key: cord-0950925-8z02t2q1
authors: Shareef, Rawaa Hadi; Zwain, Zinah Dhiaa; Mahbuba, Wadhah Abdulhussian
title: Superiority of lymphocyte ratio over total leukocyte count in detecting the severity of COVID- 19 pneumonia
date: 2021-11-16
journal: Heliyon
DOI: 10.1016/j.heliyon.2021.e08412
sha: 4c1d569824aedda8f84ac1e81a9a0c7ef76a8512
doc_id: 950925
cord_uid: 8z02t2q1

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by a recently discovered coronavirus. Blood test including complete blood count is crucial in diagnosing of several viral and bacterial infection. AIMS: This study aimed to assess the association between lymphocyte ratio and other WBC types and severity of COVID-19 pneumonia. METHODS: The design of this study was a cross-sectional study. A complete blood count and erythrocyte sedimentation rate (ESR) was done for one hundred twenty-six COVID-19 patients (76 males and 50 females; aged 20-70 years). Patients were randomly recruited from multicenter in Al-Najaf Governorate, Iraq. RESULTS: The study had revealed an inverse correlation between severity of COVID-19 infection and both lymphocytes and monocytes ratio even in patients with normal WBC count. Additionally, there was a direct correlation between platelets and leukocyte count. The relation between leukocyte count and ESR level was significant in a patient with elevated WBC only. CONCLUSION: Lymphocytes and monocyte ratios inpatient with COVID-19 infection can be used as predictors for the severity of infection. Increased leukocyte count resulted in increases in platelets inpatient with COVID-19.

Coronaviruses are positive-sense RNA virus, it has a broad range of natural host and they can influence on many systems 1 . In humans, coronavirus can cause many diseases that extend from the common cold to severe respiratory tract infection, such as, severe acute respiratory syndrome (SARS), and middle east respiratory syndrome (MERS) 2 .

At the end of 2019, an outbreak of acute respiratory infection was recorded in Wuhan business city of China. At first, the virus is named as (2019-nCoV) or COVID-19 3 . Then, this virus is named severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) by the International Committee on Taxonomy of Virus (ICTV) 4 .

The SARS-CoV-2 is a member of the order Nidovirales, from the family Coronaviridae and sub-family Orthocoronavirinae. This family can be divided into four kinds:

Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Based on molecular characterization, the SARS-CoV-2 is considered a new Beta coronavirus that originates from bats and belongs to the subgenus Sarbecovirus 5 . The transmission is thought to occur mainly by respiratory droplets and by contact with contaminated surfaces directly.

The period of incubation of COVID-19 is from 3-6 days 6, 7, 8, 9 . The most common symptoms of SARS-CoV-2 are cough, fever, and fatigue, while headache, hemoptysis, and diarrhea are considered less common symptoms 10, 11 . SARS-COV-2 have a noticeable impact on the immune system. It affects the adaptive immune system by stopping the production of antibodies and the T-cell response. Consequently, it results in inflammation 12 . Additionally, affects lymphocyte count and causing lymphopenia. Cytokine storm syndrome (CSS) could be the sequelae if the adaptive immune system did not control the inflammation within 7-10 days. CSS could be defined as abnormal secretion of inflammatory specific markers, for example, IL-1, IL-2, IL-8, IL-12, IL-18, TNF-α, GM-CSF, TNF-γ in addition to IL-6, which has a suppressive effect on the immune system 13 . Patients with CSS have continuing high fever, liver dysfunction and coagulation system disorder 14 .

Hematological parameters and blood biochemical indices as erythrocyte sedimentation rate (ESR), differential WBC count and ratios can give an idea about the severity of COVID-19 disease 15 . Many patients with COVID-19 were found to have either leukocytosis or leukopenia 16 .

This study aims to investigate the relationship between COVID-19 and changes in different blood parameters. 

A cross-sectional study that involved 126 patients (50 females and 76 males, aged between 20-70 years old). All patients had been confirmed COVID-19 by polymerase chain reaction (PCR) for throat and nasal swab. The patients were randomly recruited from multicenter (Al-Hakeem Hospital and Al-Sadder Teaching Hospital) in Al-Najaf governorate, Iraq from July 2020 to September 2020.

From each individual, five mls of venous blood was collected, were placed in two separated tubes. Blood parameters were measured by hematology analyzer (Abbott, USA). The 

Ethical approval for this study was granted from the Al-Hakeem Hospital and Al-Sadder Teaching Hospital in Al-Najaf City (No. 1105A in June 2020). Informed consent was obtained from all individual participants included in the study.

Statistical analysis was performed by using (Prism 7). Using, percentage, mean, standard error, and correlation analysis. The correlation coefficient " " was used to evaluate the strength of the association between two variables. When the P-value was < 0.05 it was considered significant .

Table [1] showed the demographic and baseline characteristics of patients infected with COVID-19. Table [2] showed the distribution of white blood cells among the population study. The figure [1a] showed that there is a significant positive correlation between white blood cells and ESR (ml/hour) only when the count of white blood cells more than 11,000 x10 3 /µL (r= 0.2; P =0.019). Figure [1b] , showed that there is a highly significant negative correlation between lymphocytes and ESR (r= 0.36; P =0.22). In addition, the figure [1c] showed that there is a significant negative correlation between monocytes and ESR (r= 0.19; J o u r n a l P r e -p r o o f P =0.02). In figure [1d] , the white blood cells showed direct proportion with platelet counts x10 3 /µL (r=0.35, p< 0.0001).

After rhinoviruses, infection by coronavirus is considered as the second leading cause of the common cold, this infection is seasonal, but the incidence is elevated in the spring and winter 17 while the other one showed no hemophagocytosis in the liver or bone marrow, but only in the spleen, there is a hemophagocytosis. This anemia could be due to hemophagocytosis 28 .

As a results the lymphocytes ratio in COVID-19 pneumonia can be a better predictor for the severity of infection than WBC count.

In COVID-19 pneumonia, there are an excessive releasing of many inflammatory cytokines and chemokine such as tumor necrosis factor-α, interleukin-1, interleukin-6, and interleukin-8 29 . Macrophage, endothelial cells, and neutrophils are activated by the release of these inflammatory molecules and results in the expression of tissue factors within the lungs, which is resulting in initiation and enhancing the pulmonary coagulopathy and microvascular thrombosis 30 . Interleukin-6 is considered as a key cytokine in severe COVID-19 infection as well as is a key activator of coagulopathy by inducing the expression of tissue factors and increasing production of fibrinogen and platelets 31, 32 . Data revealed that there is a significant positive correlation between WBC and platelet count and this confirm that the more severe infection mean higher platelet count. Interestingly, the monocytes ratio was inversely related to ESR level. Accordingly, the monocytes ratio could be a good indicator of infection severity in those patients. The monocytes cells consider as cells of innate immunity 33 J o u r n a l P r e -p r o o f One limitations in this study is the used of general classification of WBC. However, our monitoring guideline which used routinely in our hospitals rely on CBC, ESR, Interleukin and D-dimer, but not routinely done for patients with COVID. So, we depend on what routinely cheap and easy to be done which is CBC. We believe that, our paper is to get a routine marker that be used in our Iraqi hospitals and in the middle to low income countries.

So, we are implemented that lymphocytes counting can be a good predictor for COVID-19 and our results can confirm that. However, the sub classification of lymphocytes can be done for further evaluation in another study. Another limitations is small sample size. At time of data collection, the total number of confirmed cases of COVID-19 was limited. So, the number of patients that included in our study can be considered sufficient in comparison to the total numbers. Additionally, the statistic that have been used resulted in a significant P value. From the above, we believe the sample size can be considered enough to conclude the finding.

Lymphocytes and monocyte ratios inpatient with COVID-19 infection can be used as predictors for the severity of infection. Increased leukocyte count resulted in increases in platelets inpatient with COVID-19.

The study has many of limitations which are: -Low budget for our health system because our country is part of middle income-countries.

-Outdated health system (health system is an old fashion system in Iraq).

-Absence of large centers of intensive care in Iraq.

-Lack of proper registration and follow up (electronic registration of patient's data not found in Iraq).

-Lack of research teams inside hospital and highly sophisticated investigations.

-Difficulty in accessing and long term follow up to the majority of the patients after discharge from hospital because most of them never return to hospital or going to the private clinic or refuse follow up.

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