diagnosis, lab workout, disease severity, Management and Emerging Treatment of corona virus SARS-COV2

1. Presented by: Farah Al Souheil
Presented to: Dr. Fouad Sakr
1

2. Lebanese International University
School of Pharmacy
Advanced Pharmacy Practice Experience
Intensive Care Unit
Management of COVID-19 in ICU &
Promising New Treatment
April 7, 2020

3. Outline
i. Definition
ii. Epidemiology
iii. Pathophysiology
iv. Prevention
v. Diagnosis
i. Risk factors
ii. Differentials
vi. Treatment
i. Treatment approach
ii. Emerging
vii. Follow-up
i. Complications
ii. Prognosis
viii. Abbreviations
ix. References
3

4. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Identified as the cause of an outbreak of pneumonia of unknown cause
Labs ruled out SARS-CoV, (MERS)-CoV, influenza, avian influenza
Named as SARS-CoV-2 owing to the virus's genetic similarity to the SARS-CoV
Also known as Novel coronavirus (2019-nCoV)
Disease named by WHO as COVID-19 ( Coronavirus disease 2019)
Definition
Ren LL, Wang YM, Wu ZQ, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020 Jan 30
[Epub ahead of print].
4

5. Facts & Numbers
Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases
(COVID-19) in China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 17;41(2):145-51
There are two
major types (or
strains) of the
virus (L and S)
The L type was
more prevalent
during the early
stages of the
outbreak (More
aggressive)
Transmission
occurs via
respiratory
droplets
Detected in
blood, saliva,
tears, and
conjunctival
secretions, and
feces)
87% were
aged 30-79
1% were
aged ≤ 9
1% were
aged 10-19
3% were
aged ≥80
Reported cases’ age
in years
Globally, 123420
cases have been
reported as of 5
April, 2020
Spread from asymptomatic
contacts can occur
5

6. Pathophysiology
Incubation period range
from 1 to 14 days (Median =
5 days)
Virus binds to the ACE2
receptor in humans (Similar
pathogenesis to SARS)
Both symptomatic &
asymptomatic patients have
a similar viral load
World Health Organization. Novel coronavirus (2019-nCoV) situation report - 6. January 2020 [internet publication]
2-14 D
6

7. Primary Prevention
Washing hands often
Maintaining a distance of at least 1 meter from people
Seeking medical care in case of fever, cough, and dyspnea
Avoiding direct unprotected contact with live animals
Avoiding raw or undercooked animal products
Individuals with fever and/or respiratory symptoms are
advised to wear a mask
An mRNA vaccine (mRNA-1273) in phase 1 clinical trials
World Health Organization. Novel coronavirus (2019-nCoV) situation report - 6. January 2020 [internet publication]
7

8. Clinical Presentation
Most common symptoms:
• Fever (Children may be afebrile)
• Dry cough (59-82%)
• Dyspnea ( 18-55%)
• Myalgia (38-69%)
• Fatigue
Less common symptoms include:
• Anorexia
• Sputum production
• Sore throat
• Confusion, Dizziness, Headache
• Rhinorrhea
• Chest pain
• Diarrhea, N/V, Abdominal pain
• Conjunctival congestion
Symptoms range from a mild common cold like illness, to a severe viral
pneumonia leading to ARDS
15% of patients present with
fever, cough, and dyspnea
90% of patients have ≥ 1 Symptom
Signs of pneumonia present on chest imaging despite having minimal or no Sx
Patients with ARDS may have tachycardia, tachypnea, or cyanosis with hypoxia
8

9. Lab Workup
ABG (to detect
hypercarbia or
acidosis)
FBC
Coagulation screen
(D-dimer; PT) Procalcitonin &
CRP
Serum troponin Serum LDH Serum CK
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA.
2020 Feb 7 [Epub ahead of print].
Expected labs: Leukopenia/leukocytosis, lymphopenia and elevated liver transaminases
Other: neutrophilia, thrombocytopenia, decreased hgb & albumin, & renal impairment
Perform (RT-PCR), for SARS-CoV-2 in all patients with suspected infection
CXR: bilateral lung infiltrates are found in 75% of patients
9

10. Diagnosis
 A confirmed case is based on
 Epidemiological history (including cluster transmission)
 Clinical manifestations (fever and respiratory symptoms)
 Lung imaging
 Results of SARS-CoV-2 nucleic acid detection
 Serum-specific antibodies
10
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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11. Clinical Classification
Mild
Cases
Symptoms
are mild and
pneumonia
is absent on
imaging
Moderate
Cases
Fever and
respiratory
tract
symptoms
Pneumonia
present on
imaging
Severe
Cases
RR ≥ 30
breaths/min
Spo2 ≤ 93% at
rest
(PaO2)/(FiO2)
≤ 300 mmHg
> 50% lesions
progression within
24 to 48 hours in
lung imaging
Critical
Cases
11
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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12. Critical Cases Classification
No organ failure
other than the lungs
Great chance of
recovery by:
Early stage
May be
complicated by
other mild or
moderate
dysfunction of
other organs
Middle stage
Diffuse
consolidation
of both lungs
(ECMO)
Failure of other
vital organs
High mortality
risk
Late stage
Stage Oxygenation Index
(mmHg)
Compliance of Respiratory
System (mL/cmH2O)
Early 100-150 ≥30
Middle 60-100 15-30
Late ≤60 ≤15
Anti-viral
Anti-cytokine
Supportive care
12
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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13. ICU Management
Patients with respiratory
failure should be
admitted to ICU
Between 23% to 32% of
hospitalized patients
require ICU
13
Coronavirus disease 2019 (COVID-19). (2020, April 3). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

14. Management
14

15. Oxygen
• Target SpO₂
≥90%
• Rate of 5
L/min
• Patients with
severe
ARDS,
hypoxemia,
or shock
Fluids
• Aggressive
fluid
resuscitation
may worsen
oxygenation
Symptom
relief
• Antipyretic/
analgesic
• For the relief of
fever and pain
Antiviral
Treatment
• Shock
• Respiratory
failure
• Other organ
failure that
requires
monitoring in
the ICU
Empirical
Antimicrobial
s
• Antibiotics for
secondary
bacterial
infection
• Neuraminidase
inhibitor until
influenza is
R/O
• Given within 1
hour if sepsis is
suspected
• De-escalate
empirical
therapy based
on test results
Supportive Care
15
Coronavirus disease 2019 (COVID-19). (2020, April 3). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

16. Monitoring
Monitor
for
Signs of
clinical
deterioration
and sepsis
Intervene when indicated
Hemo-
dialysis
Vasopressor
therapy
Fluid
resuscita-
tion
Ventilation
Anti-
microbials
16
Coronavirus disease 2019 (COVID-19). (2020, April 3). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

17. Mechanical Ventilation
High fraction of inspired oxygen for severe hypoxic respiratory failure
High air flow rates to match inspiratory flow demand
Positive pressure breathing assistance for increased work of breathing
Lung protection through low TV /low inspiratory pressure ventilation strategy
Some patients may require extracorporeal membrane oxygenation (ECMO)
High-flow nasal oxygen and non-invasive ventilation are recommended in select patients
17
In patients who cannot maintain an
SpO₂ ≥90% with oxygen therapy
Coronavirus disease 2019 (COVID-19). (2020, April 3). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

18. Artificial Liver Support System (ALSS) & Blood Purification
• Can conduct plasma exchange, adsorption,
perfusion, and filtration of inflammatory mediators
such as endotoxins and harmful metabolic
substances
Diminish inflammatory
mediators and cytokine
cascade
• Can provide serum albumin, coagulation
factors, balance fluid volume, electrolytes
and acid-base ratio
Prevent the incidence of
shock, hypoxemia and
ARDS
Hypoxemia
Cytokine
cascade
Severe
infections
Shock
Tissue
perfusion
disorders
Multiple
organ
failure
18
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19. ALSS Indications
 IL6 level rises to ≥ 5 ULN or rising rate is ≥1x/ day
 ≥10% progression per day of involved area on pulmonary CT
19
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20. Corticosteroids
For patients with
severe COVID-19
pneumonia
Not routinely
recommend for the
treatment of viral
pneumonia or
ARDS
High dose of
glucocorticoids
should be avoided
Inhibits cytokine
cascade & prevents
disease progression
20
Short-term use
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21. Corticosteroids Indications
Severe and critically
ill stages
Persistent high fever
(above 39°c)
Patchy ground-glass
attenuation or ≥
30% of the lungs are
involved on CT scan
≥ 50% area involved
in pulmonary CT
images in 48 hours
IL-6 is above ≥ 5
ULN
(80 pg/mL)
21
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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22. Corticosteroids Dosing
Methylprednisolone
0.75-1.5 mg/kg IV
once daily
40 mg q12h for
patients with
•Falling body temperature
•Increasing cytokines
40-80 mg q12h can
be considered for
critical cases
Taper down
Decrease dose by
50% every 3 to 5
days
When body
temperature
normalizes
When involved
lesions on CT are
absorbed
Switch to oral
methylprednisolone
When the IV dose is
reduced to 20
mg/day
22
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23. Special Considerations
Screening of TB,
HBV and HCV by
antibody assay should
be performed
PPI could be
considered
Blood glucose should
be monitored
Hypokalemia should
be corrected
Liver function should
be monitored closely
Sedative-hypnotics
can be administered
temporarily for
patients with sleep
disorder
23
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24. Antivirals
 Simultaneous use of three or more antiviral drugs is not
recommended
 Treatment course is around 2 weeks
 Antiviral drugs should be stopped if nucleic acid test results
remain negative for more than 3x
 Oseltamivir
 Lopinavir/ritonavir
 Ganciclovir
 Favipiravir (used in china)
 Baloxavir marboxil
 Umifenovir
 Interferon alfa
 Remdesivir
24
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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25. Basic regimen
Lopinavir/ Ritonavir
Lopinavir/ ritonavir (2 capsules, po q12h) combined with
arbidol (200 mg po q12h)
Abnormal liver function (51.9% ), diarrhea, N/V
,jaundice, dyslipidemia, lactic acidosis, Fat
redistribution, prolong the QT/PR interval, AV
block,Pancreatitis, hyperglycemia
Amiodarone (fatal arrhythmia), quetiapine (severe
coma), simvastatin (rhabdomyolysis) , hypokalemia,
QT/PR prolonging medications
Side effects:
• Increase of serum aminotransferase
• Bradycardia (avoid combination with beta blockers
• Stop taking the drugs when the HR drops below 60/min
25
Effective in 13.5
days
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26. Moderate-Severe Covid19
Remdisivir
200 mg as a single dose on day 1
100 mg qd for a total duration of 5-10 days
Nausea, vomiting, and transaminase
elevations
Prepared in a cyclodextrin vehicle, so there is
concern for potentially toxic accumulation of
the vehicle in renal impairment
Avoid in pregnancy
26
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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Nucleotide Analogue
RNA Synthesis Inhibitor

27. Chloroquine and Hydroxychloroquine
Hydroxychloroquine: 800 mg on day 1 then 400 mg daily
Chloroquine 1 g on day 1 then 500 mg daily
Each for 4-7 days
The most severe : cardiac arrest
The main: ocular toxicity
Other: Dizziness, headache, N/V, diarrhea, skin rash
Pregnancy, Arrhythmia (e.g., conduction block), retinal
disease, or hearing loss, drugs that cause Q-T prolongation
(moxifloxacin, azithromycin, amiodarone)
In patients with severe illness, rapid viral RNA clearance
wasn’t seen when combined with azithromycin
27If the basic regimen is not effective
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28. If intolerant to basic regimin
Favipiravir
1600 mg followed by 600 mg tid
1,600 mg bid on day 1, followed by 600 mg bid for 7-14
days
• Increases uric acid, diarrhea, neutropenia, shock, fulminant hepatitis, AKI
• In elderly patients or patients with cytokine storm
• Theophyllinum increases the bioavailability of favipiravir
• It increases the bioavailability of acetaminophen & repaglinide
• Its combination with pyrazinamide increases uric acid
Contraindicated in pregnancy
28
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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RNA Polymerase
Inhibitor

29. Darunavir/Cobicistat
Initially used for HIV Mild adverse events
For patients who are
intolerant to
lopinavir/ritonavir
1 tablet daily
N/V, diarrhea, liver
abnormalities
jaundice,
dyslipidemia, lactic
acidosis
29
Handbook of COVID-19 Preventionand Treatment：Part two diagnosis and treatment. (2020, March 30). Retrieved from https://events.mybiogate.com/covid-19/handbook-of-
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30. Tociluzumab
Rheumatoid arthritis, Cytokine release syndrome, Giant
cell arteritis, Juvenile arthritis
Secondary opportunistic infections, GI perforation,
neutropenia and thrombocytopenia (discontinue
treatment for ANC <500/mm3 or platelet count
<50,000/mm3), hepatic injury
4 to 8 mg/kg (400-800 mg/dose) as a single dose
Repeat dose in ≥12 hours in patients who remain febrile
in 24 hours
ANC is <2,000/mm3
Platelets are <100,000/mm3
ALT or AST are >1.5 times ULN
30
UpToDate. (n.d.). Retrieved from https://www.uptodate.com/contents/tocilizumab-drug-
information?search=tocilizumab&source=panel_search_result&selectedTitle=1~109&usage_type=panel&kp_tab=drug_general&display_rank=1#F9773961
Severe & Critical Cases
IL6 inhibitor

31. Convalescent Plasma
Function:
• Neutralize the pathogens
• Reduce the damage of the target organs
• Block the subsequent immune-pathological damages
Donors:
• At least 2 weeks after recovery and being discharged
• 18 ≤ Age ≤ 55
• The body weight＞50 kg (for male) or ＞45 kg (for female)
• At least 1 week since last glucocorticoid usage
• >2 weeks since last blood donation
Indications:
• Severe or critically ill patients
• Immune suppressed
• Rapid disease progression in the lungs
31
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Passive Immune Antibodies

32. Interferon Nebulization
 Recommended in Protocols for Diagnosis and Treatment of
COVID-19
 It should be performed in negative-pressure wards rather than
general wards due to the possibility of aerosol transmission
32
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33. IVIG
 Intravenous immunoglobulin is being trialed in some patients
with COVID-19
 No data to support their use
33
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34. Traditional Chinese Medicine
 It is being trialled in some patients with COVID-19
 Xue-Bi-Jing
 ShuangHuang-Lian
 Xin-Guan-2)
 No data to support their use
34
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35. Stem Cell Therapy
 Stem cell therapy is being investigated to treat patients with
COVID-19 in clinical trials
 It is thought that mesenchymal stem cells
 Reduce the pathological changes that occur in the lungs
 Inhibit the cell mediated immune inflammatory response
35
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36. Angiotensin-II Receptor Antagonists
 Angiotensin-converting enzyme-2 (ACE2) receptor is the main
binding site for the virus
 Patients on ACE inhibitors or ARB have upregulated ACE2
receptors
 No supported association of increased risk to Covid19
 Stopping these agents exacerbates comorbid cardiovascular or
kidney disease and lead to increased mortality
36
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37. Short Term Complications
ARDS
15% to 29% of patients
Acute cardiac injury
7% to 12% of patients
Arrhythmias
16% of patients
Secondary infection
10% of patients
Acute respiratory failure
8% of patients
Acute kidney injury
3% to 7% of patients
Septic shock
4% to 8% of patients
DIC
71% of non-survivors
Fetal distress
Premature labour
ARDS
Thrombo- cytopenia
Abnormall liver function
37
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38. Antibiotics
Indications:
• Extensive lung lesions
• Excess bronchial secretions
• Chronic airway diseases
(copd,asthma)
• Glucocorticoids ≥ 20 mg × 7d
(in terms of prednisone)
• Critically severe patients,
especially those with invasive
mechanical ventilation
• Carbapenems, β-lactamase
inhibitor, linezolid and
vancomycin
Options:
• Quinolones
• Second or third generation
cephalosporin
• β-lactamase inhibitor
38
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39. Secondary Bacterial Infection
More expectoration, darker sputum
color, especially yellow pus sputum
Rise of body temperature
Marked increase of WBC and/or
neutrophils
Procalcitonin ≥ 0.5 ng/mL
Exacerbation of oxygenation index or
circulatory disturbance
39
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40. Pulmonary Asperigillosis
Causal Factors
• Viral infections
• Glucocorticoid
• Broad-spectrum
antibiotics
Tests
• D-Glucose (G-
test) and
galactomannan
(GM-test) of
blood or
bronchoalveolar
fluid
Fluconazole/
Echinocandin in
patients on
• Broad-spectrum
antibiotics for
>7days
• Parenteral
nutrition
• Invasive
examination or
treatment
• Positive candida
culture from two
body parts
• Positive G-test
Voriconazole/Posacona
zole/ Echinocandin in
patients
• Given
glucocorticoid for
>7 days
• With
agranulocytosis
• With COPD and
aspergillus
culture are tested
positive
• Patients with
positive GM-test
40
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41. Anti-Coagulation and Bleeding Prevention
• In case of HIT, use
argatroban
• Monitor the activity of
antithrombin III
• If reduced activity, give
FFP to restore
sensitivity
• Bleeding
• Platelet count <
50×109/L
• No active
bleeding
• No visceral
bleeding
• Platelet >
50×109/L
Heparin
50 U/kg
Heparin
25 U/kg
The target
APTT is
40—60 sec
Heparin
resistance
41
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42. The covid-19 overall
case fatality rate
(CFR) is 2.3%
CFR of SARS is 10%
and MERS is 37%
COVID-19 has so far
resulted in more
deaths than both
SARS and MERS
combined
Conclusion
42
G D. (2020, March 20). New antibodies study may lead to a solution to the coronavirus outbreak. Retrieved from https://nationalinterest.org/blog/buzz/new-
antibodies-study-may-lead-solution-coronavirus-outbreak-134687

43.  CXR: chest xray
 ACE2:angiotensin concerting enzyme
 ARDS:Acute respiratory distress syndrome
 Sx: symptoms
 N/V: nausea vomiting
 ABG: arterial blood gases
 FBC: Full Blood Count
 PT: prothrombin time
 LDH: lactate dehydrogenase
 RR: respiratory rate
 (PaO2)/(FiO2
 ECMO: extracorporeal membrane oxygenation
 R/O: rule out
 TV: tidal volume
 ALSS
 CT: computed tomography
 DIC: dissiminated intravascular disease
 Qd: every day
 Bid ; every 12 hours
 Tid: every 8 hours
Abbreviations
43