Updated protocol of management for COVID patients

1. COVID-19 MANAGEMENT
UPDATE
Sohag Heart Center Experience
Emad M. Qasem
Cardiology Department, Sohag Heart Center
Associate Alumni, CSRT, Harvard Medical School

2. Scientific Committee
Sohag Heart Center

3. ILOS:
Management of hospitalized adults
• Evaluation
• General management
• COVID-Specific therapy
• Management of Hypoxemia and ARDS
• Special considerations
• Patient discharge

4. REFERENCES:

5. BEFORE WE GO …
What about Non-hospitalized patients?

6. Non-hospitalized patient
• Mild case
• Symptomatic.
• No signs of pneumonia
• No leucopenia or lymphopenia

7. How to treat Non-hospitalized patient
• Assess the risk.
• Symptomatic (>
3 symptoms)
risky patients
should be
hospitalized
Risk score
≥ 65 y
Age
Clinical Data
Uncontrolled comorbidities (DM, HTN)
≥ 40
BMI
Pregnancy
Active malignant condition / Chemotherapy
Immunosuppresive medications
≥ 110 b/m
HR
Examination findings ≥ 25 c/m
RR
≤ 92 %
Saturation
> 3.1
Neutr/lymph ratio
Lab results

8. Medications…

9. Chloroquine and Hydroxychloroquine…
• We suggest NOT using hydroxychloroquine or
chloroquine given the lack of clear benefit and potential
for toxicity.
• Several large randomized trials failed to identify a
mortality or other clinical benefit for hospitalized patients
with COVID-19.

10. Chloroquine and Hydroxychloroquine…

11. Ivermectin in guidelines…
Not even a word !

12. Ivermectin…
 proposed as a potential therapy based on in vitro activity.
 but the drug levels used in vitro far exceed those achieved in vivo
with safe drug doses.
 receipt of ivermectin was associated with a lower mortality rate;
however, patients who received ivermectin were also more likely
to receive corticosteroids (Potential confounders!)
 we do not use ivermectin outside of clinical trials.

13. Ivermectin…

14. Ivermectin…

15. Ivermectin investment ? …

16. Ivermectin investment ? …
8 ongoing clinical trials on
ivermectin in EGYPT alone
Out of total 29 studies worldwide !!

17. Favipiravir…
 Used to treat influenza virus.
 early trials suggested some benefit.
 immunomodulatory agents were administered in these studies.
 the results are not accurate due to potential confounders.

18. Anti-thrombotic therapy…
• Patients who are receiving anticoagulant or antiplatelet therapies
for underlying conditions should continue these medications if
they receive a diagnosis of COVID-19 (AIII).
• For non-hospitalized patients with COVID-19, anticoagulants and
antiplatelet therapy should not be initiated for the prevention of
venous thromboembolism (VTE) or arterial thrombosis (AIII).
• In non-hospitalized patients with COVID-19, markers of
coagulopathy, such as D-dimer level, prothrombin time, fibrinogen
level, and platelet count, should not routinely be obtained (AIII)

19. Medications…

20. Take Home messages…
• Don’t use antiplatelets.
• Routine use of anticoagulation is NOT indicated.
• Routine use of antibiotics is NOT indicated.
• Ivermectin NOT to be used outside clinical trials.
• Hydroxychloroquine, Chloroquine, Ivermectin and Favipiravir
showed no benefit for patients up till now.

21. EVALUATION
OF COVID-19 PATIENTS

22. Classify Patient Severity
Critically ill
Severe case
Moderate case
ICU
Intermediate care
Ward
Admit to
More than 50%
involvement
Progressive lesion
within 24/48 hours
More than 50%
involvement
Progressive lesion
within 24/48 hours
Pneumonia
CT findings
Leucopenia &
lymphopenia
Leucopenia &
lymphopenia
Leucopenia &
lymphopenia
LAB
RR > 30
SaO2 < 92% on oxygen
PaO2/FiO2 < 200
RR > 30
SaO2 < 92% Room air
PaO2/FiO2 < 300
Respiratory
indices

23. EVALUATION
 features associated with severe illness
Elevations in:
D-dimer >1000 ng/mL (normal range: <500 ng/mL)
CRP >100 mg/L (normal range: <8.0 mg/L)
LDH >245 units/L (normal range: 110 to 210 units/L)
Troponin >2× the upper limit of normal
Ferritin >500 mcg/L (normal range: females 10 to 200 mcg/L; males 30 to 300 mcg/L)
CPK >2× the upper limit of normal (normal range: 40 to 150 units/L)
Decrease in:
Absolute
lymphocyte count
<800/microL (normal range for age ≤21 years: 1800 to 7700/microL)

24. NOTES
 laboratory features are associated with severe disease but they
have no prognostic value.

25. LAB Sampling

26. DAILY LAB *
• Complete blood count (CBC), focus on the total lymphocyte count.
• Complete metabolic panel
• Creatine kinase (CK)
• C-reactive protein (CRP)

27. EVERY OTHER DAY LAB
• Prothrombin time (PT)/partial thromboplastin time (PTT)/ INR.
• D-dimer.

28. Baseline and repeat if abnormal
• Lactate dehydrogenase, repeated daily if elevated
• Troponin, repeated every two to three days if elevated.
• Electrocardiogram (ECG), with at least one repeat test after
starting any QTc-prolonging agent.

29. Other LAB:
• hepatitis B virus, hepatitis C virus, and HIV antigen/antibody
testing (could affect interpretation of transaminase elevations and
exacerbate hepatotoxicity of certain therapies).

30. Echocardiography ??

31. Echocardiography
• not routinely, only in the following cases:
• increasing troponin levels with hemodynamic compromise.
• other cardiovascular findings suggestive of cardiomyopathy.

32. Repeat CT Scan ??

33. Repeating imaging
• a portable chest radiograph is sufficient to
exclude complications ex, Pneumothorax.
• reserve chest CT for circumstances that
might change clinical management.

34. GENERAL MANAGEMENT
OF SEVERELY ILL COVID-19 PATIENTS

35. 1. Antibiotic therapy
2. Treatment for Influenza virus.
3. Prevention of Thromboembolism (Anti-coagulation).
4. Use of NSAIDs.
5. Nebulizers.
6. Specific therapy; ACE inhibitors, Statins, Aspirin and
immuno-modulators.

36. Antibiotic and antiviral therapy…

37. Empirical treatment
• empiric treatment for community-acquired pneumonia (CAP) is
reasonable when the diagnosis is uncertain. Especially if new fever
after resolving with new consolidation on chest imaging.
• empiric therapy for influenza for patients hospitalized with
suspected or documented COVID-19 in locations where influenza
virus is circulating.

38. Empirical Antibiotics for CAP
CAP—
NOT in the ICU
Empiric therapy
No co-morbidity:
Atypicals—M. pneumoniae,, S.
pneumo, viral
Co-morbidity:
S. pneumo, anaerobes, coliforms,
H. influenzae,M. catarrhalis,
Ceftriaxone 1 gm IV q24h
+ azithro 500 mg IV q24h
CAP,
hospitalized—IN ICU
Empiric therapy
S. pneumoniae,
H. influenazae, Moraxella
sp., Legionella sp. Rarely
S. aureus.
Levofloxacin.
If G-ve Bacilli is suspected and/or life threatening
infection:
Anti-pseudomonal beta-lactam (4th generation
cephalos, piperacillin/tazobactam, imipenem,
meropenem + (respiratory FQ
Or aminoglycoside).
Add azithro if no FQ

39. Influenza Anti-viral therapy
• Recommended for risky patients (old age > 65 years with multiple
comorbidities or BMI > 40).
• treatment of patients with severe influenza, oseltamivir is the
preferred agent; peramivir may be used for patients who cannot
tolerate oral therapy.
• Dose of 75 mg orally twice daily for 5 days duration.

40. Anticoagulation…

41. Venous Thromboembolism
Moderate and severe cases

42. Venous Thromboembolism
• pharmacologic prophylaxis for all hospitalized patients.
• do not make changes to anticoagulation based on isolated
changes in laboratory values such as D-dimer.
• severe COVID-19 by itself is NOT an indication for therapeutic-
dose anticoagulation.

43. Anti-thrombotic therapy…
 Hospitalized non-pregnant adults with COVID-19 should receive
prophylactic dose anticoagulation (AIII).
 patients with COVID-19 who experience an incident VTE event
or highly suspected, should receive therapeutic doses
anticoagulant (AIII).
 Hospitalized patients with COVID-19 should not routinely be
discharged from the hospital while on VTE prophylaxis (AIII).

44. Full dose anticoagulation…
• Full-dose anticoagulation in the following conditions:
1. documented VTE or suspected VTE in which standard
confirmatory testing is not available.
2. Sudden deterioration in respiratory status in an intubated
patient.
3. Physical findings consistent with thrombosis (ex, superficial
thrombophlebitis )
4. Clotting of intravascular access devices (arterial lines, CVC)
despite prophylactic-intensity anticoagulation.
5. clotting in extracorporeal circuits (eg, ECMO).

45. Anticoagulation
 Use of unfractionated heparin is not preferred, reported cases of
heparin resistance.
 Prophylactic dosing:
Fondaparinux (Arixtra)
Enoxaparin (Clexane)
Unfractionated heparin (UFH)
2.5 mg by SC every 24h.
• 40 mg by SC every 24h
• weight > 120 kg:
enoxaparin 40 mg by SC
every 12h
5000 units by SC every 8 or
12h.
weight > 120 kg: 7500 units
q12h or 5000 units every 8h

46. Thrombolytic Therapy…

47. ThrombolyticTherapy (rTPA)
Indicated in :
1. Limb-threatening DVT
2. Massive PE
3. Acute stroke
4. Acute myocardial infarction

48. Could tPA be used for other indications?

49. Could tPA be used for other indications?

50. Other Medications…

51. NSAID
 minimal data available.
 if NSAIDs are needed, we use the lowest effective dose.

52. nebulized medications
 avoid the risk of aerosolization.
 Take appropriate infection control precautions if used.

53. ACE inhibitors/ARBs
 continue treatment with these agents if there is no other reason for
discontinuation (ex, AKI).

54. Statins and aspirin
 continue statins in hospitalized patients but make sure to check for
transaminases level.
 continue aspirin unless there are concerns about bleeding risk.

55. SPECIFICTHERAPY
OF COVID-19 PATIENTS

56. Dexamethasone, glucocorticoids and
immuno-modulators…

57. MOHP
• Moderate cases Severe cases Critically ill

58. For How long?
 daily for 10 days or until discharge whichever is shorter.
 Watch for adverse events !

59. Other considerations
 dexamethasone (or other glucocorticoids) not be used for either
prevention or treatment of mild to moderate COVID-19 (patients
not on oxygen).
 Monitor for the risk of hyperglycemia and an increased risk of
infections (including bacterial and fungal infections)

60. Remdesivir…

61. MOHP
• Moderate cases Severe cases Critically ill

62. Remdesivir
 approved by the Food and Drug Administration (FDA)
 For Hospitalized Adult and Pediatric Patients (Aged ≥12 Years
and Weighing ≥40 kg).
 The safety and efficacy of combination therapy of remdesivir with
corticosteroids have not been rigorously studied in clinical trials.
 suggest it reduces time to recovery, which we regard as a clinical
benefit.

63. Remdesivir
 prioritize remdesivir for those requiring low-flow supplemental
oxygen, may reduce mortality.
 WHO suggest not using it in hospitalized patients because there is
no clear evidence that it improves patient-important outcomes for
hospitalized patients (eg, mortality, need for mechanical
ventilation)

64. Remdesivir dosing…
adult dose:
 200 mg intravenously on day 1.
 followed by 100 mg daily for 5 days total.
 extension to 10 days if there is no clinical improvement and in
patients on mechanical ventilation or ECMO.
 Side effects including nausea, vomiting, transaminase elevations,
anemia, acute kidney injury, fever and hyperglycemia were
reported.

65. Tocilizumab…

66. MOHP
• Critically ill

67. Tocilizumab
 tocilizumab (8 mg/kg as a single dose) for patients requiring high-
flow oxygen or more intensive respiratory support within 24 to 48
hours of admission to ICU.
 Only to patients who are also taking dexamethasone (or another
glucocorticoid) and generally limit it to a single dose.
 Check CBC and Liver function test before starting medication.

68. Tocilizumab
 tocilizumab for select patients on low-flow oxygen if they are
clinically progressing toward high-flow oxygen despite initiation
of dexamethasone and have significantly elevated inflammatory
markers (eg, C-reactive protein [CRP] level ≥75 mg/L).

69. Tocilizumab Contraindications…
 hypersensitivity to tocilizumab.
 uncontrolled serious infections.
 absolute neutrophil count (ANC) <500 cells/microL.
 platelet counts <50K.
 alanine aminotransferase (ALT) >5 times the upper limit.
 elevated risk for gastrointestinal perforation.

70. Convalescent plasma…

71. Convalescent plasma…
 the available evidence does not support a clear role for
convalescent plasma in patients with severe disease.

72. lopinavir/ritonavir…

73. lopinavir/ritonavir…
 Treatment Guidelines Panel (the Panel) recommends against the
use of lopinavir/ritonavir and other HIV protease inhibitors for
the treatment of COVID-19 in hospitalized patients (AI).
 The Panel recommends against the use of lopinavir/ritonavir and
other HIV protease inhibitors for the treatment of COVID-19 in
non-hospitalized patients (AIII).

74. CRITICALLY ILL
MANAGEMENT

75. Oxygen targets…
 titrate oxygen to a target SpO2 of ≥94 % during initial resuscitation
 ≥90 % for maintenance oxygenation.

76. Prone ventilation…
 as much time as is feasible and safe in the prone position.
 while receiving oxygen or noninvasive modalities; HFNC or
noninvasive ventilation (NIV).

77. Next Step… NIV or Intubation
 noninvasive modalities may be used rather than proceeding
directly to intubation.
 HFNC and NIV are considered aerosol generating procedures.
 Better to use NIV mask with a good seal and not have an anti-
asphyxiation valve or port.
 Don’t delay the decision of intubation if needed.

78. Intubation
have a low threshold to intubate patients with the following:
 Rapid progression over hours.
 Lack of improvement on >50 L/minute of high flow oxygen and a
fraction of inspired oxygen (FiO2) >0.6.
 Evolving hypercapnia, increasing work of breathing, increasing
tidal volume, worsening mental status.
 Hemodynamic instability or multiorgan failure

79. PATIENT DISCHARGE

80. Anticoagulation
Patients with documented VTE:
• a minimum of three months of anticoagulation.
Patients without documented VTE:
• May need extended thromboprophylaxis but do not use routine
post-discharge thromboprophylaxis.
• patients with major prothrombotic risk factors such as a history of
VTE or recent major surgery or trauma, and low bleeding risk may
be considered for thromboprophylaxis

81. Why not to use routineThromboprophylaxis?
 The risk of post-discharge VTE appears to be similar to that of
individuals hospitalized for acute medical illnesses other than
COVID-19.

82. Anticoagulation
What to use?
• rivaroxaban 10 mg daily for 31 to 39 days .

83. Anticoagulation for non-hospitalized patients
Only in those with other thrombotic risk factors such as prior VTE or
recent surgery, trauma, or immobilization.