Effect of risk factors on the outcomes of COVID-19-infected intensive care patients: a single-center retrospective study

Background: To date, little attention has been paid to the impact of risk factors on the outcome of patients with coronavirus disease 2019 (COVID-19) hospitalized in the intensive care unit (ICU). This study was performed to examine the effects of risk factors on death among COVID-19 patients hospitalized in the ICU. Methods: From April 2020 to November 2020, data on 141 COVID-19-infected intensive care patients at 7 Air Force Hospital, Kanpur, were retrospectively retrieved. All analyses were performed using SPSS statistical software (SPSS Inc., Chicago, IL, USA, 15.0). Bivariate and multivariate logistic regression analysis was done to identify independent risk factors. A p-value <0.05 was considered statistically significant. Results: Most of study population were males (69.5%) with mean age of 59.8 ± 17.5 years. Out of 141 patients, 60 (42.6%) patients had comorbidities and 81 (57.4%) patients had no comorbidities. ICU death rates were 46.1%. Bivariate logistic regression analysis revealed that male sex (OR:0.45;95%CI:0.21-0.94), diabetes mellitus (OR:2.96; 95%CI:1.16-7.54), coronary artery disease (OR:2.48;95%CI:0.83-7.37), chronic kidney disease (OR:0.13,95% CI:0.021.12), patients with one (OR:1.25,95%CI:0.54-2.86) or more than two comorbidities (OR:1.95,95%CI:0.81-4.70), and who required high flow oxygen therapy (OR:13.30,95%CI:5.81-30.43), non-invasive (OR: 0.10,95% CI:0.02-0.45) and invasive ventilators (OR:0.04,95%CI:0.02-0.09) all were associated with higher ICU death rates. Multivariable logistic regression found following independent risk factors for death: patients with one comorbidity (OR:0.10;95%CI:0.020.66), non-invasive ventilator (OR:0.005;95%CI:0.000-0.091), and invasive ventilator (OR:0.003;95%CI:0.000-0.032). Conclusion: Identification of risk factors is of utmost importance to reduce death in COVID-19 infected intensive care patients.

Despite the rapid transmission of COVID-19 and the swiftly growing number of patients afflicted with COVID-19, there is a dearth of literature addressing the risk factors for the progression of COVID-19 in the Indian population. Therefore, the present study examined the impact of risk factors on the death of COVID-19 patients hospitalized in the ICU.

Study Design and Sample
This was a single-center, retrospective study of 141 confirmed COVID-19 patients hospitalized in the ICU in 140 bedded multispecialty hospital at 7 Air Force Hospital, Kanpur, from April 2020 to November 2020.

Inclusion and exclusion criteria
We included laboratory-confirmed all-comer COVID-19 patients with the help of chest computed tomography or realtime reverse transcription-polymerase chain reaction (RRT-PCR), including both nasopharyngeal and throat swab samples. All the diagnosis of COVID-19 was made per World Health Organization (WHO)'s interim guidance. Exclusion criteria were suspected COVID-19 patients without laboratory confirmation.

Data collection and sampling method
Medical records of demographics, comorbidities, and laboratory tests at the initial presentation were collected as per predefined proforma. The following variables were recorded: age, sex, comorbidities, the requirement of oxygen through high flow oxygen therapy, and a non-invasive or invasive ventilator. All patients received medical management as per WHO guidelines.

Definition of variables
Hypertension was defined as systolic blood pressure values ≥ 130 mm Hg and/or diastolic blood pressure ≥ 80 mm Hg. Diabetes mellitus was defined as fasting blood glucose level >126 gm/dl, or a clinical diagnosis of diabetes with dietary, oral, or insulin treatment. Coronary artery disease was defined as atherosclerotic plaque buildup in the vessel lumen. Cerebrovascular accident was defined as clinical syndrome manifested by the sudden onset (minutes to hours) of neurologic symptoms like hemiparesis and aphasia. Hypothyroidism was defined as the inability of the thyroid gland to produce enough thyroid hormone to fulfill the metabolic requirements of the body. Chronic kidney disease was defined as kidney damage characterized by abnormal albumin excretion or impaired kidney function enumerated as a measure of glomerular filtration rate that lasts for >3 months. Asthma was defined as a chronic respiratory disorder marked by inflammation and narrowing of the airway passages. Chronic obstructive pulmonary disease was defined as a chronic respiratory disorder indicated by airflow narrowing and persistent respiratory traits like dyspnea and cough.

Outcomes
The study outcomes were ICU death due to risk factors. Patients who had a negative result in RT-PCR finding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 RNA) were safely discharged.

Statistical analysis
Data are summarized using descriptive statistics. Categorical variables are presented as frequency and percentage, while continuous variables are expressed as mean ± S.D. A Chisquare test was used to compare categorical variables as appropriate. Bivariate logistic regression analysis was done to identify multivariable logistic regression analysis candidates. All explanatory variables with a value of <0.2 in the bivariate logistic regression analysis were included in the initial logistic model of multivariable logistic regression analysis to identify independent predictors. Crude and adjusted odds ratio (OR) and corresponding 95% confidence intervals (CI) were computed. All data were analyzed with the SPSS statistical software, version 15.0 (Statistical Package for the Social Sciences, Inc., Chicago, Illinois, USA). Differences were considered statistically significant at a p-value < 0.05 for all tests.

Discussion
The present study is among the few studies in India to determine the impact of comorbidities on death among COVID-19-infected intensive care patients. The main findings were as follows: a) mortality rates were higher in COVID-19-infected intensive care patients and b) male sex, diabetes mellitus, coronary artery disease, chronic kidney disease, patients with one or more than two comorbidities, and necessity of noninvasive and invasive ventilators all were independent risk factors associated with higher ICU death rates. However, we have found only the following three independent risk factors for death in multivariate analysis: a) patients with one comorbidity, b) the necessity of non-invasive ventilators, and c) invasive ventilators. The retrospective study reported 46.1% death rates in India's overall study patient population, which is concordant with the findings of Grasselli et al. [11], who had found a death rate of 48.8% in COVID-19 patients hospitalized in the ICU in Italy? However, in contrast to the present study's findings, earlier investigations by Budhiraja et al. [16]and Guan et al. [17] revealed low mortality rates of 32.2% in India and25.6% in China, respectively. Similarly, in a meta-analysis, Abate et al. [18] found a low ICU death rate of 39% in ICU admitted patients with COVID-19. The high frequency of death rate in ICU in the present study may be attributable to a substantial need for high oxygen flow therapy, a constrained number of mechanical ventilators, and a high incidence of comorbidities.

Risk factors for higher ICU death rates Gender
Numerous risk factors such as hypertension, diabetes mellitus, obesity, cardiovascular disorders, chronic obstructive pulmonary disease, male sex, and old age, present in COVID-19 patients impose a significant burden to patients' life, emphasizing the importance of assessing the effect of risk factors on death in COVID-19 patients [9][10][11][12]. In the present study, the most common risk factor for death in COVID-19-infected intensive care patients was male sex. This death rate in male COVID-19 patients hospitalized in the ICU was almost double that of the female COVID-19 patients, which is concordant with the previous studies [11,12,19]. In addition to comorbidity, a few studies have discovered the following rationale for higher death rates in males than females: higher risk behaviors such as smoking and alcohol use, occupational exposure, social difference, and biological difference. However, we have found no significant evidence of a higher prevalence of comorbidities in male patients.

Comorbidities
Patients with different comorbidities have been presented to have a poor prognosis even without COVID-19 because of late presentation coupled with lack of medical professionals, diagnostic and therapeutic equipment, and exorbitant treatment costs [20][21][22][23]. Regarding comorbidities that anticipated death in COVID-19-infected intensive care patients, our study confirms the prior finding of Grasselli et al. [11] and Osibogun et al. [12] who had found that diabetes mellitus exacerbated COVID-19 progression, and patients with diabetes mellitus have succumbed to COVID-19. The Global Burden of Disease collaboration has found that chronic kidney disease is the most common risk factor for death in COVID-19 patients [24], which is in line with the present study's finding. Furthermore, coronary artery disease was an independent risk factor for increased mortality in these patients [25,26]. Likewise, in a prior study in China [27] and Southwest Nigeria [12], our data elicits that the presence of multiple comorbidities raises the chance of death in these patients. Therefore, patients with various comorbidities must require extra vigilance.

Non-invasive and invasive ventilators
The present study found a higher death rate in critically ill COVID-19-infected intensive care patients who required invasive or non-invasive ventilators in high dependency units. Similarly, Ferreira et al. [28] also found higher death rates in patients who required mechanical ventilation. Based on the present study's findings, we can speculate that this data can aid the clinicians in identifying the patients at a higher risk of serious infections and fatality and monitoring and reporting them appropriately. The present study has a few limitations. To begin with, this was a single-center retrospective study with small sample size; thus, the data is not representative of the general population. Furthermore, because only hospitalized patients were included, statistics on morbidity from COVID-19infected intensive care patients may be understated. Hence, future studies with a large sample size are warranted.

Conclusion
Male gender, diabetes mellitus, coronary artery disease, chronic kidney disease, patients with one or more than two comorbidities, and the necessity of non-invasive and invasive ventilators all were linked to death in patients with COVID-19infected intensive patients. Most crucially, as the COVID-19 pandemic expands, proper management of patients based on risk factors, adequate well-trained personnel, and mechanical ventilation all can facilitate clinicians to reduce the disease's death.