. There is All other studies that were reviewed found a lack of significant elevation in risk for mechanical ventilation related to CAC levels. These data suggest that CAC presence and severity is not an independent risk factor for mechanical ventilation in hospitalized patients with COVID-19.

Hospitalized patients with COVID-19 are at increased risk for multi-organ systemic disease. A study of 138 patients who developed critical illness found the median time from admission to critical care service to be 2.5 days after onset of symptoms ^[21][25]. This rapid deterioration can be attributed to the severe pulmonary insult from the infection, but many of these patients have other non-pulmonary complications that lead to ICU admission. The complications most notably found during these admissions include acute kidney injury, encephalopathy, thrombosis, and cardiac injury ^[20][24]. Cardiac complications have ranged from cardiomyopathy and arrythmia to myocardial infarction and cardiac arrest ^[22][23][26,27]. One single-center cohort found a 33 percent occurrence of cardiomyopathy in critically ill patients with COVID-19 ^[24][28]. This cardiomyopathy is primarily thought to be either related to the hypercoagulable state from increased inflammation leading to coronary thrombosis and ischemic heart disease or direct cardiac myocyte injury from the viral pathogen ^[25][29]. However, the contribution of each of these complications to major adverse cardiovascular outcomes has not been fully determined. In a study examining 700 critically ill patients with COVID-19 with arrhythmias, nine patients developed cardiac arrest, all of whom were in the ICU. The development of cardiac arrest was associated with acute in-hospital mortality ^[26][30]. With a short median time from admission to an ICU transfer, as well as the known cardiovascular complications that follow, early prognosis via CAC scoring may benefit to risk-stratify patients. There was no significant difference noted between high and low CAC scores for ICU admission risk. There was also no significant difference noted in ICU admission risk whether any CAC was found. Given these findings, the risk of being admitted to an ICU for hospitalized patients with COVID-19 appears to be multifactorial in nature but independent of CAC scoring.

3. Conclusions