Our analysis indicates a significant impact of inpatient lab values and social determinants of health on inpatient COVID-19 mortality. Our study showed that age, non-white race, diagnosis of hypertension, myocardial infarction, or coronary artery disease, and high WBC count on initial lab draw were predictive of a patient developing severe COVID-19 infection, and therefore greater mortality. Elevated total protein on initial labs, conversely, was predictive of a decreased inpatient mortality.
Even after controlling for demographic and comorbidity factors, non-white race in both bivariate (X = 8.175, p < 0.005), and combined multivariate analysis (OR = 3.722, p = 0.028) were significant predictors of inpatient mortality. In general, the role of race on COVID-19 outcomes has been understudied. However, it has been established in the literature that racism and structural discrimination lead to an increased risk of worse clinical outcomes within ethnic minority communities.[21] One meta-analysis found that individuals of Black race were twice as likely to become infected with SARS-CoV-2 compared to White individuals.[21] The same study also found Asian and Hispanic groups to be more likely to become infected than White individuals.[22–24] These relationships were found to be significant when repeating the analysis with only peer-reviewed journals.[22] Even among healthcare workers, one study found ethnic minorities experience disproportionate rates of COVID-19 infections.[25] Our results indicate that non-white status alone, was associated with greater inpatient mortality. Our results suggest that social determinants of health are an effective target for intervention aimed at reducing the healthcare burden of COVID-19 hospitalization and could aid in the allocation of resources in a rural Michigan setting.
Our study suggests that a patient's age might be an indicator of poor prognosis in COVID-19 infection, however, this relationship, while significant, was weak. Other studies have also demonstrated mixed findings regarding age as a risk factor for severe COVID-19. A meta-analysis by Romero et al. tried to discern the impact of age on COVID-19 mortality, and to identify if it was age alone, or age-related comorbidities contributing to COVID-19 mortality.[26] They concluded that many studies did not separate age- and age-related comorbidities, and that age related comorbidities seemed to be better predictors of COVID-19 mortality than age alone. Some studies have looked at both age and sex in combination, as older men appear to have a higher risk profile compared to older women or younger women.[27] This body of literature suggests that the reason older men and women are at higher risk of COVID-19 outcomes is not age alone, but lack of estrogen.[27] Our study did not look at hormonal changes in an aging population, but our findings could be explained by the hormonal theory. Finally, a study looking at inpatient mortality in a hospital in the Bronx also revealed similar findings to our study, such as increasing age being associated with greater inpatient mortality independent of other factors.[28] Overall, age-related comorbidities might better explain poor outcomes in COVID-19 patients.
The literature on hypertension has been mixed, however, in our index, it was the strongest predictor of mortality. In one study, hypertension was a significant predictor of morbidity, however, multiple other clinical factors such as obesity, liver disease, renal disease, COPD and DM were more likely to contribute to severe COVID-19 than hypertension.[29] One reason that hypertension might contribute to worse outcomes in COVID-19 might be due to the increased ACE2 expression due to ACE/ARB use in this patient population.[30] However, this isn’t proven to be consistent, and in one study, patients on an ACE/ARB regimen had no significantly different risk of COVID-19 compared to those not on an ACE/ARB regimen.[31] In another study, hypertension was the most common comorbidity in those with severe COVID-19, however, hypertension and the other comorbidities were not the pre-requisite for developing severe COVID-19.[32] In both a systematic review and meta-analysis respectively, CVD (Cerebrovascular disease) and hypertension significantly increased risk of mortality from COVID-19.[33, 34] While the literature has been mixed for hypertension, many of our other variables in the index were more consistent with the literature.
It is not surprising that having a diagnosis of a prior myocardial infarction/coronary artery disease was associated with poor outcomes. In a study by Szarpak et al., coronary artery disease was associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I2 = 72%; p < 0.001).[35] In another study, patients with coronary artery disease and COVID-19 have higher rates of comorbidities, inpatient mortality and need for renal replacement therapy compared to their non-coronary artery disease counterparts. However, coronary artery disease was not associated with mortality after adjusting for other covariates, suggesting that other factors may play a larger role in the increased mortality and poor outcomes in these patients.[36] Interestingly, another study by Loffi et al., (2020) demonstrated that patients with COVID-19 and coronary artery disease have an exceedingly higher risk of mortality, which is mainly attributable to the burden of comorbidities rather than to a direct effect of coronary artery disease per se.[37] Therefore, future studies might look at comorbidities often seen in conjunction with coronary artery disease, rather than coronary artery disease alone.
One large study identified hypertension, cardiovascular disease, and coronary heart disease among the most common comorbidities of patients with COVID-19, particularly in those who developed severe complications.[38] According to various articles, patients with pre-existing coronary vascular disease and hypertension appear to have increased susceptibility to developing more severe diseases with worse clinical outcomes.[34, 39–41] Some studies have also noted the particularly strong relationship cardiovascular disease has on COVID-19 severity and mortality.[34] Our results support the idea that COVID-19 infections cause worsening cardiovascular health. Combined, we feel our study supports the idea that patients with a known history of myocardial infarction, coronary artery disease, and uncontrolled hypertension are at greater risk of mortality during COVID-19 admissions. Therefore, these patients require greater care and more regular follow-up. These factors are key determinants of inpatient risk in COVID-19 admissions and will be important variables in COVID-19 admission algorithms.
Most studies support our findings that those with severe COVID-19 have low protein counts. Low protein might be a result of organ failure or cytokine storm, both of which are seen in more severe presentations of the disease.[42–44] Chen et al, found that patients with high WBC counts and low protein levels on admission, were more likely to continue to develop severe COVID-19 infection.[44] Additionally, those with low levels of protein were more likely to go on to develop a second infection, thus implying that low protein levels might indicate a compromised immune system.[45] Albumin is a common protein measured in the body and decreased levels are seen in liver disease. Xu et al found that serum albumin levels were decreased in COVID-19 patients regardless of severity level, however those with severe COVID-19 were more likely to experience lower levels of albumin in comparison to those with mild or moderate COVID-19.[46] Furthermore, in a cohort from Chongqing China, patients that experienced fever, fatigue, headache or dizziness were more likely to have low albumin levels.[46]
Finally, our index suggested that high WBC at admission was predictive of poor COVID-19 outcomes. Other studies have shown this effect as well. In one study by Zhu et al., patients with higher WBC count, even if values were in the normal range, were more predictive of poor COVID-19 outcomes.[47] Therefore, if two patients present with similar labs, even if one does not have remarkable WBC, it might be important to rank the patient with the higher WBC count as more vulnerable or at greater risk of developing severe COVID-19. Several other resource-limited areas, such as India, have had to rely on laboratory parameters when discerning which patients were more likely to develop severe COVID-19. Interestingly, one study by Anurag et al., found that markers such as total leukocyte and WBC count were more likely to predict severe COVID-19 outcome, whereas age and sex would predict COVID-19 risk but not outcome severity.[48] Similarly, a study in Iran was able to predict one month mortality in COVID-19 patients, based on age, WBC count and neutrophil-lymphocyte ratio.[49]
In addition to factors in a patient’s history, we analyzed quantitative measurements typically collected upon initial presentation to the ED (Emergency Department). Quantitative analysis with 2-sample t-tests indicated abnormal lab values and vitals predictive of increased COVID-19 mortality. These findings were increased age (t = -5.51, p < 0.001), increased WBC count (t = -2.64, p < 0.01). These findings are consistent with findings reported by other studies. One meta-analysis found patients over the age of 50 had greater mortality from covid compared to those under the age of 50.[50] Studies have also found leukocytosis to be associated with more severe disease and poor outcomes.[51] One study found significant associations between leukocytosis and the rate of mortality in patients with COVID-19.[52] Our results suggest there may be a continuous relationship between increasing age and WBC count that can be directly correlated to increased mortality and complications from COVID-19. Therefore, the numerical values of age and WBC count are important to input variables in risk assessment algorithms.
Our study has identified key historical and objective measurements that were demonstrated to be predictive of increased inpatient mortality in those hospitalized with COVID-19. Further research should center on using identified factors and developing an assessment tool for rapid risk calculation of COVID-19 mortality. Unlike urban centers, rural communities often lack the same resources, and resource allocation is warranted to ensure patients' needs are met. Identifying at-risk individuals can further help direct resources and care to patients that have a greater need, increasing hospital efficiency. Comparisons with similarly sized community hospitals, servicing large catchment areas, would be very insightful. This is particularly valuable considering large community health centers have a disproportionate number of COVID-related mortalities. Analyzing the devastation of COVID-19 on our overtaxed hospital system is key in directing policy that aims to prepare our health care system better against further bio-threats.