Compiled by Dr N. K. Singh, Admin – CME INDIA.

Currently, we are in a mad race against time to identify prophylactic and therapeutic treatments against COVID-19. Sometimes science acts as a lunatic. So many treatment protocols confuse the physicians. Time will test these treatments, which are developed, tested, and guidelines flow in unity. Till then, let us be prudent to look into existing therapies.

There are three phases of the illness worth remembering:

1. Covid (1-9 days, infectious phase)
2. Post-Covid (after 9 days, non-infectious, persistent inflammation)
3. Non-Covid (after 3 months). After 3 months, the patient should be treated as non-Covid, instead of post-Covid.

Now let us walk through the real scenarios:

• You have come across a patient having symptoms, fever high grade, cold, sore throat, cough, malaise at this time of pandemic. It is justified, it should be taken as suspected covid.
• On Day 2 to Day 5 of symptoms you tell to get the Real Time PCR and more likely to come positive. (at present so called gold standard)

Scenario 1:

If test comes positive, then what advice you give for self-quarantine?

• Separate room and toilet
• Self-Care and hygiene
• If separate toilet not possible to flush the toilet thoroughly by disinfectant may be household phenyl after its use by infected person
• And most important, monitor SPO2 twice a day daily. It should be more than 95%. Some take 94% as cut off value.
• To do six-minute test twice a day in a room itself
• Medications:
  • Very much debated, no uniformity, but what most of centers follow is this
    • Zinc 75-100 mg/day (elemental zinc)
    • Vitamin C 500 mg BID
    • Aspirin being given in USA and at many placesA[81 -325 mg/day] (unless contraindicated)
    • Melatonin 6-12 mg at night (the optimal dose is unknown) [More use in USA]
    • Vitamin D3 2000-4000 u/day
    • Aspirin 81 -325 mg/day (unless contraindicated)
    • Optional: Famotidine 20-40 mg/day
    •  Ivermectin 150-200 ug/kg orally (Usually being used as 12 mg stat dose followed by single dose upto 3 to 5 days) Recommended in many official notifications of state governments like UP and Bihar.
    • Not recommended: Hydroxychloroquine (HCQ). The use of HCQ is extremely controversial. Still being uised widely at present. It is possible that the efficacy of HCQ requires the co-administration of Zinc.
    • No role of Prophylactic Antibiotics in home Quarantined positive patients.

• Investigations during quarantine
  • CBC
  • CRP
  • Role of HRCT Chest & Xray Chest advisable on Day 4 – 5,
  • Acts as a supportive evidence or to pick up early ground glassing If test comes negative then though welcome news, watchful for next 7to 10 days and repeat the test if symptoms worsens.
  • Few Patients with no respiratory symptoms and normal saturations can have florid changes on CT Chest/HRCT

Scenario 2:

SPO2 after walk if equal or less than 94% – likely to have hypoxia

To get hospitalized for further management

• Medicines -symptomatic
• Paracetamol (650 mg to 1gm qds being used)
• No need of NSAIDs, but Mumbai and Delhi experience found naproxen a very useful drug to control fever.
• Enoxaparin 60 mg daily. Consider increasing the dose to 1mg/kg q 12 hourly in those with a high D-Dimer or an increasing D-Dimer.
• Methylprednisolone -40 mg q 12 hourly; increase to 80 mg q 12 hourly in patients with progressive symptoms and increasing CRP.
• [The role of inhaled corticosteroids (budesonide) is unclear and appears to be rather limited.
• Ivermectin 150-200 ug/kg (dose can be repeated on day 2)
• Vit C and Zinc
• One can take antiviral as Favipiravir

• Investigations during hospitalization in first 5 days?

Three acute phase reactants– CRP, ESR and IL-6. In a resource-limited country, of the three, choose CRP. It is indicator of intensity of inflammation. CRP cannot rise without increase in IL-6. Raised CRP, presume that the d-dimer is high.

Plan for:

• CBC
• CRP
• Xray Chest
• D-dimer
• LDH
• Ferritin
• Creatinine
• LFT
• To watch for N:L ratio :More than 3.5,warrants antibiotics
• To check for Procalcitonin levels are done, if high suggests underlying sepsis.

Scenario 3:

• On Day 7, Day 8, IL6 test is done and if alarmingly high POINTS to cytokines storm
• In covid patient with hypoxia – Do you think the thumb rule in use of antiviral is “Early to start is always better?”
• Antiviral needs to be added as emerging consensus, preferred agent as now is Remdesivir. For Five days :200 mg IV First day then 100 mg IV for next four days (Creatinine clearance should be checked for) Informed Consent required for use of Remdesivir.

Pearls in COVID Management

Pearl No 1 –  Use of steroids:

THIS IS A STEROID RESPONSIVE DISEASE: HOWEVER, TIMING IS CRITICAL

• Lot of variations in doses and issues in choosing Dexamethasone vs Methyl Prednisolone?
• Methyl Prednisolone is the drug of choice?1mg/kg/BD for 5 days IV
• Use of Dexamethasone instead of Methyl prednisolone if issue with cost and availability??
• The most robust data amongst corticosteroids came with dexamethasone in the RECOVERY trial, which showed the most significant mortality benefit with low dose dexamethasone. RECOVERY trial shown an impressive 35% mortality reduction among the sickest patients on invasive mechanical ventilation and a 20% reduction of mortality amongst patients on oxygen therapy (with or without noninvasive ventilation). Patients on dexamethasone had a statistically significant reduction of hospital stay and an earlier likelihood of discharge
• Strictly not to be used on OPD basis for first five days of symptoms
• Don’t Start Dexa or any steroids just because one has diagnosed with Covid. It may have detrimental effect if started before time.
• Methylprednisolone is a short/intermediate acting glucocorticoid of 4–6 h duration, while dexamethasone is a long acting steroid with steroid induced hyperglycemia lasting for more than 24 h after the last dose, with a minimal fall after an overnight fast.

Steroid Blues

• Could thousands of lives lost to COVID-19 have been saved had the findings of this study been implemented?
• WHO had said at the beginning of the COVID-19 pandemic that steroids should not be used to treat COVID-19 patients. But medical researchers around the world have supported the advantages of steroids in reducing the mortality of COVID-19 patients with ARDS.
• Despite the concerns that corticosteroids may hamper virus clearance, the low dose corticosteroids appear to have a role in the management of severely ill COVID-19 patients. (Respiratory Medicine DOI: 10.1080/17476348.2020.1804365)
• Using steroids, the moment you find at least 10 to 15 per cent of lung involvement during the infection with LMWH is a game changer(Expert opinion)

Pearl No 2 – LMWH/Anti-coagulation

• Low Molecular Weight Heparin is another drug added on Day 5 of symptoms in view of hypoxia / who requires Oxygen

Anti-Coagulation-(Consensus – Recommendations by experts)

• If D dimer More than 2 times the normal. Start “prophylactic “dose 40 ug OD. If increasing further, Step up to “Intermediate” dose 40 ug BD. If more than 10 times the normal.
• Worsening clinical situation, then consider “Therapeutic” Dose.1 ug per kg, two times a day
• Inj  Enoxaparin (40mg) 40mg / 60 mg once a day continued till discharge and continued at home or replaced by oral anticoagulant for a week and repeated test of D dimer is important. If normal, then it is stopped.
• Sometimes if D dimer is relatively too high then higher therapeutic dose is used of Inj Enoxaparin (40mg). Reason of using it – as micro vascular thrombi – pulmonary embolism – is one of the complication LMWH in all patients irrespective of D dimer. COVID is a Coagulapathy.
• Prophylaxis or Therapeutic doses depend on D dimer levels
• Giving oxygen without anticoagulation has no significance. You have to give aspirin/anticoagulation. For cases under home care, Rivoraxaban (10 mg prophylaxis) can be given in place of LMWH; it is cheaper, can be taken by the patient, onset of action is 10 hours.

Pearl No 3 – All patients need not be discharged on routine oral anticoagulants

• Assess risk at discharge
• Obese/less mobile/prothrombotic states
• At Discharge-limit doacs only, to those risk groups

Pearl No 4 – Treatment of hypoxia

• HFNC: High Flow Nasal Canula delivery of Oxygen as high as 40 to 60 lits with closed mouth in prone position. All the time nursing in Prone Position and CARP protocol has good outcome. It leads to heart, anterior mediastinal organs fall forward, better aeration of lungs and posterior lobe involvement becomes lesser…
• NIV/CPAP not recommended by many experts now.
• NIV has got its limitations including, SILI (Self Induced Lung Injury) and difficulty in prone nursing
• If on HFNC:

1. Drowsiness
2. PCO2 increases
3. ABG not achieved as desired
4. PaO2/FiO2 ratio < 150 on HFNC

Time To shift to ventilator

(Cosmetic Ventilators are just automated AMBUs and don’t have any role)

[Expert experiences]

Pearl No 5 – Tocilizumab (anti IL6) /Eculizumab (anti CD6) injection to be used, when?

• Timing is very important ……Not early Not late, Day 8 to Day 12
• 3 digit CRP,10 to 12 times rise in IL6, IL6 reports sometime takes two days
• But as CRP too high better not to wait for IL6 report otherwise it will be too late
• Rule out infection before giving it, send Procalcitonin
• Of late cytokine storm is seen in 3rd week too
• Only one dose of Tocilizumab
• No role for second dose

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