Diagnostic & prognostic value of

hematological &
immunological markers in COVID-
19 infection:
A/P Dr. Saifeldein M. A. Elimam
MBBS, MSCP, MSCH
Consultant Hematopathology
MCH- Najran- KSA
12/05/2021 1
 Lecture contents
1- Objectives.
2- Introduction.
3-Pathological effects of COVID- 19.
4- Important Hematological & Immunological markers related to
COVID- 19 infection.
5- Diagnostic and prognostic values of hematological and
immunological markers in COVID-19 infection.
6- Conclusion.
7- References.

12/05/2021 2
 Objectives
1- To correlate the diagnostic & prognostic markers to disease severity.
2- To stratify patients according to the severity of disease.
3- To recognize patients at high risk who may need ICU.
4- To discover & manage critical cases early.
5- To conserve healthcare resources.
6- To decrease the burden on healthcare facilities.
7- To decrease the overall morbidity and mortality.

12/05/2021 3
 Introduction
• COVID- 19 is a disease detected in Wuhan, China, and led to the
risk of mortality of about 2% of patients and a wide range of
morbidity.
• It is caused by ( SARS- COV- 2).
• Symptoms appear in the first 7 days with fever, cough, shortness
of breath and fatigue.
• Afterwards, critical symptoms may develop, including dyspnea
and pneumonia that require patients management in ICU to
avoid serious respiratory complications and multiple organ failure
that may lead to death.
12/05/2021 4
 Introduction
• The heterogeneous disease course of COVID-19 is unpredictable,
ranging from mild self-limiting symptoms to cytokine storms, acute
respiratory distress syndrome (ARDS), multi-organ failure and death.
• Knowledge of the pathogenesis of COVID- 19 is very important for one
to link the infection to the hematological & immunological changes,
and to use these markers in the diagnosis of the disease and
prognosis of patients.
• Hence, I will go briefly through the pathological effects of COVID- 19
on severely affected patients.

12/05/2021 5
Pathological effects of COVID- 19
infection:
• Infection may pass unnoticed, or may cause mild sore throat with or
without other mild symptoms.
• We are mainly concerned with infection that may lead to severe
morbidity and mortality.
• In this case, what is called cytokine storm is being accused as the
cause of severe disease that require ICU.
• Following the early inoculation of SARS- COV- 2 into the airways, it will
settle into the alveoli, and attaches itself to receptors found in the
pneumocytes type 2.

12/05/2021 6
12/05/2021 7
12/05/2021 8
 Pathological effects of COVID- 19
infection:
• What is the role of micro and macro- phages?
• The virus then reach the tissue surrounding the alveoli and finds the
immune officers awaiting its arrival.
• What is the role of these immune cells?
• Main cytokines released are: TNF, IL6, IL1, IL10, IFN, and many others.
• T cells & NK cells are potent contributors of cytokine inflammatory
response; they cause: Vaso dilatation* & oedema* increase extravascular
pressure* decrease perfusion*

12/05/2021 9
Diagnostic & prognostic value of hematological
markers in COVID- 19 infection
• Coagulation:
• SARS- COV- 2 causes hyper coagulation and DIC in late stage of the
disease and this is a bad prognostic feature which starts with emboli.
• The mechanism of this hypercoagulable state is not yet clear but, there
are some hypothesis i.e. :
1- Severe inflammation & virus binding to the endothelial cells with the
release of cytokines is a risk for thrombi.
2- Renin angiotensin system could be activated because of the drop in the
blood pressure.
3- Decreased mobility.
12/05/2021 10
 Diagnostic & prognostic value of
hematological markers in COVID- 19
infection
• Coagulation:
• D- dimer increases leading to increased mortality*.
• Fibrinogen could either be normal or increased. It increases in late
stage indicating bad prognosis.
• Thrombocytopenia is found less common in DIC which is also a bad
prognostic feature.
• PT/INR often elevated and helps in monitoring severity of the disease.
• APTT could be normal or slightly reduced*.
• FV111 & VWF are elevated in severe disease.
12/05/2021 11
 Diagnostic & prognostic value of
hematological markers in COVID- 19
infection
• Lymphocytes: Are initially normal or slightly reduced. 7 – 14 days
later, with the release and increase of cytokines and inflammatory
mediators; lymphopenia occurs because they express ACE11
receptors on their surface and hence, attacked by the virus.
• Cytokine storm promotes lymphocyte apoptosis and atrophy of the
lymphoid tissue which further impair the lymphoid turnover.
• Coexisting lactic acidosis inhibits lymphocyte proliferation.
• Lymphopenia is associated with severe disease and ARDS.

12/05/2021 12
 Diagnostic & prognostic value of
hematological markers in COVID- 19
infection
• Platelets: Usually during the initial phase of COVID- 19 infection there
could be a decreased platelets count.
• Increased platelets count on the other hand, is related to platelets
activation by cytokine storm which indicates severe infection and
carries poor prognosis.
• Neutrophilia is associated with increased risk of death*.
• ESR: Increased in severe infection and it an indirect indicator for
fibrinogen level.

12/05/2021 13
 Diagnostic & prognostic value of
immunological markers in COVID- 19
infection
• Lymphoplasmacytoid cells: These cells may be seen in the peripheral
blood of severely infected and at risk patients*.
• Impaired function of CD4+ helper and hyper-activation of CD8+ T cells
lead to exhaustion of cytotoxic CD8+ T cells and lymphopenia. Hence,
serial assessment of lymphocytes count is a predictor for survival.
• Increased IL6 is associated with increased risk of death.
• Usually IgG, IgM, IgA, C3 and C4 are normal in COVID- 19 patients, but
in severe infection, IgG level could be low.

12/05/2021 14
12/05/2021 15
Comparison between markers of survivors
& non survivors of COVID- 19 infection
• Many studies related to survivors and non survivors have been
conducted to predict the course of the disease. Many studies
concluded that:
• Increased IL6 is associated with increased risk of death.
• Increased PT is associated with increased risk of ARDS.
• Increased D- Dimer is associated with increased risk of ARDS and
death.
• Increased FDP and fibrinogen are associated with increased risk of
death.

12/05/2021 16
 Conclusion:
• Difficulties in inventing specific vaccine and treatment for COVID- 19
are mainly due to the shuffling process of the mosaic part of the gene
of SARS- COV- 2, whereby, it is able to form a lot of combinations of
the viral antigen.
• Continuous researches and studies of inflammatory, hematological
and immunological markers remains of great value to understand and
predict the course of the disease and to anticipate the need for ICU
and manage healthcare resources.

12/05/2021 17
 References:
1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical
characteristics of coronavirus disease 2019 in China. N Engl J
Med. 2020. https ://doi.org/10.1056/NEJMo a2002 032.
2. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C,Gulyaeva AA, et al.
Severe acute respiratory syndrome related coronavirus: the species and its—
viruses a statement of the Coronavirus Study Group. bioRxiv. 2020.
https ://doi. org/10.1101/2020.02.07.93786 2.
3. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia
outbreak associated with a new coronavirus of probable bat origin. Nature.
2020;579(7798):270–3. https ://doi. org/10.1038/s4158 6-020-2012-7.
12/05/2021 18
 References:
4. Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, et al.
SARS-CoV-2, SARS-CoV, and MERS-COV: a comparative overview. Le
infezioni in medicina. 2020;28(2):174–84.
5. Novel coronavirus infected pneumonia treatment scheme—Sixth
edition. National Health Commission of the People’s Republic of China.
2020. https ://www.nhc.gov.cn/yzygj /s7653 p/20200 2/8334a 8326d
d94d3 29df3 51d7d a8aef c2.shtml . Accessed 19 Feb 2020
6. Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis
disease pathogenesis. Semin Immunopathol. 2017;39(5):517–28.
https ://doi.org/10.1007/s0028 1-017-0639-8.
12/05/2021 19
 References:
7. Radbel J, Narayanan N, Bhatt PJ. Use of tocilizumab for COVID- 19
infection-induced cytokine release syndrome: a cautionary case report.
Chest. 2020. https ://doi.org/10.1016/j.chest .2020.04.024.
8. Zhang S, Li L, Shen A, Chen Y, Qi Z. Rational use of tocilizumab in the
treatment of novel coronavirus pneumonia. Clin Drug Investig.
2020. https ://doi.org/10.1007/s4026 1-020-00917 -3.
9. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are
associated with poor prognosis in patients with novel coronavirus
pneumonia. J Thromb Haemost. 2020;18(4):844–7.
https :// doi.org/10.1111/jth.14768 .
12/05/2021 20
 References:
10. Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, da Ferraz
Silva LF, de PierreOliveira E, Nascimento Saldiva PH, et al. Pathological
evidence of pulmonary thrombotic phenomena in severe. J Thromb
Haemost. 2020. https ://doi.org/10.1111/ jth.14844 .
11. PubMed, Science direct, WHO and other websites.

12/05/2021 21
 THANK YOU
12/05/2021 22