COVID-19 is a global infectious disease pandemic with high morbidity and mortality for at risk individuals. This slide is intended for the medical students, medical doctors and those in training for masters of medicine (MMED).
Idiopathic Interstitial Pneumonias
Group of diffuse parenchymal lung diseases
Unknown etiology
Varying degrees of inflammation and fibrosis
In cases where diagnosis cannot be made because of overlap of CT and histological findings; Chrug & Muller proposed a three seperations on HRCT for chronic interstitial diseases.
Lecture slides about bronchiectasis with contents including definition, causes, pathogenesis and pathology, and how to make diagnosis. Treatment for bronchiectasis is presented separately.
Scott Letendre, MD
Professor in Residence
Division of Infectious Diseases & Global Public Health
Departments of Medicine and Psychiatry
University of California, San Diego
This is a presentation for all the people who are unaware about COVID-19.
COVID-19 = Corona Virus Disease 2019. Please like and share my presentation.
Presentation by:-
C. S. Nelson
VI - E
D.A.V Boys Senior Secondary School.
D.A.V Group of School.
Complications of rhinosinusitis(Dr ravindra daggupati)Ravindra Daggupati
orbital complications of rhino sinusitis,intra cranial complications of rhino sinusitis,classification of complications,diagnosis and treatment of complications
Idiopathic Interstitial Pneumonias
Group of diffuse parenchymal lung diseases
Unknown etiology
Varying degrees of inflammation and fibrosis
In cases where diagnosis cannot be made because of overlap of CT and histological findings; Chrug & Muller proposed a three seperations on HRCT for chronic interstitial diseases.
Lecture slides about bronchiectasis with contents including definition, causes, pathogenesis and pathology, and how to make diagnosis. Treatment for bronchiectasis is presented separately.
Scott Letendre, MD
Professor in Residence
Division of Infectious Diseases & Global Public Health
Departments of Medicine and Psychiatry
University of California, San Diego
This is a presentation for all the people who are unaware about COVID-19.
COVID-19 = Corona Virus Disease 2019. Please like and share my presentation.
Presentation by:-
C. S. Nelson
VI - E
D.A.V Boys Senior Secondary School.
D.A.V Group of School.
Complications of rhinosinusitis(Dr ravindra daggupati)Ravindra Daggupati
orbital complications of rhino sinusitis,intra cranial complications of rhino sinusitis,classification of complications,diagnosis and treatment of complications
Covid-19 is an infectious disease caused by SARS-CoV-2. mechsnism, pathogenesis and causes, transmission,symptoms and therapeutic strategies
Published by karuna raghuwanshi,M.pharma II semester (pharmaceutics),Pharmacy department.
corona is a pandemic disease in the world so many people are died because of this disease, it's not coming in a particular structure. it's having a different type of structure . how to prevent this disease maintain social distance, maintain hand hygiene, wear masks .nowady vaccines are available covishield ,covaxin, Pfizer, sputnik vaccine etc...this mainly helpful to prevent the corona
what is COVID-19 or corona virus.
CAUSE OF CORONA VIRUS
RISK ASSESSMENT OF SARS-COV-2
CASE FATALITY RATIO
RISK MITIGATION
Administrative controls, self care and testing
Case fatality ratio of Covid-19, Sars and Mers
1. Genome of corona viruses
2. Comparative analysis of emergence and spreading
3. Entry Mechanism
4. COVID-19 Case Study
5. Face mask Case Study
6. Pharmacologic Treatments for Coronavirus Disease
7. BCG vaccine
The Corona virus pandemic has costed a lot of lives through out the world.
Here are some in formations about what is known so far.
It includes cause, Spread, Signs and Symptoms.
it also has the ongoing myths about corona virus.
Advanced age, having comorbidities, and vitamin D deficiency are three most important reasons for increased vulnerability to COVID-19 and also worsen complications and increase the risk of death. Despite the vast amount of information available and lessons learned, many countries are still not fully utilizing these to manage secondary peaks of COVID-19 infection. Factors associated with worse COVID-19 prognosis include, older age, ethnicity, male sex, having comorbidities, obesity, diabetes, hypertension, and smoking; all these are associate with vitamin D deficiency. COVID-19 symptomatology varies from mostly asymptomatic, to, up to 2% fatality.
Similar to Coronavirus disease 2019(covid 19) (20)
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
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
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.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
3. Introduction
• Coronaviruses are important human and animal pathogens
(zoonoses).
• Together with other zoonoses, this disease form group of
emerging and reemerging zoonoses
• At the end of 2019, a novel coronavirus was identified as the
cause of a cluster of pneumonia cases in Wuhan, a city in the
Hubei Province of China.
• It rapidly spread, resulting in an epidemic throughout China,
with sporadic cases reported globally.
• In February 2020, the WHO designated the disease COVID-19,
which stands for coronavirus disease 2019.
4. Cont..
• The virus that causes COVID-19 is designated severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2); previously,
it was referred to as 2019-nCoV, this large viruses containing
a single-stranded positive-sense RNA genome enveloped by a
membrane.
• The disease spread throughout the world and on 11th March
2020, WHO declared it as the pandemic.
• To date, there are no SARS-CoV-2-specific antiviral agents,
most of the drugs used for treatment are used for treatment
of other infectious disease.
5. Epidemiology
• The worlwideCOVID-19 statistics as of 22nd May 2020
i. Total confirmed cases: 5.11million
ii. Death: 333,001 (6.5%)
iii. Recovered: 1.95 million(38.2%)
iv. Currently infected patients: 2.83 million (55.3%)
• The United Republic of Tanzania reported its 1st case of
COVID-19 on 16th March 2020
6. Cont…
• Epidemiologic investigation in Wuhan at the beginning of the
outbreak identified an initial association with a seafood
market that sold live animals, where most patients had
worked or visited and which was subsequently closed for
disinfection.
• However, as the outbreak progressed, person-to-person
spread became the main mode of transmission.
• ?? The origin of the virus still possess a lot of questions as
there have been reports that It may have originated from the
labs at the Wuhan Institute of Virology and then spread to the
community
7. Cont..
• Person-to-person spread of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) is thought to occur mainly via
respiratory droplets, resembling the spread of influenza.
• With droplet transmission, virus released in the respiratory
secretions when a person with infection coughs, sneezes, or
talks can infect another person if it makes direct contact with
the mucous membranes; infection can also occur if a person
touches an infected surface and then touches his or her eyes,
nose, or mouth.
8. Cont..
• The incubation period of COVID-19 ranges between 2- 14
days, about 80% of the patients will show no/mild symptoms
but they are potential source of viral transmission to other
individuals
• According to the WHO, recovery time appears to be around
two weeks for mild infections and three to six weeks for
severe disease.
• People with advanced age, with Comorbidities such as HIV, D.
mellitus, cancer, Heart failure, Obesity and CKD have increased
morbidity and mortality
9. Pathogenesis
• Patients with COVID-19 show clinical manifestations including
fever, nonproductive cough, dyspnea, myalgia, fatigue, normal
or decreased leukocyte counts, and radiographic evidence of
pneumonia that includes ground glass opacification.
• Although the pathogenesis of COVID-19 is not wholly
understood, the knowledge of SARS-COV & MERS-COV
pathogenesis and available data on SARS-CoV-2 give an insight
to the current knowledge
• In ~ 80% of the infected patients, the disease will be mild and
mostly restricted to the upper and conducting airways.
10. Cont..
• Preliminary reports suggested that the reproductive number
(R₀), the number of people who acquire the infection from an
infected person, was estimated to be 2.2 to 3.3.
• However, the R₀ may actually be lower in light of social
distancing measures that have been instituted.
• The secondary attack rate for SARS-CoV-2 is estimated to be
0.45% for close contacts of US patients.
11. Virology
• This is an intracellular microorganism
• Coronaviruses (CoVs) are relatively large viruses containing
a single-stranded positive-sense RNA genome encapsulated
within a membrane envelope.
• The viral membrane is studded with glycoprotein spikes that
give coronaviruses their crownlike appearance.
• There are four classes of coronaviruses designated as alpha,
beta, gamma, and delta.
12. Cont…
• the evidence from the phylogenetic analysis indicates that the
COVID-19 belongs to the genus betacoronavirus, which
includes SARSCoV, that infects humans, bats, and wild animals
• The betacoronavirus class includes:
i. Severe acute respiratory syndrome (SARS) virus (SARS-CoV)
ii. Middle East respiratory syndrome (MERS) virus (MERS-CoV)
iii. COVID-19 causative agent SARS-CoV-2 (with has 85%
genetic homology with SARS-CoV)
13. Cont…
• Similar to SARS-CoV and MERS-CoV, SARS-CoV-2 attacks the
lower respiratory system to cause viral pneumonia, but it may
also affect the gastrointestinal system, heart, kidney, liver, and
central nervous system leading to multiple organ failure.
• Evidences indicates that SARSCoV-2 is more contagious than
SARS-CoV
14. Cont…
• SARS-CoV2 genome encodes several structural proteins,
including the glycosylated spike (S) protein that functions
as a major inducer of host immune responses.
• This S protein mediates host cell invasion by both SARS-CoV
and SARS-CoV-2 via binding to a receptor protein called
angiotensin-converting enzyme 2 (ACE2) located on the
surface membrane of host cells.
• The invasion process requires S protein priming which is
facilitated by the host cell produced serine protease
TMPRSS211.
15.
16. Cont..
• In addition, the viral genome also encodes several
nonstructural proteins including RNA-dependent RNA
polymerase (RdRp), coronavirus main protease (3CLpro), and
papain-like protease (PLpro).
• Upon entrance to the host cells, the viral genome is released
as a single-stranded positive RNA. Subsequently, it is
translated into viral polyproteins using host cell protein
translation machinery, which are then cleaved into effector
proteins by viral proteinases 3CLpro and PLpro.
17. Cont…
• PLpro also behaves as a deubiquitinase that may
deubiquinate certain host cell proteins, including interferon
factor 3 and NF-κB, resulting in immune suppression.
• RdRp synthesizes a full-length negative-strand
RNA template to be used by RdRp to make more viral genomic
RNA.
18. Coronavirus entry and replication
• The inhaled virus SARS-CoV-2 likely binds to epithelial cells in
the nasal cavity and starts replicating, Coronavirus S protein is
regarded as a major determinant of virus entry into host cells.
• The envelope spike glycoprotein binds to its cellular receptor,
ACE2 for SARS-CoV and SARS-CoV-2 , CD209L(a C-type lectin,
also called L-SIGN) for SARS-CoV, DPP4 for MERS-CoV.
• The virus propagates and migrates down the respiratory tract
along the conducting airways, and a more robust innate
immune response is triggered.
19. Cont…
• The entry of SARS-CoV into cells was initially identified to be
accomplished by direct membrane fusion between the virus
and plasma membrane however it has been identified that
critical proteolytic cleavage event occurs at SARS-CoV S
protein at position (S20) mediating the membrane fusion and
viral infectivity.
• Besides membrane fusion, the clathrin-dependent and -
independent endocytosis mediate SARS-CoV entry too.
• Upon entry, the viral RNA genome is released into the
cytoplasm and is translated into two polyproteins and
structural proteins resulting into subsequent viral genome
replication.
20. Cont…
• The newly formed envelope glycoproteins are inserted into
the membrane of ER or Golgi, and the nucleocapsid is formed
by the combination of genomic RNA and nucleocapsid protein
(post-translational modification).
• Then, viral particles germinate into the endoplasmic
reticulum-Golgi intermediate compartment (ERGIC). At last,
the vesicles containing the virus particles then fuse with the
plasma membrane to release the virus
21.
22. Antigen presentation in coronavirus
infection
• Presentation to the antigen presentation cells(APCs) is a
central part of the body’s anti-viral immunity.
• Antigenic peptides are presented to the MHC/HLA and then
recognized by virus-specific cytotoxic T lymphocytes (CTLs)
which is important in comprehension of COVID-19
pathogenesis.
• The antigen presentation of SARS-CoV depends mostly on
MHC I molecules however MHC II molecules plays a role.
23. Cont..
• HLA-B*4601, HLA-B*0703, HLA-DR B1*1202 and HLA-
Cw*0801 genetic polymorphism have been associated with
increased susceptibility to SARS infection, on the other hand
HLA-DR0301, HLA-Cw1502 and HLA-A*0201 alleles offers
protection from SARS infection.
• Genetic polymorphisms of MBL (mannose-binding lectin)
associated with antigen presentation are related to the risk of
SARS-CoV infection.
24. Humoral and cellular immunity
• Antigen presentation results in stimulation of both humoral
and cellular immunity as the consequence of activation of
virus-specific B and T cells.
• Similar to common acute viral infections, the antibody profile
against SARS-CoV virus has a typical pattern of IgM and IgG
production.
25. Cont…
• SARS-specific IgM antibodies disappear at the end of week 12,
while the IgG antibody last for a long time, which indicates
IgG antibody may play a protective role, and the SARS-specific
IgG antibodies primarily are S-specific and Nspecific
antibodies.
• The most important cellular immunity response is the
significant reduction in CD4+ and CD8+ T cells in the
peripheral blood of SARS-CoV-2-infected patients (similar to
SARS-CoV) due to their excessive activation.
26. Cont..
• The interaction between viral S protein and ACE2 on the
host cell surface is of significant interest since it initiates the
infection process, the binding affinity of SARS-CoV-2 S protein
to ACE2 is about 10-20 times higher than that of SARS-CoV S
protein.
• It is speculated that this may contribute to the reported
higher transmissibility and contagiousness of SARS-CoV-2 as
compared to SARS-CoV.
27. Cont…
• ACE2 involvement with coronavirus infection is of further
interest since ACE2 is a potent negative regulator restraining
overactivation of RAAS (renin angiotensin aldosterone system)
that may be involved in elicitation of inflammatory lung
disease in addition to its well-known role in regulation of
blood pressure and balance of body fluid and electrolytes.
• Organs considered to be more vulnerable to SARS-CoV-2
infection due to their ACE2 expression levels include
pneumocytes type II of the lungs, heart, oesophagus, kidneys,
bladder, and ileum
28. Cont
• ACE2 enzyme catalyzes degradation of angiotensin II to
angiotensin (1-7).
• The balance between angiotensin II and angiotensin (1-7) is
critical since angiotensin II binds to angiotensin receptor (AT1)
to cause vasoconstriction, whereas angiotensin (1-7) elicits
vasodilation mediated by AT2.
• The chronic activation of ACE2 as a result of SARS-CoV-2
infection culminate in its downregulation which impair its
physiological functions resulting in pulmonary vascular
constriction and worsening hypoxemia
29. Cytokine storm in COVID-19
• ARDS is the main cause of death COVID-19.
• ARDS is the common immunopathological event for SARS-
CoV-2, SARS-CoV and MERS-CoV infections, it’s major
mechanism being the cytokine storm; the deadly uncontrolled
systemic inflammatory response resulting from the release of
large amounts of pro-inflammatory cytokines (IFN-a, IFN-g, IL-
1b, IL-6, IL-12, IL-18, IL-33, TNF-a, TGFb, etc.) and chemokines
(CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) by immune
effector cells in SARS-CoV/ SARS-CoV-2 infection.
30. Cont..
• The cytokine storm trigger a aggressive attack by the immune
system to the body resulting into ARDS and multiple organ
failure, and finally lead to death in severe cases of SARS-CoV-2
infection, just like what occurs in SARS-CoV and MERSCoV
infection.
• The cytokine storm results in activation of endothelium and
subsequent endothelial dysfunction culminating in excess
thrombin generation and fibrinolysis shutdown which cause a
hypercoagulable state, overt DIC occur in patients in later
stages of COVID-19 infection, while still hospitalized, often
with septic physiology and multiorgan failure.
31. Cont..
• In addition, the hypoxia found in severe COVID-19 can
stimulate thrombosis through not only increasing blood
viscosity, but also a hypoxia-inducible transcription factor-
dependent signaling pathway.
• Polyphosphates, derived from microorganisms, activates
platelets, mast cells, and FXII in the contact pathway of
coagulation, and exhibit other downstream roles in amplifying
the procoagulant response of the intrinsic coagulation
pathway. Complement pathways also contribute to activation
of coagulation factors.
32. Cont..
• Occlusion and microthrombosis formation in pulmonary small
vessels of critical patient with COVID-19 has been reported
from a recent lung organ dissection therefore early application
of anticoagulant therapy in severe COVID-19 have been
suggested in bid to improve outcome.
• Coagulopathy of COVID-19 presents with prominent elevation
of D-dimer and fibrin/fibrinogen degradation products, while
abnormalities in prothrombin time, partial thromboplastin
time, and platelet counts are relatively less pronounced
making it different from DIC.
33. Viral load and shedding
• High viral loads have been detected in nasal and throat swabs
soon after symptom onset, asymptomatic patients may have
similar viral load compared with symptomatic patients.
• Pharyngeal viral shedding is high during the first week of
symptoms when symptoms are mild or prodromal, peaking on
day suggesting active virus replication in upper respiratory
tract tissues.
• Duration of viral shedding is between 8 and 20 days after
symptoms resolution, virus can be detected in the sputum and
faeces for up to 39 days after negative pharyngeal swabs, it is
not clear if this phenomenon results in transmission of virus.
• Factors associated with prolonged viral shedding include male
sex, older age, comorbid hypertension, delayed admission to
hospital after symptom onset or severe illness on admission,
and use of invasive mechanical ventilation or corticosteroids.
34. Coronavirus immune evasion
• Multiple strategies are used by these viruses to avoid immune
responses.
i. Normally the evolutionarily conserved microbial structures
called pathogen-associated molecular patterns (PAMPs) are
recognized by pattern recognition receptors (PRRs) however
these viruses can induce production of double-membrane
vesicles which do not contain PRRs and then replicate in
these vesicles, thereby avoiding the host detection of their
dsRNA.
ii. IFN-I has protective effects in infection with these viruses
however its production is inhibited rendering them capable
of evading the immune system
iii. Down regulation of gene expression related to antigen
presentation
35. ??Why now…??Why not always
Zoonotic Evolution and Adaptation
• Quick rate of replication and reproduction in the background
of lacking Proof reading mechanisms = accumulation of
mutations. E.g. HIV-1 virus is thought to be the world’s fastest
evolving microbe (Cuevas et al, 2015).
• ?2002 China’s Guangdong twenty-first century’s first global
pandemic: SARS due to SARS-CoV = acquired two key
mutations in the receptor-binding domain of its S protein that
allowed it to use the human orthologue of the receptor ACE2
with high efficiency. The mutations enabled SARS-CoV to jump
from its natural reservoir which is bats into civets then to
human resulting into the outbreak.
• Seems to be the similar case for COVID-19 due to SARS-CoV2
36. ??Bioterrorism
• Conspiracy theorists have suggests that COVID-19 was
planned and the causative virus was created/manipulated in
the laboratory
• However SARS-COV-2 have 85% genetic homology with SARS-
COV, 50% to the MERSCoV and since zoonotic disease are
difficult to predict this may explain the normal process of
zoonotic evolution.
• Evidence from phylogenetic analysis shows that the virus was
not manipulated/manufactured in the laboratory
37. Clinical presentation of COVID-19
• The most common symptoms at onset of COVID-19 illness are
fever, cough, fatigue and anosmia as the disease progress the
patient develop sputum production, headache, haemoptysis,
diarrhoea, dyspnoea, and lymphopenia.
• Clinical features revealed by a chest CT scan presents as
pneumonia, however, there were abnormal features such as
RNAaemia, acute respiratory distress syndrome, acute cardiac
injury (myocarditis), and incidence of grand-glass opacities
that led to death.
38. Clinical course/natural hx of COVID-19
• Out of population of individuals who develop COVID-19, 80%
develop mild or no symptoms but are very infectious,
therefore they can be isolated and treated at home.
• About 20% develops moderate to severe symptoms with
pulmonary infiltrates and some of these will develop very
severe disease.
• About 5-10% develop severe symptoms with ARDS, Sepsis,
multiorgan failure and coagulopathy necessitating admission
into an ICU.
39. WHO classification
i. Mild illness (Upper respiratory tract symptoms)
ii. Moderate illness (Pneumonia)
iii. Severe illness (severe pneumonia, sepsis, septic shock and
multiorgan failure)
40.
41. Diagnosis
• Thorough hx taking P.Examination: The respiratory clinical
manifestations consistent with COVID-19 (eg, fever, cough,
dyspnea). Symptomatic patients should also be asked about
recent travel or potential COVID-19 exposure in the prior 14
days to determine the need for evaluation for COVID-19.
• RNA PCR (RT-PCR) & Viral genetic sequencing
• Viral specific IgM & IgG titres
• Radiography..CXR (hazy bilateral , peripheral opacities), CT
Chest (GGO, consolidation, rarely may be unilateral), USS:
numerous B-lines, pleural line thickening, consolidation with
air bronchograms
43. Treatment of COVID-19
• Some patients with suspected or documented COVID-19 have
severe disease that warrants hospital care.
• Since there is limited clinical and basic research information at
this time, treatment options for COVID-19 currently comprise
investigational drugs and management of symptoms.
• Ensuring appropriate infection control and supportive care.
• High-flow oxygen and noninvasive positive pressure
ventilation, Acute respiratory distress syndrome warrant
intubation with mechanical ventilation; extracorporeal
membrane oxygenation may be indicated in patients with
refractory hypoxia, the aim is SPO2 >_94%
44. Cont..
• The WHO and CDC recommend against the use of
glucocorticoids in patients with COVID-19 pneumonia unless
there are other indications (eg, exacerbation of chronic
obstructive pulmonary disease (COPD)).
• Glucocorticoids have been associated with an increased risk
for mortality in patients with influenza and delayed viral
clearance in patients with MERS-CoV and SARS-CoV.
• Most drugs for the treatment of COVID-19 are still under
clinical trials and since most of the same are safe and have
demonstrated efficacy, they are used for the purpose of
COVID-19
45. Cont..
• Anticoagulation therapy early after admission for eligible
patients.
• Antimicrobial therapy for treatment of suspected bacterial
infection should be instituted based on the local guidelines,
clinical presentation and susceptibility pattern until blood
culture can rule out the infection.
• Use of the convalescent plasma of the recovered patients
• Use of intravenous Vitamin C
• Physiotherapy that includes chest physiotherapy; avoid lying
on their back as this makes coughing ineffective and chest
physiotherapy
46.
47. Chloroquine/Hydroxychloroquine +/-
Azithromycin
• The sulfate and phosphate salts of chloroquine have both
been commercialized as antimalarial drugs.
• Hydroxychloroquine has also been used as an antimalarial, but
in addition is now broadly used in autoimmune diseases such
as lupus and rheumatoid arthritis.
• Of note, chloroquine and hydroxychloroquine are considered
to be safe and side-effects are generally mild and transitory.
• However, the margin between the therapeutic and toxic dose
is narrow and chloroquine poisoning can be life threathening.
48. Cont..
• MOA: increasing endosomal pH required for virus/cell fusion,
as well as interfering with the glycosylation of cellular
receptors of SARS-CoV2 . The anti-viral and anti-inflammatory
activities of chloroquine may account for its potent efficacy in
treating patients with COVID-19 pneumonia.
• Chloroquine is a cheap and safe drug that has been used for
more than 70 years. In light of the urgent clinical demand,
chloroquine phosphate is recommended to treat COVID-19
associated pneumonia in larger populations in the future.
• Safety concerns with hydroxychloroquine and azithromycin
include the potential for QTc prolongation, which is greater
when both agents are used together and may accounted for
increased mortality reported in some clinical trials.
49.
50.
51. Remdesivir
• =Novel antiviral drug developed for the treatment of Ebola
virus disease and Marburg virus infections.
• It is a prodrug of a nucleotide analog that is intracellularly
metabolized to an analog of adenosine triphosphate that
inhibits viral RNA polymerases.
• Remdesivir has broadspectrum activity against members of
several virus families, including filoviruses (e.g., Ebola) and
coronaviruses e.g., SARSCoV and MERSCoV).
• In vitro testing has also shown that Remdesivir has activity
against SARS-CoV-2 with an EC50 value of 1.76 μM
52. Cont
• The discussed drugs (specifically Chloroquine
/Hydroxychloroquine and Remdesivir ) have shown
improvement of symptoms and severity of the COVID-19
disease, however the their ability to improve mortality in
these patients remain inconclusive and require further clinical
trials involving large number of participants to reach such
conclusion
53. Prevention
In the health care setting
• Screening and precautions for fever or respiratory symptoms
— Screening patients for clinical manifestations consistent
with COVID-19 (eg, fever, cough, dyspnea) prior to entry into a
health care facility can help identify those who may warrant
additional infection control precautions. Symptomatic patients
should also be asked about recent travel or potential COVID-
19 exposure in the prior 14 days to determine the need for
evaluation for COVID-19.
• Any individual with these manifestations should wear a
facemask.
• PPE for healthcare workers
54. Management in Pregnancy & Paediatrics
• Pregnant women should be managed by a multidisciplinary
team, including obstetric, perinatal, neonatal, and intensive
care specialists, as well as mental health and psychosocial
support. There is no evidence to suggest that pregnant
women are more likely to contract COVID-19, or present with
increased risk of severe illness or fetal compromise.
• Mothers in labour/not in labour with suspected/confirmed
COVID-19 should isolated from the general wards , being in
room containing patients each!
• IPC guidelines should be adhered
55. • All other treatment should be done as indicated, delivery
should be conducted with other indications as COVID-19
infection is not an indication for delivery..the fetus is unlikely
to be infected during pregnancy
• When the mother has confirmed COVID-19: after delivery of
healthier baby should cared separately by a relative/caregiver
and must be tested for COVID-19.
• When with signs and symptoms of COVID-19 a baby should
admited into the NICU unless the symptoms are mild and
managed separately under care of Neonatologist .
• Other group of paediatric patients should managed with the
same protocol as adults however the drug doses and fluid
management should be adjusted accordingly.
Cont…
56. Cont…
• WHO recommends standard, contact, and droplet precautions
(i.e., gown, gloves, and mask), with eye or face protection.
• The CDC recommends that patients with suspected or
confirmed COVID-19 be placed in a single-occupancy room
with a closed door and dedicated bathroom. The patient
should wear a facemask if being transported out of the room
(eg, for studies that cannot be performed in the room).
• Adhering to Infection Prevention and Control Protocol.
57. Cont..
Preventing exposure in the community
• Diligent hand washing, particularly after touching surfaces in
public. Use of hand sanitizer.
• Respiratory hygiene (eg, covering the cough or sneeze).
• Avoiding touching the face (in particular eyes, nose, and
mouth).
• Screening and Quarantine of the contacts and travelers from
high risk geographical location
• Social distancing
• Cleaning and disinfecting objects and surfaces that are
frequently touched.
• Shielding extremely vulnerable people
58. Vaccine
• It is crucial to develop safe and effective vaccines to control
the COVID-19 pandemic, eliminate its spread, and ultimately
prevent its future recurrence.
• Since the SARS-CoV-2 virus shares significant sequence
homology with two other lethal coronaviruses, SARS and
MERS, the vaccines identified in these patents related to SARS
and MERS viruses could potentially facilitate the design of
anti-SARS-CoV-2 vaccines.
59. Cont...
• There is currently no vaccine for SARS-CoV2 however many
vaccines are undergoing clinical trials though others are still in
the animal phase and this may take up to another 12 months
to have at least one vaccine.
• The viral S protein subunit vaccines have been shown to
produce higher neutralizing antibody titers and more
complete protection than live-attenuated SARS-CoV, full-
length S protein, and DNA-based S protein vaccines.
60. Prognosis
• The following are associated with increased likelihood of poor
clinical outcome:
i. Advanced age
ii. Comorbidities: DM, COPD, Asthma, CVD, Obesity
iii. High SOFA score at admission
iv. Admission to the ICU
v. Labs findings: high levels of D-dimer, ferritin, troponin,
cardiac myoglobin
vi. Watch for complications such as secondary bacterial
infection, stress CM
61. What is next for COVID-19?
• COVID-19 does not yet have specific therapy!
• Individuals should adapt to live with the virus as cure will not
attained unless proper therapy is identified, 70% of the
population is infected and thus attaining herd immunity ( this
is not yet scientifically proven) and the safe and efficient
vaccine is developed.
• ?? There is likelihood of this disease developing 2nd/3rd …..
wave that may be more severe than what we have
experienced so far.
62. Questions
1. Distinguish suspected case from confirmed case of COVID-
19, How does their management differs?
2. Explain the major routes of transmission of SARS-CoV-2
3. Keeping in mind the Role of ACE2 receptor in pathogenesis
of COVID-19 in mind, should the patients on ACEIs/ARBs be
withheld? Explain you answer!
4. Use of Glucocorticoids are limited in these patients, when
would the continuation of steroid therapy be mandatory?
Which form of steroid therapy should not be withheld?
5. What are major causes of death in COVID-19 patients?
6. What is drug repurposing? When is it important?
7. What is the role of convalescent plasma in Management of
COVID-19?
63. Cont..
8. Can Chloroquine/Hydroxychloroquine be used as
prophylaxis against SARS-CoV-2? What gives this drug this
property? How is it safe and efficacious?
9. Where can the samples for RT-PCR testing be taken?? What
are their sensitivity and specificity?
10. What are the roles of different types of face masks in
prevention of COVID-19??
11. Discuss the role and timing of lockdown in prevention of
COVID-19 and its implication on social-economic aspects of
different societies
12. What are complications of COVID-19? Explain how they can
be managed!
64. Case scenario
• A 73-year-old man with hypertension and chronic
obstructive pulmonary disease calls to report that he has had
a fever (maximal temperature, 38.3°C) and a dry cough
for the past 2 days. He notes that his shortness of breath has
worsened. His medications include losartan and inhaled
glucocorticoids. He lives alone. How should he be
evaluated? If he has coronavirus disease 2019 (Covid-19), the
disease caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), then how should he be
treated?
65. References
• Notification of 2019-nCoV infection. National Health
Commission of the People's Republic of China. http://
www.nhc.gov.cn/xcs/yqfkdt/202002/18546da875d74445b
b537ab014e7a1c6.shtml (accessed February 17, 2020). (in
Chinese)
• Hussin A. Rothan and Siddappa N. Byrareddy, Journal of
Autoimmunity, https://doi.org/10.1016/j.jaut.2020.102433
• https://www.covid19treatmentguidelines.nih.gov/
• Mason RJ. Pathogenesis of COVID-19 from a cell biology
perspective. Eur Respir J 2020; 55: 2000607
[https://doi.org/10.1183/13993003.00607-2020]
66. References
• X. Li et al, Molecular immune pathogenesis and diagnosis of
COVID-19, https://doi.org/10.1016/j.jpha.2020.03.001
• Jianjun Gao, Zhenxue Tian, Xu Yang; Breakthrough:
Chloroquine phosphate has shown apparent efficacy in
treatment of COVID-19 associated pneumonia in clinical
studies
• Caren G. Solomon, M.D., M.P.H., Mild or Moderate Covid-19,
DOI: 10.1056/NEJMcp2009249.
• Parag Goyal, M.D et al, Clinical Characteristics of Covid-19 in
New York City, DOI: 10.1056/NEJMc2010419
• CDC Guidelines on COVID-19
• WHO Guidelines on COVID-19