Hematological and Biochemical Biomarker changes in Patients with SARS-CoV-2 in Erbil City/Kurdistan Region A thesis Submitted to the council of the College of health technology - Erbil polytechnic University – Erbil as partial fulfilment of the requirements for the Bachelor's degree in Medical laboratory Supervised by 1 Erbil polytechnic University Collage of health technology Medical laboratory 4 th level Proposal research project by 1- Zahra 2- Sima 3- Jwan
Transcript
Hematological and BiochemicalBiomarker changes in Patients with SARS-CoV-2 in Erbil
City/Kurdistan Region
A thesis
Submitted to the council of the College of health technology - Erbil polytechnic University – Erbil as partial fulfilment of the requirements for the Bachelor's degree in Medical laboratory
Supervised by
Dr Sarbaz I. Mohammed
May-2021
1
Erbil polytechnic University
Collage of health technology
Medical laboratory department
4th
level Proposal research project by
1- Zahra
2- Sima
3- Jwan
4-
Acknowledgement by the supervisor
I certify that the research tagged (Some Hematological and BiochemicalParameters changes in Patients with SARS-CoV-2 in Erbil City/Kurdistan region) has taken place under my supervision in the College of health technology and is part of the requirements for obtaining a Bachelor's degree in Science Medical laboratory
Signature:
Name: Dr. Sarbaz Ibrahim Mohammed
Date: / 5 / 2021
Acknowledgement by the head of the department
Based on the recommendations made by the supervisor in the department, filter this research for discussion.
Signature:
Name: Ass. Lecture Mr Ahmad Nawzad
Date: / 5 / 2021
The decision of the discussion committee2
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ACKNOWLEDGEMENTS
Thanks to Allah to ascribe all perfection and majesty for all the boons and
give us strength and health to achieve this project research.
I would love to express our sincere gratitude to our advisor Asst. Prof. Dr
Sarbaz I. Mohammed, for the continuous support of my B. Project research.
Study for his patience, motivation, and immense knowledge. His guidance helped
us during the study and writing of this project research. I could not imagine having
a better advisor and mentor for our B.A. study.
A special thanks to Ass. Lecture Mr Ahmad Nawzad, the Biology
Department head, for his continuous help during this study.
And from the bottom of our heart, a unique feeling of gratitude to my
beloved parents, brothers and sisters whose words of encouragement and all the
support they have provided me over the years were the most excellent gift anyone
has ever given us.
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LIST OF CONTENT
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Sections Subjects Page No.
Declaration ISupervisor's Certification IIDedication IIIAcknowledgements IVList of Contents VList of Tables VISummary VII
1 Introduction 1SARS-CoV-2 cell entry and infectivityDiagnosis
Pathophysiology of organs in COVID-19
Lung, Heart, Central nervous system
Gastrointestinal tract, Liver, Kidney, EyeHaematological and biochemical abnormalities during SARS-CoV-2 infectionComplete blood count (CBC)
ESR
CRP, D-dimer, Vitamin D
LDH, Ferritin
3 Materials and Methods4 Results & Discussion
Biochemical parametersHaematological parameters
5 ConclusionsReferences
Table (1) Shows Biochemical changes in patients with COVID 19 Infection in Erbil city
Table (2a) Shows leucocytes parameters changes in patients with COVID 19 Infection in Erbil city
Table (2b) Shows erythrocyte parameters changes in patients with COVID 19 Infection in Erbil city
Table (2c) Shows thrombocytes parameters changes in patients with COVID 19 Infection in Erbil city
List of Tables
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AbstractBackground: The coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus impacts most infected patients' physiological responses.Objective: In present studies attempted to address the changes in hematologic and biochemical biomarkers and their associations with severity and outcomes of COVID-19 in Erbil city.Methods: A cross-sectional study, 60 (30 men and 30 women) patients were included and divided into infected and non-infected groups the cases attended to Zaafaran Laboratory. Correlation between the disease criticality and peripheral blood cell and biochemical markers were analyzed.Results: A significant elevation was observed in Serum ferritin (633.17±49.5), D. dimer (P <001), C-reactive protein (CRP) (36.6187 ± 3.22) and ESR (P <001) in both genders and non-significant change in other biochemical parameters. Anaemia was not observed notably, but the increase in leukocyte count and a decrease in lymphocyte percentage were frequent.Conclusions: Hematologic and biochemical impairment showed a significantly different profile between infected patients and non-infected with COVID-19.
Keywords: COVID-19, Serum ferritin, D. dimer and CRP
Introduction
Since December 2019, coronavirus 2 (SARS-CoV-2) cause severe acute respiratory syndromes, which is responsible for the coronavirus disease 2019 (COVID-19) outbreak, has published throughout the world Wuhan, China. [1]. According to the WHO, confirmed COVID-19 patients exceeded 46 million, with over 1.2 million deaths worldwide [2]. Symptoms develop within 2–14 days; patients initially manifest symptoms including fatigue, dry cough, fever, shortness of breathing, and some less frequent symptoms, such as diarrhoea and vomiting. Although most people with COVID-19 exhibit mild to moderate symptoms, the disease can lead to severe problem. This disease more than in older adults and people with preexisting
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chronic medical conditions, such as cardiovascular disease, diabetes and cancer but in children less severe. [3].
Coronaviruses (CoVs) are a large viruses group belonging to the Coronaviridae family, presenting a single-stranded RNA genome [4]. The genome is surrounded by a helical capsid and a lipoprotein envelope containing several spicules of glycoprotein that together give the virus a crown appearance. Hence comes the word "corona", which, in Latin, means crown [5].
When infecting humans, CoVs can cause varying severity, from upper respiratory tract infections similar to the common cold to the liver, enteric, neurological disorders and lower respiratory tract infections such as pneumonia, bronchitis and severe acute respiratory syndrome (SARS) [6]. The International Virus Taxonomy Committee renamed 2019-nCoV as SARS-CoV-2 [7]. SARS-CoV-2 was quickly transmitted among humans, spreading to different countries worldwide, threatening human life and generating many financial losses [8].
On 11 February 2020, WHO announced the name for the epidemic disease caused by SARS-CoV-2: coronavirus disease 2019 (COVID‐19) and declared a pandemic state on 11 March 2020. SARS-CoV-2 diffusion occurs by inhalation and ingestion of viral droplets. The primary sources of human infection are contacted with any contaminated surfaces (viral droplets can diffuse from one to two meters (m) [9] or respiratory droplets of infected people such as (coughing or physical exposure, sneezing). SARS-CoV-2 infection can also occur by touching the mouth, eyes or nose with hands contaminated with the virus SARS [10].
The SARS-CoV-2 incubation period is more than two weeks, usually ranging from three to seven days after infection. In most cases, SARS-CoV-2 infection is asymptomatic, and, in that case, the person will not need medical assistance (more than 80%). However, asymptomatic patients are an essential source of the spread of CoV2, which can spread the virus to those in contact [11].
In symptomatic cases, symptoms of COVID-19 are non-specific [12], and the clinical presentation is identical to SARS-CoV2 infection. The most commonly reported symptoms are fever, dry cough, dyspnea and fatigue [12, 13]. Non-respiratory symptoms (e.g. diarrhoea, nausea, vomiting, and headache and muscle pain) are usually uncommon [13].
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In these cases, COVID-19 may progress to acute respiratory syndrome, followed by septic shock, refractory metabolic acidosis, coagulation dysfunction, multiple organ failure and, death [10]. Constituting 50% to 75% of deaths [9].
SARS-CoV-2 cell entry and infectivity
The initial step of virion entry to the host cell is facilitated by interactions between the S protein and its receptor. Different coronaviruses take advantage of varying host receptors through other receptor binding domains. ACE2 and dipeptidyl peptidase 4, also known as CD26, serve as the primary SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) receptors. These specific interactions between S protein and its receptor are responsible for host-specific infection and tissue tropism [14, 15].
Accumulating evidence suggests that SARS-CoV-2 also uses ACE2 and no other coronavirus receptors. It is noteworthy that SARS-CoV exploits an alternative receptor, CD 209 L, expressed on type II alveolar cells and lung endothelial cells for cell entry; similarly, CD 209 L is the portal for cell entry and infecting by other enveloped viruses, like the Ebola virus [16]. Notably, computational methods have illustrated a stronger affinity of the SARS-CoV-2 S protein receptor-binding domains to ACE2 than that of SARS-CoV, nearly 10- to 20- fold, suggesting higher pathogenicity and easier human-to-human spread of SARS-CoV-2 [17]. Upon binding to ACE2, the S protein, consisting of S1 and S2 domains, undergoes acid-dependent proteolytic cleavage by TMPRSS2, followed by viral and cellular membrane fusion. For fusion, the S1-containing receptor binding domain is cleaved, and S2, which is a fusion peptide, inserts into the membrane, followed by joining two heptad repeats in S2, which form an antiparallel six-helix bundle. The bundle formation paves the way for the fusion of viral and cellular membranes and the viral genome's eventual release into the cytoplasm [18].
Diagnosis
For COVID-19 laboratory diagnosis, to date (July/2020), tests used are based on the following methods: real-time reverse transcription-polymerase chain reaction [2]. The RT-PCR is the gold standard for SARS-CoV-2 detection, and it is the laboratory test of choice for the diagnosis of symptomatic patients in the acute phase. The diagnosis made by real-time RT-PCR uses the RNA extracted from
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samples of the respiratory tract, such as nasopharyngeal swab/ oropharyngeal, tracheal aspirate, sputum and bronchoalveolar lavage [19].
Hematological and biochemical abnormalities during SARS-CoV-2 infection. The most common hematological findings include lymphocytopenia [20], neutrophilia [21], eosinopenia [22], mild thrombocytopenia [20] and, less frequently, thrombocytosis. The presence of reactive lymphocytes has been reported only occasionally [23]. The leukocyte count may be normal, reduced [20] or increased [24]. According to a meta-analysis [25], leukocytosis, lymphopenia and thrombocytopenia are associated with greater severity and even fatality in COVID-19 cases—main laboratory changes in patients with an unfavourable evolution of SARS-CoV-2 infection.
Pathophysiology of organs in COVID-19
Lung
Schematic of a normal and an injured alveolus, in the normal state, the alveoli facilitate gas exchange and provide a medium for dispersal of surfactant and alveolar macrophages necessary for maintaining alveolar stability and host defences. When injured, e.g. in ARDS, the alveoli loss of epithelial and endothelial barrier integrity and loss of function result in increased permeability and pulmonary oedema. Increased fluid accumulation, together with the presence of pro-inflammatory mediators and activated macrophages, make difficult breathing. ARDS happen in severe cases of COVID-19 with fatal outcomes if not managed properly. ARDS: Acute respiratory distress syndrome COVID-19 and the earlier beta-coronavirus infections SARS and MERS essentially share clinical characteristics [26].
Heart
The coronavirus may directly infect and damage the heart muscle tissue, as is possible with other viral infections, including some flu strains. The heart may be damaged and inflamed indirectly by the body s immune system response to stress cardiomyopathy [27].
Central nervous system
The main target organ in SARS-CoV-2 is widely believed to be the lung; however, patients may show malfunctions in another organ, including the nervous system.
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Many individuals with COVID-19 may experience non-specific neurological symptoms such as dizziness, nausea, vomiting and headache, although laboratory result could determine clinical signs of nervous system involvement. However, based on recent clinical observations, reports of a sudden loss of smell (anosmia) and taste (ageusia) indicate nervous system involvement in SARS-CoV-2 infection [28]. Human and animal studies suggest that the coronavirus enters the CNS through the olfactory bulb. It causes inflammation and demyelination and is most likely behind the temporary loss of smell and taste in SARS-CoV-2 infection [28]. Moreover, severe hypoxia often occurs in COVID-19 patients, which can later lead to nervous system damage. In addition to the lungs and various immune cells, SARS-CoV viral particles and genetic sequences have been found in nerve cells in the brain [29].
Gastrointestinal tract
Digestive symptoms, mainly diarrhoea, With ACE2-positive cells present in the stomach, intestine and colon, the digestive system can be vulnerable to complications from COVID-19. It can also act as a route of entry for SARS-CoV-2. [30].
Liver
ACE2 expression in bile duct cells is much higher compared to hepatocytes. Bile cells are involved in the regeneration of the liver and the immune response, so the cause of liver injury in individuals with COVID-19 may be damage to the cells of the bile duct, but not the cells of the liver [31]. It is not worth that drug-induced liver injury and preexisting chronic infections are potential contributors to abnormalities observed in liver blood tests. Anti-virals medications, antibiotics and steroids, which are widely used to treat SARS-CoV-2 infection, can play a role in liver injury [31].
Kidney
Coronavirus may target kidney cells, and lack of oxygen can cause kidneys function to malfunction; cytokine storms can damage kidney tissue, COVID-19 leads to blood clots that may block the kidneys. [32].
Eye
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The eye symptoms: usually conjunctivitis, inflammations of the eye mucus and epiphora, excessive watering of the eye, without any blurred vision. Most of the patients who show visual signs were among those with more severe symptoms or abnormal blood test result. Viral RNA was detected in a patient's conjunctival sacs within the last few days of having a lower viral load. Although the SARS-CoV-2 in tear sample may represent a potential viral transmission source, usually with increased viral loads in severe eye cases, it appears that it is not an early detection source for COVID-19 [33]. Although ACE2 present in the aqueous humour, its expression in more anterior tissues, such as the conjunctiva or cornea [34]. The first thing to understand is that coronavirus can spread through the eyes just as it spreads through the mouth or nose. When a person with coronavirus coughs, sneezes, or talks, virus particles of the virus can be spray from their mouth or nose onto your face. You will likely inhale these tiny droplets through your mouth or nose. But the droplets can also enter the body through the eyes; they can also become infected by touching eyes after touching something that has the virus on it. [34]
Haematological and biochemical abnormalities during SARS-CoV-2 infection
Around the seventh to the fourteenth day of infection, the disease begins to affect the organs with an increase in the receptor index of SARS-CoV-2 cell the angiotensin-converting enzyme 2 (ACE2) [35], such as the lungs, heart and digestive system, a characteristic features of clinical symptoms and expressive increase in the inflammatory levels of mediators and cytokines [36].
From the data based on complete blood count, it is possible to calculate the ratio between its parameters, the interpretation of which has a unique clinical value. Thus, a low lymphocyte/leukocyte count ratio has already been reported indicating severe disease and fatal outcome [37].
Complete blood count (CBC)
Changes in haematological characteristics in patients with COVID-19 are emerging as essential features of the disease. Studies showed that in the early stages of COVID-19 disease, when patients have no exclusive symptoms, White blood cells (WBC) count and peripheral blood lymphocytes are normal or slightly reduced. At the same time, these indicators may change with the progression of the disease. Neutrophil/lymphocyte and neutrophil/platelet ratio may influence myocardial injury and increased mortality [38]. Therefore, it is essential to monitor
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haematological parameters to experiment with this assessment and predict the progression of COVID-19. COVID-19 may involve many organ systems in its host. Studies suggest that haematological profiles change during SARS-CoV-2 illness. Neutrophils are involved in early anti-viral defense. However, during severe pneumonia, neutrophils become cytotoxic through degranulation and lysis [4]. Studies have suggested that neutrophil recruitment may exacerbate COVID-19 immunopathology.Direct infection in lymphocytes cells, causing their lysis by SARS-CoV-2, as the lymphocytes contain ACE2 receptors on the surface. This disorder may be related to the cytokine "storm" and excessive inflammation, both seen in the developments of COVID-19 pneumonia and maybe secondary hemophagocytic lymphohistiocytosis, leading to organ failure [37, 39].Lymphopenia appears to be one of the most relevant haematological abnormalities in COVID-19, as it has been proposed to be used as a biomarker of the severity of this infection [40]. LDH increased at the starts of COVID-19 but decreased from day 13. Most of the patients who died had diagnostic criteria for diffuse intravascular coagulation (DIC). During the COVID-19 course, changes in hemostasis tests have also been reported, such as prolonged prothrombin activation times and partial thromboplastin times and increased levels of D-dimer. In cases of exacerbation of COVID-19, D-dimer levels are elevated, with the microthrombi formation in peripheral vascular and recurrent coagulation disorders [41].
The review of studies that contained analyses of peripheral blood samples showed that a more significant number of lymphopenic patients had the presence of reactive lymphocytes, of which a subset appeared to be lymphoplasmacytic 2. Thus, the monitoring of these haematological parameters is essential and can assist in the identification of patients who will need care in the intensive care unit, as they presented a deeper lymphopenia, as well as a decrease in haemoglobin, absolute monocyte count and even tend to develop neutrophilia during hospitalizationOther laboratory abnormalities included increased erythrocyte sedimentation rate (ESR), increased levels of lactic dehydrogenase (LDH), C-reactive protein (CRP) and muscle enzymes as well as changes in heart, kidney and liver functions, among others [42].
ESR
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ESR is the erythrocyte sedimentation rate under certain conditions. According to the international standard method, the cause of acceleration is divided into physiological and pathological, which is Westergren's method of determining erythrocyte sedimentation rate (ESR) [43].
ESR appears to become rapid in many COVID-19 infections during hospitalization. Although the routinely used laboratory indicators of inflammation, including erythrocyte sedimentation rate (ESR moderately increased in viral infections, it has been shown that the host inflammatory response to COVID-19 might be widespread, even leading to a cytokine storm that can cause further disease complications and multi-organ impairment. Among laboratory tests used to evaluate the acute-phase reaction reflecting the inflammatory state, ESR is considered the least specific. It is known to be affected by many physiological and pathophysiological conditions, thus narrowing its utility to several specific clinical conditions. Despite that, ESR is still persistently used in routine laboratory patient work-up regardless of the clinical question. Therefore, we aimed to assess the usefulness of ESR in differentiating severe from non-severe COVID-19 cases. [43].
CRP
CRP produced by the liver, the emerging novel coronavirus (2019-nCoV) appears to increase C-reactive protein levels (CRP) significantly due to the inflammatory reaction. Also, associated tissue destruction was seen in the SARS epidemic in 2002. One possible explanation for this phenomenon is the overproduction of inflammatory cytokines. Cytokines fight the pathogen, but when the system becomes overactive, it can damage lung tissue. Cytokines and tissue destruction stimulate CRP production. [44].
D-dimer
The D-dimer, a fibrinolysis product, is a relatively small protein fragment in the blood after the degradation of blood clots by fibrinolysis. The determination of circulating D-dimer concentrations is a sensitive test in clinical practice for diagnosing thrombotic conditions, including pulmonary embolism and DIC [45]. Therefore, elevations in D-dimer levels in COVID-19 patients might help rapidly recognize those that have high disease severity, pulmonary complications, and risk of venous thromboembolism in a prothrombotic state. Thus should aid with risk
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stratification and the early introduction of treatment measures that might reduce COVID- 19 related morbidity and mortality [45].
Vitamin D
Vitamin D deficiency affects immune function. Vitamin D plays a role in immune modulation, which increases innate immunity by secreting anti-viral peptides, which improves mucosal defences. In clinical studies, low levels of vitamin D in the blood have been associated with acute respiratory infections, including pandemic influenza. [46]
Vitamin D appears to play a prominent role in the prevention of respiratory infections1. Recent reports found that the SARS-Cov-2 infection rate is higher in countries with low vitamin D2,3, and prompted further research on this topic4. High rates of vitamin deficiency were found in the nations highly affected by the Covid-19 epidemic, and low vitamin D levels were found in patients with severe Covid-19 cases [46]LDH
Lactate dehydrogenase (LDH) is an enzyme implicated in converting lactate to pyruvate in the cells of most body tissues and increased tissue breakdown. Thus, a high level of LDH in the blood is present in numerous clinical conditions, like hemolysis, cancer, severe infections and sepsis, liver diseases, hematologic malignancies, and many others. Nowadays, there was much evidence suggesting that serum LDH levels serve as a non-specific indicator of cellular death in many diseases [47].
Lactate dehydrogenase increases in the early stage of myocardial infarction as well as in states of hemolysis. It is most active in the liver, striated muscles, heart, kidneys, lungs, brain, and red blood cells (erythrocytes). In the case of cell damage, lactate dehydrogenase is released from inside them, its concentration and activity in the blood increase. High serum LDH activity is an adverse prognostic factor in such patients. LDH is a marker of various inflammatory states, e.g., infections, malignancies, MI, sepsis, or cardio-pulmonary compromise [47]
Ferritin
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Ferritin is a protein that stores iron for metabolism. Iron is not produced by the body but can take from food (animal source and vegetables) animal sources better than vegetables. It is easily absorbed, and ferritin has apoferritin and transferrin.
Apoferrin produced by the liver in intestinal mucus apoferritin absorption of iron from food into the blood and iron not only in the blood should be binding with something like iron-binding with apoferritin equal to ferritin and mainly storage of iron in the liver and another site like bone marrow, spleen, kidney and first site primarily for story iron in the bone marrow and immune system %70 [45]. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients.
Aim of the study
The present studies aim to investigate the relation and impact physiological function of the body's induced by COVID-19 infections.
Materials and Methods
Study design
We conducted a cross-sectional study of all consecutive patients with laboratory-confirmed COVID-19 admitted at the zaafaran laboratory in Erbil city
Patients and follow-up
All patients (25 men and 25 women) with confirmed COVID-19, and ageing 42.02±3.4 and 36.7±3 respectively admitted to zaafaran hospital, and ten healthy individuals served as a control group who didn't infect with COVID-19 before between the 1 November 2020 and 28 March 2021 was followed up until death or discharge from hospital. Patients' demographics, clinical features and laboratory tests results were collected on standardized forms. COVID-19 immunological tests were performed in patients with COVID-19-like symptoms, such as fever, cough, fatigue, shortness of breath, myalgia, arthralgia, sore throat, olfactory dysfunction, taste dysfunction, and headache or those who have contacts with patients with COVID-19. The clinical data of these patients were collected from their medical records at the private laboratory in Erbil city.Blood collection
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Taken 4 ml of venous blood was withdrawn under complete aseptic conditions and divided into 1 ml on EDTA to perform hemoglobin level before transfusion. The other 3 ml was left to clot and centrifuged to separate the serum to perform the cross matching and estimation of some biochemical.
Variables studied
We analyzed CBC parameters (as continuous variables) including: neutrophils’ count (cells/mm3), lymphocytes’ count (cells/mm3), monocytes’ count (cells/mm3), platelets’ count (cells/mm3), mean platelet volume (MPV; fL), red blood cells count (RBC; cells/mm3), haemoglobin concentration (Hb; g/dL), mean red blood cell volume (MCV; fL), MCH, MCHC and red blood cell distribution width (RDW %). Values of all these parameters are recorded for 21 days since symptoms onset. CBC was performed using the fully automated haematology analyzer Sismex XN 1500.
Determination of biochemical parameters
1- Serum Ferritin concentration was determined by using microplate immunofluorescence assay (Ferritin Accu - minividas) product Code: 30411
2- Serum D-dimer concentration was determined by using a microplate enzyme-linked immunoassay (D-dimer Accu-minividas) product Code: 30455-02
5- Serum Vit D concentration was determined by using a microplate enzyme immunoassay (Vit D- Accu-minividas) product Code: 30463
Statistical analysisAll data are expressed as Means ± Standard Error of Means (M ± SEM), statistical analysis of the obtained data was done according to independent samples paired t-test. The statistical analysis was carried out using statistically available software (SPSS version 22), and (p < 0.05) considered as statistically significant.
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Results and discussion
The results of 70 individuals were included in the present study are summarized in table (1, 2a, 2b, and 2c)
1- Biochemical parametersThe comparative biochemical analysis between cases and controls showed significantly elevated Serum ferritin (633.17±49.5 and 255.3±76.89), D.dimer (5.851±25.67 and 361.6±29.70), C-reactive protein (CRP) (36.6187 ± 3.22 and 27.37±12.84 ) and ESR (34.68±12.50 and 50.74±12.18) in both genders and non-significant change in other parameters. These result in agreement with other findings, [48] who confirmed that the impact of biochemical enzymes on SARS-CoV-2 infection and the severity of the clinical course of COVID-19 and [49] showed that serum D-dimer concentrations in patients with severe COVID-19 are significantly higher when compared to those with non-severe forms or healthy
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subjects. The reasons responsible for the elevated D-dimer levels are only partially explained. It is well known that D-dimer is produced during fibrin breakdown and serve as a marker of fibrinolytic activity. A relationship between pro-inflammatory cytokines and markers of activation of the coagulation cascade, including D-dimer, has been demonstrated in critical patients or patients with sepsis [50]. There is also evidence that the alveolar haemostatic balance is shifted towards a predominance of prothrombotic activity under inflammatory conditions. Also, pro-inflammatory cytokines may be involved in endothelial injury and may activate coagulation and inhibit fibrinolysis in patients with severe sepsis [51]. [52] D-dimer was high for 46.01% of the patients presenting with symptoms. In contrast, for approximately 37%, the diagnostic tests showed a high ferritin level, C-reactive protein and alanine transaminase. Among other parameters, the erythrocyte sedimentation rate was high for 26% of the patients [52].Increased ferritin levels due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients or due to ACE2, the angiotensin-converting enzyme 2 in the liver, in the heart, kidneys and intestines when it reaches iron-bound blood vessels. When iron levels are low, iron stores lead to an elevated level of transferrin and high ferritin [53]. CRP upon infection and macrophages release interleukin, reach the blood and boost ferritin [53]. Elevated serum levels of C-reactive protein (CRP) and ESR, a systemic inflammation marker, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19[54]. The levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and ferritin (FER) in most COVID-19 patients increased in different degrees. The increased degree of severe and critically ill patients was more significant than that of regular patients, with statistical differences [50, 53, 55].
The cytokine storm is an uncontrolled and dysfunctional immune response in the immunopathogenic mechanism of COVID-19 similar to the one in severe influenza; inflammatory cytokines including TNF-α, IL-6, IL-12, and IL-8 are released in a massive amount during the disease progression, causing potential acute respiratory distress syndrome (ARDS) and systemic organ failure.4-6 Evidence shows that the levels of serum ferritin, d-dimer, lactate dehydrogenase, and IL-6 are increased during the worsening of the disease, providing an indication of the risk of mortality. Evidence shows that the levels of serum ferritin, d-dimer,
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lactate dehydrogenase, and IL-6 are increased during the worsening of the disease, providing an indication of the risk of mortality [56].
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Table 1: Shows Biochemical changes in patients with COVID 19 Infection in Erbil city
COVID-19S.
FERRITIN (ng/ml)
D.DIMER (ng/ml) CRP (mg/L) LDH (U/L) Vit. D ESR (mm/h)
The results of haematology were represented in table 2a, b, and c. In present study confirmed that there were mild changes in haematological parameters between patients and uninfected persons. Our result indicates a significant elevation in leukocyte count and a considerable fall in lymphocyte percentage compared with a healthy one. At the same time, other haematological parameter changed but not significantly. The present result is similar to other findings of [52]; total white blood cell count was elevated for around 25% of the symptomatic patients. A low lymphocyte count was found for 3% of the patients, and laboratory test results for 7.43% of the patients reported low platelet count. Almost 50% of the asymptomatic patients were found to have a low level of lymphocytes, and about 10% had a low platelet count [52].
Also, [55] showed that the white blood cell (WBC) count and neutrophil count (NEU) in COVID-19 patients were basically in the normal reference range; however, the median value in the severe and critically ill groups was significantly higher than that in the regular group, and most viruses cause lymphocytosis when they infect humans because lymphocytes are virus-fighting effector cells. The coronavirus family SARS-CoV, MERS-CoV and SARS-CoV-2 all caused lymphocytic depletion in infected patients [55, 57].
The mechanism may be caused by the direct attack of coronavirus on lymphocytes or by immune-mediated apoptosis of lymphocytes; at present, it is not clear why SARS-CoV-2 causes lymphocytopenia in the patient. Limited autopsy and pathologic findings included necrosis of the spleen, lymph nodes and other lymphoid tissues in the infected patient, reducing bone marrow hematopoiesis and lymphocytic infiltration in the alveolar septum. The deceased patient's autopsy report indicated that the number of CD4+and CD8+T cells in the patient's peripheral blood was significantly reduced. Still, they were in the state of overactivation [55, 57].
In addition, we also found that the red blood cell parameters of COVID-19 patients were relatively lower but not significantly compared with the standard reference value; these findings confirmed by [55] most merger mild anaemia; it was more evident in severe and critically ill patients. This phenomenon has not been reported
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before; it is suggested that the infection of SARS-CoV-2 significantly inhibited hematopoiesis in the bone marrow of patients [57].
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Table 2a: Shows leucocytes parameters changes in patients with COVID 19 Infection in Erbil city
The present study concluded that 1- The elevation of some biochemical marker in infected with COVID-19 is a
good indicator for inflammation progress. 2- Hyperferritinemia3- Observation lymphocytopenia and granulocytosis among patients4- Anaemia was not observed notably
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