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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 59-64

Differential white blood cell count predicting severity and mortality in patients with COVID-19


Department of Pulmonary Medicine, East Point College of Medical Sciences, Bengaluru, Karnataka, India

Date of Submission25-Jan-2021
Date of Acceptance23-May-2021
Date of Web Publication4-Aug-2021

Correspondence Address:
Dr. Sutravey Sesha Sai
Department of Pulmonary Medicine, East Point College of Medical Sciences, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_3_21

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  Abstract 


Background: In coronavirus disease 2019 (COVID-19), the excessive inflammation is known to cause changes in blood parameters including differential white blood count and derived ratios such as neutrophil–lymphocyte ratio (NLR) and lymphocyte–monocyte ratio (LMR). Aim: To compare and analyze the association between differential white blood cell count and COVID-19 disease severity and mortality. Materials and methods: The study was a retrospective, observational study including 508 patients with confirmed COVID-19. Patients were divided into three groups based on severity. The laboratory parameters of all patients were collected and analyzed. Results: Among 508 patients, 75.6% were in mild, 9.1% were in moderate, and 15.4% were in severe categories. About 5.5% of the patients died during the treatment. The mean age of patients who got discharged was 42.47 ± 17.32 years and mean age of those who have died was 66.46 ± 14.37 years (P<0.001). When compared between all three groups and, between discharged and deceased, there were significant differences in mean neutrophils, lymphocytes, monocytes, NLR, and LMR (P<0.001). Neutrophilia, lymphopenia, and monocytopenia were associated with severe disease and increased mortality. Basophil count had no association with severity and mortality. A receiver operating characteristic curve of NLR for severe patients (area under the curve [AUC]: 0.951) and for deceased patients (AUC: 0.952) showed the ratio is significantly accurate in predicting severity and mortality, while that of LMR showed inverse association with severity and mortality. Conclusion: In patients with COVID-19, advanced age, neutrophilia, lymphopenia, and monocytopenia are associated with increased severity and mortality. High NLR and low LMR can be used as a marker for predicting the severity of the disease and mortality.

Keywords: Coronavirus disease 2019, differential white blood cell count, hematological parameters, mortality, severity


How to cite this article:
Sesha Sai S, Vishwa Vijeth K, Hemalatha A. Differential white blood cell count predicting severity and mortality in patients with COVID-19. J Assoc Chest Physicians 2021;9:59-64

How to cite this URL:
Sesha Sai S, Vishwa Vijeth K, Hemalatha A. Differential white blood cell count predicting severity and mortality in patients with COVID-19. J Assoc Chest Physicians [serial online] 2021 [cited 2021 Dec 1];9:59-64. Available from: https://www.jacpjournal.org/text.asp?2021/9/2/59/323089




  Introduction Top


The coronavirus disease 2019 (COVID-19) is a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1] virus that originated in Wuhan, China affecting 9,68,77,399 people and causing 20,98,879 deaths globally until the time of writing this article.[2] The disease may range from being asymptomatic to acute respiratory distress syndrome and septic shock, sometimes leading to death.[3] The prognosis of the disease depends on the age and underlying comorbidities.

The reason for severe disease in COVID-19 is assumed to be due to excessive inflammatory response caused by the release of several cytokines, chemokines, and recruitment and degranulation of neutrophils.[4],[5],[6] The inflammation causes alteration of differential white blood cell counts leading to changes in ratios of neutrophil to lymphocyte and lymphocyte to monocyte. Neutrophil–lymphocyte ratio (NLR) is being used as a prognostic predictor in many cancers, infectious diseases, cardiovascular disorders, and sepsis.[7],[8],[9],[10] Lymphocyte–monocyte ratio (LMR) is an inflammatory mediator used to indicate the prognosis of cardiovascular disease, malignancies, autoimmune disease, and chronic infections such as tuberculosis.[11],[12],[13] Even though India has resource-limited health care, it still serves a large population. The difficulties the country’s healthcare system has to face while dealing with the pandemic are different from that of other countries.

This study is aimed to compare and analyze the association between differential white blood cell count and, COVID-19 disease severity and mortality. As differential white blood cell count is economical and easily available even in limited resource health-care facilities, predicting disease severity and mortality will aid the health-care providers for effective stratification of patients and better management.


  Materials and methods Top


This study was a single-center, retrospective, observational study which was carried out at our hospital. Five hundred and eight patients with real-time polymerase chain reaction confirmed SARS-CoV-2 admitted in September 2020 were included in this study. The study was approved by the Institutional Ethics Review Board and the requirement of informed consent was waived by the ethics committee. Based on the Clinical Management Protocol: COVID-19, Ministry of Health and Family Welfare, Government of India, patients were divided into three groups [Table 1]. Group I include asymptomatic patients and with mild disease, Group II includes patients with moderate disease, and Group III includes patients with severe disease. Groups I, II, and III patients were admitted in general ward, high dependency unit, and intensive care unit, respectively.
Table 1 Classification of clinical severity in COVID-19*

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Inclusion criteria

Real-time polymerase chain reaction confirmed patients with SARS-CoV-2 of all ages, were included in this study.

Exclusion criteria

Patients with missing hematology data transfer to other hospitals with unknown outcomes, and patients suffering from immunodeficiency conditions such as HIV and hematologic malignancies were excluded from the study.

Demographic data and history were obtained, and clinical examination was performed on every patient. The blood sample was drawn at the time of admission and sent for differential white blood cell count.

Statistical analysis

Descriptive statistics were expressed in percentages, mean with standard deviation. Shapiro–Wilk test was applied to find normality. Chi-squared test and ANOVA was performed to compare various parameters with disease severity. Independent t test was used to analyse the significance. Receiver operating characteristic (ROC) curve was drawn. Area under the curve (AUC) was calculated. P<0.05 was considered as statistically significant.


  Results Top


All 508 patients were included in this study. The mean age was 43.79 ± 18.01 years. About 338 patients (66.5%) were males and 170 patients (33.5%) were females [Table 2].
Table 2 Characteristics of differential counts and derived ratios in different severity groups of COVID-19

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Group I had 384 (75.6%), group II had 46 (9.1%), and group III had 78 (15.4%) patients. The mean age of patients in group I was 39.89 ± 16.87 years, group II was 50.80 ± 14.31 years, and group III was 58.85 ± 16.28 years (P < 0.001). In mild category, 255 (66.4%) were males and 129 (33.6%) were females. In moderate category, 33 (71.7%) were males and 13 (28.3%) were females. In severe category, 50 (64.1%) were males and 28 (35.9%) were females. The mean hospital stay was 9.89 ± 3.17 days. The mean hospital stay in group I was 9.18 ± 1.47 days, group II was 10.72 ± 3.42 days, and group III was 12.53 ± 6.21 days.

Twenty-eight (5.5%) in-hospital deaths occurred. The mean age of patients who got discharged was 42.47 ± 17.32 years and mean age of those who have died was 66.46 ± 14.37 years (P < 0.001). Out of 28 deaths, 16 (57.1%) were males and 18 (64.2%) were diabetics (P < 0.001) [Table 3].
Table 3 Characteristics of differential counts and derived ratios in discharged and deceased patients with COVID-19

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The mean TLC was 7500 ± 3340 cells/mm[3]. The mean TLC in patients with COVID-19 with mild disease was 6740 ± 2240 cells/mm3, with moderate disease was 7940 ± 3530 cells/mm3, and with severe disease was 10,990 ± 5090 cells/mm[3] (P < 0.001). The mean TLC in patients with COVID-19 who got discharged was 7180 ± 2760 cells/mm[3] and in those who have died was 13,060 ± 6350 cells/mm[3] (P < 0.001). Differential white blood cell counts for neutrophils (mean = 65.48 ± 13.29), lymphocytes (mean = 25.55 ± 11.22), monocytes (mean=7.18 ± 2.97), and eosinophils (mean = 1.53 ± 1.80) between the three groups suggested statistical significance with P < 0.001 for each group. But the basophils (mean = 0.27 ± 0.20) between all groups were found to be having no statistical significance (P = 0.560).

The mean NLR of all patients in the study was 4.76 ± 6.67. The mean NLR for patients in group I was 2.34 ± 2.31, group II was 7.39 ± 4.87, and group III was 15.16 ± 10.49, which was statistically significant. The ratio in deceased patients was 20.12 ± 12.20 which was significant when compared with that of discharged patients. The mean LMR of the study population was 3.90 ± 2.24. The mean LMR for patients in group I was 4.38 ± 2.16, group II was 2.80 ± 1.69, and group III was 2.21 ± 1.84, which was statistically significant. The ratio was 1.73 ± 1.17 in deceased patients which was significant when compared with that of discharged patients.

A ROC curve was drawn which showed NLR (AUC: 0.951) for patients with severe COVID-19 and NLR (AUC: 0.952) for deceased patients which showed that there is significant accuracy in predicting severity and mortality in patients with COVID-19. However, LMR ratio was found to be inversely related to the severity and mortality of the disease [Figure 1] and [Figure 2]; [Table 4] and [Table 5]
Figure 1 ROC curve – NLR and LMR in predicting severity in patients with COVID-19

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Figure 2 ROC curve – NLR and LMR in predicting severity in patients with COVID-19

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Table 4 Area under curve − receiver operating characteristic curves for NLR and LMR predicting severity in patients with COVID-19

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Table 5 Area under curve–receiver operating characteristic curve for NLR and LMR predicting mortality in patients with COVID-19

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  Discussion Top


Our study found that older age was associated with more severe disease and mortality. Other studies have also similar findings that increased age is directly proportional to disease severity.[14],[15],[16] Even though a study by Palaiodimos et al. found that male sex is independently associated with worse outcomes and higher mortality; this finding is not consistent with our study.[17]

In our study, total leukocyte count was significantly elevated in patients with severe disease and deceased patients when compared with patients with mild and moderate disease. Differential basophil count was showing no correlation with disease severity or mortality. Elevated counts of neutrophils (neutrophilia) and decline in lymphocyte count (lymphopenia) were observed. The change in counts of neutrophils and lymphocytes was significant when compared between mild, moderate, and severe coronavirus disease, the significance continued even when discharged patients were compared with the deceased. The above findings were synchronizing with that of many studies.[18],[19],[20],[21],[22],[23]

Neutrophilia and lymphopenia contributed to prominently raised NLR, which accurately predicted the severity of the COVID-19 and also predicted the mortality due to COVID-19. Hence, NLR can be used as a strong independent value for prognosis and also as a predictor of clinical evolution of the disease and mortality in patients with COVID-19. Our finding was consistent with other studies.[15],[16],[18],[19],[20],[21],[22],[23]

There was significant decline in differential monocyte count which was associated with increasing disease severity and mortality. Inverse association of differential monocyte count with disease severity and mortality in this study is similar to findings of studies by Anurag et al. and Pakos et al.[15],[16] But this inverse association is in contrast with many other studies which showed monocystosis.[24],[25],[26],[27]

Low monocyte count along with even more lower lymphocyte count contributed to lower ratio of lymphocytes to monocyte. LMR was inversely associated with increasing disease severity and mortality, thus demonstrating that decline in LMR can be used as predictor of poor prognosis.[25],[28],[29],[30]


  Conclusion Top


In patients with COVID-19, advanced age, neutrophilia, lymphopenia, and monocytopenia are associated with increased severity and mortality. High NLR and low LMR can be used as a marker for predicting the severity of the disease and mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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