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Research Article | Volume 3 Issue 2 (July-Dec, 2023) | Pages 1 - 4
A study of sequential absolute eosinophil count as a prognostic factor of critically ill patients with COVID-19 disease in the ICU.
 ,
 ,
1
MD, OMSB 5th year Resident, Oman
2
MD, Fellow in Neuroanesthesia and Neurocritical Care, UK
3
Senior consultant, Department of Anesthesia and ICU, Khoula Hospital, Muscat, Sultanate of Oman, Oman
Under a Creative Commons license
Open Access
Received
Aug. 3, 2023
Revised
Sept. 9, 2023
Accepted
Oct. 19, 2023
Published
Nov. 3, 2023
Abstract

Eosinophil counts in Covid 19 patients have been followed up as a diagnostic and prognostic indicator for the recovery or death of these patients by various workers. However, controversies still exist. In addition, there is little data to show if Absolute Eosinophil Count (AEC) would start to show a rising trend during patient’s road to recovery. This study hypothesized that AEC values would start to return towards normal as patients recovered from this illness. This study included 43 patients with Covid-19 infection treated in the ICU at Khoula Hospital, Muscat from 10th of May to 5th of August 2020. Seven readings of Absolute Eosinophil Count (AEC1 to AEC7) from the time of admission (AEC1) to discharge or death of patient (AEC7) from the ICU were statistically analyzed using paired ‘t’ test for patients who recovered or those who died. The aim of this study was to identify whether the sequential estimation of AEC with a rising trend can be a prognostic factor of recovery in our Covid 19 patient in Khoula Hospital ICU at Oman as compared to those who died. Our results showed that the values of AEC1 was zero in 38 out of 43 patients with the mean of 0.0190. Comparisons were made between AEC1 with other readings (AEC2 to AEC7) and they demonstrated no definite trend that could be attributed to the changes in treatment modality in patients while in ICU.

Keywords
INTRODUCTION

The coronavirus disease 19 (Covid-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. [1,2].

 

Covid-19 resulted in a universal pandemic and a global public health crisis. The symptoms of the viral infection were heterogeneous, ranging from asymptomatic forms to severe pneumonias needing hospitalization and, in some cases, intensive care unit (ICU) admission, often for life support therapies [3-5].

 

The role of eosinopenia as a marker of sepsis has been evaluated by many workers especially in patients with bacterial sepsis [1]. There has been recent interest in the role of eosinopenia as a diagnostic and prognostic indicator for Covid-19 [6-8]. The role of eosinopenia as a diagnostic indicator and as a prognostic value has been observed and studied during severe Covid-19 ARDS/pneumonia. In some studies, eosinopenia is reported to be associated with worsening of respiratory symptoms [9]. The cause for this eosinopenia in Covid-19 is not exactly clear but it is most likely to be multifactorial like diminutive production, reduced cell release from the bone marrow, increased direct eosinophil apoptosis induced by type 1 interferons (IFNs) released during the acute infection and other causes. [9-11].

 

However, controversies still exist if absolute eosinophil count (AEC) would improve towards a normal value during patient’s road to recovery. Fraissé et al demonstrated that eosinophil recovery seven days after initial eosinopenia was associated with a better outcome [12]. Conversely, the same group led by Fraissé et al. noticed that one-third of their critically ill Covid-19 patients developed an unexpected late-onset and prolonged ICU-acquired eosinophilia which was severe in almost one quarter of them and some required to be treated with anti-microbial agents [12]. A high incidence of eosinopenia has been reported in Covid-19 patients by Djangang and his colleagues [13]. Later in the same year, Yan et al. studied the relation between blood eosinophil levels and Covid-19 mortality and reported that progressively worsening eosinopenia indicates that Covid-19 patients may progress to critical disease and have a significantly higher chance of mortality [3].

 

We hypothesized that AEC would start to rise during the course of recovery from Covid-19 illness and hence could be a potential predictor of our patient’s prognosis as against those who die. To test this hypothesis, we included 43 consecutive patients with documented Covid-19 positivity who were critically ill and admitted to our intensive care unit from 10th May to August 5th 2020.

MATERIALS AND METHODS

This was a retrospective single-center study that included 43 patients with Covid-19 infection who were treated in the ICU at Khoula Hospital, Muscat. Patient’s data for analysis and reporting was collected after permission from the Departmental Management Board. 

 

All 43 patients were admitted to the ICU after meeting the admission criteria: confirmation of positive Covid-19 by (SARS-COV-2) PCR test. In addition, they had more than one other clinical features such as fever; respiratory distress with respiratory rate ≥ 30 beats/min; mean oxygen saturation < 92% while receiving >5 L/min O2; hypotension not responding to initial fluid bolus or requiring vasopressors; arterial blood oxygen partial pressure/oxygen concentration < 300 mmHg; acidosis with a pH <7.3 or PCO2 >50 mmHg; evidence of acute end organ involvement and/or patients with rapidly progressive ARDS.

 

All patients were intubated and ventilated with appropriate mode of mechanical ventilation in the ICU. Appropriate laboratory tests and imaging were done and analyzed as part of patient care. Patient’s treatment modalities were recorded in our hospital’s e-system. Complete blood cell count was assessed daily or every other day from which we collected the AEC.

 

The treatment modality was left to the discretion of the attending anesthetist/intensivist and it included the use of antiviral, antibiotic and steroids. If the treating intensivist decided to start corticosteroids, methylprednisolone 40 mg every 12 hour for 5-7 days was administered. However, few patients received dexamethasone instead of methylprednisolone. There was only one patient who received none.

 

Few patients received plasma therapy from their parent admitting hospital before being shifted to our ICU, but none of the patients had received plasma therapy while in our institution. 

 

The endpoint of this study was either discontinuation of ventilatory support and discharge of the patient to the ward/ referring institution or death of the patient while still on ventilatory support.

 

Since the duration of patient’s ventilatory and ICU management ranged from 5 days to 10 weeks, we have presented AEC in Table-2 as follows: AEC1 value on the first day of ICU admission, thereafter two initial readings on alternate day (AEC2 and AEC3), a middle reading of stay in ICU (AEC4), two readings just prior to tracheal extubation (AEC5 and AEC6) and one reading on the day of discharge to the ward or death (AEC7). 

 

We could assess the progress of AEC only till these patients were discharged from our ICU by analyzing these seven readings as we could not continue to monitor serial AEC of these patients after discharge from our ICU as several were moved to different hospital for further care.

 

Statistical Analysis

Paired ‘t’ test was used for statistical analysis in Table 1, 2 and 3 data. P< 0.05 has been taken as statistically significant finding for this study. Analyses were performed using SPSS 22.0 statistical package (SPSS, Inc., Chicago, IL, USA).

RESULTS

Table 1 shows that the mean age of the patients was 53.79 yr and it showed insignificant difference between those who recovered or died. In this study, males showed a preponderance over female patients. The incidence of successful discharge of the patients from the ICU was nearly identical among male and female patients.

 

The mean AEC1 presented different values when compared to AEC2 to AEC7 as the number of sample readings that were available (AEC2-AEC7) differed in some patients due to their death or uncollected samples. Hence, the values differed in each pair as evident from Table 2.

 

The mean AEC1 presented different values when compared to AEC2 to AEC7 due to uncollected samples on some days of admission or patients’ death which resulted in different “n” values on each day. 

 

Table 3 shows that majority of patients who underwent ICU management at our hospital were successfully resuscitated and discharged (p-value = 0.979). It can also be seen that patients who recovered had a longer stay in the ICU as compared to those who died. 

 

Table 1: Demographic Data of Covid-19 Patients in ICU at Khoula Hospital

Mean age of all 43 patients (yr) 

 

Mean ± SD

Sex ratio of all 43 patients Numbers (%) 

 

M (%) : F (%)

Mean age of patients who recovered in ICU (Yr) Mean ± SD

Mean age of patients who died while in ICU (Yr) 

Mean ± SD

Number of male patients discharged from ICU: 

No. %

Number of female patients discharged from ICU: 

No. %

53.79 ± 15.68

34(79.1) 9(20.9)

54.0 ± 14.02

53.25 ± 20.0

24/34 70.6

7/9 77.7

± SD = Standard Deviation, Yr= year, No.= Number of patients

 

Table 2: AEC of all Patients who were Admitted to the ICU according to their Recovery or Death in the ICU

Parameters

All patients

Discharged

Died

Pair

n

Mean ±-SD

p-value

n

Mean ±-SD

p-Value

n

Mean ±-SD

p-Value

AEC1

39

0.0190+/-0.0787

0.206

24

0.0258+/-0.09806

0.18

15

0.0080+/-0.02833

0.854

AEC2

0.0113+/-0.0565

0.0154+/-0.07138

0.0047+/-0.01552

AEC1

37

0.0200+/-0.0807

0.72

22

0.0282+/-0.10229

0.461

15

0.0080+/-0.02833

0.228

AEC3

0.0168+/-0.05207

0.0136+/-0.05323

0.0213+/-0.05181

AEC1

41

0.0200+/-0.07736

0.006

27

0.0259+/-0.09312

0.155

14

0.0086+/-0.02931

0.008

AEC4

0.1093+/-0.28769

0.0674+/-0.20559

0.1900+/-0.39935

AEC1

29

0.0255+/-0.09073

<0.001

18

0.0344+/-0.11268

0.011

11

0.0109+/-0.03300

0.005

AEC5

0.2928+/-0.55568

0.1378+/-0.17400

0.5464+/-0.83614

AEC1

33

0.0244+/-0.08529

<0.001

20

0.0310+/-0.10711

0.01

13

0.0092+/-0.03040

0.002

AEC6

0.2027+/-0.32668

0.1355+/-0.16794

0.3062+/-0.46990

AEC1

41

0.0180+/-0.07682

<0.001

26

0.0238+/-0.09432

0

15

0.0080+/-0.02833

0.002

AEC7

0.1280+/-0.17634

0.1227+/-0.12619

0.1373+/-0.24549

AEC = Absolute Eosinophil Count, ± SD = Standard Deviation. *P-Values are for paired comparisons of baseline AEC on day 1 with subsequent values

 

Table 3: Final Outcome of the 43 Covid-19 Patients

Patients Group  No. of patients (%)Days in ICU Mean (±-SD) 
Recovered and discharged from ICU 27 (62.8%)17.58 (11.37)
Died in ICU16 (37.2% )12.67 (5.61)
DISCUSSION

Severe acute respiratory syndrome coronavirus 2 has caused corona virus disease that has resulted in high mortality worldwide. Following the onset of Covid-19 infection, several diagnostic modalities have been evaluated. These included inflammatory markers such as CRP, D-dimer, procalcitonin, neutrophil count and lymphocyte levels besides several others [5].

 

To this list has been added the role of eosinophil as a diagnostic and prognostic criterion of Covid-19 infection [3,6,13]. However, there have been studies on eosinophil count in patients with Covid-19 infection that have not been able to show any correlation between eosinophil counts and progression of the disease [14 - 17]. Hence, suggestions have been made to carry on more studies and the role played by eosinophil counts in relation to this infection. This study was done to address this issue in patients admitted to our hospital. In this study, we did not find any correlation between the eosinophil counts and the progression of the Covid-19 infection while the patients were admitted in our ICU. This may be attributed to the technical drawbacks in measuring eosinophils in whole blood giving it a questionable status. This may also be secondary to several treatment modalities that were given to these patients and have influence over eosinophil level (glucorticosteroid induced eosinopenia) [18].

 

The mean age of the patients with Covid-19 infection in our ICU was 53.79 ± 15.79. In addition, we did not find any difference in mean age of patients who recovered or died during the admission period. This shows that age may not play an important role in the recovery or death of patient with Covid-19 infection. The mean age of patients in Yan et al series was 59.5 years [3] which is nearly identical to our study. However, they did not specify any difference in age between patients who survived or died during their study period.

 

In this study the number of male patients outnumbered the females (34 males and 9 females). However, we did not find any correlation in the recovery or death of the patients in relation to sex. Similar data is not available for comparison from other studies. 

 

Limitations of the Present Study

There are several limitations to this study that include: 1) single center study. 2) retrospective study. 3) relatively small sample size. 4) laboratory analytical methodology for analysis of whole blood may be questionable and 5) no follow up in the post discharge period.

 

In conclusion, although several studies have demonstrated correlation in the eosinophil value for diagnostic and prognostic purposes, but the present study fails to establish any cause-and-effect relationship. A larger, prospective, multi-centered may be more conclusive in establishment of the role of rising eosinophil values in recovery period.

REFERENCE
  1. Li, Q. et al. “Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study.” EClinicalMedicinevol. 23, 2020, p. 100375.

  2. Sun, Y. et al. “Characteristics and prognostic factors of disease severity in patients with COVID-19: the Beijing experience.” Journal of Autoimmunity vol. 112, 2020, pp. 102473.

  3. Yan, B. et al. “Relationship between blood eosinophil levels and COVID-19 mortality.” World Allergy Organization Journal vol. 14, 2021, p. 100521.

  4. Richardson, S. et al. “Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.” Journal of the American Medical Association vol. 323, 2020, pp. 2052–2059.

  5. Huang, C. et al. “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.” The Lancet vol. 395, 2020, pp. 497–506.

  6. Soni, M. “Evaluation of eosinopenia as a diagnostic and prognostic indicator in COVID-19 infection.” International Journal of Laboratory Hematology vol. 43, no. Suppl 1, 2021, pp. 137–141.

  7. Xia, Z. “Eosinopenia as an early diagnostic marker of COVID-19 at the time of the epidemic.” EClinicalMedicine vol. 23, 2020, p. 100398.

  8. Zhao, L. et al. “Eosinopenia is associated with greater severity in patients with coronavirus disease 2019.” Allergy vol. 76, 2021, pp. 562–564.

  9. Lindsley, A.W. et al. “Eosinophil responses during COVID-19 infections and coronavirus vaccination.” Journal of Allergy and Clinical Immunology vol. 146, 2020, pp. 1–7.

  10. Bass, D.A. “Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophil dynamics during acute inflammation.” Journal of Clinical Investigation vol. 56, 1975, pp. 870–879.

  11. Hassani, M. et al. “Differentiation and activation of eosinophils in the human bone marrow during experimental human endotoxemia.” Journal of Leukocyte Biology vol. 108, no. 5, 2020, pp. 1665–1671.

  12. Fraissé, M. et al. “Eosinophilia in critically ill COVID-19 patients: a French monocenter retrospective study.” Critical Care vol. 24, 2020, p. 635.

  13. Djangang, N.N. et al. “Eosinopenia in COVID-19 patients: a retrospective analysis.” Microorganisms vol. 8, 2020, pp. 1929–1941.

  14. Lippi, G. and Henry, B.M. “Eosinophil count in severe coronavirus disease 2019.” QJM: An International Journal of Medicine vol. 113, 2020, pp. 511–512.

  15. Qian, G.Q. et al. “Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series.” QJM: An International Journal of Medicine vol. 113, 2020, pp. 474–481.

  16. Zhang, J.J. et al. “Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China.” Allergy vol. 75, 2020, pp. 1730–1741.

  17. Wang, Z. et al. “Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China.” Clinical Infectious Diseases vol. 71, 2020, pp. 769–777.

  18. Hong, S.G. et al. “Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration.” Blood vol. 136, 2020, pp. 2667–2678.

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