Updates on COVID 19

1. Dr. Ahmed Al Montasir
Resident Physician
Department of Medicine
TMC & RCH
COVID-19 : Emerging Data and Guidance
01 December, 2020

3. COVID-NET: Lab-Confirmed COVID-19–Associated
Hospitalization Rates Stratified by Age
https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html
0-4 yrs
5-17 yrs
18-49 yrs
50-64 yrs
≥ 65 yrs
Age Group Selection
Calendar Week Ending
0
Rateper100,000Population COVID-NET | Entire Network | 2020 | Weekly Rate40
35
30
25
20
15
10
5

4. NOTE: This preprint
reports new research that
has not been certified by
peer review and should not
be used to guide clinical
practice.

6. Racial/Socio-demographic Disparities

7. CDC COVID Data Tracker:
Reported COVID-19 Cases by Race/Ethnicity
https://www.cdc.gov/covid-data-tracker/index.html#demographics
Reported COVID-19 Cases*
*Last updated November 15, 2020, 12:16 PM ET. Includes race/ethnicity data available for 4,176,183 cases.
American
Indian or Alaska
Native,
Non-Hispanic
Asian,
Non-Hispanic
Black,
Non-Hispanic
Hispanic or
Latino
Native
Hawaiian/Other
Pacific Islander,
Non-Hispanic
Multiple/Other,
Non-Hispanic
White,
Non-Hispanic
%ofTotalCases
1.1
3
15.6
26.3
4.7
0.4
48.9
20
10
0
30
40
Updated
50
UpdatedUpdated

11. Proposed Routes of SARS-CoV-2 Transmission
Galbadage. Front Public Health. 2020;8:163. WHO. Scientific Brief. July 9, 2020.
SARS-CoV-2–
Infected Host
Susceptible
Host
Aerosols
< 5 µm diameter
Suspended in air
Contact/Droplet
> 5 µm diameter
Direct contact
or
< 1 meter distance
Fomites (?)
Environmental
Stability
Points of entry:
Eyes, nose, or
mouth
Airborne (?)
> 1 meter distance
Urine/feces:
RNA found in
both; live virus
cultivated from
few specimens

12. Key Considerations on Modes of SARS-CoV-2 Transmission
 Person-to-person considered predominant mode of
transmission, likely via respiratory droplets from coughing,
sneezing, or talking
 Virus rarely cultured in respiratory samples > 9 days after
symptom onset, especially in patients with mild disease
 ACOG: “Data indicate that vertical transmission appears to be
uncommon but possible”
1. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html
2. WHO. Scientific Brief. July 9, 2020. 3. Wölfel. Nature. 2020;581:465. 4. Zou. NEJM. 2020;382:1177.
5. WHO. Scientific Brief. June 17, 2020. 6. ACOG. COVID-19 FAQs for Obstetrician-Gynecologists, Obstetrics.

13.  3 families (A, B, and C) ate lunch at a
restaurant on January 24, 2020 at 3
neighboring tables
‒ 10 of those sitting at these tables (including
the index case) were later found to have
been infected with sARS-CoV-2 at the
restaurant
‒ None of the waiters or 68 patrons at the
remaining 15 tables became infected
‒ Authors note that these results do not show
that long-range aerosol transmission can
occur in any indoor space, but that
transmission may occur in crowded/poorly
ventilated spaces
SARS-CoV-2 Transmission: Recirculated Air
and Poor Ventilation
Li. medRxiv;[Preprint]. Note: this study has not been peer reviewed.
Air Conditioning
A
B
C
A
B
C
Infected
Time Overlap
A and B: 53 mins
A and C: 75 mins
A and D: 18 mins
Patient 0
4.5 m D
D
New

14. Herd Immunity Concept
R0= 4
Transmission
No transmission
Susceptible
Immune

16. US and UK Frontline HCWs: Impact of PPE
Nguyen. Lancet. 2020;5:E475.
Risk of Positive SARS-CoV-2 Test Adequate PPE Reused PPE Inadequate PPE
Overall
 Event/person-days
 Unadjusted HR (95% CI)
 Multivariate-adjusted HR (95% CI)
592/332,901
1 (reference)
1 (reference)
146/80,728
1.46 (1.21-1.76)
1.46 (1.21-1.76)
157/60,916
1.32 (1.10-1.57)
1.31 (1.10-1.56)
Exposure to patient with
documented COVID-19
 Event/person-days
 Unadjusted HR (95% CI)
 Multivariate-adjusted HR (95% CI)
280/50,571
4.93 (4.07-5.97)
4.83 (3.99-5.85)
91/23,751
5.12 (3.94-6.64)
5.06 (3.90-6.57)
83/11,675
5.95 (4.57-7.76)
5.91 (4.53-7.71)
 In post hoc analysis, even after adjusted for exposure to patients with COVID-19, non-White
healthcare workers more frequently reported reused PPE or inadequate PPE (adjusted OR: 1.49;
95% CI: 1.36-1.63)
New

17. Screening and Diagnosis

18. IDSA: SARS-CoV-2 Nucleic Acid Testing of Symptomatic
Individuals
IDSA. COVID-19 Guideline, Part 3: Diagnostics. Version 1.0.1.
Direct SARS-CoV-2 Nucleic Acid Amplification Testing
Collect nasopharyngeal, nasal, or mid-turbinate rather than oropharyngeal or saliva specimens
Provider-collected or self-collected specimens acceptable except nasopharyngeal
Non-hospitalized Hospitalized
Lower
respiratory tract
symptoms
High Suspicion for COVID-19 Low Suspicion for
COVID-19
Known exposure
or high
prevalence area
If negative,
repeat testing
If negative, repeat
testing (from lower
tract if possible)
If negative,
repeat testing
If negative, do not
repeat testing
Prioritize testing for symptomatic patients. If resources adequate, consider testing select asymptomatic individuals
(eg, exposed, immunosuppressive procedure, major time-sensitive surgery, aerosol-generating procedure with limited PPE).

19. Temporal Profile of SARS-CoV-2 Viral Load
 Viral loads highest during
first week following
symptom onset
 Pneumonia may develop
late and when URT PCR is
negative.
MeanViralLoad,log10copies/mL(SD)
Days After Symptom Onset
Temporal Viral Load in Patients With COVID-19[1]
10
8
6
4
2
0
0 10 20 30
Saliva
Endotracheal aspirate*
Day
Saliva
Endotracheal
0
1
0
1
1
0
2
3
0
3
3
0
4
5
0
5
5
0
6
5
0
7
4
0
8
7
1
9
10
0
10
5
1
11
8
2
12
7
2
13
7
2
14
6
2
15
7
2
16
8
2
17
5
2
18
6
2
19
5
2
20
6
2
21
6
1
22
5
1
23
6
1
24
4
1
25
3
1
26
3
0
27
2
0
28
2
0
29
1
0
1. To. Lancet Infect Dis. 2020;20:565. 2. Ai. Radiology. 2020;296:E32.

20. P = .02
P < .001 P < .001
P < .001
Figure 3. A, Viral load of different tissue samples. B, Analysis of viral load in different clinical stages of ...
 Viral load assessed via digital droplet PCR of samples collected from patients in
Beijing with laboratory confirmed COVID-19 (N = 76)
Viral Load Varies by Sample Type and Disease Stage
*Early stage: multifocal bilateral or isolated round ground-glass opacity with or without patchy consolidations and prominent peripherally subpleural distribution on chest
CT. Progressive stage: Increasing number, range, or density of lung lesions on chest CT. †Recovery phase:
lesions gradually absorbed. ‡Clinical cure: temperature recovery for > 3 days, improvement in respiratory symptoms, absorption of lung lesions, and 2 consecutive negative
RT-PCR results from respiratory samples tested at least 1 day apart.
Early and progressive stages*
(n = 15)
Recovery stage† (n = 49)
Clinical cure‡ (n = 5)
MeanViralLoad(copies/test)
MeanViralLoad(copies/test)
Type of Specimens
106
Nasal swabs
Throat swabs
Sputum
Blood
Urine
104
102
100
P < .001
Clinical Disease Stage
106
104
102
100
P < .001
Sputum Viral Load By Disease StageViral Load By Sample Type
Yu. Clin Infect Dis. 2020;71:793.

21. Temporal Considerations for Diagnosis
Sethuraman. JAMA. 2020;323:2249. Reproduced with permission from JAMA. 2020. doi:10.1001/jama.2020.8259.
Copyright©(2020) American Medical Association. All rights reserved.
Wk -2 Wk -1 Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6
Symptom onset
Detection unlikely PCR – Likely positive PCR – Likely negative
Antibody detection
Nasopharyngeal swab PCR
Virus isolation from
respiratory tract
Bronchoalveolar
lavage/sputum PCR
Stool PCR
IgM antibody
IgG antibody
After symptom onsetBefore symptom onset
SARS-CoV-2
exposure
Increasingprobabilityofdetection

22. Chest CT Abnormalities
 Most common hallmark features on chest CT images include bilateral
peripheral ground-glass opacities and consolidations of the lungs with peak
lung involvement between 6 days and 11 days post-symptom onset.
 In a study in Wuhan, China, chest CT imaging demonstrated a sensitivity of
97%.
‒ 60% to 93% of patients had initial positive lung CT consistent with COVID-19 before the initial positive
RT-PCR result
1. Bernheim. Radiology. 2020;295:685. 2. Pan. Radiology. 2020;295:715. 3. Wang. Radiology. 2020;296:E55. 4. Ai. Radiology. 2020;296:E32.
29-Yr-Old Man Presenting With Fever for 6 Days
Ground-glass
opacities
Day 6 Day 9 Day 11 Day 17 Day 23

23. The evidence suggests that
chest CT is better at ruling out
COVID-19 infection than
distinguishing it from other
respiratory problems.
So, its usefulness may be
limited to excluding COVID-19
infection rather than
distinguishing it from other
causes of lung infection.

24. Three patterns on CT-chest imaging consistent with COVID-19
pneumonia according to stage of illness (from symptom onset) are:
 early (0 to 2 days): normal or rounded ground-glass opacities
 intermediate (5 to 10 days): crazy-paving opacities
 late (more than 10 days): consolidation

25. Natural History, Clinical Presentation,
and Symptom Spectrum

26. COVID-19 Clinical Presentation May Vary by Age, Sex
‒ Mean duration of symptoms (n = 264): 11.5 ± 5.7 days
‒ Ear, nose, throat complaints more common in young
patients; fever, fatigue, loss of appetite, diarrhea in elderly
patients
‒ Loss of smell, headache, nasal obstruction, throat pain,
fatigue more common in women; cough, fever in men
Among 17 fatal COVID-19 cases detailed by the China National
Health Commission, median time from first symptom to
death: 14 days (range: 6-41)
‒ Numerically faster in older patients: 11.5 days if ≥ 70 yrs vs
20 days if < 70 yrs (P = .033)
1. Lechien. J Intern Med. 2020;288:335. 2. Wang. J Med Virol. 2020;92:441.
Symptom,[1] % N = 1420
Headache 70.3
Loss of smell 70.2
Nasal obstruction 67.8
Asthenia 63.3
Cough 63.2
Myalgia 62.5
Rhinorrhea 60.1
Taste dysfunction 54.2
Sore throat 52.9
Fever (> 38°C) 45.4

27. Endocrine
 Hyperglycemia
 Diabetic ketoacidosis
Extrapulmonary Manifestations of COVID-19:
Which of These Return or Last?
Gupta. Nat Med. 2020;26:1017.
Neurologic
 Headaches
 Dizziness
 Encephalopathy
 Guillain-Barré
Renal
 Acute kidney injury
 Proteinuria
 Hematuria
Hepatic
 Elevated ALT/AST
 Elevated bilirubin
Cardiac
 Takotsubo cardiomyopathy
 Myocardial injury/myocarditis
 Cardiac arrhythmias
 Ageusia
 Myalgia
 Anosmia
 Stroke
 Cardiogenic shock
 Myocardial ischemia
 Acute cor pulmonale
Dermatologic
 Petechaie
 Livedo reticularis
 Erythematous rash
 Urticaria
 Vesicles
 Pernio-like lesions
Thromboembolism
 Deep vein thrombosis
 Pulmonary embolism
 Catheter-related thrombosis
Gastrointestinal
 Diarrhea
 Nausea/vomiting
 Abdominal pain
 Anorexia

28. Cardiovasular Sequelae
 Prospective, observational cohort study sourcing recovered
patients from the University Hospital Frankfurt COVID-19
Registry (N = 100)
‒Abnormal findings in 78% of patients, myocardial
inflammation in 60%; independent of preexisting
comorbidities, severity of acute SARS-CoV-2 infection, and
time from diagnosis
‒Reduced left ventricular ejection fraction, increased left
ventricle volumes and native T1/T2 vs risk-matched controls
1. Puntmann. AMA Cardiol. 2020;[Epub]. 2. Mitrani. Heart Rhythm. 2020;[Epub].

29. Co-infections and COVID-19

30. A Proposed Model for Viral-Induced Susceptibility
to Secondary Bacterial Pneumonia
Local and systemic immune
response
 ↑ IFNs (type I, II, III)
 ↑ Mucus responses
 Loss of ciliary function
 Epithelial cell death
 Cytokines (↑ IL-10, IL-27)
Gut dysbiosis
 ↑ Proteobacteria (H influenza,
M catarrharis, Klebsiella) and
Bacteroidetes
 ↓ Firmicutes (SFB, Lactobacillus)
 ↓ Anaerobic bacteria
Respiratory tract dysbiosis
 ↑ Firmicutes (S pneumoniae,
S aureus)
 ↑ Probacteria (H influenzae,
M catarrharis, Pseudomonas)
 ↑ Actinobacteria
Alterations in pulmonary
immune response
 ↓ Macrophage/neutrophil
function
 Decreased inflammatory
cell recruitment
Secondary
bacterial
pneumonia

31. Gut-lung axis in COVID-19
 COVID-19: gastrointestinal symptoms from the view of gut–lung axis
 Intestinal Dysbiosis and Probiotics in COVID-19
Journal of Gastroenterology & Hepatology: October 29,2020
Journal of Clinical Trials, Volume 10, issue 4, 2020

32. COVID-19 in Pregnancy

33. Case Study: Transplacental Transmission of
SARS-CoV-2 Infection
 Mother with documented viremia
delivered male neonate in third
trimester
‒ Neonatal viremia soon after birth
‒ Neonate bronchoalveolar lavage
positive for SARS-CoV-2 E and S
genes by RT-PCR
 Histologic examination of placenta
showed inflammation with
intervillositis and infiltrates of
neutrophil and CD68+ histiocytes
 On Day 3, neonate had sudden
irritability, poor feeding, axial
hypertonia, opisthotonos; CSF
negative for SARS-CoV-2 and other
pathogens; cerebral ultrasound and
EEG normal
 Neonate had radiographic evidence
of CNS involvement on MRI at Day
11:
 Neonate gradually recovered and was
discharged after 18 days
Vivanti. Nat Commun. 2020;11:3572.

34. COVID-19 in Children

35. No alternative plausible
diagnoses
CDC Case Definition:
Multisystem Inflammatory Syndrome in Children
Individual < 21 yrs of age presenting with fever,* laboratory evidence of
inflammation,† and evidence of clinically severe illness requiring hospitalization
with involvement of ≥ 2 organ systems (cardiac, renal, respiratory, hematologic,
gastrointestinal, dermatologic, or neurologic)
And:
Positive current or
recent SARS-CoV-2
infection by RT-PCR,
serology, or antigen test
Exposure to a suspected
or confirmed COVID-19
case within 4 wks prior to
symptom onset
And 1 of the following:
*Fever ≥ 38°C for ≥ 24 hrs or report of fever
lasting ≥ 24 hrs.
†Including, but not limited to, elevated CRP, ESR,
fibrinogen, procalcitonin, D-dimer, ferritin, LDH,
or IL-6; elevated neutrophils; reduced
lymphocytes; and low albumin.
CDC. Multisystem Inflammatory Syndrome in Children (MIS-C). Last reviewed August 28, 2020. https://www.cdc.gov/mis-c/hcp/

36. Assessing Disease Severity
and Risk Factors for Severe Disease

37. NIH Guidelines: Defining a COVID-19 Severity Spectrum
NIH COVID-19 Treatment Guidelines. Management of persons with COVID-19. Last updated October 9, 2020.
Stage Characteristics
Asymptomatic or
presymptomatic infection
 Positive test for SARS-CoV-2 but no symptoms
Mild illness
 Varied symptoms (eg, fever, cough, sore throat, malaise, headache,
muscle pain) but no shortness of breath, dyspnea, abnormal imaging
Moderate illness
 SpO2 ≥ 94% and lower respiratory disease evidenced by clinical
assessment or imaging
Severe illness
 SpO2 < 94%, PaO2/FiO2 < 300, respiratory rate > 30 breaths/min, or
lung infiltrates > 50%
Critical illness  Respiratory failure, septic shock, and/or multiorgan dysfunction

38. COVID-19 Prognostic Tool

39. COVID-GRAM Critical Illness Risk Score

40. Serum Procalcitonin
Pro BNP
Prothombin time
Fibrinogen level
Serum albumin

41. RT PCR – CT Value
The essential information to start antiviral

43. Current Non-Therapeutic Management
and Supportive Care

44. Non-Therapeutic Management of Mild COVID-19
1. WHO Interim Guidance. Clinical management of COVID-19. May 27, 2020.
2. NIH COVID-19 Treatment Guidelines. Management of persons with COVID-19. Last updated June 11, 2020.
3. NIH COVID-19 Treatment Guidelines. Antithrombotic therapy in patients with COVID-19. Last updated May 12, 2020.
WHO[1]
 Isolate suspected/confirmed cases to contain
SARS-CoV-2 transmission; isolation can occur
at home, in a designated COVID-19 health or
community facility
 Treat symptoms (eg, antipyretics for fever,
adequate nutrition, appropriate rehydration)
 Educate patients on signs/symptoms of
complications that, if developed, should
prompt pursuit of urgent care
NIH[2,3]
 Majority of cases managed in ambulatory
setting or at home (eg, by telemedicine)
 Close monitoring advised for symptomatic
patients with risk factors for severe disease;
rapid progression possible
 No specific lab tests indicated if otherwise
healthy
 In non-hospitalized patients, do not initiate
anticoagulants or antiplatelet therapy to
prevent VTE or arterial thrombosis unless
other indications exist

45. Management[1]
 Monitor closely, as pulmonary disease can
rapidly progress
 Administer empiric antibiotics if bacterial
pneumonia/sepsis strongly suspected; re-
evaluate daily and de-escalate/stop treatment
if no evidence of infection
 Use hospital infection prevention and control
measures; limit number of
individuals/providers entering patient room
 Use AIIRs for aerosol-generating procedures;
staff should wear N95 respirators or PAPRs vs
surgical masks
Non-Therapeutic Management of Moderate COVID-19
Initial Evaluation[1]
 May include chest x-ray, ultrasound, or CT
 Perform ECG if indicated
 Obtain CBC with differential and metabolic
profile including liver/renal function
 Inflammatory markers (eg, CRP, D-dimer,
ferritin) may be prognostically valuable
Isolation (Home vs Healthcare Facility)[2]
 Dependent on clinical presentation,
requirement for supportive care, presence of
vulnerable household contacts; if high risk of
deterioration, hospitalization preferred
1. NIH COVID-19 Treatment Guidelines. Management of persons with COVID-19. Last updated June 11, 2020.
2. WHO Interim Guidance. Clinical management of COVID-19. May 27, 2020.

46. Acute Coinfection Treatment[1]
 Administer empiric antimicrobials within 1 hr of
initial assessment based on clinical judgment,
patient host factors, and local epidemiology;
knowledge of blood cultures before antimicrobial
administration ideal
 Assess daily for antimicrobial de-escalation
Severe Pneumonia Treatment[1]
 Equip patient care areas with pulse oximeters,
functioning oxygen systems, and disposable, single-
use, oxygen-delivering interfaces
 Provide immediate supplemental oxygen to
patients with emergency signs (eg,
obstructed/absent breathing, severe respiratory
distress, central cyanosis, shock, coma, or
convulsions) and anyone with SpO2 < 90%
 Monitor for clinical deterioration (eg, rapidly
progressive respiratory failure, shock); provide
immediate supportive care
 Practice cautious fluid management in patients
without tissue hypoperfusion and fluid
responsiveness
Non-Therapeutic Management of Severe COVID-19
1. WHO Interim Guidance. Clinical management of COVID-19. May 27, 2020.
2. NIH COVID-19 Treatment Guidelines. Management of persons with COVID-19. Last updated June 11, 2020.
Evaluation[2]
 Perform evaluations outlined for moderate disease

47. Non-Therapeutic Management of Every COVID-19
1. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/coronavirus-recovery-breathing-exercises.
2. https://www.thedailystar.net/lifestyle/note-nutrition/news/faq-diet-and-covid-19-1904011
3. https://www.nhsinform.scot/illnesses-and-conditions/infections-and-poisoning/coronavirus-covid-19/healthy-living/coronavirus-covid-19-diet-and-healthy-weight
Coronavirus Recovery:
Breathing Exercises
Diet and healthy weight
: Breathing Exercises

48. Therapeutic Management

49. Key Therapeutic Classes Under Investigation for
Treatment of COVID-19
Barlow. Pharmacotherapy. 2020;40:416. McCreary. Open Forum Infect Dis. 2020;7:ofaa105. Sanders. JAMA. 2020;323:1824.
Antivirals Immunomodulators
Baloxivir
Convalescent plasma
Favipiravir
(Hydroxy)chloroquine
Interferon
Lopinavir/ritonavir
Nitazoxanide
Oseltamivir
Remdesivir
Ribavirin
Corticosteroids (eg, dexamethasone)
IL-1 inhibitors (eg, anakinra)
IL-6 inhibitors (eg, tocilizumab)
Intravenous immunoglobulin
JAK inhibitors (eg, baricitinib)

51. COVID-19 Therapies Predicted to Provide Benefit at
Different Stages
Siddiqi. J Heart Lung Transplant. 2020;39:405.
Oxygen
Remdesivir
Dexamethasone
Benefit unclear
Benefit
demonstrated
Stage I
(Early Infection)SeverityofIllness
Stage II
(Pulmonary Phase)
IIA IIB
Stage III
(Hyperinflammation Phase)
Viral Response Phase
Host Inflammatory Response Phase
Time Course
Clinical
symptoms
Clinical
signs
Mild constitutional symptoms
Fever > 99.6°F
Dry cough
Lymphopenia
Shortness of breath without
(IIA) and with hypoxia (IIB)
(PaO2/FiO2 ≤ 300 mm Hg)
Abnormal chest imaging
Transaminitis
Low-normal procalcitonin
ARDS
SIRS/shock
Cardiac failure
Elevated inflammatory markers
(CRP, LDH, IL-6, D-dimer, ferritin)
Troponin, NT-proBNP elevation

52. IDSA Recommendations on Treatment and
Management of Patients With COVID-19
IDSA. COVID-19 Guideline, Part 1: Treatment and Management. Version 3.3.0.
IDSA Guidance Patient Population Treatment
Recommends  Hospitalized with critical* COVID-19  Dexamethasone†
Suggests
 Hospitalized with severe‡ COVID-19
 Hospitalized with severe*‡ COVID-19
 Dexamethasone†
 Remdesivir‖
Recommends only in clinical trial
 Hospitalized with COVID-19
 Hospitalized with COVID-19
 Lopinavir/ritonavir
 Convalescent plasma
Recommends against
 COVID-19
 Hospitalized with COVID-19
 (Hydroxy)chloroquine
 (Hydroxy)chloroquine + azithromycin
Suggests against
 Hospitalized with nonsevere§ COVID-19
 Hospitalized with COVID-19
 Glucocorticoids
 Tocilizumab
Suggests against outside clinical trial  Hospitalized with severe COVID-19  Famotidine
*Mechanical ventilation or ECMO. †If unavailable, methylprednisolone and prednisone acceptable at equivalent total daily doses. ‡SpO2 ≤ 94% on
room air, including those on supplemental oxygen. § SpO2 > 94%, no supplemental oxygen. ‖For patients on supplemental oxygen, 5 days
suggested; for patients on mechanical ventilation or ECMO, 10 days.
Updated

53. NIH Guidelines:
Therapeutic Management
NIH COVID-19 Treatment Guidelines. Therapeutic Management of Patients With COVID-19. Last updated October 9, 2020.
Disease Severity Recommendation
Not hospitalized
or hospitalized
but does not
require
supplemental
oxygen
 No specific antiviral or
immunomodulatory therapy
recommended
 Recommends against the use of
dexamethasone
 Insufficient data to recommend for
or against remdesivir
Hospitalized and
requires
supplemental
oxygen (but does
not require high-
flow oxygen,
ventilation, or
ECMO)
 Remdesivir 200 mg for 1 day,
followed by 100 mg IV for 4 days or
until discharge
Or
 Remdesivir (same dose as above)
plus dexamethasone 6 mg IV or PO
for up to 10 days or until discharge
 If remdesivir cannot be used,
dexamethasone alone may be used
Updated
Disease Severity Recommendation
Hospitalized and
requires high-
flow oxygen or
noninvasive
mechanical
ventilation*
 Remdesivir (same dose as above)
plus dexamethasone 6 mg IV or PO
for up to 10 days or until discharge
Or
 Dexamethasone alone (same dose
and duration as above)
Hospitalized and
requires invasive
mechanical
ventilation or
ECMO
 Dexamethasone 6 mg IV or PO for
up to 10 days or until discharge
Or (for patients who have been
recently intubated):
 Remdesivir (same dose as above)
plus dexamethasone 6 mg IV or PO
for up to 10 days or until discharge
*Due to limited supply, prioritizing remdesivir for use in hospitalized
patients who require supplemental oxygen but do not require high-flow
oxygen, ventilation, or ECMO is recommended. Because of uncertainty
regarding clinical benefit in this group, the panel does not recommend
remdesivir alone.

54. NIH Guidelines:
Investigational COVID-19 Treatments
1. NIH COVID-19 Treatment Guidelines. Potential antiviral drugs under evaluation for the treatment of COVID-19. Last updated August 27, 2020.
2. NIH COVID-19 Treatment Guidelines. Immune-based therapy under evaluation for treatment of COVID-19. Last updated August 27, 2020.
Guidance Treatment
Recommends for hospitalized patients
with COVID-19 requiring supplemental
oxygen
 Remdesivir (5 days or until
discharge; some experts extend up
to 10 days)
Insufficient data to recommend for or
against in patients with mild to moderate
COVID-19 or who require high-flow
oxygen, noninvasive or mechanical
ventilation, or ECMO
 Remdesivir
Recommends against
 High-dose chloroquine (600 mg BID
for 10 days)
 (Hydroxy)chloroquine in
hospitalized patients
Recommends against except in context
of clinical trials
 (Hydroxy)chloroquine in non-
hospitalized patients
 Hydroxychloroquine + azithromycin
 Lopinavir/ritonavir or other HIV
protease inhibitors
 Ivermectin
Guidance Treatment
Recommends for patients with COVID-
19 requiring supplemental oxygen or
mechanical ventilation
 Dexamethasone (or alternative
glucocorticoid if dexamethasone
unavailable)
Recommends against if supplemental
oxygen unneeded
 Dexamethasone
Insufficient data to recommend for or
against
 IL-1 inhibitors
 IFN-β for early mild to moderate
COVID-19
 COVID-19 convalescent plasma or
SARS-CoV-2 Ig
Recommends against except in the
context of clinical trials
 IL-6/IL-6R inhibitors
 IFN-α/β for severe or critical
COVID-19
 BTK and JAK inhibitors
 Non-SARS-CoV-2–specific IVIG
 Mesenchymal stem cells
Antivirals[1] Immune-Based Therapies[2]

55. Remdesivir

56. FDA Approval for Remdesivir:
Treatment Initiation and Dosing Regimens
 Treatment of hospitalized patients with suspected COVID-19 can be considered
pending laboratory confirmation of SARS-CoV-2
 Treatment can be started any time after symptom onset
 All patients must have eGFR determined and hepatic laboratory testing before
starting and while receiving remdesivir (as clinically appropriate)
 All patients must have prothrombin time determined before starting and while
receiving remdesivir (as clinically appropriate)
IV Dosage Over 30-120 Mins
Patients Requiring Invasive
Mechanical Ventilation
and/or ECMO
Patients Not Requiring
Invasive Mechanical
Ventilation and/or ECMO
Adults and pediatric
patients ≥ 40 kg
 Loading 200 mg on Day 1 200 mg on Day 1
 Maintenance 100 mg on Days 2-10 100 mg on Days 2-5*
*Treatment may be increased to 10 days in patients not demonstrating clinical improvement at Day 5 of treatment.
Updated
Remdesivir PI.

57. Corticosteroids

58. NIH/ISDA: Dexamethasone for Severe COVID-19
1. NIH COVID-19 Treatment Guidelines. Immunomodulators under evaluation for the treatment of COVID-19. Last updated August 27, 2020.
2. IDSA. COVID-19 Guideline, Part 1: Treatment and Management. Version 3.3.0.
*Recommendation rating: A = Strong; B = Moderate; C = Optional. Evidence rating: I = ≥ 1 randomized trials with clinical outcomes
and/or validated lab endpoints; II = ≥ 1 well-designed, nonrandomized trials or observational cohort studies; III = Expert opinion.
†Mechanical ventilation or ECMO. ‡Patients with SpO2 ≤ 94% on room air, including those who require supplemental oxygen.
NIH[1]*
 The Panel recommends using
dexamethasone (6 mg per day for up to 10
days or until discharge, whichever comes
first) in patients with COVID-19 who are
mechanically ventilated (AI) or who require
supplemental oxygen but who are not
mechanically ventilated (BI)
 The Panel recommends against using
dexamethasone in patients with COVID-19
who do not require supplemental oxygen (AI)
IDSA[2]
 For hospitalized patients with critical† COVID-19, the Panel
recommends dexamethasone rather than no dexamethasone
(Strong recommendation, Moderate certainty of evidence)
 For hospitalized patients with severe‡ COVID-19, the Panel
suggests dexamethasone rather than no dexamethasone
(Conditional recommendation, Moderate certainty of evidence)
 Dose: Dexamethasone 6 mg IV or PO for 10 days (or until
discharge) or equivalent glucocorticoid dose (eg,
methylprednisolone 32 mg, prednisone 40 mg) may be
substituted if dexamethasone unavailable

59. Antibiotics
In battle, choose your weapon wisely. All right?
Some people choose a gun. I choose a Phillips-head screwdriver.
The Flash (TV Series)

60. THE LANCET, GLOBAL HEALTH, COMMENT, VOLUME 8, ISSUE 12., COVID-19 pneumonia and the appropriate use of antibiotics
NICE guideline [NG173]Published date: 01 May 2020 Last updated: 09 October 2020

61. Teicoplanin: an alternative drug for the treatment of
coronavirus COVID-19?
International Journal of Antimicrobial Agents . May 20, 2020
IIT Delhi researchers find Teicoplanin effective in treating COVID -19 virus, Indian Express, Sept 28, 2020
Is teicoplanin a complementary treatment option for COVID-19? The question remains. International Journal of Antimicrobial Agents, 23 May 2020

62. Meropenem was related to increased mortality and organ damage in both
SI group and NI group.
It means meropenem may not be the first choice for empirical antibiotic
use in patients with COVID-19.

63. O2

64. Happy Hypoxia
The pathophysiology underlying the dissociation between profound
hypoxemia and overt dyspnea in COVID-19 pneumonia is, at this point,
unclear.
The possibility that the novel SARS-COV-2 is neuro-invasion remains
controversial.
Regardless of the uncertain underlying pathology, reduced perception of
dyspnea is a disorder of blood-gas interoception. It may mask the severity
of the medical status and ultimately delay patients from seeking urgent
medical care.

65. Patients admitted with COVID-19 can suffer sudden death after voluntary
“breaks” from the oxygen supplementation. Recognizing “happy hypoxia”
as a feature of COVID-19 pneumonia has led to better patient care, with
physicians relying on other markers of disease, such as tachycardia, fever,
or serum inflammatory acute reactants, to guide treatment or discharge
patients from the hospital.
Is 'happy hypoxia' in COVID-19 a disorder of autonomic interoception? A hypothesis, Respiratory Research, 2020 Jul 15

66. Coagulopathy in COVID-19

67. Burden of Thrombosis in Patients With COVID-19
Study Country Design Population N Thromboprophylaxis Screening VTE Rate, %
China[1] Retrospective ICU 81 No No 25.0
France[2] Prospective ICU 150 Yes No 11.7*
France[3] Retrospective ICU 26 Yes Yes 69.0
France[4] Retrospective ICU 107 Yes No 20.6†
The
Netherlands[5] Retrospective ICU 184 Yes No 27.0
Italy[6] Retrospective Inpatient 388 Yes No 21.0
United
Kingdom[7] Retrospective ICU 63 Yes No 27.0
*Pulmonary embolisms in COVID-19 ARDS vs 2.1% in matched non-COVID-19 ARDS.†Pulmonary embolism vs 6.1% in non–COVID-19 ICU patients.
1. Cui. J Thromb Haemost. 2020;18:1421. 2. Helms. Intesive Care Med. 2020;46:1089. 3. Llitjos. J Thromb Haemost. 2020;18:1743. 4. Poissy.
Circulation. 2020;142:184. 5. Klok. Throm Res. 2020;191:145. 6. Lodigiani. Thromb Res. 2020;191:9. 7. Thomas. Thromb Res. 2020;191:76.
New

68. Laboratory Predictors of Thrombosis in COVID-19
Al-Samkari. Blood. 2020;136:489.
Median Value
No Thrombotic
or Bleeding
Complication
(n = 347)
Thrombotic
Complication
(n = 38)
P Value
D-dimer, ng/mL
 Initial
 Minimum
 Peak
891
760
1377
1538
1336
4001
.0002
.0006
< .0001
Fibrinogen, mg/dL
 Initial
 Minimum
 Peak
579
549
662
696
669
828
.0045
.0028
.0001
CRP, mg/L
 Initial
 Minimum
 Peak
63.3
35.4
130.3
124.7
94.2
277.7
.0011
< .0001
< .0001
Median Value
No Thrombotic
or Bleeding
Complication
(n = 347)
Thrombotic
Complication
(n = 38)
P Value
ESR, mm/hr
 Initial
 Minimum
 Peak
38
36
56
47
43
91
.020
.079
.0077
Ferritin, mg/L
 Initial
 Minimum
 Peak
504
453
707
825
750
1182
.015
.0056
.0020
New

69. Guidance on Thromboprophylaxis
NIH[1] ASH[2]
 Hospitalized adults with COVID-19 should receive VTE
prophylaxis
 Currently insufficient data to recommend for or against
the use of thrombolytics or increasing anticoagulant
doses for VTE prophylaxis in hospitalized COVID-19
patients outside of clinical trial
 Hospitalized patients should not be routinely discharged
on VTE prophylaxis (extended VTE prophylaxis can be
considered in patients with low bleeding risk and high
VTE risk)
 All hospitalized adults with COVID-19 should receive
thromboprophylaxis with low-molecular-weight
heparin over unfractionated heparin, unless bleeding
risk outweighs thrombosis risk
 Fondaparinux is recommended in the setting of
heparin-induced thrombocytopenia
 In patients in whom anticoagulants are contraindicated
or unavailable, use mechanical thromboprophylaxis
(eg, pneumatic compression devices)
 Encourage participation on clinical trials rather than
empiric use of therapeutic-dose heparin in COVID-19
patients with no other indication for therapeutic dose
anticoagulation
1. NIH. COVID-19 Treatment Guidelines. Updated: May 12, 2020. 2. American Society of Hematology. COVID-19 and VTE/
Anticoagulation: Frequently Asked Questions. 3. Spyropoulos. J Thromb Haemost. 2020;18:1859. 4. Moores. Chest. 2020;158:1143.
*Additional recommendations available from the International Society on Thrombosis and Haemostasis[3], and CHEST.[4]
Recommending Organization*
New

70. Duration of Immunity

71. Potential Immune Correlates of Protection to
SARS-CoV-2 Infection
Cox. Nat Rev Immunol. 2020;20:581.
Days/Weeks
Weeks/Months
Months/Years
SARS-Cov-2
Infection
Innate Immune
Response Adaptive Immunity Immune Memory to
SARS-CoV-2
Memory T-cell
Memory B-cell
Plasma cellB cell
DC activation and
uptake of viral
antigens
Cytokine production
Regulation of inflammation
Killing of infected cells
Induction of antibodies
TH
CTL
TFH
Treg
New

72. CDC Remarks on Reinfection
 If a person is asymptomatic during the 90-day period following recovery
from COVID-19, re-testing is not recommended given the potential for
persistent viral shedding
 If a person develops new symptoms during the 90-day period following
recovery from COVID-19 and no other diagnosis is identified, then evaluation
for reinfection may be warranted in consultation with an infectious disease
or infection control expert
“At this time, we have limited information about reinfections with
the virus that causes COVID-19 . . . CDC recommends that all
people, whether or not they have had COVID-19, take steps to
prevent getting and spreading COVID-19.”
CDC. Duration of Isolation and Precautions for Adults with COVID-19. Updated September 10, 2020.
New

74. Background: Passive Immunization
 Multiple ways to infuse neutralizing antibodies
Monoclonal
Antibodies[1]
Hyperimmune
Immunoglobulins[2]
 Produced in
laboratories
 Scalable
 Genetic modification of
Fc domain can reduce
the risk of ADE and
extend half-life
 Derived from plasma
 Standardized product
Convalescent
Plasma[1,2]
 Plasma from recovered
individuals
 Batch-to-batch
variability
 Requires blood-type
matching
1. Abraham. Nat Rev Immun. 2020;20:401. 2. Piechotta. Cochrane Database Syst Rev. 2020;7:CD013600.

75. Convalescent Plasma

76. Donor Apheresis Plasma Infusion (1-2 Units)
Theory of Using Convalescent Plasma to Treat COVID-19
IDEA. COVID-19 Tx. https://covid.idea.medicine.uw.edu/page/treatment/drugs/human-coronavirus-immune-plasma-hcip
Donors Recovered
From COVID-19
Patients With
COVID-19
Convalescent Plasma
Matching: ABO Compatible
SARS-CoV-2
Neutralizing Antibodies
SARS-CoV-2
Neutralizing Antibodies
YYYY YYYY
Blood Plasma Plasma

77. Immunomodulatory Therapies

78. Anti–IL-6 Receptors
Anti–IL-6 receptors
Fu. J Translational Medicine. 2020;18:164. Slide credit: clinicaloptions.com
Inflammatory storm
Soluble IL-6 receptor
IL-6
gp130
Signal transduction
Calm inflammatory storm
Blocking signal transduction
X
X

79. Key Ongoing Trials Investigating IL-6 Inhibitors
Agent and Comparator Trial Phase Primary Endpoint/Patient Population
Tocilizumab vs SoC[1] RECOVERY
II/III
(factorial
design)
 All-cause mortality; patients with SARS-CoV-2 infection
Tocilizumab vs no
immune modulating tx[2] REMAP-CAP
IV
(factorial
design)
 All-cause mortality; adults admitted to the ICU with community
acquired pneumonia with signs and symptoms of LRT infection
and radiologic evidence of new onset consolidations
Tocilizumab + remdesivir
vs remdesivir[3] REMDACTA III
 Clinical stats on 7-category ordinal scale at Day 28; hospitalized
patients with COVID-19 pneumonia
Sarilumab vs no immune
modulating tx[2] REMAP-CAP
IV
(factorial
design)
 All-cause mortality; adults admitted to the ICU with community
acquired pneumonia with signs and symptoms of LRT infection
and radiologic evidence of new onset consolidations
Sarilumab vs placebo[4] NCT04327388 III
 Time to improvement of 2 points in clinical status on 7-point
ordinal scale; hospitalized adults with evidence of pneumonia
and laboratory-confirmed SARS-CoV-2 infection
1. NCT04381936. 2. NCT02735707. 3. NCT04409262. 4. NCT04327388.

80. JAK1/2 Inhibitors
Stebbing. EMBO Mol Med.2020;12:e12697.
Elevated in blood
IL-1b, IL-2, IL-6, IL-7, IL-8,
IL-9, IL-10, IL-17, G-CSF, GM-CSF,
IFNα, IFNγ, TNF-α, IP10, MCP1,
MIP1A, MIP1B
Hyperinflammatory
Stage
P
IL6 mRNA
R R
STAT
STAT STAT
P
P
Jak1 Jak2
Cytokine
JAK1/2 inhibitorJAK1/2 inhibitor

81. NIAID ACTT-2: Baricitinib + Remdesivir vs Remdesivir
in Hospitalized Patients With Severe COVID-19
 Multicenter, adaptive, randomized, double-blind, placebo-controlled phase III trial[1]
Adult patients ≥ 18 yrs of age;
hospitalized with confirmed
SARS-CoV-2 infection and
≥ 1 of following: radiographic
infiltrates by imaging; SpO2 ≤ 94% on
room air; requiring supplemental
oxygen; or requiring mechanical
ventilation
(N = 1034)
Baricitinib PO* + Remdesivir IV QD†
Placebo PO + Remdesivir IV QD†
1. NCT04401579. 2. https://investor.lilly.com/news-releases/news-release-details/baricitinib-combination-remdesivir-reduces-
time-recovery. Press release only, not peer reviewed.
Daily assessment to Day 29
for time to clinical
improvement while
hospitalized;
if discharged, assessments at
Days 15, 22, and 29
 Primary endpoint: time to recovery by Day 29 defined as the first day patient satisfies 1 of
these categories from ordinal scale: 1) hospitalized, not requiring supplemental oxygen or
ongoing medical care; 2) not hospitalized, limitation on activities and/or requiring home
oxygen; or 3) not hospitalized, no limitations on activities
‒ Press release report of 1-day reduction in median recovery time[2]
*4 mg administered for duration of hospitalization, up to 14 days.
†200 mg on Day 1 followed by 100 mg on Days 2-10.

82. ≥ 24 hrs since resolution
of fever, last antipyretics
CDC: Discontinuation of Transmission-Based
Precautions for Patients With Confirmed SARS-CoV-2
 “A test-based strategy is no
longer recommended [except for
rare situations] because, in the
majority of cases, it results in
prolonged isolation of patients
who continue to shed detectable
SARS-CoV-2 RNA but are no
longer infectious.”
Symptom-Based Strategy
And
https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html
Improvement in symptoms
(eg, cough, shortness of breath)
And
≥ 10 days since symptom onset
for mild to moderate illness,
10-20 days for severe to critical illness
or those severely immunocompromised
Updated

83. ……and everything else

84.  There was limited evidence supporting the use of antihistamines for
short-term symptomatic relief of the common cold and none for the use
of mast cell stabilisers, leukotriene antagonists or antihistamines in
COVID-19.
 Clinical trials would be required to elucidate whether these drugs may be
repurposed for the treatment of this disease.

85. On balance, given the negligible risk profile of supervised nutritional
supplementation, weighed against the known and possible benefits, it appears
pertinent to ensure adequate, if not elevated intake of these key vitamins and
minerals in people both at risk of, and suffering from COVID-19.

88. Post-COVID Syndrome

89. How common are lingering COVID symptoms?
Tens of thousands of people in the United States have such a lingering illness
following COVID-19. In the US, we call them post-COVID “long haulers.” In
the United Kingdom, they are said to be suffering from “long COVID.”
Around 10% of patients who have tested positive for SARS-CoV-2 virus
remain unwell beyond three weeks, and a smaller proportion for months.
This is based on the UK COVID Symptom Study, in which people enter their
ongoing symptoms on a smartphone app. This percentage is lower than that
cited in many published observational studies, whose denominator
populations were those admitted to hospital or attending specialist clinics. A
recent US study found that only 65% of people had returned to their
previous level of health 14-21 days after a positive test.
Harvard health publishing, Harvard Medical School, OCTOBER 15, 2020
BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3026 (Published 11 August 2020)

90. https://www.bbc.com/news/health-54296223
'Long Covid': Why are some people not recovering?
By James Gallagher
Health and science correspondent
Published
5 October

94. Thank You