This document discusses the pathophysiology and laboratory investigations of COVID-19. It begins with an overview of the objectives and then discusses the direct viral infection process, the immune response, and COVID-19 induced coagulopathy as they relate to the pathophysiology. It also discusses several diagnostic and prognostic laboratory parameters including viral detection methods, antibody detection, and hematological parameters seen in complete blood counts. Specifically, it notes the role of hypoxia-inducible factors, inflammation, and endothelial injury in driving the coagulopathy seen in COVID-19 patients.
TheNeuroSurgeons sponsored the presentation to the Zimbabwe Association of Neurological Surgeons.
we are learning more about the neurological manifestations of the novel coronavirus as we are frantically looking for solution to this formidable pandemic.
Chronic Obstructive Pulmonary Disease BY
Dr Akram Yousuf
Resident Internal Medicine
Liaquat University of Medical Health and Sciences Jamshoro Pakistan
COVID-19 can cause lung complications such as pneumonia and, in the most severe cases, acute respiratory distress syndrome, or ARDS. Sepsis, another possible complication of COVID-19, can also cause lasting harm to the lungs and other organs.
This presentation discusses about the etiology, clinical features, complications and management of Septic Shock.
The information compiled in this presentation (from medical textbooks and internet sources) does not belong to me, but has been done so for educational purposes
PATHOGENESIS OF BRONCHIECTASIS BY DR BASHIR AHMED DAR ASSOCIATE PROFESSOR MED...Prof Dr Bashir Ahmed Dar
Dr Bashir Ahmed Dar associate professor medicine chinkipora sopore kashmir presently working in malaysia speaks about bronchiectasis.Bronchiectasis which is defined as the irreversible dilatation of the cartilage-containing airways bronchi or bronchioles.
Monitoring Cellular Immune Response in Real Time with Next Generation Immunoa...InsideScientific
To learn more and watch the webinar, go to:
https://insidescientific.com/webinar/monitoring-cellular-immune-response-in-real-time-with-next-generation-immunoassays-on-the-ella-platform/
Experts discuss the use of Simple Plex immunoassays on Ella to monitor the cellular immune response to SARS-CoV-2 in real time.
Ella enables the rapid and high quality cytokine and pro inflammatory biomarker monitoring in support of disease severity and progression research in a multi-analyte, automated and standardized format.
Carmen Cámara Hijón, PhD – Usefulness of Cytokine Measurement to Support Decision-Making in Patients with COVID-19
The correct characterization of the immune response induced by SARS-Cov-2 includes the pattern of cytokines in peripheral blood. Dr. Carmen Camara discusses how assaying cytokine profiles allows us not only to establish a cause-effect relationship in unusual conditions (e.g. chiblain lesions and COVID-19) but even to make therapeutic decisions in some of them (e.g. pediatric multisystemic inflammatory syndrome).
She also describes a fast and cost-efficient method of measuring the cellular response induced by vaccines by measuring IFN-γ and IL-2 after whole-blood overnight stimulation with SARS-CoV-2 peptides, to identify the correlate of immunity in patients at risk, such as those with primary immunodeficiencies.
Martina Fabris, MD – Cytokines and COVID-19: The Value in Risk Stratification Within the First 72 Hours of Hospitalization
It is increasingly clear that the immune response to COVID-19, and not the pathogen itself, is responsible for the exaggerated release of inflammatory molecules during infection. Several cytokines play a key role in SARS-CoV-2 pathogenesis and can help to identify patients with worse prognosis or in a different phase of the pathological process. However, these cytokines can be difficult to assay, and we do not yet understand their relationship with classic inflammatory markers like CRP.
Dr. Martina Fabris discusses which cytokines, alongside standard markers of systemic inflammation, are most valuable in identifying patients at a high risk of an unfavorable outcome, and on the other hand, low-risk patients who can reasonably be discharged from the hospital. She also describes the challenge of using these new biomarkers effectively in daily clinical practice to support complicated diagnoses, to evaluate risk more effectively, and to ensure increasingly targeted therapies.
DISCLAIMER: The Ella™ automated immunoassay platform is currently offered for research use only; not for use in diagnostic procedures.
TheNeuroSurgeons sponsored the presentation to the Zimbabwe Association of Neurological Surgeons.
we are learning more about the neurological manifestations of the novel coronavirus as we are frantically looking for solution to this formidable pandemic.
Chronic Obstructive Pulmonary Disease BY
Dr Akram Yousuf
Resident Internal Medicine
Liaquat University of Medical Health and Sciences Jamshoro Pakistan
COVID-19 can cause lung complications such as pneumonia and, in the most severe cases, acute respiratory distress syndrome, or ARDS. Sepsis, another possible complication of COVID-19, can also cause lasting harm to the lungs and other organs.
This presentation discusses about the etiology, clinical features, complications and management of Septic Shock.
The information compiled in this presentation (from medical textbooks and internet sources) does not belong to me, but has been done so for educational purposes
PATHOGENESIS OF BRONCHIECTASIS BY DR BASHIR AHMED DAR ASSOCIATE PROFESSOR MED...Prof Dr Bashir Ahmed Dar
Dr Bashir Ahmed Dar associate professor medicine chinkipora sopore kashmir presently working in malaysia speaks about bronchiectasis.Bronchiectasis which is defined as the irreversible dilatation of the cartilage-containing airways bronchi or bronchioles.
Monitoring Cellular Immune Response in Real Time with Next Generation Immunoa...InsideScientific
To learn more and watch the webinar, go to:
https://insidescientific.com/webinar/monitoring-cellular-immune-response-in-real-time-with-next-generation-immunoassays-on-the-ella-platform/
Experts discuss the use of Simple Plex immunoassays on Ella to monitor the cellular immune response to SARS-CoV-2 in real time.
Ella enables the rapid and high quality cytokine and pro inflammatory biomarker monitoring in support of disease severity and progression research in a multi-analyte, automated and standardized format.
Carmen Cámara Hijón, PhD – Usefulness of Cytokine Measurement to Support Decision-Making in Patients with COVID-19
The correct characterization of the immune response induced by SARS-Cov-2 includes the pattern of cytokines in peripheral blood. Dr. Carmen Camara discusses how assaying cytokine profiles allows us not only to establish a cause-effect relationship in unusual conditions (e.g. chiblain lesions and COVID-19) but even to make therapeutic decisions in some of them (e.g. pediatric multisystemic inflammatory syndrome).
She also describes a fast and cost-efficient method of measuring the cellular response induced by vaccines by measuring IFN-γ and IL-2 after whole-blood overnight stimulation with SARS-CoV-2 peptides, to identify the correlate of immunity in patients at risk, such as those with primary immunodeficiencies.
Martina Fabris, MD – Cytokines and COVID-19: The Value in Risk Stratification Within the First 72 Hours of Hospitalization
It is increasingly clear that the immune response to COVID-19, and not the pathogen itself, is responsible for the exaggerated release of inflammatory molecules during infection. Several cytokines play a key role in SARS-CoV-2 pathogenesis and can help to identify patients with worse prognosis or in a different phase of the pathological process. However, these cytokines can be difficult to assay, and we do not yet understand their relationship with classic inflammatory markers like CRP.
Dr. Martina Fabris discusses which cytokines, alongside standard markers of systemic inflammation, are most valuable in identifying patients at a high risk of an unfavorable outcome, and on the other hand, low-risk patients who can reasonably be discharged from the hospital. She also describes the challenge of using these new biomarkers effectively in daily clinical practice to support complicated diagnoses, to evaluate risk more effectively, and to ensure increasingly targeted therapies.
DISCLAIMER: The Ella™ automated immunoassay platform is currently offered for research use only; not for use in diagnostic procedures.
Immune Responses To The Pandemic New Coronavirus (COVID-19)by Prof. Mohamed L...Prof. Mohamed Labib Salem
In response to an invitation from Benha University, in this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt, presents entitled "Immune Responses To The Pandemic New Coronavirus (COVID-19)".
في هذه المحاضرة يقدم يا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر محاضرة عن فيروس كورونا والمناعة
Lymphocytopenia and COVID19 A Literature Reviewijtsrd
The novel coronavirus SAR CoV 2 has resulted in huge wave of worldwide fear by its contagious nature, virulence and high mortality. Persistence condition of the disease with T cells and Natural killer cells exhaustion leads to Lymphopenia or Lymphocytopenia. Lymphocytopenia is a condition of low lymphocyte count in the blood. Lymphocytopenia is an important adverse effect of COVID 19 as well as negative prognostic marker in many malignancies. It leads to hyper activation of immune system that can cause immunosuppression and promote cytokine storm that eventually leads to multi organ failure and death. Restoration of lymphocytes and its function would be helpful to boost the immune response against COVID 19 disease. This review analyses the possible causes that may lead to the lymphocyte reduction in COVID 19 patients, and highlighting the possible therapeutic strategies that will help to control and prevent lymphocytopenia in COVID 19 patients. Shatabdi Dey | P. K Sahoo "Lymphocytopenia and COVID19: A Literature Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38373.pdf Paper Url: https://www.ijtsrd.com/biological-science/immunobiology/38373/lymphocytopenia-and-covid19-a-literature-review/shatabdi-dey
The coronavirus infection coronavirus disease 2019 (COVID-19) first presented as an outbreak of atypical pneumonia in Wuhan, China, on December 12, 2019.1,2 Since then, it has spread globally to infect >1 963 943 individuals and killed >123 635 in >200 countries as of April 14, 2020. This infection has affected health and the economy worldwide on an unprecedented scale.
Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus.
Most people who fall sick with COVID-19 will experience mild to moderate symptoms and recover without special treatment.
Similar to COVID-19; Updates on Pathophysiology and Laboratory Investigations (20)
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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How to Give Better Lectures: Some Tips for Doctors
COVID-19; Updates on Pathophysiology and Laboratory Investigations
1. Dr. Abdulsalam Al-Ani
Consultant Haematopathologist
College of Medicine, University of Anbar, IRAQ
COVID-19;
Updates on
Pathophysiology and
Laboratory Investigations
A Short Review
2. • Pathophysiology of SARS-CoV-2 Infection.
This require a further work to elucidate.
Direct Viral Infection.
Immune Response in COVID-19.
COVID-19 Induced Coagulopathy.
• Diagnostic and Prognostic Laboratory Parameters.
• Impact of Laboratory investigations.
OBJECTIVES
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
3. OBJECTIVES
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
• Pathophysiology of SARS-CoV-2 Infection.
This require a further work to elucidate.
Direct Viral Infection.
Immune Response in COVID-19.
COVID-19 Induced Coagulopathy.
• Diagnostic and Prognostic Laboratory Parameters.
• Impact of Laboratory investigations.
4. Poland G. A. et al, The Lancet, Oct, 2020. DOI: 10.1016/S0140-6736(20)32137-1
Viruses of the Coronaviridae family
have a single strand, RNA structure
with 26 to 32 kilobases length.
Same as other, severe acute
respiratory syndrome coronavirus
SARS-CoV, SARS-CoV-2 uses for
angiotensin-converting enzyme 2
(ACE2) as its S-protein main receptor,
which is broadly expressed in
vascular endothelium, respiratory
epithelium, alveolar monocytes, and
macrophages.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Su S. et al, Trends Microbiol. 2016;24:490–502
5. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
The SARS-CoV-2 has structural differences from
other coronavirus, in its surface proteins that enable
stronger binding to the ACE 2 receptor.
Greater efficiency at invading host cells.
Also it has greater affinity (or bonding) for the
upper respiratory tract and conjunctiva
Thus it can conduct airways more easily.
Muge Cevik et al. BMJ, Oct 2020;371:bmj.m3862
6. The virus binds to ACE 2
receptor in synergy with the
host’s transmembrane
serine protease 2
(TMPRSS2), which is
expressed in the airway
epithelial and vascular
endothelial cells.
This leads to membrane
fusion and releases the
viral genome into the
cytoplasm.
The Virus replicate leading
to viral assembly,
maturation, with the release
of the virus.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Muge Cevik et al. BMJ, Oct 2020;371:bmj.m3862
7. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Marcello C. and Agnello L. Diagnosis 7,4: doi; 10.1515/dx-2020-0057, 2020.
8. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Neutrophi
l
Neutrophi
l
Pluripotent SC
9. TMPRSS2;
Transmembrane
Serine Protease
Tay, M.Z. et al. Nat Rev Immunol; 20, 363–374,
2020.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
When SARS-CoV-2 infects cells
expressing the surface ACE2
receptors and Transmembrane
Serine Protease2 (TMPRSS2), the
active replication and release of
the virus cause the host cell to
undergo pyroptosis and release
damage-associated molecules.
10. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
MCP; Monocyte chemoattractant protein MIP ; Macrophage inflammatory protein
IP-10; IF gamma-
induced protein 10
Tay, M.Z. et al. Nat Rev Immunol; 20, 363–374,
2020.
Infected cells are recognised by
neighboring cells, endothelial cells
and alveolar macrophages, triggering
the generation of pro-inflammatory
cytokines and chemokines.
These proteins attract monocytes,
macrophages and T cells to this site,
promoting further inflammation.
11. Tay, M.Z. et al. Nat Rev Immunol; 20, 363–374,
2020.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
In a healthy immune response,
the initial inflammation attracts
virus-specific T cells which can
eliminate the infected cells before
the virus spreads.
Neutralizing antibodies in these
individuals can block viral
infection, and alveolar
macrophages recognize
neutralized viruses and apoptotic
cells and clear them by
phagocytosis.
12. G-CSF, granulocyte
colony-
stimulating factor
TNF, tumour necrosis
factor
Tay, M.Z. et al. Nat Rev Immunol; 20, 363–374,
2020.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
In a defective immune response,
this may lead to further
accumulation of immune cells,
causing overproduction of pro-
inflammatory cytokines, which
eventually damages the lung
tissue.
The resulting cytokine storm
circulates to other organs, leading
to multi-organ damage.
13. Parasher A, Postgrad Med J. doi:10.1136/postgradmedj-2020-138577 (modified image)
CXCL-10; C-X-C; chemokine ligand 10,
IFN; interferon, IL; interleukin, MCP-1;
monocyte chemoattractant protein-1,
MIP-1α; macrophage inflammatory
protein-1α, SARS-CoV-2, severe acute
respiratory syndrome coronavirus-2,
TNF-α; tumour necrosis factor-α, G-
CSF, granulocyte colony-stimulating
factor, GM-CSF, granulocyte-
macrophage colony-stimulating factor.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
About 80%
of all
patients
1
2 3
14. OBJECTIVES
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
• Pathophysiology of SARS-CoV-2 Infection.
This require a further work to elucidate.
Direct Viral Infection.
Immune Response in COVID-19.
COVID-19 Induced Coagulopathy.
• Diagnostic and Prognostic Laboratory Parameters.
• Impact of Laboratory investigations.
15. Mechanism of Coagulopathy
The novel coronavirus, SARS-CoV-2, activates the
thrombotic
process in addition to the inflammatory reaction.
The disease it causes is associated with hypoxia, an
increase in
inflammatory cytokines (storm) and coagulation disorders,
by endothelial injury, with predisposition to thrombus
formation.
3 main mechanisms play as procoagulants
predisposing for the coagulopathy;
1. Severe and prolonged hypoxemia.
2. High incidence of cytokine storms.
3. Local pulmonary endothelial injury.
B. Marchandot et al, J. Clin. Med. 2020, 9, 1651:
1-17
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
16. Serebrovska Z.O., et al. Acta Pharmacol Sin, Oct, 2020. https://doi.org/10.1038/s41401-
020-00554-8
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
1. Hypoxia-Inducible Factors.
HIF; are nuclear transcriptional factors essential for genes that
mediate cellular and tissue homeostatic responses to altered
oxygenation.
Cells adapt to hypoxia through the dynamic equilibrium
between ACE-1 and ACE-2, under the control of HIF-1 and
HIF-2.
Hypoxia is a primary feature and main cause of mortality
in patients with severe COVID-19, almost all disease
stages.
17. 1
2
3
4
5
C. S. Lim et al, J. OF V. Surgery, 58, 1; 219-230,
2013
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Effect of Hypoxia-inducible Factors
Pathway
18. Tay, M.Z. et al. Nat Rev Immunol; 20, 363–374,
2020.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
2. Inflammatory Effects
Inflammation is the triggering factor for thrombogenesis.
Cytokines and chemokines have been associated with an
important role in immunity and immunopathology during viral
infections.
In SARS-CoV-2 infection;
1- Immune response with the surge of cytokines and
inflammatory mediators, leading to activation of pro-coagulant
pathways.
2- On other hand, cytokines impaired the natural coagulation
pathways and shut down of fibrinolysis.
19. Perico, L. et al. Nat Rev Nephrol (2020). https://doi.org/10.1038/s41581-020-00357-4
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Tay, M.Z. et al. Nat Rev Immunol; 20, 363–374, 2020.
3. Endothelial Injury
Endothelial injury, can up-regulate tissue factor expression
and further drive a pro-thrombotic state.
Endothelial cell activation/damage with collagen exposure
tigering the activation of (TF), promoting hypercoagulation
may be explain the high thrombotic burden observed.
Disseminated Intravascular Coagulation (DIC) develops as an
advanced complication of sever infection and sepsis, which is
the causative factor of high mortality rate.
20. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Kumar V., Abbas A.K. & Aster J.C. Robbins and Cotran Pathologic Basis of Disease. 9th ed.: Saunders Elsevier.
21. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
COVID-19 Coagulopathy vs DIC
DIC, is a generalized consumptive process with
microangiopathic hemolytic process, while COVID-19 is a localized
process mostly to the lung alveoli.
1. Mild thrombocytopenia.
2. Prothrombin time (PT) not always elevated.
3. Normal activated partial thromboplastin time (aPTT).
4. No microangiopathic hemolytic process.
Iba T. et al, J Thromb Haemost. 2020;18:2103–2109.
22. OBJECTIVES
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
• Pathophysiology of SARS-CoV-2 Infection.
This require a further work to elucidate.
Direct Viral Infection.
Immune Response in COVID-19.
COVID-19 Induced Coagulopathy.
• Diagnostic and Prognostic Laboratory Parameters.
• Impact of Laboratory investigations.
23. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Laboratory Parameters
Laboratory medicine has a crucial role for the
appropriate COVID-19 management from the early
recognition to the assessment of disease severity.
Also for the prediction risk of evolution towards
severe disease, characterised by the impairment of several
organs and tissues.
Marcello C. and Agnello L. Diagnosis 7,4: 10.1515/dx-2020-0057, 2020.
24. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
1- Viral Detection
Samples are collected from the upper respiratory tract via
nasopharyngeal and oropharyngeal swabs and from the lower
respiratory tract via expectorated sputum and bronchoalveolar
lavage (for mechanically ventilated patients).
The sample examined by polymerase chain reaction (PCR)
The PCR results usually show positivity after 2–8 days and can
remain detectable up to 25–50 days after the onset of symptoms
and longer in the stool.
The sensitivity of these tests is not very high, approximately 53.3%
had positive oropharyngeal swabs, and about 71% with sputum
samples.
Parasher A, Postgrad Med J. doi:10.1136/postgradmedj-2020-138577
Peeling R. W. et al, Lancet Infect Dis; 20: e245–49, Sept. 2020
25. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Peeling R. W. et al, Lancet Infect Dis; 20: e245–49, Sept. 2020
2- Rapid Antigen Test
Rapid antigen detection tests are simple and can give results in
less than 30 min.
Although it offers an effective means in community settings, it
shows suboptimal sensitivity to be recommended for clinical
diagnosis.
26. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Peeling R. W. et al, Lancet Infect Dis; 20: e245–49, Sept. 2020
3- Antibody Detection (Serology Tests)
IgM antibodies start to be detectable around 5–10 days after
onset of symptoms and rise rapidly.
Seroconversion from IgM to IgG is typically within the first 3
weeks.
Neutralising antibodies can be detected approximately 7 days
after onset of symptoms and rise steeply over the next 2
weeks.
IgG titres (levels) usually remain for months or years.
WHO, Update: August 2020
27. Sethuraman N, Jeremiah SS & Ryo A. JAMA. 2020;323(22):2249–2251.
doi:10.1001/jama.2020.8259
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
28. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Liani D. et al, The Lancet Haematology 2020; 7: e671-e678
Parasher A, Postgrad Med J. doi:10.1136/postgradmedj-2020-138577 Tan L. et al. The Nature, Target. Ther., vol. 5, no. 1, pp. 16–18, 2020
4- Haematological Parameters in CBC
Haemoglobin concentration usually not affected.
A normal or decreased white blood cell count can be observed.
Lymphopenia found to be one of the commonest CBC parameters
abnormality.
This may due to a direct target of viruses or Inflammatory cytokines
on lymphocytes or the lymphatic organs (thymus and spleen).
Elevated blood levels of metabolites may inhibit lymphocytes
proliferation.
An elevated neutrophil-to-lymphocyte (N/L) ratio also reported.
Other WBC differential counts usually show variable results.
Mild thrombocytopenia can be present which correlates with the
severity.
30. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Tan L. et al. The Nature, Target. Ther., vol. 5, no. 1, pp. 16–18, 2020
5- Blood Film
Presence of reactive lymphocytes was reported, but still needs more
confirmative results.
Two lymphocyte subsets where observed; the large with abundant
cytoplasm with more darkly stained at the peripheral margins
(Hyperbasophilic) and the lymphoplasmacytoid forms.
Other WBC lineage showed variable degrees of changes.
As a complementary test, white blood cell (WBC) differential
fluorescence (WDF) scattergram shows atypical form. This consisted
of a discontinuous cluster of lymphocytes characterized by the
presence of more than four dots in the upper graduation of the
scattergram (‘sandglass’ aspect).
31. V. C. L. Chong, et al., Br. J. Haematol., 189.5;844, 2020 Al-Ani A., AMJ. doi.org/10.33091/AMJ.1001622020
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
32. Osman J. et al, British Journal of Haematology; 190 : 5; 718-722, 2020,
DOI: (10.1111/bjh.16943)
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
White blood cell (WBC)
differential fluorescence
(WDF) scattergram, displaying
a classification of WBCs
based on their morphology
and their intracellular
components.
33. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Al-samkari H. et al. Blood, 136 (4): 489–500.2020Iba T. et al. J Thromb Haemost.18:2103–2109, 2020.
6- Coagulation Parameters
Thrombotic complications can developed in about; 5% and 18%
in noncritically ill and critically patients respectively.
The coagulation study is one of crucial tests for disease
progression.
PT and PTT in most of the cases are normal or showed slight
prolongation.
Elevated D-dimer and fibrinogen degradation product (FDPs) at initial
presentation was reported as a predictive of coagulation-associated
complications and associated with poor outcome.
Nonsurvivors developed higher D‐dimer and FDP levels, with longer
PT and aPTT compared with survivors at admission
Incidence of thrombocytopenia is relatively low. A low platelet count
is associated with increased risk of disease severity and mortality.
34. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Liani D. et al, The Lancet Haematology 2020; 7: e671-e678 (modified)
https://rebelem.com/covid-19-thrombosis-and-hemoglobin/
Disease Progression
35. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Imazio M. et al, Heart 2020;106:1127-1131, BMJ.com
Manson J. J. et al, Lancet Rheumatol; 2: e594–602, 2020Lin Z. et al. J Infect. 2020;81(4):647-679.
7- Biomarkers;
Most important are; CRP, Ferritin, Procalcitonin (PCT) and Troponin I.
A clear associations was found between elevated biomarkers, and
survival in COVID-19 patients.
COVID-19 hyperinflammatory syndrome (COV-HI), which might
contribute to morbidity and mortality in sever disease.
COV-HI; CRP>150 mg/l with doubling within 24hrs or Ferritin>1500
μg/L.
Hyperferritinemia, was a common feature in sever disease.
Increased CRP level correlates with higher serum ferritin. Both were
able to predict an increased risk of disease severity in patients with
COVID-19.
36. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Lin Z. et al. J Infect. 2020;81(4):647-679.
37. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Imazio M. et al, Heart 2020;106:1127-1131, BMJ.com
Lippi G, Plebani M. Clin Chim Acta. 2020;505:190-191.
ESR may be elevated, but it is usually showed a variable values
Substantial increase of PCT would reflect bacterial coinfection in
those developing severe form. Nevertheless, the synthesis of this
biomarker is inhibited by interferon, which increases during viral
infections.
Troponin I levels were significantly higher in those with severe
COVID-19 infection compared with those with non-severe disease.
Its elevation was related to non-ischaemic myocardial injury.
38. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Imazio M. et al, Heart 2020;106:1127-1131, BMJ.com
Troponin elevation in COVID-19 can be related to non-ischaemic myocardial injury.
39. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Huan H, et al; Emerg Microbes Infect,9:1, 1123-1130
8- Serum Cytokines
Results showed that COVID-19 patients have higher serum level
of certain cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) than
control individuals.
Within COVID-19 patients, serum IL-6 and IL-10 levels are
significantly higher in critical group than in moderate and severe
group.
The levels of IL-10 is positively correlated with CRP amount.
40. The levels of cytokines ( Median & range) in COVID-19 patients and controls
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Huan H, et al; Emerg Microbes Infect,9:1, 1123-1130
41. The levels of cytokines ( Median & range) in covid-19 patients with different severity
Huan H, et al; Emerg Microbes Infect,9:1, 1123-1130
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
42. Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
9- Biochemical Parameters
Elevated lactate dehydrogenase (LDH), found to be on the most
important biochemical changes at time of diagnosis.
Assessment of renal and liver functions are essential for detection
of any organ damage.
For prognostication purposes, increased values of LDH, aspartate
aminotransferase (AST, GOT) and alanine aminotransferase (ALT,
GPT), total bilirubin, together with decreased values of serum
albumin, have been found of value.
Marcello C. and Agnello L. Diagnosis 7,4: 10.1515/dx-2020-0057, 2020.
Lippi, G., & Plebani, M. Clinical Chemistry and Laboratory Medicine, 58(7), 1063-1069. 2020
44. Inflammatory
C-reactive protein, CRP Increase
Ferritin Increased
Procalcitonin Increased
Troponin Increased
Cytokines Increased
Biochemical (Cont.)
Alanine aminotransferase, ALT Increased
Aspartate aminotransferase, AST Increased
Urea & Creatinine Increased
Total bilirubin Increased
Urea & Creatinine Increased
Albumin Reduced
Creatine kinase, CK Increased
Biochemical
Lactate dehydrogenase, LDH Increased
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
Silvia Toledo et al, Clin Chim Acta. 2020 Nov; 510: 170-1
45. OBJECTIVES
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
• Pathophysiology of SARS-CoV-2 Infection.
This require a further work to elucidate.
Direct Viral Infection.
Immune Response in COVID-19.
COVID-19 Induced Coagulopathy.
• Diagnostic and Prognostic Laboratory Parameters.
• Impact of Laboratory investigations.
46. Impact of COVI-19
The COVID-19 indebtedness was so serious from the social and
economic aspects.
Burden on the community.
Effect on the healthcare system and workers.
The Bulletin of RCPath, number 191, 2020
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
47. Impact on the Patients and Families
(Social and Economic)
Avoidance of unnecessary laboratory tests is crucial.
Precise selection of laboratory investigations, both, at the time of
diagnosis and follow up and a balance between the requested laboratory
tests and its importance.
Reducing the patients’ burden and who take care of them and the
psychological stress needs to be taken into consideration when request
frequent tests.
Associated financial costs also need to be aware of it.
The pandemic necessitates reducing the test volumes to decrease the
laboratory workload.
The Bulletin of RCPath, number 191, 2020
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
48. Impact on Laboratory Workers
The pandemic has necessitated significant changes in how pathology
laboratories operate.
Strict social distancing requirements have imposed limitations on
staff and workflows in all workspaces.
Laboratory staff were affected from their pattern of life and family
time.
Additional burden due to the use of personal protective equipment
requirements meant that some processes newly required use of
masks, gowns and goggles.
The coronavirus pandemic has required significant changes to
workflow, sample collection and processing within the laboratory.
Dr. Abdulsalam Al-Ani, COVID-19; Updates on Pathophysiology and Laboratory Investigations #AIMCO2020
The Bulletin of RCPath, number 191, 2020