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ORIGINAL ARTICLE
Year : 2022  |  Volume : 21  |  Issue : 3  |  Page : 278-282  

A study to evaluate the role of eosinophil count as a prognostic marker for assessing the outcome in patients with COVID-19 infection


Department of Medicine, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India

Date of Submission04-Jun-2021
Date of Decision04-Jun-2021
Date of Acceptance01-Sep-2021
Date of Web Publication26-Sep-2022

Correspondence Address:
Vishwanath Krishnamurthy
New BEL Road, M. S. Ramaiah Nagar, MSRIT Post, Bengaluru - 560 054, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aam.aam_41_21

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   Abstract 


Background and Objectives: The triaging of COVID-19 patients is of paramount importance to plan further management. There are several clinical and laboratory parameters that help in categorizing the disease severity, triaging, and prognostication. Little is known about the prognostic significance of eosinopenia in predicting the severity of COVID-19 from large hospital data, especially from low- and middle-income countries. The objective of this study is to evaluate the level of eosinopenia as an early prognostic marker for assessing the outcomes in COVID-19 patients and to assess the superiority of eosinopenia as a prognostic marker for assessing the outcomes in COVID-19 patients compared to lymphopenia and neutrophil-to-lymphocyte ratio (NLR). Methods: The study was carried out in a tertiary care hospital. A retrospective longitudinal approach was adopted wherein the hospital records of COVID-19 patients were analyzed. In our study, two separate groups of patients were included for analysis to describe the association between initial eosinophil counts of the patients and the clinical outcomes. In the first group, the disease severity in terms of clinical and radiological parameters was compared in patients of COVID-19 presenting with and without the presence of initial eosinopenia. Commonly used markers for triage, namely lymphopenia and NLR, were compared with the presence of initial eosinopenia among the patients who progressed to moderate and severe disease. In the second group, an analysis of eosinopenia was made among the patients who succumbed to the illness. Results: It was seen that 29.6% of patients with eosinopenia had moderate and severe disease compared to those without eosinopenia where only 10.8% had moderate disease, none had severe disease. It was seen that 19.7% of patients with eosinopenia but no lymphopenia had more severe disease compared to patients with lymphopenia but no eosinopenia where 10.8% of the patients had moderate disease, none had severe disease. In patients younger than 60 years who died of COVID-19, it was found that initial eosinopenia was found in 86%, whereas a high NLR >17 was seen in only 25.6% of patients who died, thus implying that is eosinopenia is an important marker of disease severity in COVID-19. Conclusions: Eosinopenia is an important parameter in the evaluation of COVID-19 and the presence of it should alert the clinicians regarding the further progression of the disease. It is not only an important marker but also an early marker for severe disease.

Keywords: COVID-19, eosinopenia, lymphopenia, marker, neutrophil-to-lymphocyte ratio, triage


How to cite this article:
Krishnamurthy V, Sujatha K J, Kumar T A, Phaniraj P, Shankar T, Raj MP. A study to evaluate the role of eosinophil count as a prognostic marker for assessing the outcome in patients with COVID-19 infection. Ann Afr Med 2022;21:278-82

How to cite this URL:
Krishnamurthy V, Sujatha K J, Kumar T A, Phaniraj P, Shankar T, Raj MP. A study to evaluate the role of eosinophil count as a prognostic marker for assessing the outcome in patients with COVID-19 infection. Ann Afr Med [serial online] 2022 [cited 2023 Feb 6];21:278-82. Available from: https://www.annalsafrmed.org/text.asp?2022/21/3/278/356828




   Introduction Top


Eosinophils account for 1%–3% of the circulating leukocytes. They play an important role in immunopathology of many diseases such as asthma and atopy.[1] In addition to being pro-inflammatory, they demonstrate antiviral properties and reduce inflammation and are known to play a key role in viral infections.[2],[3] Eosinopenia is associated with various conditions of acute inflammation, including during sepsis, and multiple studies have consistently shown that low eosinophil levels correlate with poor outcomes in critically ill patients.[4],[5],[6] The presence of eosinopenia has been reported in patients with COVID-19. The pathophysiology of eosinopenia in COVID-19 remains unclear, but it may be multifactorial. Mechanisms may include inhibition of eosinophil egress from the bone marrow, blockade of eosinophilopoiesis, reduced expression of chemokine receptors/adhesion factors, and/or direct eosinophil apoptosis induced by type 1 interferons released during the acute infection.[7] The importance of eosinophil response in COVID-19 also can be understood from the fact that bronchial asthma has not yet been identified as a major risk factor for the severity of SARS-CoV-1 infections though, at the beginning of pandemic, they were thought to be highly vulnerable group.[8] There are studies that have used eosinopenia as a marker adding to specificity in the diagnosis of COVID-19 in a fever clinic compared to a non-COVID illness,[9],[10],[11] whereas the literature is scanty regarding the prognostic significance of eosinopenia in predicting the severity of COVID-19 from large hospital data focusing on triage of patients, especially from the low- and middle-income countries (LMIC).[12] In the management of COVID-19, initial triaging of the patients is of paramount importance to plan the next line of management. Along with the clinical features, there are several laboratory parameters to address this issue. The commonly used laboratory parameters include neutrophil-to-lymphocyte ratio (NLR),[13],[14] C-reactive protein (CRP),[15] lymphopenia, and coagulation profile.[16] They help us in prognostication and assessing the severity of the disease. Routinely eosinophil counts are not looked into during the triage. The objective of this study is to evaluate the level of eosinopenia as an early prognostic marker for assessing the outcomes in COVID-19 patients and to assess the superiority of eosinopenia as a prognostic marker for assessing the outcomes in COVID-19 patients compared to lymphopenia and NLR.


   Materials and Methods Top


The study was conducted at a tertiary care hospital, wherein an exclusive block was dedicated for the treatment of COVID-19 patients, and has been in operation since June 2020. Being a multispecialty referral center with state-of-the-art facilities and intensive care units, the hospital caters to a large number of patients across different sections of the society. At the time of presentation, all patients undergo a thorough triaging and risk stratification based on clinical examination and relevant investigations to determine the severity of the disease which guides the further management according to a standard institutionalized treatment protocol. The institution maintains a database of all admitted patients.

The study adopted a case–control and retrospective longitudinal approach. All patients aged 18–70 years with a confirmed diagnosis of COVID-19 as evidenced by positive nasopharyngeal/oropharyngeal swab by reverse transcription–polymerase chain reaction done in an authorized laboratory were included in the study. Patients with known malignancy, Cushing's syndrome, anaphylaxis, skin allergy, and chronic obstructive pulmonary disease and patients who were on steroids or ivermectin before hospitalization were excluded from the study, as these conditions can independently alter the eosinophil counts. The duration of the study was 3 months from July 2020 to September 2020. The medical records of patients with COVID-19 infection admitted to the hospital during this period were collected and analyzed. Patients fulfilling the inclusion criteria were enrolled in the study. Information relating to each patient from the time of admission to discharge was extracted into a predesigned and a pretested pro forma. The information consisted of sociodemographic profile, clinical features, laboratory and radiological findings, severity of the disease, and the details of the treatment offered. The laboratory parameters included CRP, complete blood counts (CBC), and peripheral smear. The absolute eosinophil count (AEC) and NLR were calculated from the CBC and confirmed by the peripheral smear. Normal AEC was defined as a count of 100–400 cells/mm3. Eosinopenia was defined as an AEC <100 cells/mm3[11] and was confirmed by the peripheral smear examination. The patients with eosinopenia were further subdivided into three quartiles of AEC (AEC 0, 1–50, 51–100) for subgroup analysis. The NLR was calculated by diving the absolute number of neutrophils by the absolute number of the lymphocytes and an NLR of <3.2 was categorized as mild, >3.2 as moderate, and 17 as severe COVID-19 as per the institutional protocol.[13],[14] The outcome of the patient was recorded in terms of severity of the disease. Patients were categorized into mild, moderate, and severe disease as per the government's national guidelines.[17] The association between initial eosinophil count of the patient and outcome measured based on the highest severity of the disease for which the patient was diagnosed and treated was analyzed. The computed tomography (CT) scan of the chest was done as indicated as per the institutional protocol. The chest CT-severity score (CT-SS) was defined as the sum of the individual scores in the 20 lung segment regions, which range from 0 to 40 points.[18] Consecutive patients fulfilling the inclusion criteria were enrolled in the study and derived from two groups as described below:

Group 1

The first group consisted of two pools of COVID-positive patients who were categorized based on the presence or absence of eosinopenia. This group consisted of 175 patients. Sample size of the population in this group was estimated based on a study carried out by Zhao et al.[10] The findings of this study revealed that a greater proportion of eosinopenia patients were categorized into a severe condition (66.7%) as compared to patients with normal eosinophils (27.3%) at admission. Based on the above findings of the study with a power of 99% and an alpha error of 1%, it was estimated that a minimum of 71 cases of eosinopenia and another 71 cases of normal eosinophil counts were needed to be recruited for the study. In the present study, we recruited a total of 175 cases comprising 101 and 74 cases with and without eosinopenia respectively. A pool of patients with normal eosinophil counts were matched based on age (±5 years), sex, and presence of comorbidities such as diabetes or hypertension with the pool of patients with eosinopenia.

Group 2

The second group of patients were those below the age of 60 years who succumbed to the illness. The main outcome in this group was mortality and consisted of 43 patients. This group excluded patients aged above 60 years as old age in itself is a major risk factor for severe COVID disease and mortality and the study intended to analyze the risk stratification in the patients below 60 years who died during the study period.

Statistical methods: The data were extracted and entered into an Excel sheet. The analysis was carried out using SPSS 2009 PASW statistics for Windows version, 18.0.Chicago. All the quantitative variables such as age and laboratory values were expressed in terms of descriptive statistics such as mean and standard deviation (SD). All the categorical variables such as presence of comorbidities and diagnosis at discharge were expressed in terms of percentages. The differences in mean values between the groups were tested for statistical significance by Student's t-test. The association of categorical variables was tested by Chi-square test of significance or Fisher's exact test as applicable.


   Results Top


The results are described in the two groups of patients with COVID-19 infection.

Group 1

The baseline characteristics of the study population in Group 1 are represented in [Table 1]. A total of 175 COVID-positive cases were included in this group of which 101 (57.7%) cases had eosinopenia and 74 (42.3%) had normal eosinophil count. The mean (SD) age in cases with eosinopenia was 49.2 (16.1) years as compared to 45.7 (16.9) years in those with normal eosinophil count. The differences in the mean ages were not statistically significant (P = 0.171). The two pools of patients were similar with respect to other aspects such as sex and presence of comorbidities such as diabetes and hypertension.
Table 1: Baseline characteristics of patients with COVID-19 infection in Group 1

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We compared the outcome of the patients with and without eosinopenia, the results of which are represented in [Table 2]. It was found that the eosinopenia group had 29.6% of moderate and severe cases compared to patients with normal eosinophil counts where 10.8% of the patients had moderate disease and none had severe disease (P = 0.003). The mean chest CT score in the eosinopenia group was 10.59 compared to a mean of 1.53 in patients with normal eosinophil counts and this difference was statistically significant (P = 0.01), as shown in [Table 3]. Further, we did a subanalysis among the patients in the eosinopenia cluster based on the AEC, as shown in [Table 4]. It was found that moderate and severe cases were more in patients with an AEC count of 0 and a count <50 compared to an of AEC of 50–100. The difference was found to be statistically significant (P = 0.028).
Table 2: Comparison of disease severity of COVID-19 patients with eosinopenia and those with normal eosinophil counts

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Table 3: Comparison of severity of COVID-19 infection based on radiological criteria in patients with eosinopenia and in those with normal eosinophil counts

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Table 4: Absolute eosinophil count subanalysis among COVID-19 patients in the eosinopenia cluster

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In the next step, we analyzed the outcomes in patients having eosinopenia with and without coexisting lymphopenia [Table 5]. They were categorized into patients having eosinopenia plus lymphopenia, eosinopenia alone without lymphopenia, and lymphopenia alone without eosinopenia. It was found that severe cases were more in patients with both eosinopenia plus lymphopenia and also in the subgroup having eosinopenia alone without lymphopenia compared to patients having lymphopenia alone. The difference was found to be statistically significant (P < 0.001).
Table 5: Outcome of three subgroups of COVID-19 patients in Group 1 – those having eosinopenia plus lymphopenia, eosinopenia alone without lymphopenia, and lymphopenia alone without eosinopenia

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Group 2

The second group consisted of 43 patients aged below 60 years who succumbed to the illness. It was found that eosinopenia was seen in 86% of the patients who died, whereas only 25.6% of them had a high NLR >17. There were 16 patients with AEC values of 1–50 and 8 patients had an AEC of 0, further indicating that eosinopenia was associated with poor outcomes, as shown in [Table 6].
Table 6: Lymphopenia, NLR and Eosinopenia in group 3 patients with COVID 19 infection who succumbed to the illness

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   Discussion Top


This study shows the importance of eosinopenia with regard to the severity of disease and mortality associated with COVID-19. In this study, two groups of patients were enrolled for analysis to understand the role of eosinophils in COVID-19 infection. In the first group of patients, two subsets of patients were considered, first set with eosinopenia and second set with normal eosinophil count. It was seen that 29.6% of patients with eosinopenia had moderate and severe disease compared to the second set of patients where only 10.8% of the patients with normal eosinophil count had moderate disease and none had severe disease. This difference which was statistically significant was not only seen in clinical severity but also on radiological criteria such as the chest severity score. The eosinopenia group had a higher mean CT SS of 10.59 compared to the group without eosinopenia where it was 1.53. It was seen that patients with eosinopenia alone but no lymphopenia had more moderate and severe disease (19.7%) compared to patients with lymphopenia alone (10.8%). In patients who had both lymphopenia and eosinopenia, the proportion of patients having moderate and severe disease increased substantially (60%). It was found that patients with 0 eosinophil count had more severe disease (20.8%), thus implying that eosinopenia was an important marker of severity compared to lymphopenia alone. Eosinophil counts are routinely not considered while triaging the patients, whereas NLR, CRP, and lymphopenia are frequently used parameters for triaging the patients. Although there have been innumerable studies on lymphopenia and NLR ratio in COVID-19 patients, the literature on the significance of eosinopenia as a prognostic marker in such patients is scanty to the best of our knowledge, especially from the LMIC. The initial set of observations came from Lippi and Henry who found an association between eosinophil count and COVID-19.[9] The results of our study were similar to Zhao et al. where it was found that after controlling confounding factors, there was a significant association between eosinopenia and COVID-19 severity.[10] A study by Li et al.[12] showed that a combination of eosinopenia and elevated CRP can effectively triage suspected COVID patients.

In the second group of 43 patients aged below 60 years who succumbed to the disease, it was found that initial eosinopenia was found in 86% of the patients, whereas a high NLR >17 was seen in 25.6%. A study done by Du et al. showed that in an analysis of 85 fatal cases of COVID-19, 81% of the patients had AECs below the normal range at the time of admission.[19] In the study by Tanni et al., it was seen that out of 30 patients in the COVID-19 group who had a 0 AEC at presentation, 17 (56.7%) died and among the 17 patients in the COVID-19 group who had a low but detectable eosinophil count at the time of presentation, 4 (23.5%) died.[20]

The main strength of this study is that it is a unique study to the best of our knowledge and one of its first kind from a tertiary care referral center in Southern India, to look into the eosinophil count in patients who progressed from mild to severe disease and also proved that eosinopenia is superior to NLR ratio and lymphopenia, the most commonly used laboratory parameters for triaging and predicting severity. Although these findings were from a single-center experience, they might have implications at a global level during the pandemic. The prognostication using eosinophil count can be done in a quick and cost-effective manner as it is less labor intensive compared to CT scan or other inflammatory blood markers which are expensive and might take a longer time for the reports to be available, which may eventually delay the triaging process. Assessment of eosinopenia with or without lymphopenia requires only a CBC and can quickly help in triaging patients, especially in remote parts of developing/underdeveloped countries. Hence, our study can be generalized to health-care settings in primary health-care centers and rural areas where eosinopenia can be used as a prognostic marker for early referral to a tertiary care center. A limitation of our study is that we have not correlated an improvement in eosinopenia with the recovery of patients with severe COVID infection as our main focus was on initial prognostication. Furthermore, we have considered eosinopenia on admission and initial triaging and did not look into the trend of eosinophil count during the entire course of the illness. The description of treatment modalities, associated coinfections, and complications is beyond the scope of this paper.

Further studies are needed to validate if combining eosinopenia with other parameters, newer and better scores can be evolved which can be used for triaging of COVID-19 patients which can be more sensitive in predicting the set of patients who need rigorous monitoring if at home isolation or may require hospitalization. Thus, eosinopenia can be a simple yet an important laboratory parameter in determining the outcomes of the COVID-19 patients. Currently, there is limited information on whether eosinophils have a protective role during COVID-19 infection. Does this explain the relatively lower mortality in LMICs with higher rates of tropical infections and infestations, are some of the questions which need further research?


   Conclusions Top


Eosinopenia is an important parameter in the evaluation of COVID-19, the presence of which should alert the clinicians regarding the disease severity. It is not only an important marker but also an early marker for severe disease.

Acknowledgments

The authors are grateful to Prof. Dr. N. S. Murthy, Ex-Emeritus Medical Scientist (ICMR), Research Director (M. S. Ramaiah Medical College) for statistical analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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