Dont PANIC it is just a Pandamic

1. COVID-19
Dr. S.Sridevi MBBS
10 th April 2020

2. ➢ SARS - 2002-2003"
!
➢ MERS - 2012 -2013"
!
➢ DEC 2019 - In WUHAN ( Hubei) Unusual cases of pneumonia reported.
➢ They presented with :
▪ "" Dry cough "
▪ "" Shortness of breath (SOB)"
▪ " " Fever
▪ "" B/L lung infiltrates on imaging
!
➢ CASES - reported to “WHO” county office in China on Dec 31st 2019
!
➢ SEARCH OF SOURCE
" Landed up in wet animal market on Jan 1st 2020 and these markets were
closed.
COVID19 - AN EMERGING DISEASE

3. ➢Jan 12 , 2020 — China reveals Genetic code of this coronavirus.
➢End of Jan 2020 — this virus found to be originated from bats and came
to a conclusion that this virus also belongs to the group that caused SARS, so
was named SARS CoV-2
➢By Jan 30 - SARS CoV-2 -- declared an outbreak and emergency by
WHO
➢Feb 11th 2020 - WHO names the virus COVID-19 (Corona virus
disease 19)
➢March 11th 2020 - COVID-19 declared a pandemic (global outbreak of a
d/s).
➢March 15th 2020 - > than 1.5 Lac cases affected with a mortality rate of
3%. (Every hundred cases 3 deaths)

4. ▪ SARS 2003 8000 Cases
" MR - 9.5%
▪ MERS 2012 2500 Cases
" MR - 35%
▪ Influenza virus causing seasonal flu
" MR- 0.2%"
▪ SARSCoV2 MR varies based on the geographic and demographic
patterns.

5. ABOUT THE VIRUS AS SUCH:
Coronavirus - A million years old. had been in research since 1949.Infects
many species of animals and humans."
It has been described for more than 50 yrs."
They were not studied in detail as they did not cause severe human diseases
until SARS in 2002 - 2003."
they are ENVELOPED, non-segmented, positive sense single
stranded RNA viruses

6. TAXONOMY
The name coronavirus was coined in 1968 from latin word “corona” meaning
CROWN like
coronavirus has the largest identified RNA genome - 30 kb(kilobase)
Classification:
coronaviruses are the largest grp of viruses belonging to NIDOVIRALES
order which includes :-
1) coronaviridae"
2)arteriviridae families.
3)roniviridae

7. coronaviridae — has 2 subfamilies"
!
"
corovirinae torovirinae
(Divided into 4 sub-groups)
a) Alpha - eg: 229E, NL63
b)Beta - SARS ,MERS ,SARS CoV-2, OC - 43,HKU - 1
c)Gamma
d)Delta

8. coronaviruses are divided into three genera (I to III) referred to as groups
based on serological cross reactivity.
Recent genome sequence analysis has confirmed this grouping."
Group I and II cause infection in humans .
Group I - consists of 7 viruses. Among these only NL-63 ( Netherlands in
2004 in a 7 mth old baby) causes infection in humans — respiratory infection
only .
cellular receptor for NL 63 is — ACE 2 rp.
Group II - consists of 7 viruses . Among these SARS CoV and SARSCoV 2 -
causes SARS/COVID19 in humans - typically a respiratory infection and 25%
intestinal .
cellular rp for SARS CoV and SARS CoV2 is also ACE 2 rp.
cellular rp for MERS is DPP4 rp. (Dipeptidyl peptidase - 4)
Group III - consists of 2 viruses . (avian coronavirus)

9. Coronaviruses
!
Incubation period : for novel coronavirus is b/w 2 to 14 days.
.
R0 - (R naught) - 2 to 3.11, could even be higher. Reproductive ratio
of this virus and degree of spreadability.It means that one person can
spread infection to about 3 persons.
Super spreaders – they spread the infection to as many as 10 to 20
persons at a time.
!
Series interval – 5 to 7.5 days (relatively high) – it is the time
between successive cases in a chain of transmission.
!
Novel corona virus – incubation period — is b/w 2 to 14 days ( even upto
28 days in some persons) after exposure, but recently in Japan by mid march
they have found it takes 14- 27 days for the symptoms to appear .
EPIDEMIOLOGY

10. TRANSMISSION
!
By contact
!
Droplet/Micro droplet — Airborne
!
Fomites
!
Feco - Oral route
!
Environmental sources – such as sewage or water may also play a
role in transmission
!
Though the virus enters and affects the respiratory system, it is
also found in the bloodstream, in the urine, sweat and for
upto two months in the stool.
!
Virus persists in the respiratory tract for 2 to 3 weeks..

11. Corona virus d/s
Causes acute & Chronic respiratory / Enteric / CNS d/s
Transmission : Zoonotic D/S.
!
Dangerous human CoVs - are all Beta CoVs
1) SARS CoV SARS Epidemic (2002-2003) 9% Fatality
Bat (Reservoir) Himalayan Humans (Wet animal markets)
palm Civet
(Intermediate host)

12. 2) MERS CoV MERS(2012) 40% mortality
Bat Dromedary Camel Humans
(Reservoir) ( Intermediate host)
3) 2019 n CoV COVID 19 SARS -CoV 2 ( 2.5 to 10%
mortality )
Bat ???? Human"
(reservoir) ( Intermediate host)

13. CULTIVATION
Difficult in cell lines"
!
Human tracheal ring organ culture- grows only in this tissue"
!
SARS, MERS - Exceptions - these can be easily grown on vero cell lines.
!
Common cold 10- 35% are d/t Human CoVs. depending on the season
Increased prevalence in late fall, winter & early spring

14. VIRAL TRANSPORT MEDIUM
!
It is a combination of :
!
• Fetal Bovine Serum (FBS)
• Hanks Balanced Salt Solution (HBSS)
• Gentamicin Sulphate
• Amphotericin B
• Sheep blood agar plate
• 70% Ethanol as Disinfectant

15. TEMPERATURE & RELATIVE HUMUDITY
!
!
!
!
▪ Effects of Temp. & relative humidity on the viability of
the coronavirus.
!
▪ Dried virus on smooth surface viability > 5 days @ Temp of 22 – 25 deg C. &
relative humidity of 40-50% (Typical air conditioned environments)
!
▪ The viability of virus rapidly lost at higher temperatures & higher relative
humidity (38degC & relative humidity of >95%)
!
▪ Better stability of SARS CoV at low temp. & low humidity – may facilitate
its transmission.

16. VIRION
!
It is a Large , ENVELOPED , Single strand positive sense RNA molecule"
RNA is coded with structural proteins — which forms a complex
NUCLEOCAPSID.(N)
Nucleocapsid is enclosed in an ENVELOPE (E) - highly hydrophobic ."
This envelope is a lipid membrane with embedded proteins M and E.

17. ❖From the envelope — spikes emanate.
(glycoprotein S) spike protein (S)"
"
!
❖giving the shape of a crown - “CORONA”
( latin word)"
The origin of SARSCoV - describes the evolution
and species specificity of this virus.
!
!
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!
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❖INTEGRITY OF ENVELOPE IS ESSENTIAL FORTHE VIRAL INFECTION.
!
❖ LIPID MEMBRANE — easily destroyed by soap, alcohol and disinfectants."
!
❖Enveloped viruses are the easiest to inactivate when they are outside the host.

18. PATHOGENESIS
• SARS CoV-2 —Uses ACE 2 rp to enter the human cell"
!
• Infection starts with the cells of the respiratory mucosa - infect ciliated
epithelial cells in the nasopharynx…
!
• Then spreads to the epithelial cell of the alveoli in the lungs ( Type II
Pneumocytes)
!
• Receptor binding Fusion of the viral memb. with the host cell memb."
!
• Release the nucleocapsid into the cell (using host machinery)

19. Replicates ( copies produced)
!
!
To produce Viral RNAs and proteins
!
!
new virions are formed and released
!
!
the host cell dies
!
!
Uncontrolled multiplication of virus destroys the respiratory tissues.
"
The whole lung gets inflammed.
Release the nucleocapsid into the cell (using host machinery)

20. PULMONARY PATHOLOGY
!
!
!
It consists of hyaline membrane formation"
!
Desquamation of pneumocytes in alveolar spaces"
!
Interstitial infiltrate consisting of lymphocytes and mononuclear cells"
!
Giant cells frequently seen"
!
Coronavirus particles detected in type II pneumocytes.

21. After infecting ciliated epithelial cells in the nasopharynx --
the virus replicates – this replication leads to damage of ciliated
cells and induction of chemokines and interleukins, which result
in common cold symptoms similar to those induced by
rhinoviruses.
❖ Capillaries around the alveoli becomes leaky and further more
large barrier of fluid that goes into the interstitial space +
fluids starts leaking into the alveolar space. The alveolar space
fills up with proteinaceous liquid which prevents oxygen
exchange between the alveolar membrane and the capillaries.
!
❖ So this blood becomes hypoxic —- and the patients becomes
hypoxic —- SOB — ARDS — Ventilatory support.

22. PATHO PHYSIOLOGY IN SARS CoV 2
!
The exact mechanism of lung injury and cause of severe d/s in humans
remains undetermined
Spike proteins binds to ACE 2 rps (Angiotensin converting enzyme2)"
Causing down regulation of ACE2 rps "
So ACE2 reduces.

23. PATHOPHYSIOLOGY
This is bad for two reasons:
1. ACE2 naturally protects against
acute lung injuries.
2. RAAS pathway — Renin
Angiotensin Aldosterone system
pathway. Excessive Angiotensin
II production by the enzyme
ACE . "
So excessive angiotensine II causes
excessive stimulation of type I A
angiotensine II receptor which
increases pulmonary vascular
permeability.
On Down regulating ACE 2
!
!
Compensatory in ACE1
(-ve feedback)
RAAS
Pathway
!
Angiotensine II
!
!
AGTR 1A
(found in lungs)
!
!
Pulmonary vascular permeability
!
!
Tissue damage in lungs

24. IMMUNO PATHOLOGY
SARS CoV primarliy infects epithelial cells within the lungs. It mainly enters
the macro phages and dentiritic cells. Infection of the cell types induce pro
inflammatory cytokines and contributes to the disease worsening.
Progression to ARDS is assoc. with the up regulation of pro inflammatory
cytokines and chemokines "
!
Cytokines Pro inflammatory (before) - Preliminary steps "
of inflammation IL- 1, IL-18, TNF
Anti inflammatory (against) - Trying to stop"
inflammation IL-1, 4,6,10,11,13

25. Alveoli in early stage of ARDS Normal Alveoli
hyaline membrane formation
Desquamation of pneumocytes in alveolar spaces
Interstitial infiltrate consisting of lymphocytes and mononuclear cells
Giant cells frequently seen

27. Patients who recovered from SARS have shown an early expression of IFN α
, IFN γ, CxCL10 , CCL2 and proteins that are encoded by IFN stimulated
genes."
IFN α – antiviral ( released by infected cell )"
IFN γ – antiviral ( released by immune cell )"
CXCL10 and CCL2 are chemoattractants / chemochine"
!
As soon as the host cell is infected with a virus"
!
The host cell starts producing IFNs"
!
IFNα ( by the infected cell ) serves as the signal to the nearby cell "
!
to make them alert in producing antiviral proteins ( IFNγ )

28. !
CLINICAL PRESENTATIONS :
Fever, dry cough, Sorethroat, malaise, headache and myalgias."
Shortness Of Breath (SOB) / dyspnoea"
Severe Acute Respiratory Infections ( SARI )
Pneumonia, "
Cytokine Storm Syndrome (CSS) -- ARDS"
Septic shock
Gustatory and Olfactory symptoms ( Ageusia and anosmia) also
encountered in persons with covid19 infection."
25% Intestinal symptoms"
Causes acute & Chronic respiratory / Enteric / CNS d/s"
NOTE : I ) cases of Influenza like illness (ILI) also to be
monitored in health facilities – COVID19 and NON – COVID
cases

29. ▪ II ) Illness in pregnant women - may be particularly severe.
!
▪ III ) SARSCoV – infection appears to be milder in children – for 3
reasons
1) ACE2 rps might be low in numbers in the lower respiratory tract
compared to upper resp.tract and so they often develop URI
symtoms with covid19 .
•
2) As they are exposed to a large number of novel respiratory
infections – results in them having higher baseline levels of
antibodies against viruses than adults.
!
• 3) Children , with immature immune systems appear to be less
capable of mounting cytokine storms to fight off viral infections

30. !
!
LAB. FINDINGS OF SARSCOV2
❖CBC - Lymphopemia – in 80% of cases – mostly affects CD4+T , CD8+T and
NK cells., leukopenia"
❖TCP ( Thrombocytopemia ) , NLR ( Neutrophil Lymphocyte Ratio)
!
❖CHEMISTRIES:
❖Elevated BUN / creatinine"
❖elevated LDH, creatinine kinase
❖elevated SGOT , SGPT and total bilirubin
!
❖INFLAMMATORY MARKERS:
❖Normal or low procalcitonin, high CRP, high ferritin
INVESTIGATIONS

31. ❖ RT -PCR of Respiratory Tissue samples & Plasma - in early phase
of illness. ( Nasopharyngeal swab / broncho alveolar swab)"
❖ RT - PCR in urine & Stool — later phase of illness.
❖ Culture on Vero - 6 cell lines
❖ ELISA / IFAT — antibodies detectable within one month.
(Enzyme linked immunosorbent Assay) – 1-5 hrs"
IFAT – Immunofluoresence Antibody Tests"
❖ Rapid Diagnostic Tests(RDT) – result in 10 to 30 minutes , sensitivity –
90% specificity – 95% , tests IgG / IgM antibodies.
❖ Pooled testing can make a difference in a society with dense
population. Pools of 16, 32 or 64 swab samples can be tested at one
go. If positive – can go for individual testing. – very costeffective
too.
INVESTIGATIONS

32. IMAGING STUDIES :
X-Ray Chest – B/L patchy infiltrates / Interstitial infiltrates, including
patchy areas of opacities (consolidation) most frequently in peripheral and
lower lung fields, progress on to diffuse involvement.

33. NormalARDS
ARDS

34. CT CHEST -- B/L ground glass opacities and consolidation may be seen.

35. CT - IMAGES

36. Risk factors for ARDS with multi organ
failure
1. Age over 50yrs
2. DM
3. COPD
4. CVS d/s"
5. Pregnancy
6. Children under infection"
7. High Sequential Organ Failure Assessment score (SOFA )

37. CYTOKINE STORM
SYNDROME(CSS)
During cytokine storm
Excessive immune response ravages healthy lung tissue
!
❖ ARDS & Multiorgan failure
!
❖ Untreated cytokine syndrome is fatal.
!
❖ Dynamic cytokine detection was necessary to timely identify cytokine storms "
and application of artificial liver Blood purification System – could rapidly "
remove inflammatory mediators and block cytokine storm

38. Focus on to block the cytokines which are harmful to the host
!
1) Neutralising antibodies
!
2) Soluble receptors
!
3) Receptor antagonist
!
4) Inhibitors of proteases
!
5) 2 to 3% survival rates on using anticytokine therapy
"
!

39. !
1.The exact treatment is based on symptomatic management only.
The following has been tried successfully
2. Protease Inhibitors – Lopinavir/Ritonavir combined with Arbidol (Umifenovir)
It inhibits the fusion b/w the viral envelope and the cell membrane of
the target cell.
3.Ribavarin – belongs to Nucleoside analogue - has frequently been used.
4. Four – Anti
& Strategy effectively increased
cure rate and reduced mortality
Two - Balance
TREATMENT

40. Four – Anti strategies:
!
a) Anti – viral treatment
b) Anti - Shock
c) Anti – Hypoxemia
d) Anti – Secondary Infection
!
Two Balance Strategies :
!
a) Maintaining water / Electrolyte acid- Base balance
b) Micro – Ecological balance
!
5) Early antiviral Rx could alleviate d/s severity & prevent illness
progression.
!
6) Shock & Hypoxemia – Caused by cytokine storms.

41. 7) Glucocorticoid Rx – Supported
!
!
8) O2 Therapy preferred - HFNO
!
!
9) Patients on mechanical ventilation should be strictly supervised –
& strategies to prevent ventilator associated pneumonia should be taken.
!
!
10) Non Invasive ventilation (NIV) – Not recommended.
" " " " Positive pressure ventilation
" " " " " CPAP – Continuous positive airway pressure
" NIV" " " " BiPAP- Bilevel positive airway pressure
" " " "
" " " " Negative pressure ventilation.

42. ❖11) Antimicrobial Rx – prescribed rationally.
!
❖12) In patients with PCT (Procalcitonin) ! Elevated in
patients with cytokine storm synd.
!
❖13) Sr. Ferritin !Screening tool for the possibility of a CSS in
sick patients. Ferritin increases in inflammation – functions as an
immune response and not as a marker of iron status."
!
❖ 14) Secondary fungal infection also should be checked
!
❖ 15) Nutritional support & application of prebiotics & or
probiotics – to regulate the balance of interstitial microbiota & se
the risk of secondary infection due to bacterial translocation.

43. ❖16) Alleviate anxiety & fear – Psychological crisis – to be dealt with.
!
❖17)Traditional medicines were also integrated – to promote d/s
rehabilitation. It was unclear about viral clearance pattern after the SARS"
CoV-2 infection – So 2 weeks of quarantine for discharged patients was"
required & a regular follow up was also needed.

44. When Patient on Ventilation – These are the recommendations :
!
1. Reduce tidal volume and increase PCO2 (published in 2000). It has
shown to reduce mortality from 40% to 31%
!
2. Paralyse the ventilated patients with neuro muscular blockers
(published in 2010). This reduces mortality from 41% to 32%.
!
3. Prone positioning (17 to 18 hours a day. published in 2013) This
reduces mortality from 33% to 16%.

45. • Explanation for these recommendations:
• When you put people on ventilator the ventilator puts the breath into
their airways we were thinking that we were ventilating the patients well.
• The blood that is poor in oxygen also has CO2 from the muscles this CO2
has to be ventilated so that CO2 is coming out So to do that we should
make sure enough volume of air is going back & forth.
• The problem with this is that when we are putting pressure (inflating) &
releasing it these alveoli will close down so they are opening & closing
causing lot of shear stress.
• The whole problem here is that it was inflammation that has caused the
ARDS leading to alveolar membrane thickening and no exchange of
oxygen.
• By ventilating these patients with large tidal volumes we are actually making
the inflammation to get even worse than it would have been if we had not
done that.

46. Explanation for Prone position in mechanical ventilation
Improves perfusion to the lungs ! better V:Q matching "
Diaphragm drops and the heart shifted forward ! improved compliance"
Lung protective "
Reduces atelectasis , Barotrauma & Volutrauma"
Better V:Q matching ! improves oxygenation"
Duration 16 to 24Hrs.

47. GENERAL TREATMENT
RECOMMENDATIONS
!
The following treatment strategies are recommended based on experience
to date:
1. Due to aerosol spread, nebulizers should be converted to MDIs
( Metered Dose Inhalers).
2. Initiating or discontinuing ACE I and ARBs have been an area of
intense discussion.
3. Corticosteroids – Indicated in conditions like asthma or COPD
exacerbations, refractory shock or evidnce of CSS.
4. The treatment followed in India – Hydroxy Chloroquine +
Azithromycin /Doxycycline.
5. Oseltamivir ( Tami Flu) is also being added to the protocol.
6. Lopinavir + ritonavir combination is also tried.

48. ❖Key Suggestion:"
❖ECMO - Extra Corporeal Membrane oxygenation.
❖To be considered if prone ventilation fails for patients with refractory
hypoxemia due to progressive pneumonia (ARDS)"
❖ECMO is associated with high mortality rate."
❖Convalescence plasma therapy also to be considered.
!
❖Late Complications of Covid 19. "
❖Cardiomyopathy "
❖Cardiogenic shock"
❖Deep Vein Thrombosis"
❖Pulmonary Embolism

49. PHARMACOLOGY
1) Camostat Mesylate (serine protease inhibitor ) – Inhibits TMPRSS2
(Transmembrane Protease Serine 2 )"
!
2) Monoclonal Antibodies – that bind to spike protein of the virus & block the
interaction with the human ACE2 rps – are highly expressed in Type II alveolar cells (in
the lungs)"
!
ACE2 Rps also found in many extrapulmonary tissues - Heart/kidney/Endothelium/
Intestine"
!
3) Compound against ACE2 rp & spike protiens - "
" " Hesperidin

50. !
• 4) SARsCoV – binding to ACE2 down regulates ACE2 & thereby causes
severe lung injury"
!
• 5) Delivery of excessive soluble form of ACE2 may competitively bind to
SARs CoV - & not only neutralize the virus but also regulates the RAAS to
protect the lungs"
!
• Remdesivir"
• Favipiravir Inhibit RNA dependent RNA"
polymerase.

51. 6) Chloroquine – increasing the pH in host cell lysosomes
" " " Which Inturn inhibits hydrolytic activity of protease
" " " enzymes required for processing of viral glycoproteins
" " " during Infection.
!
!
7) Protease Inhibitors -- Lopinavir/Ritonavir
!
!
8) Darunavir/Cobicistat ( anti – retroviral) - They interrupt some proteins that are
required for replication of SARSCoV 2"

52. By TN Govt.

53. By TN Govt.

54. By MoHFW

55. PUBLIC HEALTH MEASURES FOR COVID -19
!
▪ Flattening of this curve.
▪ How to flatten this curve ?
▪ Protect yourself
▪ using hand sanitizers
▪ Washing hands"
▪ Avoid close contacts with people -Avoid gathering
▪ Protect others
▪ Stay at home if you are sick
▪ Cover mouth when coughing or Sneezing
▪ Social distancing + herd masking + hand washing is having
added advantage.
PREVENTION

57. Cases identification
!
Isolation of individual this vicious
cycle goes on.
Contact tracing
!
Appropriate treatment of cases.

58. Three Levels of Quarantine Facilities
1. Home quarantine
Asymptomatic low risk contacts
COVID negative patients.
!
2. Facility quarantine
Asymptomatic high risk contacts
Discharged COVID positive patients from the Hospital.
!
3. Institutional quarantine
a.) Symptomatic low risk & b). high risk contacts.

59. PREVENTION
!
➢ Case definition – establish
➢ Travel advisories - propose
➢ Quarantines – impose
!
➢ HERD MASKING
!
➢ SOCIAL DISTANCING
!
➢ HAND WASHING – As the lipid layer of the
virus is susceptible to soap / detergent /
alcohol based hand sanitisers.
!
➢ ISOLATION ( confirmed cases) – till 2
subsequent RT-PCR – reports are negative
!
➢ QUARANTINE - Who are exposed and
asymptomatic – for 14 to 28 days

60. VACCINES
!
!
!
UNDER TRIAL…….
!
!
!
!

61. References
Harrison’s Internal Medicine
https://mmbr.asm.org/
https://ncbi.nlm.nih.gov/pmc/articles/
https://mohfw.gov.in
!
Youtube- ninja nerd science
PGMEE microbiology
Catalyst university
Speed pharmacology
!

62. NATURE UNLEASHES HEALING TOUCH
WORLDWIDE ! !
!
THE GLOBE IS FILLING WITH CLEAN AIR AND
CLEAN WATER !!
!
TWO SIDES OF A COIN !!