Guidelines on COVID 19 Management in Adults As per AIIMS / ICMR / Joint Task Force NIH / CDC / OCO

1. CLINICAL MANAGEMENT
OF
ADULT COVID-19 PATIENTS
Presented by : Dr. Sunil Mishra
MD, DNB (Medicine)

2. FEVER CLINIC
Flu like symptoms
Testing (RAT)
Positive Negative
Hospital Admission Home Isolation
High Suspicion Low Suspicion
RT PCR Advice
Negative

3. Endocrine
 Hyperglycemia
 Diabetic ketoacidosis
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
EXTRAPULMONARY MANIFESTATIONS

4. GUIDELINES
• AIIMS
• ICMR-COVID-19 National Task Force
• Joint Monitoring Group MoH&FW, GoI

5. CASE SEVERITY
MILD
• URTI Symptoms
• +/- Fever
• NO Shortness of breath
MODERATE
Any one of following
• Shortness of breath
• Respiratory Rate ≥ 24 /min
• SpO2 = 90 – 93 % in RA
• Admit in WARD
SEVERE
Any one of the following
• Shortness of breath
• Respiratory Rate >30/min
• SpO2 = <90 % in RA
• Admit in ICU

6. HIGH RISK FACTORS
• > 60 years
• Obesity
• Cerebrovascular disease
• Cardiovascular disease
• Hypertension
• CAD
• Immunocompromised states
• DM
• Chronic lung disease
• Chronic kidney disease
• Chronic liver disease

7. INVESTIGATIONS
• ASYMPTOMATIC CASES
• MILD CASES
• Baseline Investigations
• CBC
• AST / ALT
• Urea / Creat
• RBS
• CXR
• MODERATE CASES
In addition to baseline INV
• CRP
• D-DIMER
• HRCT CHEST
• FERRITIN
• LDH
• ESR
• SEVERE CASES
• Additional INV
• IL-6
• CTPA
• Procalcitonin
( NA in our setup )

8. MILD CASES

9. ASYMPTOMATIC / MILD CASES
NON-THERAPEUTIC MEASURES
• Physical distancing
• Indoor Mask use
• Strict Hand Hygiene.
SYMPTOMATIC MANAGEMENT
• Hydration
• Anti-pyretics
• Anti-tussive
• Multivitamins

10. DRUGS THAT MAY BENEFIT
DRUGS
• Tab IVERMECTIN
• 200 mcg/kg once a day for 3 days
• Avoid in pregnant and lactating women.
(OR)
• Tab HCQS
• 400 mg BD for 1 day f/b
• 400 mg OD for 4 days
• Unless contraindicated.
MDI / DPI
• Cough &/or Fever > 5d
• Inhalational Budesonide
• 800 ug BD x 5d

11. ASYMPTOMATIC / MILD CASES
MONITORING
• Stay in contact with treating physician
• Monitor
• Temperature
• SpO2 (via probe)
SEEK MEDICAL ATTENTION IMMEDIATELY
• Difficulty in breathing
• High grade fever
• Severe cough >5d
• A low threshold for
those with any of the high-risk features

12. MODERATE / SEVERE CASES

13. TREATMENT
OXYGEN
IMMUNO-MODULATION
ANTI-COAGULATION
MODERATE / SEVERE CASES

14. MODERATE CASES

15. MODERATE CASE
OXYGEN SUPPORT
• Target SpO2: 92-96% (88-92% in patients
with COPD)
• Oxygenation Device: 1) Nasal Canula
2) Face Mask
3) NRBM

16. MODERATE CASE
OXYGEN SUPPORT
• Awake PRONING
• encouraged in all patients requiring
supplemental oxygen therapy
• Sequential position changes every 2 hours

17. MODERATE CASE
ANTI-INFLAMMATORY / IMMUNOMODULATORY THERAPY
• Drugs
• Inj Methylprednisolone
• 0.5 to 1 mg/kg in 2 divided doses
• Inj Dexamethasone
• 0.1 to 0.2 mg/kg /d
• Duration
• 5-10 days
Patients may be initiated or switched to
oral route if stable and/or improving.

18. MODERATE CASE
ANTICOAGULATION
• Unfractionated Heparin
• 5000 IU BD
(or)
• Low Molecular Weight Heparin
• Enoxaparin 0.5mg/kg per day SC).
• Rule out high risk (≥3) of bleeding.
CONDITION
Points
H Hypertension: (uncontrolled, >160 mmHg systolic) 1
A
Abnormal renal function: Dialysis, transplant, Cr
>2.26 mg/dL or >200 µmol/L
Abnormal liver function: Cirrhosis or Bilirubin >2x
Normal or AST/ALT/AP >3x Normal
1
1
S Stroke: Prior history of stroke 1
B
Bleeding: Prior Major Bleeding or Predisposition to
Bleeding
1
L
Labile INR: (Unstable/high INR),
Time in Therapeutic Range < 60%
1
E Elderly: Age > 65 years 1
D
Prior Alcohol or Drug Usage History
(≥ 8 drinks/week)Medication Usage Predisposing to
Bleeding: (Antiplatelet agents, NSAIDs)
1
1
HASBLED SCORE

19. MODERATE CASE
MONITORING
CLINICAL
• Work of breathing,
• Hemodynamic instability
• Change in oxygen requirement.
RADIO-IMAGING
• Serial CXR
• HRCT
• ONLY If there is worsening.
LAB MONITORING
• CBC
• KFT
• LFT
• CRP
• D-dimer
• IL-6 levels
• to be done if deteriorating
(subject to availability).
48 -72 hrly
24 -48 hrly

20. SEVERE CASES

21. SEVERE CASE
OXYGEN SUPPORT
NIV / HFNC
Work of breathing : LOW
Increasing O2 requirement

22. SEVERE CASE
OXYGEN SUPPORT
ARDS protocol for ventilatory management.
INTUBATION on PRIORITY
NIV not tolerated
Work of breathing : HIGH
Increasing O2 requirement

23. SEVERE CASE
ANTI-INFLAMMATORY /
IMMUNOMODULATORY THERAPY
• Drugs
• Inj Methylprednisolone
• 1 to 2 mg/kg in 2 divided doses
• Inj Dexamethasone
• 0.2 to 0.4 mg/kg /d
• Duration
• 5-10 days
SUPPORTIVE MEASURES
• Maintain Euvolemia
• Standard ICU Care
• If sepsis/septic shock
• Upgrade IV Antibiotics
• SEPSIS Protocol

24. SEVERE CASE
ANTICOAGULATION
• Unfractionated Heparin
• 5000 IU BD
(or)
• Low Molecular Weight Heparin
• Enoxaparin ( 0.5 - 1 mg/kg s/c ).
• Rule out high risk of bleeding.

25. SEVERE CASE
MONITORING
CLINICAL
• Hemodynamic instability
• Change in oxygen requirement
• PEEP
• FIO2
• Tidal Volume
RADIO-IMAGING
• Serial CXR
• HRCT
• ONLY If there is worsening.
LAB MONITORING
• CBC
• KFT
• LFT
• CRP
• D-dimer
• IL-6 levels
• to be done if deteriorating
(subject to availability).
24 - 48 hrly
24 hrly

26. TREATMENT
NOT IN VOGUE
• Doxycycline
• Favipiravir
• Convalescent
plasma
OFF LABEL
Criteria based
• Remdesivir
• Tocilizumab
EXPERIMENTAL
• 2-Deoxy - 2 Glucose
• Interferon – Alpha
• IL-1 inhibitors
• (eg. anakinra)
• IL-6 inhibitors
• (eg. tocilizumab)
• IVIG
• JAK inhibitors
• (eg. baricitinib)

27. OFF LABEL USE
(based on limited available evidence and only in specific circumstances)

28. REMDESIVIR
INDICATION
• Moderate to severe disease (requiring
SUPPLEMENTAL OXYGEN)
• ≤ 10 days of onset of symptom/s
Recommended Dose 200 mg IV - D1 f/b 100 mg IV OD x 4d
• Renal dysfunction
• eGFR <30 ml/min/m2
• Hepatic dysfunction
• AST/ALT >5 times ULN
• Patients who are NOT on oxygen support
or in home settings
CONTRA -INDICATION

29. TOCILIZUMAB
INDICATIONS
• Presence of severe disease
• Significantly raised inflammatory
markers (CRP &/or IL-6).
• Not improving despite use of steroids.
CONTRA - INDICATIONS
• Active Infection
• Bacterial
• Fungal
• Tubercular
Recommended Dose 4- 6 mg/kg (400mg) - Once
(preferably within 24 to 48 hours of onset of severe disease / ICU admission)

30. 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)
Severity
of
Illness
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

31. Ivermectin
 Ivermectin inhibits the
replication of SARS-CoV-2 in
cell cultures
 Several randomized trials and
retrospective cohort studies of
ivermectin use in patients with
COVID-19 have had mixed
results
 Most studies had incomplete
information and significant
methodologic limitations
NIH COVID-19 Treatment Guidelines. Ivermectin. Last updated February 11, 2021.
NIH COVID-19 Treatment
Guidelines Panel:
“There are insufficient data . . .
to recommend either for or against
the use of ivermectin for the
treatment of COVID-19.”

32.  Hospitalized patients with clinically suspected or laboratory confirmed SARS-CoV-2
‒ Initial recruitment was in patients ≥ 18 yrs of age but age limit was removed on 5/9/2020
 Patients randomized to usual care plus: no additional tx, lopinavir/ritonavir,
dexamethasone, hydroxychloroquine, or azithromycin
‒ Factorial design with simultaneous allocation to no additional tx vs convalescent plasma
‒ If progressive disease (hyperinflammatory state), subsequent randomization to no
additional tx vs tocilizumab
 As of 3/9/2021, 38,779 total participants recorded from 177 active sites in the UK
Randomised Evaluation of COVid-19 thERapY
(RECOVERY) Trial Among Hospitalized Patients
6/8/2020: recruitment to dexamethasone arm halted because sufficient
patient numbers enrolled to establish potential benefit
Updated
RECOVERY Collaborative Group. NEJM. 2021;384:693. NCT04381936. https://www.recoverytrial.net.

33. RECOVERY Trial: Mortality With Dexamethasone +
Usual Care vs Usual Care Alone
All Participants (N = 6425) No Oxygen (n = 1535)
Mortality
(%)
50
40
30
20
10
0
0 7 14 21 28
Days Since Randomization
Patients at Risk, n
Dexamethasone
Usual care
2104
4321
1903
3754
1725
3427
1659
3271
1621
3205
Usual care
Dexamethasone
+ usual care
RR: 0.83 (95% CI: 0.75-0.93)
P < .001
Mortality
(%)
50
40
30
20
10
0
0 7 14 21 28
Days Since Randomization
Patients at Risk, n
Dexamethasone
Usual care
501
1034
478
987
441
928
421
897
412
889
Usual care
RR: 1.19 (95% CI: 0.91-1.55)
Dexamethasone
+ usual care
RECOVERY Collaborative Group. NEJM. 2021;384:693.

34. RECOVERY Trial: Mortality in Patients on Oxygen
or Mechanical Ventilation ± Dexamethasone
Mortality
(%)
50
40
30
20
10
0
0 7 14 21 28
Days Since Randomization
Patients at Risk, n
Dexamethasone
Usual care
1279
2604
1135
2195
1036
2018
1006
1950
981
1916
RR: 0.82 (95% CI: 0.72-0.94)
Mortality
(%)
50
40
30
20
10
0
0 7 14 21 28
Days Since Randomization
RR: 0.64 (95% CI: 0.51-0.81)
Oxygen Only (n = 3883) Invasive Mechanical Ventilation (n = 1007)
Usual care
Dexamethasone
+ usual care
Usual care
Dexamethasone
+ usual care
Patients at Risk, n
Dexamethasone
Usual care
324
683
290
572
248
481
232
424
228
400
RECOVERY Collaborative Group. NEJM. 2021;384:693.

35. RECOVERY Trial: Mortality at Day 28
(Primary Outcome)
 Addition of Dexamethasone to usual care associated with lower
mortality among subsets receiving invasive mechanical ventilation or
oxygen alone but not in those receiving no baseline respiratory
support
P Value
28-Day Mortality RR
(95% CI)
Usual Care Only
Respiratory Support at
Randomization
Invasive mechanical ventilation
Oxygen only
No oxygen received
All patients
Chi-square trend across 3 categories: 11.5
95/324 (29.3%)
298/1279 (23.3%)
89/501 (17.8%)
482/2104 (22.9%)
Dexamethasone +
Usual Care
283/683 (41.4%)
682/2604 (26.2%)
145/1034 (14.0%)
1110/4321 (25.7%)
0.64 (0.51-0.81)
0.82 (0.72-0.94)
1.19 (0.91-1.55)
0.83 (0.75-0.93) < .001
0.5 0.75 1 1.5 2
Dexamethasone
Better
Usual Care
Better
RECOVERY Collaborative Group. NEJM. 2021;384:693.

36. FDA EUA for Casirivimab + Imdevimab
 Must be administered by single IV
infusion (1200 mg casirivimab +
1200 mg imdevimab over
≥ 60 mins) following dilution
 Should be given as soon as possible
after positive SARS-CoV-2 viral test,
within 10 days of symptom onset
 No recommended dose
adjustments for pregnant or
lactating women, patients with
renal impairment
Casirivimab With Imdevimab. EUA Fact Sheet for Healthcare Providers. Last updated February 2021.
“ . . . permit the emergency use of the
unapproved product, casirivimab
with imdevimab to be administered
together, for the treatment of mild to
moderate COVID-19 in adults and
pediatric patients (≥ 12 yrs of age
weighing ≥ 40 kg) with positive
results of direct SARS-CoV-2 viral
testing, and who are at high risk for
progressing to severe COVID-19
and/or hospitalization.”

37. FDA EUA for Baricitinib
 Recommended dosage under EUA:
‒ Adults and pediatric patients ≥ 9 yrs
of age: 4 mg orally once daily
‒ Pediatric patients 2 yrs to < 9 yrs of
age: 2 mg orally once daily
‒ Optimal duration of treatment
unknown; 14 days or until hospital
discharge (if first) recommended
 eGFR, aminotransferase levels, and
CBC with differential must be
determined before first dose
Baricitinib. EUA Fact Sheet for Healthcare Providers. Last updated November 2020.
“. . . permit the emergency use of
baricitinib, in combination with
remdesivir, for treatment of
suspected or laboratory confirmed
COVID-19 in hospitalized adults and
pediatric patients ≥ 2 yrs of age
requiring supplemental oxygen,
invasive mechanical ventilation, or
extracorporeal membrane
oxygenation (ECMO).”

38. Anti–IL-6 Receptor Antibodies
Anti–IL-6 receptor antibodies
Fu. J Translational Medicine. 2020;18:164.
Inflammatory storm
Soluble IL-6 receptor
IL-6
gp130
Signal transduction
Calm inflammatory storm
Blocking signal transduction
X
X

39. TOCIBRAS: Tocilizumab + SoC vs SoC Alone for
COVID-19 With Increased Inflammatory Markers
 Prospective, multicenter, open-label, randomized phase III trial in 9 Brazilian
hospitals from May 7 to July 17, 2020
Veiga. BMJ. 2021;372:n84. NCT04403685.
Adults with severe or critical COVID-19;
receiving supplemental oxygen or
mechanical ventilation; abnormal levels of
≥ 2 serum biomarkers (ie, CRP, D-dimer,
lactate dehydrogenase, or ferritin)
(N = 129)
Tocilizumab 8 mg/kg IV + SoC
(n = 65)
SoC Alone
(n = 64)
 Primary endpoint: clinical status at Day 15 by multi-level ordinal scale; analyzed as
composite of death or mechanical ventilation
 Data monitoring committee recommended early trial stop due to increased
mortality at Day 15 with tocilizumab: 11 (17%) deaths in tocilizumab + SoC group
vs 2 (3%) deaths in SoC group

40. RECOVERY: Results for Tocilizumab + Usual Care vs
Usual Care Alone
 Secondary endpoint:
reduced receipt of mechanical
ventilation in patients not
receiving ventilation at time of
randomization
‒ 12% with tocilizumab vs 15%
with usual care (RR: 0.81;
95% CI: 0.68-0.95)
Recovery Collaborative Group. medRxiv. 2021;[Preprint]. Note: this study has not been peer reviewed.
Days Since Randomization
Mortality
(
%)
40
30
20
10
0
RR: 0.86 (0.77-0.96)
Log-rank P = .0066 Usual care
Tocilizumab
+ usual care
28
0 7 14 21
Patients at Risk, n
Active
Control
2022
2094
1741
1740
1556
1518
1386
1372
1284
1250
New

41. NIH Guidelines on Baricitinib
 “There are insufficient data for the COVID-19 Treatment Guidelines
Panel (the Panel) to recommend either for or against the use of
baricitinib in combination with remdesivir for the treatment of
COVID-19 in hospitalized patients, when corticosteroids can be used.”
 In the rare circumstance where corticosteroids cannot be used, the
Panel recommends baricitinib in combination with remdesivir for the
treatment of COVID-19 in hospitalized, non-intubated patients who
require oxygen supplementation.”
 “The Panel recommends against the use of baricitinib without
remdesivir, except in a clinical trial.”
NIH COVID-19 Treatment Guidelines. Kinase inhibitors. Last updated February 11, 2021.
Updated

42. MUCORMYCOSIS

43. MUCORMYCOSIS – The BLACK Fungus

44. MUCORMYCOSIS - TYPES
• Rhino-Orbito-Cerebral
Mucormycosis (ROCM)
• Cutaneous & Soft Tissue
Mucormycosis
• Pulmonary Mucormycosis
• Gastrointestinal Mucormycosis
• Bones & Joints Mucormycosis
• Disseminated Mucormycosis

45. MUCORMYCOSIS
ROCM
• Nasal stuffiness, Nasal discharge
• Epistaxis
• Unilateral facial oedema/ Proptosis
• Diplopia / Loss of vision
• Blackish discolouration over bridge of nose/palate
• Loosening of teeth / Jaw involvement
• Altered mental status
CUTANEOUS
• Erythema
• Induration f/b
• Black eschar at trauma/puncture site

46. RISK FACTORS
• Case of concurrent or recently (<6wks)
treated Severe COVID-19
• Prolonged ICU stay
• Prolonged Neutropenia
• Immunocompromised States
• Uncontrolled DM
• HIV / AIDS
• Post-transplant/malignancy
• Malnutrition
• DRUGS
• Steroids
• (any dose use for >3weeks or high dose >1week)
• Tocilizumab
• Immunomodulators
• Voriconazole therapy
• Deferoxamine or other iron overloading
therapy
• Contaminated Fomites
• Adhesive bandages
• wooden tongue depressors
• Hospital linens

47. MUCORMYCOSIS - DIAGNOSIS
• Diagnostic nasal endoscopy
• CECT Nose and PNS:
• Erosion and thinning of bones
• Enlargement of masticatory muscle
• Mucosal thickening of sinuses Changes in
Fat Planes
• CEMRI Brain Orbit and Face:
• Optic neuritis
• Intracranial involvement,
• Cavernous sinus thrombosis
• Infratemporal fossa involvement
• KOH staining & microscopy
• Direct microscopy using fluorescent
brightener and histopathology with special
stains (e.g. PAS and GMS)
• Non-septate/Pauci-septate, ribbon-like
hyphae (at least 6–16μm wide)
• Vessel occlusion
• Histopathology
• Haemorrhagic infarction
• Coagulation necrosis
• Angioinvasion, infiltration by neutrophils (in
non-neutropenic hosts)
• Perineural invasion.
• Fungal culture-
• Routine media at 30°C and 37°C
• Cotton white or Greyish black colony

48. MUCORMYCOSIS - TREATMENT
SURGICAL
• Urgent surgical debridement
MEDICAL
• Strict Glycaemic Control
• Inj Liposomal amphotericin B
• 5-10mg/kg/day
• intra cranial involvement-10 mg/kg /day
• 14 to 21 days

49. MUCORMYCOSIS - PREVENTION
• Environmental cleanliness to have NO exposure to
decaying organic matters like
breads/fruits/vegetables/soil/compost/excreta/etc.
• Control hyperglycaemia
• Glucose monitoring in COVID-19 patients requiring
steroid therapy
• Optimally steroid usage -right timing of initiation,
right dose, and right duration
• Use clean distilled water for humidifiers during
oxygen therapy
• Use antibiotics/antifungals only and only when
indicated
• Simple tests like pupillary reaction, ocular motility,
sinus tenderness and palatal examination should be a
part of routine physical evaluation of a COVID-19
patient.

50. MUCORMYCOSIS - PREVENTION
• Always use distilled or sterile water
• Never use un-boiled tap water nor mineral
water
• Fill up to about 10 mm below the
maximum fill line
• Water in the humidifier should be changed
daily
• All the components of the humidifier
should be soaked in mild antiseptic
solution for 30 minutes, rinsed with clean
water and dried in air.
• Once a week (for the same patient)
• Before Re-use for another Patient

51. ≥ 24 hrs since resolution
of fever, last antipyretics
CDC: Discontinuation of Transmission-Based
Precautions for Patients With Confirmed SARS-CoV-2
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
*If patient is asymptomatic, not severely
immunocompromised, precautions may be
discontinued ≥ 10 days after positive viral test.
Test-Based Strategy
Not generally recommended 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”

52. THANK YOU
Dr. Sunil Mishra
MD, DNB (Medicine)