Hematological, biochemical, biomarkers alteration association

with Covid-19 disease prognosis and complications.

Review Submitted to Midnapore City

College for the Partial Fulfilment of the
Degree of Bachelor of Medical Laboratory
Technology

Submitted by
Pradip Dinda
Vidyasagar university Reg. No. – 0001433 Of 2018-2019
Roll- 1597766 No.- 180157
Guided by
Dr. Avinandan Ghosh (Phd, MSc. BMLS and M)

Department of Paramedical and Allied Health Science

MIDNAPORE CITY COLLEGE
Kuturiya, P.O.
Bhadutala, Paschim
Medinipur, Pin-721129
West Bengal, India

Year-2021

1
 Certificate

This is to certify that the review report entitled “Hematological, biochemical, biomarkers
alteration association with Covid-19 disease prognosis and complications” submitted by
Pradip Dinda, Roll No.-1597766 180157 to the Midnapore City College, Midnapore, West
Bengal, India during the year of 2021 in partial fulfillment for the award of the degree of BMLT
is a bona fide record of review work carried out by him under my supervision. The contents of
this report, in full or in parts, have not been submitted to any other Institution or University for
the award of any degree.

Guide name and Designation

Dr. Avinandan Ghosh (Phd, MSc. BMLS and M)
Dept. of BMLT

Dr. Sudipta Chakraborty

Principal
MIDNAPORE CITY COLLEGE

Dr. Pradip Ghosh

Director

MIDNAPORE CITY COLLEGE

Date: 13.08.2021
Place: Midnapore City College, Paschim Medinipur

2
 Declaration

I do hereby declare that the present review entitled „” Haematological, biochemical,

biomarkers alteration association with Covid-19 disease prognosis and complications ‟
embodies the original work carried out by me in the Department of Biological Sciences,
Midnapore City College, Paschim Medinipur, West Bengal, India under the supervision of Dr.
Avinandan Ghosh, Assistant professor, Dept. of Paramedical and allied health science,
Midnapore City College, Paschim Medinipur. No part thereof has been submitted for any
degree or diploma in any University.

- Pradip Dinda

Date: 13.08.2021
Place: Midnapore City College, Paschim Medinipur

3
 Acknowledgement

I would first like to acknowledge Dr. Pradip Ghosh, Hon’ble Founder Director, Midnapore
City College, Paschim Medinipur for providing me the opportunity to study and complete my
review work in this college. I am gratefully indebted to him for his very valuable comments
on this thesis.
I would like to thank my review advisor Dr. Avinandan Ghosh of the Dept. of Paramedical
and allied health science at Midnapore City College. The door to Prof. Ghosh office was
always open whenever I ran into a trouble spot or had a question about my writing. He
consistently allowed this paper to be my own work, but steered me in the right the direction
whenever he thought I needed it.
I would also like to thank the other Faculties Dr. Kuntal Ghosh, Dr. Srabani Pradhan, Dr.
Adity Dey, Dr. Santanu Kar Mahapatra, Dr. Suchismita Roy and other non-teaching staffs
for their support to carry out this review work. Without their passionate participation and
input, the validation survey could not have been successfully conducted.
Finally, I must express my very profound gratitude to my parents for providing me with
unfailing support and continuous encouragement throughout my years of study and through
the process of researching and writing this review. This accomplishment would not have been
possible without them.

Thank you.

Author
Pradip Dinda

4
 Table Of Content

Content Page Number

Introduction 6-30
 Symptoms  7-8
 Diagnosis  8-12
 Adverse Effect of Covid-19  13-14
 Prevalence Rate  15-26
 Management of Covid-19  27-30
Aims and Objective 31
Review of Literature 32-40
Discussion 41-45
Materials and Methods 46
Conclusion 47
Reference 48-66

5
 Hematological, biochemical, biomarkers alteration association with
Covid-19 disease prognosis and complications.

INTRODUCTION

COVID-19 or “CO” stands for corona, “VI” stands for Virus, and “D” for disease. Formerly,
this disease was referred to as ‘2019 novel coronavirus’ or ‘2019-nCoV’(Agrawal A et al.,
2020).
Coronavirus belongs to order nidovirales, sub-family orthocoronavirinae in the family of
coronaviridae. It is unsegmented enveloped single stranded positive stained RNA virus.
Structurally the wreath shaped protrusions surround the virus. According to serotype and
genomic characteristics the coronavirus is divided into four genera – α β γ δ(Anurag et al.,
2020).
In human coronavirus causes respiratory infection including: -
 Common cold, bronchitis, pneumonia
 Middle east respiratory syndrome (MERS)
 Severe acute respiratory syndrome (SARS)
 COVID-19
The new strain novel corona (SARS-CoV 2) causes coronavirus disease (COVID-19).
The world health organization identified SARS-CoV2 as a new type of coronavirus. The
outbreak quickly spread around the
world. The first known case was
identified in Wuhan, China in
December 2019. The disease was since
spread worldwide, leading to an
ongoing pandemic (Valint et al., 2020).
The coronavirus particles are
organized with long RNA polymers
tightly packed into the center of the
particle, and surrounded by a protective
capsid, which is a lattice of repeated
protein molecules referred to as coat or
capsid proteins. In coronavirus, these
proteins are called
nucleocapsid(n)(Baszczuk and
Kopczynski 2020). The coronavirus
core particles are farther surrounded by
an outer membrane envelope made of
lipids (fats) with proteins inserted (Bhat
et al., 2020).
These membranes derive from the cells in which the virus was last assemble but are modified
to contain specific viral proteins, including the spike (S), membrane (M), and envelope €,
protein (Huang and Wang, 2020).
6
A key set of the proteins in the outer membrane project out from the particle and are known as
spike proteins (S). It is these proteins which are recognized by receptor proteins on the host
cells which will be infected (Lagunas-Rangel, 2020).
SARS-CoV-2 spreads from person to person through close communities. When people with
COVID-19 breathe out or cough, they expel tiny droplets that contain the virus. These droplets
can enter the mouth or nose of someone without the virus, causing an infection to occur. The
most common way that this illness spreads is through close contact with someone who has the
infection. Close contact is within around 6 feet Trusted Source (Lei et al., 2020). The disease is
most contagious when a person’s symptoms are at their peak. However, it is possible for
someone without symptoms to spread the virus. A new study suggests that 10% of infections
are from people exhibiting no symptoms (Okugawa et al., 2020). Droplets containing the virus
can also land on nearby surfaces or objects. Other people can pick up the virus by touching
these surfaces or objects. Infection is likely if the person then touches their nose, eyes, or mouth.
It is important to note that COVID-19 is new, and research is still ongoing. There may also be
other ways that the new coronavirus can spread (Qian et al., 2020).
Symptoms
o Fever
o Coughing
o Shortness of breath
o Trouble breathing
o Fatigue
o Chills, sometimes with shaking
o Body aches
o Headache
o Sore throat
o Congestion/runny nose

7
 o Loss of smell or taste
o Nausea
o Diarrhea (Ruan and Yang, 2020)
The virus can lead to pneumonia, respiratory failure, heart problems, liver problems, septic
shock, and death. Many COVID-19 complications may be caused by a condition known as
cytokine release syndrome or a cytokine storm. This is when an infection triggers immune
system to flood bloodstream with inflammatory proteins called cytokines. They can kill tissue
and damage organs (Sahu and Siddiqui, 2020).

Clinical Features: -
 Incubation period: - 1-27 days
 Recovery time: - 3 weeks to 6 weeks (Shi et al., 2020)
Frequently reported signs and symptoms of patient include: -
o Fever (7-98%)
o Cough (46-82%)
o Myalgia or fatigue (11-52%)
o Shortness of breath (3-31%) (Zou et al., 2020).
Diagnosis
For patients with suspected infection, the following diagnosis techniques are utilized:
Performing real-time fluorescence (RT-PCR) to detect the positive nucleic acid of SARS-CoV-
2 in sputum, throat swabs, and secretions of the lower respiratory tract samples [30]. In patients
with COVID-19, the white blood cell count can vary (Yang et al., 2020). Leukopenia,
leukocytosis, and lymphopenia have been reported, although lymphopenia appears most
common. Elevated lactate dehydrogenase and ferritin levels are common, and elevated
aminotransferase levels have also been described. On admission, many patients with pneumonia
have normal serum procalcitonin levels; however, in those requiring ICU care, they are more
likely to be elevated. High D-dimer levels and more severe lymphopenia have been associated
with mortality. Imaging findings—Chest computed tomography (CT) in patients with COVID-
19 most commonly demonstrates ground-glass opacification with or without consolidative
abnormalities, consistent with viral pneumonia (Xu et al., 2020). Other’s study has suggested
that chest CT abnormalities are more likely to be bilateral, have a peripheral distribution, and
involve the lower lobes. Less common findings include pleural thickening, pleural effusion,
and lymphadenopathy. Chest CT may be helpful in making the diagnosis, but no finding can
completely rule in or rule out the possibility of COVID-19. An oropharyngeal swab can be
collected but is not essential; if collected, it should be placed in the same container as the
nasopharyngeal specimen (Arentz and Yim, 2020). An oropharyngeal swab is an acceptable
alternative if nasopharyngeal swabs are unavailable. Expectorated sputum should be collected
from patients with productive cough; induction of sputum is not recommended (Bertsinas et
al.,2020). A lower respiratory tract aspirate or bronchoalveolar lavage should be collected from
patients who are intubated. Data from this study suggested that viral RNA levels are higher and
more frequently detected in nasal compared with oral specimens, although only eight nasal
swabs were tested. SARS-CoV-2 RNA is detected by reverse-transcription polymerase chain
reaction (RT-PCR) (Deng et al., 2020). A positive test for SARS-CoV-2 generally, confirms

8
the diagnosis of COVID-19, although false-positive tests are possible. If initial testing is
negative but the suspicion for COVID-19 remains, the WHO recommends resampling and
testing from multiple respiratory tract sites (Fan et al., 2020). The accuracy and predictive
values of SARS-CoV-2 testing have not been systematically evaluated. Negative RT-PCR tests
on oropharyngeal swabs despite CT findings suggestive of viral pneumonia have been reported
in some patients who ultimately tested positive for SARS-CoV-2(Henry et al., 2020). Serologic
tests, once generally available, should be able to identify patients who have either current or
previous infection but a negative PCR test. Coinfection with SARS-CoV-2 and other respiratory
viruses, including influenza, has been reported, and this may impact management decisions
(Tang et al., 2020).
2.Detection of Hematological Parameters
Total RBC count
The blood specimen is diluted 1:200 with the RBC diluting fluid and cells are counted under
high power (40X objective) by using a counting chamber. The number of cells in undiluted
blood are calculated and reported as the number of red cells per cu mm (μl) of whole blood (Xia
et al., 2020).
Total WBC count
The glacial acetic acid lysis the red blood cells while the gentian violet slightly stains the
nuclei of the leukocytes. The blood specimen is diluted 1:20 in a WBC pipette with the diluting
fluid and the cells are counted under low power of the microscope by using a counting chamber.
The number of cells in undiluted blood are reported per cu mm (μl) of whole blood (Lippi and
Plebani, 2020).
Deferential leukocyte count
The polychromic staining solutions (Wright, Leishman, Giemsa) contain methylene blue
(basic dye) and eosin (acidic dye). These basic and acidic dyes induce multiple colors when
applied to cells. Methanol acts as fixative and also as a solvent (Kundi et al., 2020). The fixative
does not allow any further change in the cells and makes them adhere to the glass slide. The
basic component of white cells (i.e., cytoplasm) is stained by acidic dye (eosin) and they are
described as eosinophilic or acidophilic (Doobay et al., 2020). The acidic components (e.g.,
nucleus with nucleic acid) take blue to purple shades by the basic dye (methylene blue) and
they are called basophilic. The neutral components of the cell are stained by both the dyes
(Gong et al., 2020).
Platelet Count
The determination is done by placing a small volume of diluted whole blood that was
treated with a red cell lysing reagent, such as ammonium oxalate, in a counting chamber
(hemocytometer) and counting platelets using phase-contrast light microscopy. The count is
then adjusted by the dilution factor (Tian et al., 2020).
D-dimer
The D-dimer is fragment of fibrin that contains one intermolecular cross-link between the
gamma chains of two fibrin monomers (Wai et al., 2020). This cross-linkage takes place
specifically in fibrin (and not in fibrinogen). Increased levels of D-dimer (cross-linked fibrin
fragments) have been found in patients with deep vein thrombosis, acute pulmonary embolism,

9
unstable angina, disseminated intravascular coagulation and myocardial infarction (Wu et al
2020).
It is measured by Elisa technique.
ESR
When anticoagulated blood is allowed to stand vertically. RBC’s settle towards the bottom
of the tube under the influence of gravity resulting in packed column in a given interval of time
leaving the clear plasma above. The process of sedimentation is called ESR (Zhang et al., 2020).
Hemoglobin
When blood is added to 0.1 N hydrochloric acid, hemoglobin is converted to brown colored
acid hematin. The resulting color after dilution is compared with standard brown glass reference
blocks of a Sahli hemoglobinometer (Mirzaie et al., 2020).
PT
Prothrombin time determination test determines the clot ting time of plasma in the presence
of an optimal con centration of thromboplastin (prepared from human or rabbit brain) and
indicates the efficiency of the extrinsic clotting system. Thrombokinase preparation containing
calcium ions is added to citrated plasma of patient's blood (Lin et al., 2020). In the presence of
factor VII, stage 2 of coagulation mechanism is triggered and the clotting time is record ed.
Since factors XII, XI, VIII and platelets are bypassed, the test depends upon the activity of
factors VII, V, X, II and I. Deficiency of any of these factors may cause prolongation of clot
formation in this test (Grivennikov et al., 2020).
APTT
APTT measures the clotting time of plasma after the activation of contact factors but without
the addition of tissue thromboplastin, hence this test indicates the overall efficacy of the
intrinsic pathway. To standardize the activation of contact factors, the plasma is first pre-
incubated for a standardized period of time with kaolin (contact activator). During this phase
of the test, factor Xlla is produced, which acts on factor XI and factor Xla forms. Factor Xla
requires calcium ions for coagulation process. After the addition of calcium ions, factor Xla
activates factor IX and coagulation follows. Standardized phospholipid reagent is used to allow
the test to be performed on platelet poor plasma. APTT depends not only on the contact factors
and on factors VIII and IX but also on the reactions with factors X, V, prothrombin and
fibrinogen (Han et al., 2020).
Ferritin
The method principle for measurement of Ferritin is immuno-turbidimetry using Roche kits on
the Hitachi 912 clinical analyzer. Latex bound Ferritin antibodies react with the antigen in the
sample to form an antigen/antibody complex. Following agglutination, this is measured
turbidimetrically (Quradakhi et al., 2020).
3.Detection of Biochemical Parameters
Glucose
a) Glucose Oxidase Method:
Glucose oxidase catalases the oxidation of glucose to gluconic acid and

10
hydrogen peroxide. This H2 O2 is broken down to water and oxygen by a
peroxidase in the presence of an oxygen acceptor which itself is converted to
a colored compound, the amount of which can be measured calorimetrically. This method is
used in various autoanalyzer (Xiao et al., 2020).

Glucose H2O2
Reaction: Glucose-----------Gluconolactone------------ Gluconic Acid+H2O2
Oxidase O2

Peroxidase
H2O2 + Chromogenic ---------------------------Chromogen + H2O
O2 acceptor (Measured)

Urea
Urea reacts with diacetyl monoxime in acidic conditions at nearly 100oC to give a red coloured
product which is measured calorimetrically at 520nm. Thiosemicarbazide and ferric ions are
added to catalyse the reaction and increase the intensity of colour. This method is linear only
up to 300mg% urea. For higher values if expected, the blood sample should be diluted (Gao
and Han, 2020).
Creatinine
Creatinine in alkaline medium reacts with picric acid to form a red tautomer of creatinine
picrate the intensity of which is measured at 520nm. The two chief disadvantages with Jaffe's
reaction are:
- Lack of specificity: - Only 80% of the colour developed is due to creatinine in serum. other
non-specific chromogens that react with picric acid are proteins, ketone bodies, pyruvate,
glucose, ascorbate etc.
- Sensitivity to certain variables like PH temperature etc (Chen et al., 2020).
Total Protein
Cupric ions form chelates with the peptide bonds of proteins in an alkaline medium. sodium
potassium tartrate keeps the cupric ions in solution. The intensity of the violet colour that is
formed is proportional to the number of peptide bonds which, in turn, depends upon the number
of proteins in the specimen (Bhat et al., 2020).
Serum Albumin and Globulin
The method is based on the protein error of indicators. Biding of a protein to an indicator
changes its colour. Among serum proteins, only albumin binds to BCG this binding produces a
change in the colour of BCG which is measured calorimetrically. The pH is maintained during
the reaction by a buffer (Karzai et al., 2020).

11
Aminotransferases (Transaminases)
The amount of oxaloacetate or pyruvate produced by transamination is reacted with 2,4
dinitrophenyl hydrazine (DNPH) to form a brown colored hydrazone,The color of which in
alkaline solution is read at 520nm (ranzani et al., 2020).
Alkaline Phosphatase
The serum is incubated with the buffer substrate under optimum, conditions of temperature and
pH to release phenol. This reacts with 4-amino antipyrine in alkaline medium to give a red
colored compound which is estimated at 520nm against a reagent blank. Color development is
rapid and is stable for at least an hour sodium hydroxide is added immediately after incubation
to raise the pH and stop the reaction. Potassium ferricyanide is the oxidizing agent. Sodium
Bicarbonate provides the alkaline medium (Simon et al., 2020).
Serum Bilirubin
When reacted with diazotized sulfanilic acid (Ehrlich's Reagent), bilirubin is converted to
azobilirubin molecules which give a red purple colour in acid the intensity of which is read
colorimetrically. Both conjugated and unconjugated bilirubins give purple azobilirubins with
diazotized acid. Conjugated bilirubin can react in aquous solution 67 (Direct Reaction), whereas
unconjugated requires an accelerator or solubiliser, such as methanol (Indirect Reaction-which
gives total bilirubin i.e., conjugated + unconjugated bilirubin) (Simon et al., 2020).

Serum Tryglycerides
The serum lipids are extracted by isopropanol, which also precipitates serum proteins. The
interfering phospholipids, containing glycerol as integral part, are removed by adsorption on
alumina. Filtrate is used for saponification and glycerol is separated from triglycerides. Action
of metaperiodate converts glycerol into glyceraldehydes, which forms a yellow coloured
complex with acetyl acetone. The intensity of the coloured complex is measured at 410 nm.
(Violet filter) (Gao and Han, 2020).
Serum Cholesterol (Total)
Cholesterol esters are hydrolysed by cholesterol ester hydrolase to free cholesterol & fatty acids.
the free cholesterol produced and pre-existingh one is oxidised by cholesterol oxidase to
Cholestenone-4-en-3-one and hydrogen peroxide. Peroxidase acts on hydrogen peroxide and
liberated oxygen reacts with the chromogen (4-amino phenazone/phenol) to form a red coloured
compound which is read at 510 nm (505-530 nm) (Bhat et al., 2020).
Serum HDL cholesterol
In the presence of phosphotungstic acid and magnesium chloride, LDL, VLDL & chylomicrons
are precipitated. Centrifugation leaves only the HDL in the supernatent. Cholesterol in the HDL
fraction can be tested by the usual methods (Karzai et al., 2020).
Serum Uric Acid
Phosphotungstic acid in alkaline medium oxidizes uric acid to allantion and itself gets reduced
to tungsten blue which is estimated colorimetrically at 700mm (ranzani et al., 2020).

12
Adverse effect of Covid-19 infection: -
Several studies showed the virus has club shaped spikes that are visible as a solar corona
under the electron microscope; hence the name coronavirus. It attaches to the angiotensin-
converting enzyme 2 receptor (ACE2) via the spike protein and enters into the host cell. ACE2
receptors are located in the lungs, nasopharynx, heart, kidneys, liver, intestines, vascular
endothelium, testicles, and also in cortex, especially in cardiovascular regulatory areas of the
brain stem (Wang et al., 2020).
It is known that in SARS-CoV-2 virus infections, as well as in other infectious disease such
as influenza, varicella, dengue, acquired human immunodeficiency virus (HIV), SARS-CoV
and MERS-CoV, hematological changes can occur and often present, the potential to optimize
the monitoring of infectious process or to indicate the suspicion of their severity. Laboratory
abnormalities, particularly hematological changes, allow checking the status of SARS-CoV-2
infection, since the hematopoietic system and hemostatic suffer significant impacts during the
evolution of covid-19 (Mohammadpour et al., 2020). The most common hematological
findings include lymphocytopenia, neutrophilia, eosinopenia, mild thrombocytopenia and, less
frequently, thrombocytosis, red cell and hemoglobin abnormalities. The presence of reactive
lymphocytes has been reported only occasionally. The leukocyte count may be normal, reduced
or increased. According to meta-analysis, leukocytosis, lymphopenia and thrombocytopenia are
associated with greater severity and even fatality in COVID-19 cases (Okugawa et al., 2020).
During the COVID-19 course, changes in hemostasis tests have also been reported, such as
prolonged prothrombin and activated partial thromboplastin times and increased D-dimer
levels. In cases of worsening COVID-19, D-dimer levels become raised, with formation of
microthrombi in peripheral blood vessels and recurrent coagulation disorder (Pushpakumar et
al., 2020).
Another study reported changes in inflammatory markers in patients with COVID-19, including
C-reactive protein (CRP),
erythrocyte sedimentation rate
(ESR), and Interleukin-6.
Likewise, another work reported
lymphocytopenia, high blood
sugar, gamma-glutamyl
transferase (GGT), high lactate
dehydrogenase (LDH), increase
cardiac troponin, increase urea,
increase creatinine kinase, lower
level of lactic acid, decrease
sodium, potassium, calcium,
albumin in more COVID-19
patients (Ramana et al., 2020).

13
Alteration Biomarkers

Hematological ↑ Lymphocyte count

↑ Neutrophil count
↑NLR
↓Platelet count
Inflammatory ↑ESR
↑CRP
↑PCT
↑Ferritin
↑IL-6
↑LDH
↑MDW
Coagulation ↑D-dimer
↑FDP
↑PT
↑aPTT
↑Fibrinogen
Electrolytes ↓K+
↓Na+
↓Ca+
Hepatic ↑Alanine aminotransferase
↑Aspartate aminotransferase
↑Total Bilirubin
↓Albumin
Muscular ↑CK
↑Myoglobin
↑Creatinine
Renal ↑cTn
Cardiac ↑BNP/nt-proBNP

14
Prevalence rate in west Bengal: -
According to west Bengal health bulletin, 1481707 population is affected by covid-19
from total population 99609303, during Covid-19 infection second phase till 20 th June, 2021.
So, positivity rate is 1.488%. And total recovery till 20th June, 2021 is 1441343. So, the recovery
rate is 97.27%. Total death from covid-19 till 20 th June,2021 is 17348. So, the mortality rate is
1.17%.

Posiivity Rate Recovery Rate

Total
Affected Total
1481707 Affecte
(1.488%) d…

Total
Total Recovery
Populatio 1441343
n (97.27%)
99609303

Total Affected Total Population Total Recovery Total Infected

Mortality Rate
Total Death
17348
(1.17%)

Total Infected
1481707

Total Death Total Infected

According to west Bengal health bulletin 20th June,2021, the north 24 pargana district of west
Bengal is highly affected by covid-19 comparatively to another district of west Bengal. 313953
population is affected and 4384 are died by covid-19 infection.
The capital of west Bengal-Kolkata is second highly affected district in west Bengal. 306428
population are affected by covid-19 infection and 4839 are died by this infection, reported by
west Bengal health bulletin 20th jume,2021.

15
The kalimpong district are comparatively lowest covid-19 exposer district in west Bengal.
According to the west Bengal health bulletin 20th june,2021 5475 people are affected and 37
people are died by this infection.

Other districts are also affected by covid-19 infection. The data are as follows: -
District Total Affected Total Recovery Total Death

Source:- 20th june 2021

16
 0
50000
100000
150000
200000
250000
300000
350000

North 24 paragana
Kolkata
South 24 Paragana
Howrah
Hooghly

Total Cases
Nadia
Purba Medinipur
Paschim Bardhaman
Darjeeling
Paschim Medinipur
Birbhum
Purba Bardhaman
Jalpaiguri

Total Discharge
17
Murshidabad
Bankura
Malda
coochbehar
Purulia
Uttar dinagpur

Total Death
Other Districts Data

Dakshin dinagpur
Alipurduar
Jhargram
Kalipong

0
1000
2000
3000
4000
5000
6000

Total active Cases

Prevalence rate in India: -
According to worldometer21th june,2021, 29,973,457 population is affected by covid-19
from total population 1,393,409,976, during Covid-19 infection second phase till 21th June,
2021. So, positivity rate is 2.15%. And total recovery till 21th June, 2021 is 28,913,191. So, the
recovery rate is 96.46%. Total death from covid-19 till 21th June,2021 is 389,268. So, the
mortality rate is 1.29%.

According to worldometer 21th June,2021, the Maharashtra state of west Bengal is highly
affected by covid-19 comparatively to another state of India. 5979051 population is affected
and 118313 are died by covid-19 infection in this state.
The ultimate southern state of Kerala is 2nd highly affected state of India. 2816844 are affected
and 12155 are died in this state, reported by worldometer 21th June 2021.
The Andaman Nicobar state are comparatively lowest covid-19 exposer state in India.
According to the Worldometer 21th june,2021 7415 people are affected and 127 people are died
by this infection.

18
Other State are also affected by covid-19, the data are given below: -

Total Cases Total Recovered Total Death

Maharastra 5987521 5742258 118795
Kerala 2829461 2716284 12296
Karnataka 2815029 2662250 34164
TamilNadu 2436819 2348353 31580
Andhra Pradesh 1857352 179056 12416
Uttar Pradesh 1704678 1678486 22282
West Bengal 1485438 1445493 17437
Delhi 1432778 1405927 24933
Chandigarh 991653 970244 13402
Rajasthan 951393 940101 8904
Odisha 883490 848960 3724
Gujrat 822620 807424 10037
Madhta Pradesh 789415 778902 8806
Haryana 767726 756231 9295
Bihar 720207 707833 9563
Telengana 615574 595348 3586
Punjab 593063 571207 15888
Assam 488179 450924 4280
Jharkhand 344775 338256 5102
Uttarakhand 338978 323225 7052
Jammu and Kashmir 312584 301134 4269
Himachal Pradesh 200791 195060 3437
Goa 164957 159029 3008
Paducherry 115364 110423 1727
Manipur 64993 54714 1065
Tripura 62742 58120 651
Chandigarh 61467 6383 806
Meghalaya 45976 40915 788
Arunachal Pradesh 33664 30956 160
Nagaland 24438 21513 477
Sikkim 19458 16481 296
Mizoram 17979 13770 85
Dadra Nagar Haveli 10521 10422 4
Lakshadweep 9504 9103 47
Andaman And Nicobar Islands 7425 7195 127
Ladakh 0 0 0

Source: - Daily Hunt

19
Prevalence rate in World: -
According to worldometer21th June,2021, 179614366 population is affected by covid-
19 from total population 7874341993, during Covid-19 infection second phase till 21th June,
20
2021. So, positivity rate is 2.28%. And total recovery till 21th June, 2021 is 164314156. So, the
recovery rate is 91.48%. Total death from covid-19 till 21th June,2021 is 3890270. So, the
mortality rate is 2.1%.

According to worldometer 21th June,2021, the United States is highly affected by covid-19
comparatively to another country. 34419838 population is affected and 617463 are died by
covid-19 infection in this state.
The India is 2nd highly affected country of world. 29973457 are affected and 389268 are died
in this state, reported by worldometer 21th June 2021.
The African sub-continent Tanzania is comparatively lower covid-19 exposer country of
world. According to the Worldometer 21th june,2021 509 people are affected and 21 people
are died by this infection.

21
Other Countries are also affected, the data are as follows: -

22
23
24
25
26
Managements of Covid-19
Self-care
Asymptomatic cases, mild cases of COVID-19:
o Isolate in a well-ventilated room.
o Use a triple layer medical mask, discard mask after 8 hours of use or earlier if they
become wet or visibly soiled. In the event of a caregiver entering the room, both
caregiver and patient may consider using N 95 mask.
o Mask should be discarded only after disinfecting it with 1% Sodium Hypochlorite.
o Take rest and drink a lot of fluids to maintain adequate hydration.
o Follow respiratory etiquettes at all times.
o Frequent hand washing with soap and water for at least 40 seconds or clean with
alcohol-based sanitizer.
o Don’t share personal items with other people in the household.
o Ensure cleaning of surfaces in the room that are touched often (tabletops, doorknobs,
handles, etc.) with 1% hypochlorite solution.
o Monitor temperature daily.
o Monitor oxygen saturation with a pulse oximeter daily.
o Connect with the treating physician promptly if any deterioration of symptoms is
noticed.
Instructions for caregivers:
Mask: The caregiver should wear a triple layer medical mask. N95 mask may be considered
when in the same room with the ill person.
Hand hygiene: Hand hygiene must be ensured following contact with ill person or patient’s
immediate environment.
Exposure to patient/patient’s environment: Avoid direct contact with body fluids of the
patient, particularly oral or respiratory secretions. Use disposable gloves while handling the
patient. Perform hand hygiene before and after removing gloves.
Medical treatments
Treatment for patients with mild/asymptomatic disease in home isolation
 The antiviral drug Remdesivir is now wildly used for the treatment of COVID-19
patient.
 Currently there are some vaccines named Oxford–AstraZeneca, Pfizer–BioNTech,
Sputnik V, Sinopharm-BBIBP, Moderna, Johnson & Johnson, CoronaVac , Covaxin,
Sputnik Light, Convidecia, Sinopharm-WIBP, EpiVacCorona, RBD-Dimer, CoviVac,
QazCovid-in, Minhaiare are used for the prevention or spread of COVID-19.
 Patients must be in communication with a treating physician and promptly report in case
of any worsening.
 Continue the medications for other co-morbid illness after consulting the treating
physician.
 Patients to follow symptomatic management for fever, running nose and cough, as
warranted.
27
  Patients may perform warm water gargles or take steam inhalation twice a day.
When to seek immediate medical attention:
 Difficulty in breathing
 Dip in oxygen saturation (SpO2 < 94% on room air)
 Persistent pain/pressure in the chest, Mental confusion or inability to arouse

MANAGEMENT OF HEMATOLOGICAL ABNORMALITIES

IN COVID-19
Platelets. As severe thrombocytopenia is not common in COVID-19 patients, treatment of this
aspect is usually not needed. There are some case reports of patients with COVID19, who
developed ITP or TTP, and all of them had favorable outcomes.
Coagulation and fibrinolytic system. The routine uses of antithrombotic prophylaxis with
low-molecular-weight heparin is recommended for inpatients by the International Society on
Thrombosis and Hemostasis.117 Moreover, the role of heparin as an anti-inflammatory agent
is of additional benefit in patients with COVID-19.118 However, severe COVID-19 infections
may be complicated by liver dysfunction which may worsen the coagulopathy and increase the
risk of bleeding. Therefore, the dose and the type of anticoagulants should be adjusted based
on the clinical severity of the disease and associated organ impairment. Higher doses in obese
patients were shown to be necessary. In a study by Wan get al., in those with higher body mass
index (> 40 kgm−2), a higher antithrombotic prophylaxis dose decreased the odds of
symptomatic venous thrombosis by 50%.
There is increasing debate over antithrombotic prophylaxis post-discharge. During the 6-
week post-discharge period,4.8/1,000 discharges were associated with VTE. However, the odds
were not significantly higher than hospitalization for other acute medical illnesses. Therefore,
the role of routine post-discharge thromboprophylaxis remains uncertain.
The treatment with a full dose of anticoagulation may be beneficial for patients with sepsis-
induced coagulopathy (SIC). In a retrospective study by Tang et al., the use of heparin was
shown to reduce mortality in patients who met the SIC criteria or had a markedly increased D-
28
dimer levels. In patients with a thromboembolic event or an increased suspicion for
thromboembolic disease, therapeutic anticoagulation is recommended. Furthermore,
therapeutic anticoagulation should be considered in patients on continuous renal replacement
therapy, extracorporeal membrane oxygenation, or diagnosed thrombosis of extracorporeal
filters or catheters. Heparin resistance has been reported among critically ill COVID patients.
In such patients, anti-factor Xa levels may be of use to guide therapy.
Importantly, greater than 50% of VTE were diagnosed on the first day of admission,
emphasizing the need for early detection and management. However, routine screening is not
practical in the context of a pandemic and, therefore, not recommended. The need for imaging
is assessed based on clinical grounds. As an alternative to sophisticated imaging modalities,
bedside ultrasound has been used with acceptable sensitivity (100%) and specificity (95.8%) in
the diagnosis of VTE. Bedside cardiac ultrasonography may suggest a diagnosis of pulmonary
embolism based on the analysis of right ventricular function in clinically suspicious patients.
Patients on warfarin should be converted to other anticoagulants such as heparin, as close
monitoring of international normalized ratio would be difficult during isolation for COVID19.
Low molecular weight heparin (LMWH) would be preferred over unfractionated heparin, as
the need for regular monitoring is lower. The patients may be transitioned to direct oral
anticoagulants if they are able to tolerate oral intake. However, clinicians should be aware of
possible drug interactions with antivirals such as ritonavir, lopinavir, or darunavir, and anti–IL-
6 such as tocilizumab which may be used for treatment of COVID-19 infections. Moreover, in
the context of critical infection with associated renal impairment, decreased excretion of direct
oral anticoagulants may increase the risk of bleeding. Therefore, direct oral anticoagulants are
best avoided in the critically ill.
Several clinical trials are underway on the use of anticoagulants in patients with COVID-
19. Anticoagulants should be given carefully in patients with some hematological disorders
such as hemophilia and von Willebrand disorder. D-dimer has no utility in the diagnosis of
VTE; it has a poor positive predictive value but a high negative predictive value so may be used
to exclude pulmonary embolism (PE) in patients with a low clinical suspicion. Thachil et al.
have suggested thromboprophylaxis for patients requiring hospital admission with a view to
reducing poor outcomes. Further well-designed clinical trials on thromboprophylaxis would be
helpful.
Red blood cells. Although anemia has been reported in some patients, no studies have shown
transfusion support for this indication alone, to improve outcomes. Patients with
hemoglobinopathies and COVID-19 should continue to receive transfusions and chelation
therapy as needed.
White blood cells. The use of corticosteroids for reducing COVID-19–related inflammation
has been studied. The RECOVERY trial gained much attention when it found an 8–26% lower
mortality among patients who received 6 mg/day of dexamethasone for up to 10 days. Several
clinical trials on the use of mesenchymal stem cells (MSCs) as therapy for COVID-19 are
undergoing. Leng et al. treated seven patients with MSCs and observed an increase in the
lymphocyte count and a decrease in C-reactive protein (CRP) and cytokine secreting T and
natural killer cells within 3–6 days. However, the cost of such procedures and the prolonged
time period needed for gaining treatment approval are factors that need to be considered.

29
Managements of biochemical Abnormalities in COVID-19
Reduction excessive creatinine in blood: do not take supplements containing creatine.
Reduce protein intake excessively. Eat more fiber & grain. Lower salt intake. Avoid overusing
NSAIDs. Avoid smoking& alcohol intake during and after covid infection.
Management of serum LDH: pentoxifylline treatment is associate increase lymphocyte
count and decrease in serum LDH.
medication for increase BUN: amphotericin B (Ambystoma, Fungizone) carbamazepine
(Tegretol) cephalosporins, a group of antibiotics furosemide (Lasix), methotrexate,
methyldopa, rifampin (Rifadin), spironolactone (Aldactone), tetracycline (Sumycin), thiazide
diuretics, vancomycin (Vancocin).
Reduction increase AST, ALT, Total bilirubin: Increasing fiber intake, reducing saturated
fats and processed foods, as well as consuming a range of nutrients from fruits and vegetables
may all help to lower levels of AST, ALT, Total Bilirubin.
Management of increase albumin: captopril (Capoten) and benazepril (Lotensin).
Medications used to suppress immune system can also help keep inflammation from lowering
albumin levels. Albumin downregulates the expression of the ACE2 receptors and has been
shown to improve the ratio of arterial partial pressure of oxygen/fraction of inspired oxygen in
patients with acute respiratory distress syndrome as soon as 24 hours after treatment and with
an effect that persisted for at least seven days (4). Moreover, researchers who have studied the
clinical characteristics of Covid-19 patients have reported again and again that lower serum
albumin levels were associated with an increased risk of death, even to suggest that albumin
therapy might be a potential remedy.
Management of cardiac troponin: If troponin levels are high (elevated above normal) and
the EKG indicates an acute heart attack, cardiac intervention such as a catheterization with
angioplasty and possibly stents, or an evaluation for coronary artery bypass graft (CABG)
surgery may be required.

30
Aims and objective:
COVID-19 is a pandemic that causes high morbidity and mortality, especially in severe
patients. In this study, we aimed to search and explain the relationship between biochemical
markers, which are more common, easily available and applicable to diagnose and to stage the
disease. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2) is centered on the unpredictable clinical course of the disease that can rapidly develop,
causing severe and deadly complications. The identification of effective laboratory biomarkers
able to classify patients based on their risk is imperative in being able to guarantee prompt
treatment. The ana-lysis of recently published studies highlights the role of systemic vasculitis
and cytokine mediated coagulation disorders as the principal actors of multi organ failure in
patients with severe COVID-19 complications. The following biomarkers have been identified:
hematological (lymphocyte count, neutrophil count, neutrophil–lymphocyte ratio (NLR)),
inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin
(PCT)), immunological interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase
(CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in
disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS).
New laboratory biomarkers could be identified through the accurate analysis of multicentric
case series; in particular, homocysteine and angiotensin II could play a significant role.
 Immediate aims:
a. Hematological and biochemical parameters are important to support the diagnosis of
COVID-19.
b. Our aim in this study was to evaluate the relationship of biochemical parameters with
the confirmed group and the suspected group.
c. We aimed to evaluate whether these biomarkers predict the severity of the disease
with the first-look values in admission in COVID-19 patients. It is urgent to evaluate
the capability of these features to accurately differentiate cases of COVID-19 from
severe to non-severe. Therefore, we designed the study aiming to evaluate the ability
of routine laboratory tests for distinguishing COVID-19 from severe to non-severe
and help clinicians to effectively, quickly and calmly deal with COVID-19.

 Ultimate objectives:
The main objective of the review work is to gather previous information and develop
the strong field of research for hematological and biochemical biomarker parameter
alteration in covid -19 infection as high chances of mortality & predicting disease
severity and outcome in severe covid-19 patient and also biochemical marker as early
indicators for covid - 19 infection as disease prognosis.

31
Review Of Literature: -
A great proportion of COVID-19 studies concluded risk factors contributing to severe disease
and adverse outcomes include advanced age (>60 years) and male sex, with comorbidities, such
as hypertension, diabetes mellitus, and cardiovascular disease. The most common initial clinical
symptoms were fever, cough, dyspnea, and fatigue. (Quian et al., 2020) However, it is unclear
whether the symptoms will become more insidious as the pandemic progresses and will
gradually evolve into a virus similar to influenza or remain latent in humans for a long period
of time, as suggested by Chen et al., 2020.
Wide ranges of laboratory abnormalities were reported with different disease severity, but
marked changes were more commonly seen in samples from severe and critically ill
patients.(Xu l et al., 2020) Hematologic parameters, including lymphopenia, leukocytosis with
increased neutrophil count, increased NLR, and thrombocytopenia, were the most common
findings observed and positively correlated with disease severity.(Zhang et al., 2020) A
strikingly decreased lymphocyte count was associated with severe disease and higher
complication rate. The decreases in both CD4 and CD8 T lymphocytes are best explained by
the roles these T-lymphocyte subsets play in eliminating virus-infected cells, and this is
consistent with low lymphocyte counts being associated with poor case outcomes. (Henri et
al., 2020)
An upward trend of CRP, ferritin, SAA, procalcitonin, and the most prominent cytokine, IL-6,
and a downward trend of albumin and/or prealbumin were frequently observed during
progression from mild to severe/critical condition, and in no survivors. Serial measurements of
these markers can be used to predict disease course, severity, and mortality. (Gang t al., 2020)
It has been postulated that SARS-CoV-2 may target alveolar macrophages via the angiotensin
converting enzyme 2 (ACE2) receptor, leading to an increase in cytokine secretion, including
IL-6 and TNF-α, which subsequently induces the elevation of various APPs, such as CRP, SAA,
and complement factor, which are significantly upregulated in the severely ill group. Changes
in coagulation parameters, including prolonged PT, elevated D-dimer, and elevated fibrinogen
or FDP, were common findings in severe disease and no survivors. (Liao et al., 2020)
Prolonged PT and higher serum D-dimer levels were postulated to demonstrate a
hypercoagulable state rather than consumptive coagulopathy. It was proposed that
hyperfibrinogenemia leads to fibrin polymerization, thrombus formation, and eventually
complications or adverse outcome. (Spiezia et al., 2020) Other biomarkers, such as LDH, CK,
BNP, AST, and ALT, have been associated in several studies with severe and critically ill
disease, and their levels likely indicate adverse outcome. (Xu l et al., 2020) AST-dominant
elevations were common in COVID-19 patients and appeared to reflect true hepatic injury.
(Bloom et al., 2020) Additionally, AST level correlated with markers for muscle injury,
including LDH and CK. (Bloom et al., 2020)
To date, molecular testing identifying viral particles on nasopharyngeal specimens by RT-PCR
remains the gold standard in the diagnosis of SARS-CoV-2 infection. Concurrent antibody
testing can aid in increasing detection sensitivity.(Espejo et al., 2020) Other specimen sources,
such as self-collected saliva, which is less painful and does not require trained personnel for
collection, should be considered as preferable alternatives for SARS-CoV-2 screening of health
care workers and asymptomatic cases.(Azzi et al., 2020) The sensitivity of SARS-CoV-2
detection from saliva samples was demonstrated to be comparable to that of nasopharyngeal

32
swabs in early hospitalization.(Willie et al., 2020) The results were more consistent during
extended hospitalization and recovery, most likely because of less temporal SARS-CoV-2
variability. (Willie et al., 2020) Routine blood tests may also be used as early predictors of
the molecular testing result. They can serve as an alternative for identifying SARS-CoV-2
infection in countries with heavy outbreaks and a shortage of RT-PCR reagents or specialized
labs, because they have been shown to have detection rates comparable with those of molecular
tests. (Ferrari et al., 2020) Moreover, early recognition of severe disease or disease that is
likely to progress is absolutely essential for timely triage of patients. Measurement of soluble
PSP or sCD14-ST in peripheral blood may be used for early diagnosis of sepsis and for risk
stratification. (Zaninotto et al.,2020) The use of proteomic approaches and nontraditional
samples, like cerebrospinal fluid, may identify additional biomarkers that may be helpful in the
pathophysiology and prognosis of COVID-19 disease. (Shen et al., 2020)
Interpretation of the results of several studies presented in this review is limited because of the
predominantly retrospective study designs, small sample sizes, multiple sampling biases (i.e.,
most were single-center studies with cohorts from east Asian ethnic groups), lack of uniformity
of disease severity definition based on variable RT-PCR methods, and lack of exact timeline of
laboratory sample collection, as well as lack of serial sample measurements. This information
is important because a defined timeline of collection and serial sampling performance may aid
in clinical decision-making during the acute phase of disease. In addition, a great proportion of
studies were cut short and failed to report final outcomes because of the need for prompt data
publishing during the current pandemic. Overall, the reader should be cautioned when viewing
medRxiv papers presented prior to peer review. It is recommended that updated peer-reviewed
published versions of these original studies be evaluated when/if available. (Youley et al.,
2020)
The dynamic changes in biomarker levels may assist in predicting disease course, prognosis,
and outcome. Indicators of systemic inflammation, such as NLR and systemic immune-
inflammation index or coagulopathy screening using a DIC scoring system, could be
appropriately used to predict disease severity, possible complications, and outcome. Finally,
COVID-19 Severity Score and clinical decision support tools can additionally be used
employing combined measurements of multiple biomarkers to predict mortality. In summary,
WBC, lymphocyte, and platelet counts, CRP, ferritin, and IL-6 may be potential prognosticators
of progression to critical illness. Therefore, prospective studies with larger cohorts, clearly
defined disease severity, and serial measurements with defined sampling collection timelines
are imperative to further confirming the correlation and significance of the current findings.
(Youley et al., 2020)
In the presence of rapidly emerging novel coronavirus infection, identification of hematological
parameters could help predict disease severity and prognosis thus guiding clinical care.
Significant lymphopenia is becoming evident at this point.
There are eight retrospective studies from China by Guan W et al, Huang et al,
Wang et al, Wu et al, Yang et al, Zhou et al, Liu et al and Chen et al comprising of 1099,
41, 138, 201, 52, 191, 12 and 99 confirmed cases of COVID-19, respectively. The majority of
patients in these studies were over 50 years of age with a median of around 55 years. The
median age of patients in these studies was 47,49,56,59.7,56,54 and 55.5 respectively. All these
studies showed a male predominance (58.1%, 72%, 54.3%, 67%, 62%, 67% and 68%).
Two studies from Singapore by Young et al. and Fan et al. included 18 (critically
ill) and 69 (not critically ill) confirmed cases of COVID-19 respectively, , with a median age
33
of 47 and 41 years. One study showed a male predominance (55.2%) while the other had equal
sex distribution., Two studies from the USA by Arentz et al and Bhatraju et al were published
including 21 and 24 critically ill confirmed cases of COVID-19.18,19 The median age was 58
and 51.9 years respectively. The age in these studies ranged from 22-95 years and 23-97 years.
Both studies showed a male predominance (82.1% and 70%). Arentz M et al., 2020 Two studies
from India by Anurag A et al and Agrawal A et al., 2020 comprised of 148 and 102 confirmed
cases of COVID-19. The age in these studies ranged from 7-74 years (median 42.6 years) and
10-85 years (median 32.5 years). Both studies showed a male predominance (58.8% and
75.4%). In the present study majority of the case were above 50 years with a median age of 49
years and age range from 6 months to 82 years. Male predominance (70%) was noted.
In the studies done by Guan et al, Huang et al, Young et al, Fan et al, Zhou et
al, Liu et al and Chen et al hemoglobin concentration (gm%) were 13.4, 12.6, 13.5, 14.2, 12.8,
12.8 gm and 14.8 respectively. In a study by Agrawal A et al., hemoglobin concentration
(gm%) was 13.85 & 13.12 in asymptomatic and symptomatic patients respectively. In the
present study HB concentration was 11.85 gm% (range: 8.2-15.5).
The median of total WBC count in a study by Huang et al., was 6.2x109/L,
4.5x109/L in Wang et al., 5.94 x109/L in Wu et al., 4.6 x109/L in Young et al., 4.7 x109/L in
Fan et al., 6.2x109/L in Zhou et al., and 8.4x109/L in Bhatraju et al., Chen et al. had 9 cases
(9%) with leukopenia and 24 cases (24%) with leucocytosis. Two studies from India by Anurag
A et al., and Agrawal A et al., showed mean total WBC count 8.6 x109/L and 7.1 x109/L
respectively. In the present study median of total WBC count was 7.3 x109/L (3.4-23.2) and 2
cases (4%) had leukopenia with TLC of 3.4 x109/L & 3.6 x109/L.
The median of absolute neutrophil count in a study by Huang et al., was 5.0
x109/L, 5.0 x109/L in Wang et al., 4.47 x109/L in Wu et al., 2.7 x109/L in Young et al. and
2.6 x109/L in a study by Fan et al., Chen et al., found a median absolute neutrophil count of
5.0 x109/L and 38 cases (38%) had neutrophilia. In the present study, the absolute neutrophil
count ranged from 0.87-19.72 x109/L with a median of 6.8 x109/L. Only one case showed
moderate neutropenia with a count of 0.87 x109/L.
In the study by Guan et al., there were 914 patients out of 1099 with
lymphopenia on admission while 370 cases (33.7%) had leukopenia. Huang et al., highlighted
an association between lymphopenia and the need for ICU care. They had 11 out of 13 cases
(85%) in ICU patients and 15 out of 28 cases (54%) in non-ICU patients with lymphopenia.
Wang et al., had 97 out of 138 cases (70.3%) with lymphopenia. Wu et al., showed an
association between lymphopenia and the development of acute respiratory distress syndrome
(ARDS). They had observed lymphopenia in 126 out of 201 cases (64%). In a study by Young
et al., lymphopenia was also documented in approximately 40% of the first 18 hospitalized
patients with COVID-19 in Singapore. Fan et al., reported lymphocytopenia in 24 (36.9%)
patients. In another retrospective study by Yang et al., including 52 critically ill patients from
Wuhan, China, lymphopenia was reported in 44 cases (85%). Zhou et al., published laboratory
parameters in 191 COVID-19 cases, in which lymphopenia was noted in 77 cases (40 %), while
32 cases (17 %) had leukopenia. Studies by Arentz et al., and Bhatraju et al., in critically ill
COVID-19 patients showed lymphopenia in 14 out of 21 cases (67%) and 18 out of 24 cases
(75%) respectively. Tan et al., in a study of COVID-19 patients (hospitalised and succumbed)
by monitoring dynamic changes in blood showed that decreased lymphocyte percentage was
associated with increased severity of the disease. Furthermore, they had demonstrated that
lymphopenia can be used as a reliable indicator to classify the moderate, severe, and critically

34
ill patient types by using the Time-lymphocyte% model for disease classification. Liu et al.,
had 5 patients with lymphopenia in a study of 12 patients. In a study by Chen et al., the median
of absolute lymphocyte count was 0.9 x109 with 35 cases (35%) having lymphopenia. Agrawal
A et al., from India highlighted a comparison of hematological parameters among
asymptomatic and symptomatic COVID-19 patients. They had 9 out of 17 cases (52.94%) that
were symptomatic and 10 out of 85 cases (11.76%) of asymptomatic patients with lymphopenia.
Total 19 out of 102 (18.63%) patients with lymphopenia. In the present study lymphopenia
(range: 0.37-0.49 x109/L) was found in 18 patients (36%) with 15 (30%) having moderate
absolute lymphopenia and 3 patients (6%) with severe absolute lymphopenia.
In the study by Guan et al., median platelet count was 168 x109/L with 398 cases
(36.2%) had thrombocytopenia, 164.5 x109/L in Huang et al., with 2 cases (4.9%) had
thrombocytopenia, 163 x109/L in Wang et al., 159 x109/L in Young et al 201 x109/L in Fan
et al., with 13 patients (20%) had mild thrombocytopenia, 206 x109/L in Zhou et al., with 13
cases (7%) had thrombocytopenia, 160.3 x109/L in Liu et al., with 1 patient (8.33%) had mild
thrombocytopenia and 213.5 x109/L in Chen et al., with 12 patient (12 %) had
thrombocytopenia. In the study by Agrawal A et al., mean platelet count was 214 x109/L in
asymptomatic patients and 182 x109/L in symptomatic patients. In the present study
thrombocytopenia (range: 90-149 x109/L) was found in 8 patients (16%) with 6 (12%) having
moderate thrombocytopenia and 2 patients (4%) with severe thrombocytopenia.
The host’s humoral response, including IgA, IgM, and IgG, to SARS-CoV-2, has been
investigated using recombinant viral nucleocapsids and an ELISA based assay. Two hundred-
eight plasma samples, including 82 confirmed cases and 58 suspected cases, were obtained
from the patients. By these samples, the IgM diagnostic value was assessed. IgM with 85.4%
and IgA with 92.7% were detected after 5 days (IQR 3-6), and IgG with 77.9% was detected
after 14 days (IQR 10-18) of the onset of symptoms. The positive IgM antibody level was
estimated to be 75.6% in confirmed cases and 93.1% in suspected cases. IgM ELISA had higher
diagnostic efficiency than qPCR in 5 days from the onset of symptoms. Compared to the single
qPCR test, the use of IgM ELISA with PCR for each patient significantly increased the rate of
positive diagnosis so that this value for qPCR and IgM ELISA with PCR was (51.9%) and
(98.6%), respectively (Guo l et al., 2020)
To et al. conducted a cohort study at two hospitals in Hong Kong and assessed the
serum antibody value against two essential proteins including surface spike RBD and internal
nucleoprotein for 14 days or more after the onset of symptoms using the EIA method. They
observed that 15 (94%), 14 (88%), 16 (100%), and 15 (94%) out of 16 patients were positive
for anti- internal nucleoprotein IgG, anti- internal nucleoprotein IgM, anti-RBD IgG, and anti-
RBD IgM, respectively. They believed that IgG anti-SARS-CoV-2- internal nucleoprotein or
anti-SARS-CoV-2-RBD levels are associated with virus neutralization (R2 >0. 9).
In another study, Wu and co-workers measured the antibody level against RBD, S1,
and S2 proteins in the 175 recovered patients using ELISA. All patients manifested mild
symptoms. 10 to 15 days after the onset of disease, specific neutralizing antibodies against
SARS-CoV-2 were detected in patients’ samples without cross-reactivity with SARS-CoV.
Plasma neutralizing antibody titers and S-antibodies targeting S1, RBD, and S2 were in
correlation and were significantly lower in young people than in middle-aged people (P <0.0001
and P = 0.0003, respectively).
The neutralizing antibody titers were positively correlated with plasma C-reactive
Protein (CRP) levels but negatively correlated with the lymphocyte counts of patients at the
35
time of admission, indicating an association between humoral response and cellular immune
response (Wu X et al., 2020). The neutralizing antibody titers were negatively associated with
the number of lymphocytes in patients at the time of hospitalization and were positively
correlated with the levels of the plasma CRP, indicating a link between cellular immune and
humoral response. According to some observations in patients, there are some memory B cells
specified for viruses and capable of detecting RBD on the surface of SARS-CoV-2. They
produced 206 specific SARS-CoV-2 RBD monoclonal antibodies using B-cell Recptor (BCR)
sequencing and single-cell sorting. Antibodies were derived from different genes of
immunoglobulins families with no evident enrichment for any particular family. Two clones of
98-99% showed blocking activity against virus entry, which correlated with high competition
capacity against ACE2 receptors (which is considered a vector for COVID-19) (Catalan
Dibene J 2020) (Heiat AN et al., 2020).
Liu et al., investigated the variation of the subsets of lymphocyte and cytokines in
40 patients using flow cytometry and immunoassay. 13 out of 40 patients with severe symptoms
showed considerable lymphocyte reduction, especially of CD8+ T cells, but exhibited a
neutrophil increase in comparison with the 27 mild patients. In addition, IL-6, IL-10, IL-2, and
IFN-γ levels in the peripheral blood were significantly higher in patients with severe symptoms.
In surviving patients with acute symptoms, the levels of T cells and cytokines gradually
decreased and reached levels similar to those patients with mild symptoms. The authors
believed that the ratio of neutrophil to lymphocyte and neutrophil to CD8+ T cells could be a
valuable prognostic indicator to screen the severe diseases in the early stage. In another study
on the 60 patients who suffered from COVID-19, the peripheral blood lymphocyte subscales
were investigated using flow cytometry both before and after treatment. The levels of all
lymphocytes, including CD4+ and CD8+ T cells, B cells, and NK cells, were reduced, and it
was directly related to the severity of the disease. There has also been a correlation between
inflammation and subsets, includingCD8+ T cells and the CD4 / CD8 ratio. In addition, in 67%
of treated patients, increased rates of CD8+ T cells and B cells were observed [20].
According to another study, the level of CD8+ T and NK cells in SARS-CoV-2
infection patients has been significantly reduced. In addition, NKG2A expression was
upregulated on NK cells and CTLs in patients with a reduced ability to produce CD107a, IFN-
γ, IL-2, granzyme B, and TNF-α. Also, in the patients, NK and CTLs increased the expression
of NKG2A, although the ability to produce CD107a, IFN-γ, IL-2, granzyme B, and TNF-α was
decreased. The level of NKG2A292 The Open Microbiology Journal, 2020, Volume 14
Ranjbar et al., + cytotoxic lymphocytes has also reduced after the patients’ recovery. It can be
due to the functional exhaustion of cytotoxic lymphocytes (Liao M et al., 2020). Zheng et al.
provided a detailed analysis of the immunological characteristics of peripheral blood leukocytes
from 16 patients, including 10 mild cases and 6 severe cases. The levels of IFN-γ and TNF-α
in CD4+ T cells were lower in the severe group than in the mild group, whereas the levels of
granzyme B and perforin in CD8+ T cells were higher in the severe group than in the mild
group. Another study was conducted on 16 patients infected with COVID-19 (10 mild and 6
severe cases) for evaluating peripheral blood leukocytes and their immunological
characteristics. The study showed that the more group of acute patients had lower levels of IFN-
γ and TNF-α in their CD4+ T cells compared to the mild patient’s group, and on the other hand,
they had a higher level of granzyme B and perforin in CD8+ T cells. Although the activation
molecules displayed no differentiation in CD4+ T cells, the mild group had lower levels of
HLA-DR and TIGIT in CD8+T cells. According to this report, COVID-19 behaves in a similar
manner to some chronic infections, so that it disrupts the function of CD4+ T cells and makes

36
CD8+ T cells more active and possibly exhausts them. The number of CD4+T multifunctional
cells (with at least two positive cytokines) in the severe group was reported to be less than the
healthy control group and the mild group. The amount of the non-exhausted (PD-1−CTLA-
4−TIGIT−) subsets of CD8+ T cells in the severe group was significantly lower compared to
the healthy control group and the mild group.
Various laboratory researches are ongoing to search for signs for early
diagnosis and understanding the pathological mechanism of the virus.
The virus load in patients’ respiratory secretions using RTPCR is one of the ways for diagnosing
COVID-19. The following are some of the findings regarding it:
One of the early diagnosis methods for the severity of the disease is to evaluate viral load
from the patient’s respiratory tract. According to a report from 76 patients with COVID-19, the
virus load can be used to assess disease severity and prognosis, so in acute cases, the viral load
was found to be at least 60 times higher than that of the mild cases (Lin D et al., 2020) (Liu T
et al., 2020). However, it has been reported that the rate of viral load in the respiratory tract of
two patients with mild symptoms was 5.2 and 7.4 log10 copies per 1000 cells 24 hours after the
onset of the disease (Lescure et al., 2020). There are conflicting reports on the relationship
between viral load and age, which sometimes links older age to higher viral load, and some
reports do not associate the two (To et al., 2020) (Zhou B et al., 2020).
In a research study, the samples of 82 patients were examined. In the daily
examination of the samples of throat swab and sputum of 2 patients, it was observed that the
viral load reached its peak in 5-6 days from the onset of symptoms (104 to 107 copies per mL).
At different severity levels of infection, the viral load ranged from 641 to 1.34×1011 copies per
mL. The average viral loads for throat samples and the sputum samples were 7.99 × 104 and
7.52 × 105, respectively. In deceased patients, the sputum samples collected in 8 days after the
onset of the disease had a high number of 1.34 × 1011 copies per mL. Positive results of RT-
PCR in 2 people who were exposed to infection before the onset of symptoms indicate the
possibility of people getting infectious before the onset of symptoms. Stool samples from 11 of
the 17 cases, 0-11 days after the onset of the disease, were positive with a lower viral load using
RT-PCR analysis (Tan Y et al., 2020). In another report, the authors found RNA of SARS-
CoV-2 in the blood of 6 of 57 patients. Since all of these 6 patients showed severe symptoms,
they concluded that there is a strong association between the disease severity and the serum
viral RNA (p-value = 0.0001) (Chen W et al., 2020).
Lagunas-Rangel investigated the neutrophil to lymphocyte and Lymphocyte-to-CRP
ratio in COVID-19 patients to understand if these values can predict the severity of the disease.
He conducted a meta-analysis on six studies with 828 patients and reported in severe COVID-
19 patients, the neutrophil to lymphocyte ratio is significantly increased (SMD=2.404, 95%
CI=0.98 to 3.82), whereas the lymphocyte to-CRP ratio is decreased (SMD= -0.912, 95% CI=
-1.275 to -0.550] (Lagunas Rangel 2020).
According to the study findings presented by Liu et al., in which 61 patients were
monitored, it was concluded that neutrophil to lymphocyte ratio could be a prognostic marker
for the identification of severe diseases. This marker has overridden the MuLBSTA score
known for monitoring COVID-19 patients. The following report from 40 patients’ data verified
the conclusion above. The number of lymphocytes in severe cases is considerably lower (0.7 ×
109 /L) than in moderate cases (1.1 × 109 /L), based on Chen’s report. The absolute number of
T lymphocytes, CD4+ T, and CD8+ T cells experienced a decline in almost all the patients and

37
was significantly lower in severe cases (294.0, 177.5, and 89.0 × 106 /L) than that in the
moderate cases (640.5, 381.5 and 254.0 × 106 /L). The expressions of IFN-γ by CD4+ T cells
were lower in severe cases (14.1%) than in moderate cases (22.8%) (Chen G et al., 2020).,
Moreover, Zheng et al., assessed the differences between 103 COVID-19 and 22 non-COVID-
19 pneumonia cases through examining the laboratory parameters. The lymphocyte subsets
number had a remarkable negative relationship with biochemical indices that are related to
organ injury in the patients infected by COVID-19. In a similar way, the phenomenon of
lymphocyte depletion (PLD) was explained by Zeng et al., This phenomenon was reported in
a 100% proportion of severe or critical cases [ICU]. With the advancement of the disease, the
lymphocyte amount fell drastically. An investigation by Tan et al., affirmed the observation of
Lymphopenia. In the beginning, the number of lymphocytes declined in severe patients, after
which it rose by above 10% till discharge. However, there was a briefA Review on Biochemical
and Immunological Biomarkers the Open Microbiology Journal, 2020, Volume 14 293
fluctuation in the number of lymphocytes after initiation of disease, followed by an increase
above 20% during discharge in moderate patients. Since eosinopenia is regularly noticed in
COVID-19 patients (79% in SARS-CoV-2 positivepatients compared to 36% in SARS-CoV-2
negative patients), a straight forward alternate method has been offered to assist triage of
patients. This method resulted in a diagnosis specificity and sensitivity of 64% and 79%,
respectively (Xiuli Ding M et al., 2020). As reported in previous studies, severe cases had the
tendency have higher leukocytes amount, lower number of lymphocytes, a lower proportion of
eosinophil, monocytes, basophils, and a higher neutrophil to lymphocyte ratio. The majority of
severe cases showed an increased number of inflammatory cytokines and infection-related
biomarkers. Lymphocyte subgroups were examined in 44 patients with COVID-19 on
admission. There was a dramatic decrease in total number of T cells, B cells, and NK cells in
patients with COVID-19, especially in severe cases. On the other hand, the proportion of naïve
helper T cells (CD3+, CD4+, CD45RA+) rose while that of memory helper T cells
(CD3+CD4+CD45RO+) fell in severe cases (Quin C et al., 2020).
High CRP is a significant trait of COVID-19 (Zhang z et al., 2020). A study of 12
patients demonstrated that blood biochemistry indexes such as lactate dehydrogenase (LDH),
CRP and albumin might be a hallmark of disease severity (Lin D et al., 2020). Also, based on
the report by Liu et al., CRP was found to be high in a group of patients with progressive
disease compared with improved/stabilized group (38.9 [14.3, 64.8] vs. 10.6 [1.9,33.1] mg/L,
U = 1.315, P = 0.024). The level of albumin was considerably higher in the
improvement/stabilization group than that of the progression group (41.27 ± 4.55 g/L vs. 36.62
± 6.60, U = 2.843, P = 0.006). Based on the observations by Li et al., there was a dramatic rise
in the levels of CRP and Serum Amyloid A (SAA). Over the disease progression, the levels of
SAA and CRP increased, while the number of lymphocytes declined. By analyzing the ROC
curve, it could be concluded that the levels of CRP, SAA, lymphocyte numbers, and
SAA/lymphocyte ratio are useful data for assessing the severity of COVID-19 and separation
of severe cases from mild ones. Also, it is more likely that the CT images of patients who have
initially high levels of SAA are poor [39]. As explained in the report by Fan et al., 50.7% of
148 patients had an aberrant liver function on admission with increased Gamma-glutamyl
Transferase (GGT), AKP, Aspartate Aminotransferase (AST), and Alanine Aminotransferase
(ALT) levels. Levels of LDH, high-sensitivity CRP, ALT, and ferritin were considerably higher
in severe cases (41.4 U/L,567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than that in moderate cases
(17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). Moreover, the concentrations of TNF-α, IL-
2R and IL-10 were higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL)

38
compared to mild cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL) on admission (Chen G et al.,
2020).
Also, the level of the plasma angiotensin II fromCOVID-19 patients was raised and
had a linear correlation with lung injury and viral load (Lin D et al., 2020). The enhanced
amount of procalcitonin is related to an almost 5-fold higher risk of severe SARS-CoV-2
infection (OR, 4.76; 95% CI, 2.74-8.29) based on a meta-analysis by Lippi et al., Among
various studies, the heterogeneousness was moderate (i.e., 34%). Since this biomarker synthesis
is prevented by INF-γ, its concentration is assumed to rise over the period of viral infections;
the authors think that an elevated amount of procalcitonin could illustrate bacterial
superinfection in severe cases. However, more researches are required to be carried out to
determine the biomarker’s origin. Lippi et al., evaluated the level of cardiac troponin I (cTnI)
in patients with COVID-19 by conducting a meta-analysis. Despite high heterogeneity, the
amount of cTnI rose in the patients with severe illness compared to those without severity
(SMD, 25.6 ng/L; 95% CI, 6.8–44.5 ng/L).
Serum ferritin, IL-10, and IL-6 levels were considered an essential determinant for
severe diseases. According to the findings by Terpos et al., different criteria are capable of
determining the severity. For instance, thrombocytopenia, lymphopenia, and neutrophilia could
anticipate acute respiratory distress syndrome (ARDS), as well as cardiovascular
complications. Increased levels of ferritin, CRP, LDH, IL-6, procalcitonin, and coagulation
disorders (PTT, Ddimer, aPT, and increased fibrin degradation) have also been emphasized.
In another study on 47 patients by Han et al., the author reported that LDH had
the most positive relationship with the severity of disease; there is also a strong correlation of
LDH with lung damage. They also reported that LDH had a positive correlation with CRP,
AST, Blood Urea Nitrogen (BUN) and cTnI, and a negative correlation with lymphocytes. In
severe cases, during the 14-days monitoring period, they observed an increase in CRP and a
decrease in lymphocytes, especially CD3+, CD4+, and CD8+ T cells.
Zhou et al., performed blood and urine analysis in 178 patients. The serum
creatinine (Scr) did not increase in patients; also, BUN increased in 2.8% of the patients,
indicating “kidney dysfunction” in a few cases. In 54.2% of 83 patients without any kidney
disease history, 45 (54.2%) patients showed proteinuria, hematuria, and leukocyturia, in their
urinalysis, whereas no Acute Kidney Injury (AKI) parameter was observed. It is noteworthy
that patients who show such abnormalities in their urinalysis, usually have higher liver injury
inflammation and coagulation parameters, and they are more severe cases compared to the
others. It has been suggested to use urinalysis which could be an excellent method to evaluate
disease severity.
Tian et al., studied the patterns of the longitudinal changes in immunological
and biochemical parameters in 59 patients with COVID-19. At the onset of the disease, the
value of eosinophils reduced by 52.6%, and it increased significantly after that. Also, in 40.4%
of cases, the number of lymphocytes reduced at the onset of the disease, and then after 5 days,
it started to increase gradually. The platelet count in 12.3% cases reduced at the onset of the
disease, and after 7 days, the average value of mean platelet volume reduced significantly. After
day 7, in 30.6% of patients, the values of AST, LDH, creatine kinase, creatinine kinase-
muscle/brain activity, and cTnI, serum cardiac markers, were more than the upper limit of294
The Open Microbiology Journal, 2020, Volume 14 Ranjbar et al., RI. Also, the abnormity of
liver function tests, kidney function tests, electrolytes was 2.0%~59.2%, 2.0%~4.1%,
6.0%~30.0%, respectively.
39
 The coagulation data of 183 successive patients with verified COVID-19
pneumonia was explained by Tang et al., The levels of Fibrin Degradation Product (FDP) and
D-dimer were higher in non-survivors. Also, longer activated partial thromboplastin time and
prothrombin time were revealed in non-survivors compared to survivors on admission (P<0.05).
Zhou et al., realized that increased likelihood of in-hospital death is related to
the concentration of D-dimer higher than1·0 μg/L (18·42, 2·64–128·55; p=0·0033) on
admission [47]. In addition, according to the findings of Gao et al., levels of IL-6 and D-dimer
were associated with the occurrence of severe COVID-19 infection in adult patients, and their
combination provides the most sensitive and specific detection for predicting the severity of
disease in the early stage. In this study, the specificity of prediction was almost 93.3%, while
the sensitivity stood at 96.4%.

40
Discussion: -

According to 20 peers reviewed and 12 non- peer reviewed journal Hematological,

Biochemical and biomarker(inflammatory) abnormalities alterations related to covid-19
infection (ponti et al., 2020). These abnormalities are help to pre diagnosis of severe Covid-19
infection. These changes can cause high risk of mortality rate during and after Covid-19
infection occur. So, it is important to screen all patient with Covid-19 for hyperinflation using
laboratory parameters and/or indexes and to previewed the prognosis of severe disease in the
early period in terms of discussing mortality (Ranjbar et al., 2020). Hematological and
biochemical changes can occur and obtained present, the potential to optimize the monitoring
the infectious process or to indicate the suspension of their security laboratories abnormalities
particularly Hematological, biochemical and biomarkers changes allow checking the status of
sars cov-2 infection (Hang et al., 2020). Hematological abnormalities associated with Covid-
41
19 infection that cause life threatening to help predilecting Covid-19(Mareellociacio and luise
Angello 2020).
Differential Alterations in Covid-19 infection infection
Lymphocyte
According to who Covid-19 is a viral infection as research proved Covid-19 infection induce
lymphocyte activation, undifferentiated lymphocyte proliferation and antibody cytokinesis
lymphokine secretion. The immune defense against viral infection (Covid-19) is more
dependent on t and b lymphocyte and less dependent on antibodies. Cytotoxins t cells are
important in killing virally infected cells. So as a auto immunization process of human body
leucocyte count is increase then normal in Covid-19 infected patient.
Neutrophil
During Covid-19 as respiratory viral infection neutrophils are recurred to activated the lung
infection during and after the infection occur neutrophil numbers increase early during infection
and neutrophils exert their affecter function and add in tissue repair and resolutions of viral
(Covid-19) information (JK et al., 2020 and Sakt et al., 2020).
Eosinophil
As eosinophils contribute innate antiviral immunity and promote clearance respiratory
synthetical virus.
In during Covid-19 infection eosinophils count is also slightly increase in this infection as auto
immunization or to fight against this viral infection.
Basophil
Basophil are responsible for fighting fungal or bacterial infection and viral infection. They are
granulocytes cells which means they release granules of enzymes (histamine, heparin) to fight
against virus. So, if Covid-19 infection is occurring the basophil count is slightly upper than
normal to help fight against this virus (Slight et al., 2020).
Monocyte
As body fighting any kind of severe infection that may attributes to a high monocyte count as
regulate immunity against foreign substance. So, monocyte count is slightly increase during
Covid-19 infection occurs (Medieinet and Cheang et al., 2020).
Red cell abnormalities in Covid-19
Viral infection that affects bone marrow can play a role in the development of aplastic anemia.
As RBC develop in bone marrow, they lose their structural characteristics. Red blood cell of
Covid-19 patient had increased oxidation of structural proteins and alter lipid metabolism. So
structural characteristics is altered to be noted (BS Nagoba 2020).
Hemoglobin abnormalities in Covid-19
Certain sars cov-2 Proteins may attack the beta chain of hemoglobin thus reducing its level. A
reduction in hemoglobin (and thus oxygen content) may explain some of the symptoms.
Platelet alterations in Covid-19

42
As Covid-19 infection the host defense generally induces a systematic inflammatory response
which leads to platelet activation. Which in turn triggers platelet activation and decrease platelet
life spam. So, during infection increase immature platelet and after infection is cure platelet
count are slightly low in normal level.
Recent finding shows, beyond its hemostatic functions platelet play a main role in fighting
against pathogen including virus with their receptors platelet interacts with viral pathogen and
this infection between platelet and viral pathogen result in activation of platelet.
Coagulopathy (hypercoagubility) associated Covid-19 finding as Hematological changes
D-dimer level
D-dimer is a fibrin degradation product that is often used to measured and assess clot formation
our hypothesis is that probable mechanism for the increased D-dimer in Covid-19 related to
virus lifecycle. The apoptotic process target the endothelial cell of the vascular structure
resulting in triggered coagulopathy and the ultimate result of increase D-dimer. However, any
pathogenic or nonpathogenic process that increase fibrin production or breakdown also increase
plasma D-dimer as Covid-19 infection (pathogenic) that increase fibrin production or
breakdown that trigger increase D-dimer.
Fibrinogen
Plasma fibrinogen is synthesized in the liver is increased amount during the acute phase
response and these is mediated by the cytokine. IL-6 respiratory virus infection (corona) can
increase IL-6 produce by blood monocyte and thus increase the plasma fibrinogen level during
covid infection.
PT&APTT
Several mechanisms have been altered coagulation in covid-19. The antiviral inflammatory
response may shift the balance in the anticoagulant and procoagulant pathway leading the
alteration coagulation (Giamis et al.,2020). Von Willebrand Factor (VWF) is procoagulant that
is release, ed in the presence of endothelial cell damage and has been formed to elevated PT
and APTT covid -19 (Eseher et al., 2020). Increased level of several inflammatory biomarker
including cytokine such as IL-6, IL-2, IL-7, TNFd, Interferon y, monocyte chemoattraction
protein; macrophage inflammatory protein, procalcitonin, ESR&CRP.
Interleukins 6,2,7,8
Interleukins are group of naturally occurring proteins that medicate communication between
cell. Interleukins regulate cell growth, Cliff rendition and motility. They are partiality important
in stimulation immune response such inflammation (Beachbord and hormer) as covid is severe
type of inflammation in respiratory system. Interleukins are permanently increase in normal.
Tumor Necrosis factor-α
TNF a plays a critical role in the control of viral infection such as covid through the recruitment
and activation of macrophages so TNF α is increase in after severe covid patient treatment.
Interferon γ
Interferon γ is not only marker of T(H), CD4, CD8 and Natural mediator which is ertral to the
elimination of virus. Interferon y is hallmark alteration in covid 19 (Robba et al., 2020).

43
Monocyte chemoattraction protein
Monocyte chemoattraction protein belongs to the small inducible cytokine family and is
involved in recruitment of monocyte to site of injury, infection and carcinogenesis. During
Covid-19 infection cytokine are formally increase as relatively MCP-1 is also increase in this
disease pathogenesis.
Macrophage inflammatory protein
Macrophage inflammatory protein suggest potentially unique role for this monocyte-derived
cytokinesis in combination with IL-12. As MIP -1 is known to potential the action of IFN-
gamma. On monocyte to sugar virus replication. The MIP may important during the innate
immune response to infection. So, the sever type of infection like COVID-19 may elevated
macrophage inflammatory protein.
Procalcitonin
Procalcitonin is the substance produce by many types of cells in the body. Often in response to
bacterial infection but also in response to tissue injury relative to viral infection. As in Covid-
19 infection severe type of tissue injury are found so procalcitonin can elevated in this infection.
ESR
Moderately elevated ESR occurs with inflammation but also with anemia, infection pregnancy.
A very high ESR usually has an obvious cause, such as a severe infection. So Covid-19 is severe
type of infection ESR level is highly elevated in this infection.
CRP
CRP is protein made by liver and sent in blood stream. Blood level may be higher when body
survive against any type of infection and inflammation. CRP level go up before any type of
pain or fever and drop down as recover. The CRP test useful for travelling infection as Covid-
19 severe type of infection. The CRP level may high in this infection. The elevated CRP level
might be linked to inflammatory cytokinesis in severe patient with Covid-19 infection (Grabaye
et al., 2020). So, CRP level may increase in Covid-19 infection.
Different type of biochemical markers which are produced by different organ damage in human
body like hepatitis muscular, renal, cardiac biomarkers may also alter in Covid-19 infection,
which causes high mortality high disease severity, high risk of mobility in general the
biochemical biomarkers that are alter amino in during and after Covid-19 infection like Alanine
aminotransferase, Aspartate aminotransferase, Total bilirubin , Albumin, Creatinine kinase,
Myoglobin, Creatinine, Cardiac troponin, Brain matraite peptide, LDH, MDW, GGT.
Alkaline aminotransferase, Aspartate aminotransferase, Total bilirubin, Albumin
Increase serum level of AST, ALT, Total bilirubin, Albumin indicate hepatocellular injury.
Increased serum level of ALT and AST indicate severe type of liver damage such as viral
infection, toxic injury. While ALT is liver specific and AST is indicated also multiple organ
damage. In severe type of covid infection liver cell are damage with multiple organs. So, AST,
ALT and Total bilirubin, serum albumin are increased in this infection.

44
Creatinine kinase myoglobin
Creatinine kinase and myoglobin increase indicate muscle injury. CK can rise after skeletal
muscle injury where increased myoglobin level can occur after muscle injury kidneys are
falling.
In Covid-19 infection the virus binds to the angiotensin converting enzyme (ACE-2)
receptors present in the vascular epithelial cell, lungs, heart, kidneys, intestine, liver, muscle
and other tissue. Then the tissue is damaged rapidly thats why creatinine kinase and myoglobin
increase in Covid-19.
Creatinine
Serum creatinine increase that reported kidneys are falling several studies reported (Jomdis et
al., 2020). Sars cov-2 could directly infected kidney tubular cell which expresses ACE 2
receptors on their cellular surface. So, creatinine level is high in normal.
Cardiac troponin Brain matraite peptide
Damage to the heart muscle cell is the classic cause to high troponin level and BNP is increased
when hypertension is occurred. In Covid-19 infection the heart is severally infected reported
several studies that CTN, BNP increases.
LDH
Lactate dehydrogenase is an enzyme found in almost all body tissues. It plays an important role
in cellular replication. Although LDH is abundant in tissue cells blood level of the enzyme
normally low. However, tissue is damaged by injury or disease the release more LDH in to
blood stream in Covid-19. Several tissues are affected due to cytokines Strome or ACE2
receptors that bind sars in covid infection LDH is highly increase in normal level.

45
MATERIALS AND METHODS:
Databases including PubMed, medRxiv, and bioRxiv were searched for peer-reviewed and
non–peer-reviewed papers. Search terminology included COVID-19 search terms (COVID-19,
SARS- CoV-2, 2019-ncov) and laboratory parameters: white blood cell count (WBC),
lymphocyte count, platelet/thrombocyte count, coagulation, prothrombin time (PT), D-dimer,
fibrinogen, LDH, ferritin, CRP, SAA, procalcitonin, and interleukin 6 (IL-6). A total of 100
papers, including 68 peer-reviewed papers and 32 non–peer-reviewed preprints, with data
including hematologic, coagulation, biochemical, or inflammatory parameters and their role
and predictive value in mild, severe, and critically ill patients were reviewed. Within the total
reviewed papers, 43 cohort studies and 11 systematic reviews (including meta-analysis) were
extract- ed. Where applicable, statistical significance was represented in the literature by
minimum P values of P 0 .05. Relevant data were collected by 2 independent reviewers.

46
 Conclusion
The emergency pandemic situation is of high scientific significance to analyze the
discriminative ability of hematologic, biochemical, inflammatory, and immunologic
biomarkers in patients with and without the severe or fatal forms of COVID-19. It is necessary
to determine risk categories following COVID-19 diagnosis, to ensure an optimal resource
allocation and to improve clinical management and prevention of serious complications. To
sum up, we can conclude from the analysis of published studies that hematological (lymphocyte
count, neutrophil count, and NLR), inflammatory (CRP, ESR, IL-6), and especially
biochemical (D-dimer, Troponins, CK) parameters correlate with severe prognosis or exitus in
COVID-19 patients and can therefore be used as predictive biomarkers. Coagulation and liver
parameters might play a crucial role in identifying severe cases of COVID-19. Understanding
the weight of the pathophysiological processes of systemic cardiovascular damage (vasculitis,
DIC, myocardial infarction) and metabolic processes associated to the critical course of the
infection, also thanks to autopsy cohorts [68,108–110], sets new light on biochemical
biomarkers related to coagulation disorders. These are in fact not only predictive of disease
severity, but are also helpful for the therapeutic man- argument, based on drugs preventing the
activation of coagulation processes. A laboratory score, taking into account hematological,
inflammatory, biochemical and immunological parameters, would help to stratify COVID-19
positive patients into risk categories, which would be of outmost importance in the clinical
setting and therapeutic management. In addition to above discussed laboratory parameters,
which are currently used in clinical practice, novel biomarkers potentially useful for screening,
clinical management, and prevention of serious complications are under investigation. These
include Hcy, Ang II, Ang- (1-7), Ang-(1-9), and almandine, which need to be evaluated in
larger case series in order to clearly deter- mine their predictive clinical value as indicators of
severe prognosis in COVID-19 patients.

47
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