Retrospective Observational Study of Complete Blood Count (CBC) Parameters and ICU Mortality of COVID-19 Disease in Delta Variant and Omicron Variant in a Community-Based Hospital in New York City

Background: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the official name of COVID-19, a respiratory infection that had the first case reported from the Hubei province of China on December 8, 2019. This virus is the main etiological agent behind the most dreaded pandemic of pneumonia that has spread to the entire world in a brief period and continues to pose a threat. The first wave corresponded with the period from February 2020 to June 2020, the Delta variant occurred around the middle of June 2021 and the Omicron wave was reported from December 2021 to February 2022. Objective: This study aims to compare the Delta and the Omicron variants of COVID-19 infection in a community-based hospital in New York City considering the comparison of ICU admissions in both variants. We aim to study the comparison of complete blood count (CBC) parameters and inflammatory markers of patients admitted to ICU stratified by two waves of COVID-19 infection. We aim to analyze the association of CBC parameters at admission and the discharge during ICU stay in both variants. We also aim to study the association of CBC parameters at admission and discharge with ICU mortality in both variants. Methods: We conducted a retrospective observational study based on data from randomly selected hospitalized patients with COVID-19 in a community-based hospital in New York City during the Delta variant and the Omicron wave. A total of 211 patients COVID-19 positive from June to July 2021 (Delta variant) and 148 patients from December to February 2022 (Omicron wave) were included in the study. A comparison was done between the basic characteristics of patients with and without ICU admissions in both variants of COVID-19. We compared the relationship of different parameters of CBC (hemoglobin (Hgb), white blood count (WBC), lymphocytes, neutrophils, and platelets) on ICU admission and further analyzed any changes associated with ICU mortality. Logistic regression was performed to evaluate the relationship of different presenting CBCs on patients’ disposition to ICU. Result: A total of 211 patients (106 female) in the Delta wave (2021 variant) and 148 patients (80 female) in the Omicron wave (2022 variant) with an average ages of 60.9 ±18.10 (Delta variant) and 63.2 ± 19.10 (Omicron variant) were included in this study. There were 45 patients (21.3%) in the Delta wave and 42 patients (28.4%) in the Omicron wave were admitted to ICU. The average length of hospital stay was seven days in the Delta wave and nine days in the Omicron wave. No significant association was found between presenting cell count and ICU admission (p>0.05). Significant associations were found between different cell counts on admission and discharge and death in Delta waves except Hgb and platelets on admission. However, in the Omicron variant, a significant association was found only between WBC on admission and discharge, and Hgb and neutrophil on discharge with death in the univariate model. Conclusion: Comparative study of different clinical parameters between the Delta and the Omicron variants of COVID-19 with the correlation of ICU stay and mortality can be used as a beneficial modality in assessing the outcome of the disease.


Introduction
Wuhan city, the capital of Hubei province in China, became the center of the deadliest outbreak of pneumonia in December 2019. By January 7, 2020, a novel virus was isolated by Chinese scientists from the infected patients and was named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2, previously called 2019-nCoV), later designated as COVID-19 by the WHO [1]. The WHO labeled this disease 1 2 3 1 1 as a pandemic on March 11, 2020 and, since then, the virus has infected more than 101 million individuals and killed over one million persons in the United States [2]. The Centers for Disease Control and Prevention (CDC) has been monitoring all variants and subvariants of the original SARS-CoV-2 virus circulating in the United States. SARS-CoV-2 underwent several mutations since the beginning and the mutants were associated with higher transmissibility, higher mortality, and hospitalization rates, which were named the variants of concern. B.1.617.2, better known as the "Delta" variant, which was initially discovered in India, overtook all other variants in the United States in the late summer/fall of 2021 [3]. The Omicron variant, B.1.1.529, was first detected in Botswana and South Africa and by December 2021, and it spread to the rest of all other continents with San Francisco identifying the first cases in United States [4]. In contrast to the first wave, where knowledge about COVID-19 was limited, the second and third waves saw a better medical response from healthcare systems, owing to a better scientific understanding of the epidemiology as well as the pathophysiology of the disease. The voluminous scientific data that was used to identify mortality risk factors and the efficacy of respiratory support measures have helped in curtailing the morbidity and mortality seen during the different waves of this pandemic [5]. Studies have shown the association of COVID-19 infection and severity with several hematological parameters such as platelets, white blood count (WBC), lymphocytes, neutrophils (together with neutrophil-lymphocyte and platelet-lymphocyte ratio), and hemoglobin (Hgb) [6]. The purpose of our retrospective study was to evaluate the index of ICU admissions in the Delta and the Omicron variants. We aimed to evaluate the association between specific CBC parameters at admission and discharge in both waves and their association with ICU mortality. Our study could be useful in the identification of effective biomarkers of this dreaded progressive disease and might be helpful for diagnosis, prevention of complications, and effective therapy of COVID-19 infection.

Materials And Methods
We conducted a retrospective observational study based on data from randomly selected hospitalized patients with Data were presented as mean and standard deviation for continuous variables and categorical variables, frequencies, and proportions were generated. The mean of continuous variables was compared using independent t-tests or the Wilcoxon rank sum test where applicable. Categorical variables were compared using a chi-square or Fischer exact test. Basics characteristics and laboratory data were compared by the status of ICU admission among two waves of COVID-19 separately. We compared the relationship of different parameters of CBC (Hgb, WBC, lymphocytes, neutrophils, and platelets) on ICU admission and further compared them between two waves of COVID-19. Logistic regression was performed to evaluate the relationship of different presenting CBCs on patients' disposition to ICU. The different blood counts on admission and discharge were also entered into logistic regression models to evaluate the association between these cell counts and death. Both crude and multivariable models (adjusted for age, sex, race, BMI, and co-morbidities (hypertension, diabetes, coronary artery disease (CAD), cancer, end-stage renal disease (ESRD), chronic obstructive pulmonary disease (COPD)/asthma, smoking, and mechanical ventilation status)) were run. Separate regression models were run for each variable of blood as of strong correlation among them. All statistical tests were two-sided with a significant level of 0.05. Statistical analyses were performed using Statistical Software STATA 14.2.  The relationship between different presenting cell counts and ICU admission is presented in Table 1. No significant association was found between presenting cell count and ICU admission (p>0.05). Further, different cell counts were compared among the participants admitted to ICU in two waves and no significant difference was found among these cell lines in two waves as shown in Table 2.  Regression analysis results showed that there was no significant association between different cell counts on admission and patients' disposition to ICU as shown in Table 3. To further explore the influence of cell count on ICU admission we use the normal range of the WBC as the cutoff value but still, no association was found between WBC and ICU admission.  The relationship of different blood cell counts (admission and discharge) and death is presented in Table 4. Significant associations were found between different cell counts on admission and discharge and death in the Delta wave except for Hgb and platelets on admission. However, in the Omicron variant, a significant association was found only between WBC on admission and discharge, and Hgb and neutrophil on discharge with death in the univariate model. The significance of these cell lines still exists after adjusting for covariables. In the adjusted regression model (separate regression analysis for each cell count), a significant association between odds of death and WBC on admission (odds ratio (OR)  The association of different blood counts (at admission and at discharge) and death * Adjusted for age, sex, race, BMI, co-morbidities (hypertension, diabetes, CAD, cancer, ESRD, COPD/asthma, smoking), mean arterial blood pressure on presentation, and mechanical ventilation status.

Delta variant Omicron variant
# Separate regression models were run for each variable as of strong correlation among them.

Discussion
Almost every patient admitted with COVID-19 infection undergoes a routine CBC, which provides crucial information that further affects clinical management during a hospital stay. According to a study done in five different nations throughout the world, CBC is the most widely used initial laboratory test in all patients hospitalized for various indications [7]. There are an increasing number of studies being done to highlight the different clinical characteristics of several variants of COVID-19 infection, and one of them is the prospective longitudinal observational study done by Cristina Menni et al quantifying the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population in Delta and Omicron variant [8]. Important hematological parameters in COVID-19 infection were studied by Regolo et al recently concluding that patients with a high neutrophil/lymphocyte ratio (NLR) at admission were more likely to have disease progression as well as ICU admission and mortality when compared to those with lower/normal NLR [9]. NLR represents a rapid, widely available, and inexpensive tool that could be useful in the management and early risk stratification of patients with COVID-19 [9]. Saurabh et al, in their retrospective analysis done in April-May 2021, studied the hematological parameters including Hgb, platelet count, total leukocyte count (TLC), neutrophils, lymphocytes, NLR, and absolute eosinophil count (AEC) in COVID-19 positive patients within 24 hours of admission concerning both ICU and non-ICU admissions [10]. They found that relative neutrophilia 70% (p-value 0.007), relative lymphopenia 20% (p-value 0.002), and NLR 9.1 (p-value 0.001) were all significantly associated with ICU disposition. However, there was no association between Hgb levels (p-value 0.29) or platelet counts (p-value 0.61) and COVID-19 patients' admission to the ICU in their study. They concluded that routine hematological tests like CBC are quick, cost-effective predictors for patients with severe COVID-19, especially in limited resource settings [10]. In their analysis of 90 COVID-19-positive patients (51 ICU and 39 non-ICU), Pozdnyakova et al, who focused more on the WBC, discovered that all COVID-19 patients had striking quantitative and morphologic WBC changes with a significant positive correlation between disease severity, neutrophilia, and lymphopenia [11]. In our study in an adjusted regression model (separate regression analysis for each cell count), a significant association between odds of death and WBC on admission (OR  [12]. Hypertension, obesity, and diabetes were the most common comorbidities and among patients who were discharged or died, 14.2% were treated in the intensive care unit, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, 21% died [12]. In our study group, 21.3% (delta variant) and 28.4% (omicron variant) of the total patients were admitted to ICU. Among the patients admitted to ICU, 73% had hypertension and 49% diabetes in Delta, while 69% had hypertension and 62% diabetes in Omicron wave. There have been studies showing a comparison of clinical characteristics between the Delta variant and the Omicron variant of SARS-COV-2 infections [13] however not much research has been done comparing the CBC parameters and emphasizing its relevance.
There are several limitations to our study. First, the number of patients were less in the Omicron variant as compared to the Delta variant. Second, the study population only included patients within the New York City area. Third, the data were collected from the electronic health record database precluding the minute details. Fourth, subgroup descriptive statistics were not adjusted for potential confounders.

Conclusions
The average length of hospital stay was seven days in the Delta wave and nine days in the Omicron wave in our hospital-based study. Regression analysis results showed that there was no significant association between different cell counts on admission and patients' disposition to ICU in both variants of COVID-19. Significant associations were found between different cell counts on admission and discharge and death in the Delta wave except for Hgb and platelets on admission. However, in the Omicron variant, a significant association was found only between WBC on admission and discharge and Hgb and neutrophil on discharge with death in the univariate model. More studies need to be conducted in the future to emphasize the importance of the clinical parameters in standardizing the treatment options for COVID-19 variants.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.