key: cord-0710164-wfvou897
authors: Taj, Sadia; kashif, Ambreen; Arzinda Fatima, Syeda; Imran, Sheharbano; Lone, Ayaz; Ahmed, Qasim
title: Role of hematological parameters in the stratification of COVID-19 disease severity
date: 2021-01-08
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2020.12.035
sha: 412fe0bfd7c53f1b1a159aa1d53351ca7171ff01
doc_id: 710164
cord_uid: wfvou897

OBJECTIVE: COVID-19 virus involves respiratory as well as other body systems including cardiovascular, gastrointestinal, neurological, immunological and hematopoietic system. Patient of covid-19 pneumonia presents with wide range of hemostatic abnormalities. These hemostatic abnormalities in COVID-19 are related with disease progression, severity and mortality. The Objective of our study is to evaluate the role of hematological parameters in determination of COVID-19 disease severity. MATERIAL AND METHOD: This was a retrospective study, conducted in Department of Pathology and Department of medicine, FMH college of Medicine and Dentistry from May 2020 to July 2020. Total of 101, confirmed cases of covid-19 disease, both genders between 17 and 75-year age were included. Hematological parameters were compared in mild, moderate, severe and critical disease group. Continuous variables were analyzed by using non parametric, Kruskal Wallis test while categorical variables were analyzed by chi-square test. RESULTS: Out of 101 patients, 20.8%, 51.8%,19.8% and 7.9% were in mild, moderate, severe and critical group respectively. Median (IQR) values of WBCs (p-value 0.004), ANC (p-value 0.002), NLR (p-value 0.001), D-dimer level (p-value 0.001), ferritin (0.0001), LDH (0.0001) were significantly increased in patients with critical disease. Median (IQR) values of APTT (p-value 0.003) and CRP (p- value 0.0001) were suggestively higher in patients with severe disease. Other parameters like Hemoglobin, MCV, HCT, ALC, Platelet count, prothrombin time did not show statistically significant association with severity of disease. CONCLUSION: The study concluded that Leukocytosis, neutrophilia, elevated Neutrophil to lymphocyte ratio, APTT, D-dimer, LDH and serum ferritin and CRP are associated with severity of covid-19 disease.

Covid-19 disease, Neutrophil to Lymphocyte ratio, hematological manifestations.

Coronavirus disease causing severe acute respiratory syndrome has rapidly evolved into a global pandemic effecting more than 1 million individuals worldwide. (1) Although, primarily it was documented as a respiratory tract infection, emerging researches indicate that covid-19 causes an illness which has a wide variety of clinical features, ranging from mild to moderate upper respiratory tract infection to severe systemic disease which involves respiratory as well as other body systems including cardiovascular, gastrointestinal, neurological, immunological and hematopoietic system. (2, 3) Patients with clinical symptoms, progress to pneumonia frequently with radiological evidence of parenchymal disease. Most of the patients 80.9% present with mild disease, 13.8% with severe and 4.7% with critical disease.(4) Patients admitted to intensive care units manifest high plasma levels of proinflammatory cytokines including interleukins and tumor necrosis factor-α , which suggests that individuals with severe disease may be develop cytokine storm effect.(5) Patients may develop acute respiratory distress syndrome immediately after onset of disease, therefore, there is a great need to diagnose COVID-19 and determine disease severity as early as possible.

The association of hematological abnormalities in severe COVID-19 pneumonia is multifactorial. Hematological abnormalities in COVID-19 are related with disease progression, severity and mortality. Lymphopenia, thrombocytopenia, abnormal coagulation profile and sepsis leading to disseminated intravascular coagulation (DIC) is very well documented in patients of COVID-19.(6) Platelet count is a simple and effortlessly available hematological parameter, which is independently associated with disease severity and risk of mortality in the intensive care unit (ICU). (7) Coagulopathies like disseminated intravascular coagulation, sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation have been associated with COVID-19. In this study, we aim to investigate the association of hematological parameters with COVID-19 disease, and to evaluate the role of hematological parameters in stratification of COVID-19 disease severity.

This was a retrospective cross-sectional study, conducted in Department of Pathology and Mild disease was defined as symptoms of fever, sore throat, cough and no sign of pneumonia on X-rays. Moderate disease was defined as fever and respiratory symptoms with radiological imaging of less than 50% lung involvement and oxygen saturation< 93%. Patients with respiratory distress (respiratory rate >30 breath per min, O2 saturation less than 93% and more than 50% lung infiltrate were classified as severe disease while patients with respiratory failure requiring mechanical ventilation, shock or other organ failure were classified as patients having critical disease. Our study demonstrated that Leukocytosis, neutrophilia and increased neutrophil to lymphocyte ratio, which might be due to inflammatory response, have a significant association with the disease severity. Neutrophil to lymphocyte ratio was highest in patients with critical disease. Coagulopathy (14) .

In our study, values of serum ferritin, LDH and CRP were significantly increased in severe and critical patients as compared to mild and moderate patient. In a retrospective cohort study from Wuhan, China, Terpo E et.al, reported that increased ferritin and LDH were risk factors for Acute Respiratory distress syndrome, ICU support and mortality. Higher CRP has also been related to adverse aspects of COVID-19 disease, such as ARDS development, higher troponin-T levels and myocardial injury, and death. (1, 15) Mortality rate in admitted patients was found in 7.9 % patients, which is much more than the overall disease mortality in Pakistan. This mortality rate could be falsely high because it only protrudes the mortality among the admitted patients. Mehra MR et al, reported 5.8% death rate among the total of 8910 patients with covid-19. (16) We observed in our study that most of the patients who expired had likely pulmonary embolism, but unfortunately, we could not investigate them. One of the patients developed refractory thrombotic thrombocytopenic purpura who couldn't survive even after 11 sessions of plasma exchange. Albion N et. al, also documented autoimmune thrombotic thrombocytopenic purpura in a 57-year-old woman of covid-19. (17) Hematological complications of the corona virus disease are associated with bad prognosis.

However, we could not investigate the other hemostatic parameters like fibrinogen, von Willebrand factor antigen and ADAM-TS 13 in our study because of low resources.

Limitation of the study was small sample size, because the covid-19 disease started to settle in Pakistan by end of July so we could not increase the number of patients. However, as the second wave of covid-19 is expected to hit the world, this study can provide a help in disease stratification in resource restraint countries.

The study concluded that Leukocytosis, neutrophilia, elevated Neutrophil to lymphocyte ratio, APTT, D-dimer, LDH and serum ferritin and CRP are significantly increased in patients with severe and critical disease. Hematological and coagulation manifestations are directly related to covid-19 disease and these markers may be utilized as useful prognosticator for early J o u r n a l P r e -p r o o f prediction of disease severity. Thus, appropriate management can be planned for such patients before the patient develops organ failure or shock. 

Hematological findings and complications of COVID-19. American journal of hematology

COVID-19: consider cytokine storm syndromes and immunosuppression

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet

Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia

Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis

Hemostatic laboratory derangements in COVID-19 with a focus on platelet count

Gender differences in patients with COVID-19: Focus on severity and mortality

Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study

The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients

Hematologic parameters in patients with COVID-19 infection

A Systematic Review and Meta-analysis of D-Dimer Levels in Patients Hospitalized with Coronavirus Disease

Coagulopathy in COVID-19

Association of Plasma CRP Level with the Severity of COVID-19

Cardiovascular disease, drug therapy, and mortality in COVID-19

Autoimmune thrombotic thrombocytopenic purpura (TTP) associated with COVID-19

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• Hematological abnormalities in COVID-19 are related with disease progression, severity and mortality.• The hematological and inflammatory biomarkers like Complete Blood Count, coagulation profile, d-dimer, C-Reactive Protein and Ferritin can play a vital role in early prediction of disease severity and can provide a better guide for prompt management of patients.• Leukocytosis, neutrophilia, elevated Neutrophil to lymphocyte ratio, APTT, D-dimer, LDH and serum ferritin and CRP are significantly increased in patients with severe and critical disease.J o u r n a l P r e -p r o o f

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Please specify the contribution of each author to the paper, e.g. study concept or design, data collection, data analysis or interpretation, writing the paper, others, who have contributed in other ways should be listed as contributors.Sadia Taj: conceptualized and planned the study. Ambreen Kashif: was involved in collection and organization of data. Shehar Bano and Ayaz Lone: analyzed the data and helped in literature search. Sadia Taj and Ambreen Kashif: prepared the manuscript. Qasim Ahmed: reviewed and refined the manuscript.J o u r n a l P r e -p r o o f

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