An elderly woman with multiple comorbidities suffered from COVID 19 moderate disease - was managed conservatively Case presentation with current treatment modalities

1. A case of respiratory Distress –
managed with Non Invasive
Ventilation and HFNO
DR. SANGHAMITRA SINHA
MBBS, FCCCM
SR CRITICAL CARE
SHRI MOOLCHAND KHAIRATIRAM HOSPITAL
DR. ASHISH ARORA
MD PULMONOLOGY, IDCCM
ICU CONSULTANT
SHRI MOOLCHAND KHAIRATIRAM HOSPITAL

2. History
 66y, F
 Comorbidities: HTN, BA, post B/L TKR,
Hysterectomy, Umbilical Hernia Repair
 Allergic to Aspirin, Sulpha Drugs
 CC:
 Fever (T max 1020F) with Chills + Rigor x 5days
 SOB x 5days
 COVID 19 RT PCR + on Day 4 of illness
 Started on: Tab Doxycycline, Tab Ivermectin, Tab
Prednisolone at home

3. Day 6  Presented to ED → admitted to Covid ward
 Generalised weakness
 Vitals:
 BP 160/90mmHg
 HR 88/min
 Afebrile
 RR 24/min
 SpO2 94% on RA
 Chest: B/L Coarse creps with wheeze
 Other systems - WNL
 Relevant investigations sent
 Initial Treatment :
 Oxygen therapy
 Inj Ceftriaxone 1gm IV q12h
 Inj Methylprednisolone 40 mg IV q24h
 Inj Enoxaparin 40 mg SC q24h
 Other supportive medications including nebulisation,
PPI, Bronchodilators, MVI, Vitamin C
 Insulin for glycemic control

4. Significant investigations
 Blood
 CRP: 24 ↑
 IL-6: 9.32 ↑
 Sr Ferritin: 268 ↑
 CXR: B/L heterogeneous opacities with GGOs
 ABG: ↓ PaO2 with ↑ lactate

5. Day 7
 Clinical deterioration:
 SOB
 Cold clammy extremities
 Chest : b/l crepitations + wheeze
 Transfer to COVID ICU
 NIV support
 Started on Inj. Remdesivir for 5 days
Day 8 1 unit convalescent plasma transfused

6. Day 9
 Remained critically ill :
 On continuous NIV support: FiO2 0.8
 Hyperglycemic on Insulin infusion
 ABG : persistent ↓ PaO2 with ↑ lactate
 CXR: ↑ opacities (GGOs)
 Interventions:
 Central venous catheterization: CVP monitoring
+ Central venous access
 Repeat cultures sent and antibiotics escalated
to Piperacilin – Tazobactam
 Started on HFNO @40L/min

7. Day 21 Started on Oral Hypoglycemics
Day 20 Transferred to ward on Portable BiPAP (Intermittent)
Day 18
Clinically stable:
Oxygen tapered, 6L/min on portable BiPAP
After 9 days of ICU Care

8. Day 22
 Decompensated post ambulation:
 Sudden onset breathlessness
 Desaturation to SpO2 78%
 Cold clammy extremities
 Progressive drowsiness with gasping respiration
 Interventions:
 Connected to portable BiPAP with high flow Oxygen
 Managed with bronchodilators, IV Mg++, Steroids, LMWH
 Urgent CT Chest: s/o worsening b/l COVID pneumonitis
 Repeat cultures – sterile
 Patient improved clinically
 Conscious, alert
 Maintained with portable BiPAP – intermittent during the day and continuous overnight

9.  Day 26
 CVC removed
 All medications deescalated to oral
 Day 28
 Started on Tab Nintedanib 100mg q12h (to prevent further fibrosis)

10. Day 30: PATIENT WAS DISCHARGED
OXYGEN INHALATION (TITRATE TO SPO2 94%)
NIV SUPPORT (18/6) DAYTIME WHILE SLEEPING, OVERNIGHT CONTINUOUS
DRUGS:
ANTIBIOTICS/ANTIFUNGAL – 3DAYS MORE
TAB NINTEDANIB 100MG Q12H X 7DAYS (ANTIFIBROTIC)
TAB RIVAROXABAN 10MG Q24H X 7DAYS
TAB METHYLPREDNISOLONE (MEDROL) 8MG Q12H X 7DAYS → TO TAPER THEREAFTER
FORMOTEROL NEBULIZATION 0.5MG Q12H
OHA + INSULIN AS PER SLIDING SCALE
ANTIHYPERTENSIVES
OTHER SUPPORTIVE MEDICATIONS

11. Home Care
Oxygen Support:
Needed BiPAP support as
mentioned upto 2-3 weeks
Oxygen concentrator for
occasional desaturations on
mobilisation
Now tapered to only 1hour
during daytime and 2hrs during
night
Mobilization:
Anxiety to mobilise due to event
on Day 22
Presently ambulatory without
support
Physiotherapy:
Steam inhalation q12h
Incentive spirometry q24h
(evening)
Chest physiotherapy q24h at
bedtime

12. CT Chest
revealed
clearing of
peripheral
opacities

13. Discussion on
Pharmacotherapy

14. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulation

15. Treatment of Moderate COVID-19
• Supportive care
• Oxygen
Therapy
• Corticosteroids
• Anticoagulation
?
• Antivirals
• Anti-IL6
therapy
• Monoclonal
antibodies

16. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulati
on
Corticosteroids
Anti-IL6 Therapy

17. Corticosteroids
 WHO interim guidelines (March 22, 2020)
 This was extrapolated from studies in Influenza, SARS, and MERS

18. NEJM, July 17, 2020

19. Corticosteroids
 RECOVERY: Randomized Evaluation of COVID-19 therapy trial among
hospitalized patients
 > 11,500 patients enrolled from > 175 NHS hospital organizations in
the UK
RECOVERY Collaborative Group. NEJM. 2020 Jul 17.

20. Corticosteroids
RECOVERY Collaborative Group. NEJM. 2020 Jul 17.
Recovery trial : evidence that treatment with Dexamethasone at a dose of 6mg once daily for upto 10days reduces
28day mortality in COVID 19 patients on respiratory support

21. Corticosteroids
 Recommendation for use
• Any oxygen requirement (with or without elevated inflammatory markers)
• Inflammatory markers raised
 Dose
• IV Methylprednisolone 0.5 to 1 mg/kg
• Dexamethasone 0.1 to 0.2 mg/kg
 Duration: 3 to 5 days (may be prolonged on a case-to-case basis)
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5

22. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulati
on
Corticosteroids
Anti-IL6 Therapy

23. Anti IL-6 Therapy
 Use has been extrapolated from
other cytokine release syndromes
 Shown to be beneficial in
observational studies
Fu. J Translational Medicine. 2020;18:164.

24. Tocilizumab
 RCTs showed that tocilizumab did not reduce short-term mortality
 Reduced risk of mechanical ventilation in hospitalized COVID-19 patients (RR = 0.71, 95%
CI 0.52-0.96, I2 = 0%)
 No higher risk of infections or adverse events seen
Tleyjeh IM, et al. CMI. 2020 Nov 5.

25. Tocilizumab
 Indication
 Off-label use
 May be in Moderate to severe
disease
 Not improving despite steroids
 Considered in severely raised
inflammatory markers (IL-6 > 5x
ULN)
 Active bacterial infections to be
ruled out before starting therapy
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5
Other parameters used are at least 3 of the
following in patients with p/f ratio < 300
CRP > 10 x ULN
Ferritin > 1000 ng/mL
D-dimer > 10 x ULN
LDH > 2 x ULN
Sciascia S, et al. Clin Exp Rheumatol. 2020;38(3):529-532.
Dose
4 to 8 mg/kg (with a maximum dose of 800 mg
at one time) in 100 ml NS over 1 hour (dose can
be repeated once after 12 to 24 hours, if
needed)

26. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulation

27. Anticoagulation
 LMWH is preferred in once daily S/C dosing of 0.5 mg/kg
 UFH is preferred in patients with renal insufficiency
 D-dimer levels may help guide anticoagulation
 Estimate bleeding risk with well validated risk scores (eg. HAS-
BLED score of ≥ 3 signifies a high bleeding risk)
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5

28. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulati
on
Remdesivir
Convalescent
Plasma

30. WHO Solidarity Trial
Consortium. NEJM.
2021, Feb 11.
 Remdesivir did not show any
statistical significance
 Hydoxychloroquine showed to
have increased Mortality

32. Remdesivir
 Adenosine nucleotide
analogue prodrug
 Mechanism: Competes
for incorporation with
adenosine triphosphate
(ATP)
WHO Solidarity Trial Consortium. NEJM. 2021, Feb 11.

33. Remdesivir
 Effects are seen best in patients with early presentation and those requiring only low
flow oxygen
 All patients must have eGFR determined and hepatic laboratory testing before
initiation
 Recent report on 46 patients with renal dysfunction (30 with AKI and 16 with ESRD)
found no drug related worsening of renal function
IV Dosage Over 30-120 Mins
Patients Not Requiring
Invasive Mechanical
Ventilation
Patients Requiring
Invasive Mechanical
Ventilation
Adults and pediatric
patients ≥ 40 kg
Loading 200 mg on Day 1 200 mg on Day 1
Maintena
nce
100 mg on Days 2-5* 100 mg on Days 2-10
*Treatment may be increased to 10 days in patients not demonstrating clinical improvement at Day 5 of treatment.
Thakare S. et al. Kirereports. 2020. Oct 10.

34. Remdesivir
 Contraindications
 AST/ALT > 5 x Upper limit of normal
 Renal insufficiency
 eGFR < 30 mL/min/1.73m2
 Need for hemodialysis
 Pregnancy and lactating women
 Children < 12 years
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5

35. Treatment of Moderate COVID-19
Antivirals
Anti-
inflammatory
Anticoagulation
Remdesivir
Convalescent
Plasma

36. Convalescent
Plasma

37. Convalescent Plasma
 PLACID Trial
 Open label, multicenter, parallel group RCT
 235 Convalescent plasma vs 229 SoC
 Primary outcome mesure: Composite of progression to severe disease (p/f <
100) or all cause mortality at 28 days
 Number of events: 44 (19%) vs 41 (18%) with SoC
 Adjusted risk ratio = 1.04 (95% CI 0.71-1.54)
 Limitations exist: Limited data in mild disease, unknown
efficacy with early administration, lack of
standardization of antibody titres
Agarwal A, et al. BMJ. 2020 Oct 22;371.

38. Convalescent Plasma
 228 Plasma vs 105 Placebo
 Median time of institution = 8 (5, 10) days
 Patients with oxygen saturation < 93%
 This trial and a Cochrane living meta-analysis suggest no
benefit in terms of mortality or clinical improvement with
plasma
 If considered for therapy, best given in early disease (within 1
week of illness onset)
Simonovich VA et al. NEJM. 2020. Nov 24.

39. Convalescent Plasma
 Considerations
 ABO compatibility and cross-matching required
 Plasma IgG (against S-protein) > 1:640
 Monitoring required for reactions
 Avoided in patients with IgA deficiency or immunoglobulin allergy
 Dose
 Variable, ranging from 4 to 13 mL/kg
 Usually used as a single dose of 200 mL given over at least 2 hours
Ministry of Health and Family Welfare. DGHS. Government of India. Version 5

40. Convalescent Plasma
Potential Adverse Events
Transfusion-transmitted infections (i.e., HIV,
HBV, HCV)
Allergic or anaphylactic reactions
Hemolytic reactions
Febrile nonhemolytic reactions
TRALI
TACO
Hypothermia
Metabolic complications
Posttransfusion purpura
Theoretical Risks
Antibody-dependent enhancement of
infection
Attenuation of immune response and
susceptibility to re-infection
Convalescent Plasma EUA Fact Sheet for Healthcare Providers.

41. Few words on High
Flow Nasal Oxygen

42. HFNO/ HFNC
 Relatively new technique – ICU/OR
 Avoid endotracheal intubation
 Facilitate Extubation
 Aka THRIVE - Transnasal Humidified Rapid-Insufflation Ventilatory
Exchange

43. Courtesy: Up to date

46. Thank you