Examining the correlation between ICU patients’ laboratory results and death caused by COVID-19

Authors

Abstract

Aim This study aims to determine the clinical and laboratory parameters that can predict mortality in COVID-19 patients admitted to the intensive care unit (ICU) in the Adıyaman region of Turkey. By identifying significant prognostic markers, the study seeks to support early risk stratification and informed clinical decision-making to improve patient outcomes in ICU settings.
Materials and Methods This retrospective observational study included 66 adult patients (≥18 years) diagnosed with COVID-19 and treated in the ICU. The diagnosis was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing of nasopharyngeal swabs. Clinical and laboratory data were obtained from electronic medical records. Patients were followed until December 31, 2020, and were categorized into survivor and non-survivor groups based on outcomes during hospitalization.
Results Among the 66 patients, 33 (50%) were male and 33 (50%) were female. Thirteen patients (19.6%) died during the follow-up period. Compared to survivors, non-survivors had significantly higher red cell distribution width (RDW) (14.6±3.1 vs. 12.6±1.7; p = 0.01), neutrophil count (10,026±5594 vs. 6831±4706; p = 0.04), and creatinine levels (6.8±2.07 vs. 1.5±0.2; p = 0.01).
Discussion The study findings indicate that elevated RDW, neutrophil counts, and creatinine levels are significantly associated with mortality in COVID-19 patients. These parameters may serve as useful prognostic markers for clinicians in assessing the severity of illness and guiding therapeutic decisions in ICU settings.

Keywords

Introduction

Turkey was rapidly impacted by the Coronavirus disease 2019 (COVID-19) pandemic during the first months of 2020. Several studies have been conducted to identify the mechanism of severe disease and to determine prognostic methods for identifying patients who are at high risk of death or progression to severe disease. These studies have revealed that higher age, male gender, chronic diseases, immunosuppression, and obesity are risk factors associated with severe COVID-19, which can lead to death. In addition, comorbidities such as hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease are other important risk factors for severe disease.It is imperative to identify clinical, demographic, and laboratory factors that predict clinical worsening and prognosis of patients infected with this virus to reduce the effects of the virus and improve medical outcomes. In COVID-19 patients, leukopenia, lymphopenia, and thrombocytopenia have been found to be more prevalent at the time of hospital admissions [1]. Intensive care unit patients were found to have elevated D-dimer levels and lymphopenia [2]. Furthermore, high RDW values during hospitalization and increased RDW values during hospital follow-up were associated more with morbidity and mortality in COVID-19 patients [3]. There is a close relationship between neutrophils and lymphocytes in the pathophysiology of COVID-19 disease. Several studies have demonstrated that neutrophilia and lymphocytopenia in circulating leukocytes are physiologically induced by stress, trauma, major surgery, bacteremia, systemic inflammation, and sepsis [4, 5]. Testing routinely and cost-effectively, such as hemogram would help determine the severity of COVID-19 and its clinical course during follow-up and treatment.This ensures that medical resources are used effectively and efficiently, especially in environments where resources are limited. As a result, mortality can be reduced with timely and early clinical intervention [6]. Additionally, finding potential biomarkers for future pandemics and epidemics may guide clinicians in identifying risky patient groups and selecting treatments.Therefore, we aimed to evaluate the clinical and prognostic effects of neutrophils and RDW in COVID-19 patients followed in the intensive care unit in our hospital, and to investigate whether high neutrophil count and RDW are associated with higher mortality in severe COVID-19 disease.

Materials and Methods

Study Design
This study is retrospective; all patients were followed between April 1, 2020, and December 31, 2020, and all data were obtained from the hospital’s computer database. A total of 66 patients, over the age of 18, whose diagnosis of COVID-19 was confirmed by the RT-PCR test of nasopharyngeal swabs in a laboratory, were included in the study voluntarily. The exclusion criteria were as follows: 1. Not having a confirmed COVID-19 diagnosis, 2. Not giving informed consent 3. Having any mental or psychiatric problem that prevents understanding the informed consent form, 4. Being in a state of coma, pre-coma, or the intensive care unit, one cannot give informed consent, 5. Having an atopic body or allergies. The study collected various clinical information about patients, including age, gender, length of stay, additional disease status, and whole blood and biochemical laboratory values. The patients’ clinical outcomes were also assessed, such as death rate and duration of hospital stay.
Statistical analysis
Data were analyzed by the statistical package SPSS for Windows 22.0 (SPSS Inc.). A Kolmogorov-Smirnov test and a Shapiro-Wilk test were applied to assess whether the data were normally distributed. In the case of normally distributed parameters, the independent T-test was used to assess statistical significance. The Mann-Whitney U test was used to compare two nonparametric samples or groups and determine statistical significance. P <0.05 was considered statistically significant for comparisons.
Ethical Approval
This study was approved by the Ethics Committee of Clinical Researchers linked to Adıyaman University (Date: 2020-06-23, No: 2020/6-19).

Results

66 patients were enrolled in the study, 33 were males and 33 were females. As a result, the patients were divided into two groups, survivors and non-survivors. Thirteen patients (19.6%) died during follow-up. In the analysis, there were statistically significant differences in WBC, neutrophil count and creatinine values between the two groups. The mean WBC values of the patients were 8780±4995 in the survivor group and 11950±5851 in the Non-survivor group (p value=0.05). The mean RDW (%) values of the patients were 12.6±1.7 in the survivor group and 14.6±3.1 in the Non-survivor group (p value=0.01The mean neutrophil values of the patients were 6831±4706 in the survivor group and 10026±5594 in the non-survivor group (p value=0.04 The mean creatinine values of the patients were 1.5±0.2 in the survivor group and 6.8±2.07 in the non-survivor group (p value=0.01). In this study, 52 of 66 patients (86.67%) had comorbid diseases. When the comorbidities are examined, 1.5% of the patients have Alzheimer’s disease, 6% Asthma, 24.2% COPD, 7.5% Diabetes Mellitus, 7.5% Hypertension, 9% Chronic renal failure, 7.5% had Heart failure, 6% had coronary artery disease, 6% had Malignancy, 1.5% had Cirrhosis, and 1.5% had Cerebrovascular disease. Results were summarized in Tables 1 and 2.

Discussion

The COVID-19 pandemic has brought to light the critical need for intensive care when managing severely ill patients. With no specific treatments available, healthcare professionals rely on supportive care, particularly respiratory support, to help patients recover. However, despite these efforts, mortality rates remain alarmingly high, influenced by various factors such as age, comorbidities, and the presence of multi-organ dysfunction, with acute respiratory failure and ARDS being the primary causes of death in COVID-19 patients. The high mortality rates among COVID-19 patients highlight the urgent need for more effective treatment options. Researchers are actively exploring potential therapies, including antiviral drugs and immunomodulatory agents, to improve patient outcomes. Additionally, efforts are being made to develop vaccines that can prevent severe illness and reduce the burden on healthcare systems. The COVID-19 disease, which is caused by the Coronavirus (SARS-CoV)-2, was initially identified in December 2019 in Wuhan, Hubei, China, and has since evolved from a quickly spreading epidemic into a global pandemic that is infecting millions of people worldwide (7). Over the course of Over almost two years in the COVID-19 pandemic caused by the Coronavirus (SARS-CoV-2), more than 396 million cases and 5,7 million fatalities have been recorded worldwide (8 February 2022, WHO COVID-19 report). Governments all over the world have imposed rigorous lockdown procedures and travel restrictions as a result of the virus’s high rate of spread. The unprecedented effects of COVID-19 on public health systems, economies, and daily life underline the urgent need for successful containment tactics and vaccine development. Clinical manifestations of the illness range from asymptomatic individuals to those with a life-threatening hyperinflammatory syndrome (hypercytokinemia) connected to pneumonia, acute respiratory distress syndrome (ARDS), and excessive cytokine release (hypercytokinemia) [8]. The asymptomatic individuals may not show any signs or symptoms of the illness, making it difficult to detect and control the spread of the disease. On the other hand, patients with life-threatening hyperinflammatory syndrome experience severe respiratory complications and [8]. Our mortality rate for patients hospitalized in the intensive care unit was 19.6%. Studies conducted worldwide on COVID-19 critically ill patients display a notable variation in mortality rate, from 16% to 78% (9-16). These variations in mortality rates can be attributed to several factors such as differences in healthcare systems, patient demographics, and treatment protocols. It is crucial to further investigate these factors to better understand and improve outcomes for critically ill COVID-19 patients.COVID-19 mortality was found to be significantly correlated with some laboratory parameters in some previous studies. Lorente L. et al. Noted a strong relationship between high RDW values and mortality related to COVID-19 infection in their study [17]. In a meta-analysis by Tian W. et al., it was observed that high creatinine levels correlated with higher mortality rates in cases of COVID-19 infection [18]. It was observed in Hazeldine J. et al. review that severe cases of COVID-19 were associated with elevated neutrophil values [19]. We examined the relationship between routine laboratory parameters and mortality in this study. Parallel to the medical literature, high neutrophils, creatinine, and RDW were statistically significantly correlated with mortality. These findings suggest that elevated levels of neutrophils, creatinine, and RDW may serve as potential prognostic markers for predicting mortality risk. Further research is needed to explore the underlying mechanisms behind these associations and to validate their clinical utility in predicting patient outcomes. Neutrophils and leukocytes are known markers of inflammatory events. However, the exact mechanism by which RDW elevation develops in COVID-19 patients is unclear. Previous studies have demonstrated a relationship between elevated RDW and increased inflammatory markers, oxidative stress, and impaired iron metabolism, which may consequently affect RBC [20]. Additionally, studies reporting the potential relationship between RDW and inflammation also support our conclusions [21]. A 2025 observational, retrospective cohort study by Tejas et al. found no significant improvement in mortality rates despite improvements in disease knowledge, treatment protocols, and healthcare system management. Strict social distancing, regular screening, early patient reporting of symptoms, well- established isolation, strict adherence to standard operating procedures (SOPs), and health advisory guidelines reduced ICU occupancy for patients diagnosed with COVID-19 pneumonia alone, freeing up space for complex cases to receive adequate, timely care and treatment during the second wave [22]. In a 2025 multicenter, multinational retrospective observational study by Palmowski et al. the SARS-CoV-2 pandemic led to significant improvements in treatment and vaccination, contributing to a decrease in overall mortality rates associated with COVID-19. It also shows that although public health measures reduce the overall severity of COVID-19, critical illness remains highly lethal [23]. The pathophysiological mechanisms linking these biomarkers to mortality are multifactorial. Neutrophilia reflects an exaggerated inflammatory response and is often associated with cytokine storm and acute lung injury. Elevated serum creatinine indicates renal impairment, a common manifestation of multi-organ dysfunction in severe COVID-19 [24]. The association between RDW and mortality is more complex; RDW elevation may be driven by systemic inflammation, oxidative stress, impaired erythropoiesis, and altered iron metabolism [20, 21]. A 2022 prospective study by Wang et al. further corroborated the prognostic value of RDW in COVID-19, suggesting that it could serve as a cost- effective, widely available marker for risk stratification in ICU settings [25]. In this study, the limited number of patients and the retrospective design contributed to its limitations. During patients’ hospitalization, laboratory changes were not tracked, which constituted another limitation of the study. Due to all the limitations stated, more studies are needed in the field of the current study. These limitations hindered the ability to draw definitive conclusions and generalize the findings to a larger population. Future research should aim to include a larger sample size and employ a prospective design to overcome these limitations and provide more robust evidence in this area of study.

Limitations

The limitation of the study is that COVID-19 patients were included in the study only in a single center, in a small number of patients, and in intensive care patients who received treatment between certain dates, and only laboratory data of the patients were evaluated; clinical symptoms, vital signs and radiological findings were not evaluated.

Conclusion

In this study, it was found that elevated neutrophils, high creatinine, and high RDW were associated with mortality. These findings suggest that monitoring neutrophil levels, creatinine levels, and RDW may serve as indicators for predicting mortality risk. Additionally, this study has implications for clinical practice as it suggests that clinicians should pay attention to these biomarkers in order to identify those at risk of mortality and take preventive measures. Furthermore, further research should be conducted to explore the mechanisms behind these associations and to determine if there are other biomarkers that can be used to predict mortality risk. This could enable clinicians to develop more effective treatments and interventions to reduce mortality risk and improve patient outcomes. Clinicians should also be aware that the findings of this study may not be applicable apply to all patient populations, and further research is needed to explore the generalizability of these findings.

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