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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 2  |  Page : 61-66

Haematological parameters in COVID-19 disease: A tertiary care centre experience


Department of Pathology, GCS Medical College; Department of Medicine, GCS Medical College, Hospital and Research Centre, Ahmedabad, Gujarat, India

Date of Submission29-Dec-2021
Date of Decision18-Mar-2022
Date of Acceptance22-Mar-2022
Date of Web Publication26-Apr-2022

Correspondence Address:
Dr. Anupama Ishwer Dayal
B-62, Shakuntal, Near Rajhans Cinema, Nikol Naroda Road, Nikol, Ahmedabad - 382 350, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_125_21

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  Abstract 


Background: The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and was declared as a pandemic by World Health Organization. Various haematological parameters alteration has been documented in SARS-CoV-2 infection. However, there is a need for research to evaluate the pattern of the haematological parameters of COVID-19 patients.
Aims: The main aim of this study was to determine demographic characteristics, to study various haematological parameters and their relation with the outcome of the disease.
Materials and Methods: A total of 150 patients who tested positive for COVID-19 were included in the study. A prospective study was done in the Department of Pathology, GCS Medical College, Hospital and Research Centre, Ahmedabad, for the period of 15 days (01 August 2020–15 August 2020). Patients were categorised according to severity, oxygen (O2) requirement and their the outcome. Haematological parameters and clinical data were obtained. Median values of age and haematological parameters were compared between these groups.
Results: Patients who needed oxygen support had higher median age, absolute neutrophil count and platelet-to-lymphocyte ratio. Patients in the intensive care unit (ICU) had higher age, leucocytosis with absolute lymphopoenia and a high neutrophil-to-lymphocyte ratio. The parameters found to be associated with a poor outcome were higher median age with low haemoglobin, low mean corpuscular volume and absolute lymphopoenia.
Conclusions: Males and older people are more prone to COVID-19 infection. Parameters such as high total leucocyte count, high absolute neutrophil count, low absolute lymphocyte count and high neutrophil-to-lymphocyte ratio may be considered cardinal laboratory findings with prognostic potential for the requirement of O2, ICU admission and poor outcome of COVID-19 disease.

Keywords: Coronavirus disease-2019, infection, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, severe acute respiratory syndrome coronavirus-2


How to cite this article:
Thakkar HP, Dayal AI, Prajapati VB, Suri S. Haematological parameters in COVID-19 disease: A tertiary care centre experience. Curr Med Res Pract 2022;12:61-6

How to cite this URL:
Thakkar HP, Dayal AI, Prajapati VB, Suri S. Haematological parameters in COVID-19 disease: A tertiary care centre experience. Curr Med Res Pract [serial online] 2022 [cited 2022 May 19];12:61-6. Available from: http://www.cmrpjournal.org/text.asp?2022/12/2/61/343932




  Introduction Top


The first outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was reported in China in December 2019 which then swiftly spread globally, with the World Health Organization declaring it as a pandemic on the 11 March 2020. The first case was reported in India on 30 January 2020 and since then it has spread rapidly with more than 40,036,928 cases and 521,071 deaths have been reported.[1] SARS-CoV-2 is approximately 80% similar to SARS-CoV, invades host human cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor.[2] Although it is well documented that coronavirus disease-2019 (COVID-19) is primarily manifested as a respiratory tract infection, emerging data indicates that it should be regarded as a systemic disease involving multiple systems, including the cardiovascular, respiratory, gastrointestinal, neurological, haematopoietic and immune systems.[3],[4],[5] Mortality rates of COVID-19 are lower than SARS and middle east respiratory syndrome (MERS);[6] however, COVID-19 is more infectious and lethal than seasonal flu. Older people and those with comorbidities are at increased risk of death from COVID-19.[7],[8] COVID-19 is a systemic infection with a significant impact on the haematopoietic system and haemostasis. Lymphopoenia may be considered a cardinal laboratory finding, with prognostic potential. In this study, we examined various haematological parameters as prognostic markers to assess the disease progression, severity and outcome in COVID-19 patients.


  Materials and Methods Top


A prospective study was under taken in the Department of Pathology, GCS Medical College, Hospital and Research Centre, Ahmedabad, for the period of 15 days (01 August 2020–15 August 2020). This study was approved by the Ethics Committee of our institute GCSMC/EC/PROJ/APPROVE/2020/159 and registered under Clinical trial registry India CTRI/2020/07/026954. For COVID-19 rapid antigen test or real-time reverse transcription-polymerase chain reaction (RT-PCR) test samples were collected by nasopharyngeal swab. A total of 150 patients who tested positive for COVID-19 by rapid antigen test or real-time RT-PCR were included in the study. Patients who tested positive for coronavirus by either of these methods but not admitted to GCS Medical College Hospital and Research Centre were excluded from the study. At the time of the study, real-time RT-PCR was performed in B. J. Medical College as per ICMR guidelines. Rapid antigen test was performed bedside on patients who presented with fever, respiratory tract illness or a history of close contact with COVID-19-positive patients. Blood samples in properly labelled vacuettes were collected for all patients. Three ml of blood was taken into ethylenediaminetetraacetic acid (EDTA) vacuettes for haematology investigations. EDTA samples were inverted several times to prevent coagulation. Haematological parameters were obtained using the 5 part haematology analyser (SYSMEX XT 2000i) and then peripheral smears were prepared and stained with field's stain. Patients were categorised according to severity, oxygen (O2) requirement and outcome into two groups as patients admitted to intensive care unit (ICU) versus those admitted to wards; requiring O2 support versus patients without O2 support and survivor versus non-survivors. Median values of age and haematological parameters were compared between these groups. All the relevant clinical details were retrieved from patients' file and the health management information system. For continuous variables, median and interquartile range were calculated. Mann–Whitney test was used to assess if the difference between these groups was statistically significant. P < 0.05 was considered to indicate a statistically significant difference.


  Results Top


The median age of COVID-19 patients was 60 years with a male: female ratio of 1.7:1 [Figure 1]. The most common age group affected was 60–69 years, in both males and females [Figure 2].
Figure 1: Gender-wise distribution of COVID-19 patients

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Figure 2: Age-wise distribution of COVID-19 patients

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Lymphopoenia was the most common finding present in 70.6% of patients. Out of total 150 patients , 43.3% had neutrophilia (absolute neutrophil count >7000 cells/μl), 40% had anaemia (<11.5 g/dl) and 28% had leucocytosis (>11,000 cells/μl) [Table 1].
Table 1: Haematological parameters in corona virus disease 2019 patients

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The common symptoms noted in all groups were cough (57.3%), fever (47.3%) and shortness of breath (40%), whereas diarrhoea and weakness were infrequent complaints and seen in 2%–5% of the cases. However, cough with shortness of breath was more common presenting symptom in the ICU group as compared to the non-ICU group [Table 2].
Table 2: Clinical symptoms among intensive care unit and non-intensive care unit group

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Patients requiring O2 support had higher median age, higher absolute neutrophil count and higher platelet-to-lymphocyte ratio than the patients who did not require O2 support, and the difference was statistically significant for all three parameters (P < 0.05). Median values of absolute lymphocyte count were lower, whereas total leucocyte count and neutrophil-to-lymphocyte ratio were higher in patients requiring oxygen support though not statistically significant. Other parameters such as haemoglobin, mean corpuscular volume, absolute monocyte count, absolute oeosinophil count, platelet count and mean platelet volume were almost in a similar range in these both groups [Table 3].
Table 3: Comparison of age and various haematological parameters between patients with oxygen support and patient without oxygen support

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On categorisation of patients into ICU and non-ICU groups, patients requiring intensive care had higher median age (P = 0.00038), leucocytosis with absolute lymphopoenia (P = <0.05) and high neutrophil-to-lymphocyte ratio (P = 0.0006). Median Mean corpuscular volume was also found to be lower in this group comparatively [P ≤ 0.00001, [Table 4]].
Table 4: Comparison of age and various haematological parameters between intensive care unit group and non-intensive care unit group patients

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The parameters associated with a poor outcome in patients with COVID-19 were seen in non-survivors which were higher median age with low haemoglobin, low mean corpuscular volume and absolute lymphopoenia (P ≤ 0.05). Median values of total leucocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio were also higher in this group but were not found to be statistically significant [Table 5].
Table 5: Comparison of age and various haematological parameters between survivors and non-survivors

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  Discussion Top


Coronaviruses are large, enveloped, single-stranded RNA viruses found in humans and other mammals, such as dogs, cats, chicken, cattle, pigs and birds. Coronaviruses causes respiratory, gastrointestinal and neurological diseases. Previously pandemics have been reported due to different strains of coronavirus the first being SARS resulting in the 2002–2003 SARS-CoV pandemic.[9] The second was MERS, in 2012.[10] SARS-CoV-2 is the third coronavirus that has caused severe disease in humans to spread globally in the past two decades. Coronaviruses consist of four structural proteins; Spike (S), membrane (M), envelop (E) and nucleocapsid (N).[11] SARS-CoV-2 has a diameter of 60–140 nm and distinctive spikes, ranging from 9 to 12 nm, giving the virions the appearance of a solar corona.[12] Through genetic recombination and variation, coronaviruses can adapt to and infect new hosts.

Comparison of age and gender of coronavirus disease 2019 patients in various studies

In the present study, majority of the patients were within 60–69 years of age. This indicates that though any age group can be affected, the elderly age group is at a higher risk of acquiring the infection. Similar findings were also seen in studies done by Fan et al.,[13] Liu et al.[14] and James et al.[15] Males were more commonly affected than females with a male:female ratio of 1.7:1. Studies done by Fan et al.,[13] Liu et al.,[14] Singh et al.[16] and Guan et al.[17] also indicate the same trend. This may be because males have higher chances of exposure as they are more involved in outdoor work. Age was found to be an important prognostic indicator and elderly patients were more likely to require oxygen support or ICU admission. Furthermore, higher mortality was observed in the older age group. These findings were consistent with the studies done by Fan et al.[13] and Karuna et al.[18] which also suggested more severe disease in the older age group. This could be due to reduction in immune response in older age.

Comparison of haematological parameters among various studies

The most common and consistent haematological derangements observed in COVID-19 patients were leucocytosis with neutrophilia, absolute lymphopoenia and increased neutrophil-to-lymphocyte ratio. On admission, leucocytosis was seen in 28%, lymphopoenia was observed in 70.6% of patients and increased neutrophil-to-lymphocyte ratio (>3.3) was found in 69.3% of patients.

Lymphopoenia was the most consistent and significant finding in patients requiring intensive care, thus establishing their role as prognostic parameters for assessing the severity of the disease. Lymphocytes form one of the important cornerstones of cell-mediated immunity required to overcome viral diseases. Tan et al.[19] postulated four different mechanisms for lymphopoenia. One involving direct destruction of lymphocytes by the SARS-CoV-2 virus through the ACE2 receptors expressed on the surface, other mechanisms involved are direct damage of lymphatic organs such as thymus and spleen or lymphocyte apoptosis induced by inflammatory cytokines like tumour necrosis factor (TNF-α) and interleukin (IL-6). Studies done by Guan et al.[17] Young et al.[20] and Fan et al.[13] also showed that lymphopoenia was observed at admission in these patients.

Another finding observed was that leucocytosis with neutrophilia could be an early indicator for the development of acute respiratory distress syndrome (ARDS) as it was significantly higher in patients requiring oxygen support and also in critically ill patients. COVID-19 is a potentially fatal and highly contagious infection with its potential for a rapid progression to ARDS. This leading to low blood oxygen levels which can be life-threatening because of the body's organs dependence upon adequately oxygenated blood.[21] Hence, O2 support is the mainstay for treatment. Infection by CoV-2 leads to the release of various inflammatory cytokines, among these several cytokines are involved in TH-17 type responses. IL-1b and TNF-α both promote TH-17 responses and vascular permeability and leakage. TH-17 cells themselves produce IL-17, granulocyte macrophage colony stimulating factor, IL-21 and IL-22. IL-17 have broad pro-inflammatory effects on induction of cytokines granulocyte colony-stimulating factor which is responsible for the increased granulopoeisis.[22] Neutrophils and neutrophil extracellular traps are mainly responsible for the necroinflammation in COVID-19. Various studies[13],[23],[24] have shown that neutrophil counts correlate with the development of cytokine storm and high neutrophil-to-lymphocyte ratio leading to ARDS. Neutrophil-to-lymphocyte ratio is an important biomarker for sepsis and it can predict the probability of ICU admission in COVID-19 patients. Increased total leucocyte count and increased neutrophils were found independent predictors of an adverse clinical outcome.[25] Studies done by Terpos et al.,[23] Fan et al.,[13] and Li et al.[24] also suggest that increased total leucocyte count, increased absolute neutrophil count and high neutrophil-to-lymphocyte ratio were associated with severe cases and ICU admission. Therefore, it can be concluded that these parameters can be used as prognostic markers for monitoring of COVID-19 patients. Identification of high neutrophil-to-lymphocyte ratio as a marker for disease progression can guide the development of novel therapeutic strategies targeted at neutrophils, for example, inhibitors of neutrophil recruitment or NET formation which may help reduce the overall disease mortality rate of COVID-19.[26]

Elevated platelet-to-lymphocyte ratio was observed in patients admitted in ward and requiring O2 support which may be an indication of worsening disease. However we could not find any significant association of platelet-to-lymphocyte ratio with the severity or mortality of COVID-19 disease. There are varying reports in literature regarding this parameter with some showing positive association[27],[28] while other studies showing no significant correlations.[29],[30] Platelet-to-lymphocyte ratio is dependent upon factors such as age, gender and also comorbidities like anaemia, diabetes, cardiovascular disease. Hence, a detailed analytical study is required to assess the efficacy of this parameter as a prognostic marker in COVID-19.

In this study, serial measurements were not done, however on categorisation of patients into various groups significantly low haemoglobin values with low mean corpuscular volume were observed in critically ill patients and with mortality. Median haemoglobin values of around 12.0 g/dl were observed in patients who were admitted in wards, but a fall in haemoglobin values was observed in critically ill and in non-survivors. Studies done by Fan et al.,[13] Karuna et al.[18] and Lippi and Mattiuzzi,[31] also showed significantly lower haemoglobin in severe patients. Various inflammatory cytokines such as IL-1, IL-6, TNF-α and interferon gamma have been reported to cause suppression of erythropoiesis.[32] Anaemia observed in critically ill and in non-survivors could be due to the release of these inflammatory cytokines in COVID-19. However, whether low haemoglobin levels led to increased severity of the illness or vice versa could not be clearly established and require studies with dynamic follow-up of various parameters.


  Conclusions Top


In this study, we compared demographic data and routine haematology parameters of various group patients. It was observed that older age and males are more prone to COVID-19 infection. In a highly populous and limited resource country like India, complete blood count is an easily available and inexpensive tool to assess the progress of COVID-19 disease. Parameters such as high total leucocyte count, high absolute neutrophil count, low absolute lymphocyte count and high neutrophil-to-lymphocyte ratio may be considered cardinal laboratory findings with prognostic potential for the requirement of O2, ICU admission and outcome of COVID-19 disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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