The document summarizes the Recovery Trial, which is a large-scale randomized controlled trial in the UK investigating potential treatments for COVID-19. It is testing several proposed interventions, including hydroxychloroquine, lopinavir-ritonavir, dexamethasone, and convalescent plasma. Initial results found no benefit from hydroxychloroquine or lopinavir-ritonavir. Dexamethasone was found to reduce mortality in patients requiring oxygen or ventilation. The document also outlines protocols for managing COVID-19 cases based on severity, including investigations, treatment approaches, and discharge criteria.

1. Advanced Management of COVID 19 -
Recovery Trial
Dr. Mohammad Ashiqur Rahman
MBBS, MRCP (UK), MACP (USA)
Registrar (Medicine)
NIDCH

2. Recovery Trial

3. Recovery Trial at a Glance
• Large-scale, Randomized Controlled Trial (RCT)
• “Open level” study
• Run by the Nuffield Departments of Public Health and Medicine at
the University of Oxford, and led by Professor Peter Horby.
• Involves 175 NHS hospitals of UK.
• Began in March 2020 and has an estimated duration through June
2021.

4. • Six proposed interventions: five repurposed drugs and convalescent
plasma
Lopinavir-Ritonavir (an HIV medication)
Low-dose Dexamethasone
Hydroxychloroquine (used to treat malaria and rheumatism)
Azithromycin
Tocilizumab (an anti-inflammatory)
Convalescent plasma

5. Initial results
Hydroxychloroquine
On 5 June 2020, the trial determined that there was no clinical benefit from
use of hydroxychloroquine in people hospitalized with COVID-19
Lopinavir-ritonavir
On 29 June 2020, chief investigators of the trial reported there was no clinical
benefit from use of lopinavir-ritonavir in 1,596 people hospitalized with
severe COVID-19 infection over 28 days of treatment. As of June 2020, the
results have not been published.

6. Dexamethasone Result

10. Dexamethasone
 dexamethasone reduced the 28-day mortality rate by 17% with a highly
significant trend showing greatest benefit among those patients requiring
ventilation.
But it is important to recognise that there is no evidence of benefit for
patients who does not require oxygen.

11. Management of COVID-19

12. Clinical Classification
• 6 syndromes of COVID-19 have been categorized into
mild, moderate, severe and critical cases.

13. Clinical Case definition
1. Mild cases
 The clinical symptoms are mild, and there is no sign of pneumonia on
imaging.
 Symptoms may be: fever, cough, sore throat, malaise, headache, muscle pain
without shortness of breath or abnormal imaging.

14. 2. Moderate cases
Fever and respiratory symptoms with radiological findings of pneumonia.
Respiratory rate < 30 breaths /min
Pulse oxymetry showing saturation > 93% at ambient air.

15. 3. Severe cases
Respiratory distress (≧30 breaths/ min);
Finger oxygen saturation≤93% at rest;
PaO2/ FiO2 ≦300mmHg

16. 4. Critical cases
Respiratory failure and requiring mechanical ventilation.
Shock.
With other organ failure that requires ICU care.

17. Diagnosis
• RT-PCR for COVID-19
• HRCT of chest

18. Investigations (for admitted patient)
• First line
CBC
CXP
CRP
SGPT
S. Creatinine
RBS
S. Electolyte
D-Dimer
Blood C/S
Procalcitonin
S. Ferritin
Urine R/E
• Second line
 Trop-I
 ECG
 HRCT Chest
 Urine C/S
 LDH
 PT, APTT
 S. Lactate
 Pro BNP
 NS1 Ag for Dengue
 Other test according to
need.

19. Treatment Protocol
Treatment venue will be determined according to severity of the
disease:
• Suspected and confirmed cases should be isolated and preferably
treated at designated hospitals with effective isolation, protection
and infection prevention conditions in place.
• A mild case may be treated in isolation in a single room at home.
(Home isolation protocol should be followed).
• Admit the patients to hospital according to admission criteria.

20. Admission Criteria
1. All suspected/ confirmed cases of COVID-19 presenting with
• Mild case with major risk factor [DM, HTN, IHD, Prior Asthma/ COPD/ILD
patients, Known CKD, CLD, Known Malignancy, High risk pregnancy, Obesity
(BMI>25)] and deteriorating mild cases in home/ institutional isolation
• Moderate case- clinical or radiological evidence of pneumonia with CRB-65
score 1 or
• Severe Pneumonia
• ARDS, Sepsis, Septic shock
• Hypoxia (SpO2 <94%) in the absence of any clinical signs
2. All cases with respiratory distress must be admitted for further
evaluation and testing.

21. • General management:
• Bed rest & strengthening support
• Ensuring sufficient calorie intake.
• Monitoring water and electrolyte balance to maintain internal environment stability.
• Monitoring vital signs and oxygen saturation.
• Antipyretic if temperature > 100° F.
• Antihistamine and bronchodilator when appropriate.
• Timely providing effective oxygen therapy starting with low flow, including nasal
catheter and mask oxygenation, and if necessary, nasal high-flow oxygen therapy.
• Critical cases should be admitted to ICU as soon as possible.

22. Asymptomatic Case Management
• Supportive care + Isolation protocol (either home or institutional depending
on national strategy).
• Patient can take immune enhancing food or medication containing Vit-C, D,
Zinc.

23. Mild Case Management
Follow general management+
• Thromboprophylaxis (mild cases with risk group):
Enoxaparin :
if CrCl >30 mL/min: 40 mg SC once daily
if CrCl <30 mL/min, 30 mg once daily.
• Antibiotic: Not recommend empirically.

24. Moderate Case Management
 In Isolation ward (any clinical or radiological pneumonia case)
• General management
Plus
• Proning: Prone position at least 4-6 hrs/day
• Oxygen through nasal cannula 2L /min if required (max 6L/min possible).
• Anti Viral: Tab Favipiravir 200 mg
Day 1: 1600 mg BD
Day 2 to 10: 600 mg BD

25. • Anticoagulant: LMWH
• According to D-dimer level (mcg/ml)
• < 0.5 : Enoxaparin 40 mg daily
• 0.5-3.0 : Enoxaparin 40 mg BD
• >3.0 : Enoxaparin 1mg/kg BD
• Dose adjust is required with CrCl< 30ml/min
• if LMWH cant be given or contraindicated,
Inj Unfractionated heparin (UFH):
• 60U/kg bolus+12units/kg/hr infusion-for ACS
• 80U/Kg bolus +18 units/kg/hr infusion-for VTE and AF

26. • Thromboprophylaxis should be given until symptom resolves or improves and
followed by Tab rivaroxaban 10 mg once daily for 1 month.
• Steroids:
i. If patient has AE of COPD, Asthma or patient is getting steroids beforehand.
ii. Any Moderate case on treatment , if no response or deterioration at 24 hours
in hospital, Oral Methylprednisolone (60-80 daily) in single or two divided
doses for 7 days with anti-ulcerant coverage.

27. • Empirical Antibiotics: only required if
Elderly > 50 years or children < 5 years
Productive cough with purulent sputum
Unilateral lobar consolidation
High CPR and Procalcitonin or only high Procalcitonin.

28. Protocol for the management of coagulopathy in COVID-19 patients.

29. Severe Case Management
• O2 therapy
• Proning: Atleast 6-10 hours/day
• Judicious fluid management: Crystalloids are preferred with
conservative approach.
• Early norepinephrine for hypotension.
• Steroids:
oOral or IV dexamethasone 6mg daily for 10 days, or
oInj. Methylpredniolone 250 mg daily for 5 days (switch to IV from oral if
already started)

30. • Thromboprophylaxis: Enoxaparin 1mg/kg BD
• Dose adjust is required with CrCl< 30ml/min
• if LMWH cant be given or contraindicated,
Inj Unfractionated heparin (UFH):
• 60U/kg bolus+12units/kg/hr infusion-for ACS
• 80U/Kg bolus +18 units/kg/hr infusion-for VTE and AF
• Thromboprophylaxis should be given until symptom resolves or improves and
followed by Tab rivaroxaban 10 mg once daily for 1 month

31. • Antiviral: Inj Remdesavir 100mg
• Day 1: 200 mg IV infusion over 30 min-2 hours
• Day 2 to Day 5: 100 mg infusion over 30 min to 2 hours
Remdesivir should be used at the discretion of consultant working in the
hospital. (If favipiravir started in moderate case, it should be stop)
• Antibiotics: Broad spectrum I/V antibiotic coverage.

32. Critical Case Management
• Should be managed at ICU/ Critical Medicine.
• Try to avoid intubation if at all possible
• Prone positioning: >12 hours/day
• O2 therapy
• Antiviral: inj. Remdesavir for 10 days.
• Antibiotics: broad spectrum IV
• Anticoagulant as severe case protocol.
• Convalescent Plasma therapy

33. • Steroids: can be used as following dosage
ARDS
Inj. Methylprednisolone 1-2 mg/kg IV BD,
OR
Inj. Dexamethasone 10mg daily (According to RECOVERY Trial)
OR
20 mg IV daily for 5 days and then
10 mg IV daily for 5 days and then
5 mg IV daily for 5 days and
Refractory Sepsis
Inj. Hydrocortisone 50 mg 6 hourly daily
Cytokine Release Syndrome (CRS)
inj. Methylprednisolone 1-2 mg/kg IV BD,
OR
Inj. Dexamethasone 10 mg 6 hourly

34. • For Cytokine storm/CRS consider
• Tocilizumab

35. • Tocilizumab:
• Adult Dosing (≥18 years): 8 mg/kg (max: 800 mg/dose).
• Pediatric Dosing (<18 years): Wt <30 kg—12 mg/kg; Wt >30 kg—8 mg/kg
(Max: 800 mg/dose)
• Duration: 1 dose;
• Can repeat in 12 hours if no clinical improvement. Max 2 doses
Remember: Tocilizumab itself may precipitate CRS if given early.

36. How to recognize CRS/CSS
• Bilateral infiltrate+ severe respiratory failure
Plus
• Lab evidence
1.One marker of inflammation
• Ferritin >1000
• CRP> 125
• Elevated IL-6
2.Other supportive finding
• D dimer >1000
• LDH> 300
• Absolute lymphocyte count <0.8

37. O2 Therapy
1- Low flow O2 delivery devices:
• Nasal cannula (up to 6LPM and provide up to 50% FiO2);
• Simple mask (up to 10 LPM and provide up to 60% FiO2);
• Venturi mask (up to 15 LPM and provide 50% FiO2);
• Partial rebreather mask (15 LPM and provide 70% FiO2);
• Non rebreather mask (15 LPM and provide 100% FiO2)
2- High flow delivery device:
• High Flow Nasal cannula (HFNC): up to 70 LPM and provide 100% FiO2
• Advantages: Well tolerated, generate PEEP (1 PEEP for every 10L)

38. 3- Non-invasive positive pressure ventilation:
• CPAP: (Setting 5-20 cmH2O) and used for type I respiratory failure;
• BiPAP (Setting EPAP 4-16 cm H2O, IPAP 10-20 cmH2O and minimum pressure
support 4 cmH2O) and used for both type I and type II respiratory failure.
• Increase CPAP or EPAP for hypoxia Increase pressure support (IPAP-EPAP)
for hypercapnia
4- Mechanical ventilation.

39. 5- Pulmonary vasodilator: Nitric oxide causes localized vasodilatory
effects in the pulmonary vascular bed. It is used to combat
vasoconstriction, V / Q mismatching, arterial hypoxemia, and
pulmonary hypertension associated with ARDS.
6- ECMO

42. Feeding strategies (Nutrition):
1. Early enteral feeding within 24-48 hours is helpful.
2. Starting feeds at 25-50% caloric goal and increasing to 100% over 3-7
days is reasonable.
3. Use trophic or trickle diet (10-20 cc/hour) in hemodynamically or
respiratory unstable patient
Blood glucose (BG):
1. Target BG 140-180 mg/dl.
2. Use sliding scale initially but change to drip if requiring higher insulin
or BG is not well controlled.

43. Hemodynamic support:
1. Target MAP>60, instead of >65.
2. Consider balanced crystalloid fluid (Ringer lactate, Hartmann’s) over normal saline
(higher incidence of AKI) and colloid.
3. Norepinephrine as the first-line vasoactive agent, over other agents.
4. If norepinephrine is not available, either vasopressin or epinephrine as the first-line
vasoactive agent, over other vasoactive agents.
5. Vasopressin as a second-line agent over increasing norepinephrine.
6. If there is evidence of cardiac dysfunction and persistent hypoperfusion despite fluid
resuscitation and norepinephrine, add dobutamine, over increasing norepinephrine
dose.
7. Refractory shock add low-dose corticosteroid therapy (“shock-reversal”), over no
corticosteroid therapy (IV Hydrocortisone 50 mg q6).

44. Anticoagulation
Contraindication for anticoagulant
1. When there is no bleeding-
i. Platelet count <25K/cmm
2. When there is bleeding-
i. Platelet count <50K/cmm
ii. Plasma fibrinogen level <1.5 g/L
iii. PT ratio >1.5 or INR >1.8
(To be noted that prolonged APTT is not a contraindication for anticoagulant.
Anticoagulant can be/should be restarted after correction of contraindicating condition by
transfusion.)

45. Proning

46. Discharge criteria
1. Resolution of fever without the use of fever-reducing medications
e.g paracetamol for at least 3 (three) days and
2. Significant improvement in the respiratory symptoms (e.g., cough,
shortness of breath) for 3 days, and
3. After discharge, continue home or facility isolation for the duration
which extends from the day of symptom onset to 21th day for
hospitalized patients
4. For severe or critical patients – physician’s discretion

47. Follow-up
i. By Phone:
• Within 48 hours after discharge.
ii. OPD F/U:
• 1 week, 2 weeks, and 1 month after discharge.
• Examinations include liver and kidney functions, blood test, nucleic acid test
of sputum and stool samples, and pulmonary function test or lung CT scan
should be reviewed according to the patient's condition.
iii. By phone F/U:
• 3 and 6 months after discharge.

48. Prevention

49. Prevention

51. Thank you