CME INDIA Presentation by Admin.

“If you don’t know where you are going, you’ll end up someplace else.” – Yogi Berra, former New York Yankees catcher.

It is our collective opinion that the historically high levels of morbidity and mortality from COVID-19 is due to a single factor: the widespread and inappropriate reluctance amongst hospitalists and intensivists to employ anti-inflammatory and anticoagulant treatments, including corticosteroid therapy early in the course of a patient’s hospitalization. It is essential to recognize that it is not the virus that is killing the patient, rather it is the patient’s overactive immune system. The flames of the “cytokine fire” are out of control and need to be extinguished. Providing supportive care (with ventilators that themselves stoke the fire) and waiting for the cytokine fire to burn itself out simply does not work… this approach has FAILED and has led to the death of tens of thousands of patients. – East Virginia Medical School, COVID guideline, dated 27th December 2020.

Recently many guidelines updated their protocols. Many even advocated to start steroid as early as Day 1 to Day 3. We bring you some of the important, modifications in protocol.

First it is very important to review the science of steroids in COVID.

यक्ष प्रश्न (Yaksha Prashna) – When to prescribe steroid in Covid 19?

Dr Nishith Kumar, Pulmonologist, Ranchi:

How do steroid work against COVID?

• We all know that Glucocorticoids modulates inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.
• Basically, the benefit of corticosteroids in COVID 19 results from tempering the host immune response to prevent cytokine storm.

Key findings from RECOVERY Trial:

• The Landmark RECOVERY trial established that 6mg Dexamethasone mg daily for 10 days reduced mortality in hospitalised patients with COVID-19 and respiratory failure who required therapy with supplemental oxygen.
• The data also indicated that dexamethasone might increase mortality in hospitalised patients who were not receiving oxygen.
• To simplify things: Dexamethasone improves survival if it is prescribed to patients who have SPO2 <94%.

Why corticosteroid is indicated in patients with SpO2 <94%?

• In pneumonia, pulmonary shunt often occurs & the alveoli gets filled with fluid, causing parts of the lung to be unventilated although they are still perfused. Intrapulmonary shunting is the main cause of hypoxemia in lung consolidation. SpO2 levels below 94% in a c/o Covid 19 are considered low & indicates that the patient has developed pneumonia /entered Stage 2/Pulmonary Phase. It’s important to note that in early pulmonary phase (Stage IIA) patient may continue to have normal SpO2 levels as mild pneumonia in an otherwise healthy individual may not lead to fall in SpO2 levels. In majority of patients without Pre-existing lung disease resting SpO2 falls below 94% when more than 40-50% of the lung gets affected by Covid 19 related pneumonia.

So, a HRCT Severity Score of 6/25 (Mild Pneumonia) may not lead to fall in SpO2 levels.

Many patients suffering from mild pneumonia generally recovers without needing supplemental oxygen. Again, these subsets of patient do not require a course of corticosteroid.

Patients with moderate/severe pneumonia early in the course of disease (5-10 days) may benefit with a course of corticosteroid even if their SpO2 levels are above 93% as majority of them are bound to deteriorate with time and enter Stage III (hyperinflammatory phase).

So how to pick this group of patients 👆🏼

• (Normal oxygen saturation (SpO2 >93%) but with moderate-severe pneumonia).
• Get a HRCT Thorax done between Day 6-8 (from symptom onset) & assess CT severity Score. A severity score of more than 10 on day 6-8 should be taken as a warning sign.
• Rapid radiological deterioration/worsening of pneumonia on chest radiology on serial HRCT Thorax is a tell sign of disease progression.

1. AIIMS-Delhi /ICMR modified Guideline dated 22nd April 2021

Dated 22nd April

Moderate disease

Change

• SpO2: 90% to < 93% on room air / initially it was <94%
• Remdesivir position –Removed from frontline

Any one of:

1. Respiratory rate > 24/min, breathlessness.

2. SpO2: 90% to < 93% on room air.

Admit in ward.

Oxygen Support:

• Target SpO2: 92-96% (88-92% in patients with COPD).
• Preferred devices for oxygenation: non-rebreathing face mask.
• Awake proning encouraged in all patients requiring supplemental oxygen therapy (sequential position changes every 2 hours). Anti-inflammatory or immunomodulatory therapy
• Inj. Methylprednisolone 0.5 to 1 mg/kg in 2 divided doses (or an equivalent dose of dexamethasone) usually for a duration of 5 to 10 days.
• Patients may be initiated or switched to oral route if stable and/or improving.

Anticoagulation

• Conventional dose prophylactic unfractionated heparin or Low Molecular Weight Heparin (weight based e.g., enoxaparin 0.5mg/kg per day SC). There should be no contraindication or high risk of bleeding.

Monitoring

• Clinical Monitoring: Work of breathing, Hemodynamic instability, Change in oxygen requirement.
• Serial CXR; HRCT chest to be done ONLY If there is worsening.
• Lab monitoring: CRP and D-dimer 48 to 72 hrly; CBC, KFT, LFT 24 to 48 hrly; IL-6 levels to be done if deteriorating (subject to availability).

What is on fire for recommendations in mild disease?

MAY DOs – Therapies based on low certainty of evidence

• Tab Ivermectin (200 mcg/kg once a day for 3 days). Avoid in pregnant and lactating women.
• OR Tab HCQ (400 mg BD for 1 day f/b 400 mg OD for 4 days) unless contraindicated.

Inhalational Budesonide (given via Metered dose inhaler/ Dry powder inhaler) at a dose of 800 mcg BD for 5 days) to be given if symptoms (fever and/or cough) are persistent beyond 5 days of disease onset. [NEW]

Remdesivir – position cleared

EUA/Off label use (based on limited available evidence and only in specific circumstances):

• Remdesivir (EUA) may be considered ONLY in patients with
  • Moderate to severe disease (requiring SUPPLEMENTAL OXYGEN), AND
  • No renal or hepatic dysfunction (eGFR 5 times ULN (Not an absolute contradiction), AND
  • Who are within 10 days of onset of symptom/s.
  • Recommended dose: 200 mg IV on day 1 f/b 100 mg IV OD for next 4 days.
  • Not to be used in patients who are NOT on oxygen support or in-home settings

Tocilizumab position cleared

• Tocilizumab (Off-label) may be considered when ALL OF THE BELOW CRITERIA ARE MET
  • Presence of severe disease (preferably within 24 to 48 hours of onset of severe disease/ICU admission).
  • Significantly raised inflammatory markers (CRP &/or IL-6).
  • Not improving despite use of steroids. o No active bacterial/fungal/tubercular infection.
  • Recommended single dose: 4 to 6 mg/kg (400 mg in 60kg adult) in 100 ml NS over 1 hour.

• Convalescent plasma (Off label) may be considered ONLY when following criteria are met:
  • Early moderate disease (preferably within 7 days of symptom onset, no use after 7 days).
  • Availability of high titre donor plasma (Signal to cut-off ratio (S/O) >3.5 or equivalent depending on the test kit being used).

2. AIIMS-Patna recommends Early Steroids dated 21st April 2021

Additional advice deemed appropriate for other associated symptoms such as:

• Tab pantoprazole (40mg) 1 tab once daily empty stomach for gastritis. (20 mg for children).
• Probiotic sachet (1 twice a day for diarrhoeal manifestation) (age appropriate for children).
• Throat soothing lozenges or syrup SOS.
• Oral steroid (dexamethasone 6 mg per day or equivalent dose of methylprednisolone) in cases with mild symptoms but laboratory markers suggestive of inflammatory changes. Prednisolone 1 mg/kg/day or equivalent doses of methyl prednisolone or dexamethasone in children.

3. MSHS Guideline dated 24 Feb 2021 – Available here

4. The ACEP (American College of Emergency Physicians) Emergency Department COVID-19 Management Tool – Available here

Diagnostic Interruption Imaging Interpretation

• Pulmonary US (POCUS) is appropriate as a COVID rule-in test (with diagnostic accuracy similar to CT) but should not be used for risk classification.
• Models to prognostic risk based on CXR 4 results have been published.

Lab Interpretation

• AST (>40 U/L) is associated with increased mortality.
• Creatinine (>133 μmol/L) is associated with increased mortality.
• CRP (>125 mg/L) is associated with increased mortality 27 and intubation within 48-hours.
• D-dimer (≥1μg/mL) is associated with increased mortality.
• Ferritin (>300 μg/L) is associated with increased mortality and worsening oxygenation within 48-hours.
• LDH (>250 U/L) is associated with increased mortality and worsening oxygenation or intubation within 48-hours.
• Lymphopenia (8,000/mm3) is associated with increased mortality.
• Thrombocytopenia (99%) is associated with increased mortality.
• WBC (>10,000/ mm3) is associated with increased mortality.

5. HCFI (Heart Care Foundation of India) have made SUTRAS but be Alert – So controversial /Do not follow blindly. CME INDIA does not advocate it. We are displaying it to bring Facts before you.

HCFI Round Table Expert Zoom Meeting on “Consequences of COVID situation today” 17th April, 2021 – Consensus Statement of HCFI Expert Round Table

Sutra 1: In view of the controversy of vaccine clots, consider low-dose (75mg) aspirin before vaccination in all women (hormone bearing or on HRT), if no contraindication.

Sutra 2: Consider low-dose (75mg) aspirin in comorbid or high-risk people with suspected or silent/confirmed, vascular blockages, if no contraindication, before during and after Covid or Covid vaccine.

Sutra 3: If not contraindicated, in high risk or comorbid Covid confirmed or suspected persons, starting early low dose steroids (prednisolone 40mg) and blood thinners (aspirin or warfarin or NOACs) may not harm and may prevent complications. Steroids are needed for 10 days and blood thinners are needed for at least 4 weeks.

Reality

Dr Keyur Acharya, Intensivist, UK:

•  I found mention of Aspirin puzzling here. Arterial thrombus is a platelet phenomenon along with atherosclerosis.  Ruptured plaque and high shear force bind and unfolds von Willebrand factor and this causes platelet aggregation and activation. Classically ” white clots” causing MI, Stroke and PVD.
• Venous thrombosis is thought to be because of disorder of plasma coagulation and originating in low flow states and this classically gives ” red clots.”
• Aspirin inhibits COX 1 and reduces thromboxane A2 generation which is important for platelet aggregation and activation. So, it does have some basis here.
• Now primary prevention of VTE is mainly evidence based in orthopedic surgery- mainly after hip and knee arthroplasty. Historically we are being taught Antiplatelet Trialists collaboration and PEP (pulmonary embolism prevention) study where aspirin reduced VTEs by 1/3rd compared to placebo. There is still debate about aspirin compared to anticoagulants.
• Then there were other trials like EPACT 1 and 2, systemic reviews etc. But high-risk groups like obese, prior VTE known thrombophilia were excluded and there was significant heterogeneity across trials.
• We are waiting for PEPPER and EPACT 3 trials- again hip and knee surgeries. 
• So, I think as of now it is safe to say that Aspirin is to be used as thromboprophylaxis in mainly low risk post arthroplasty setting.
• We don’t have much evidence in medical setting/ post vaccines for primary prevention.

Sutra 4: Covid inflammation is at its peak by day 3; pneumonia also starts developing by Day 3. This is the time for CT scan also. CRP is at its peak by Day 3 (Th1 response).

Sutra 5: If inflammation is not targeted by Day 5, it may lead to Th17 response, which is neutrophil recruitment leading to thromboinflammation.

Sutra 6: You must control inflammation by Day 3 and thromboinflammation by Day 5.

Sutra 7: Steroids must start before Day 3 and anticoagulant must be started before Day 5.

Sutra 8: CRP should be less than 5 by Day 5; if this target is missed, CRP should be less than 10 by Day 10. After that, the situation is bad.

Sutra 9: Budesonide / fluticasone with salmeterol inhaler may be considered to be given in all Covid patients with lower respiratory symptoms, if not on oral steroids.

Sutra 10: All diabetics when given oral steroids (not inhaled steroids) will have high postprandial blood sugar and will need s insulin (0.3 units/kg/day in divided doses).

The earliest marker of inflammation is CRP. It increases in 4 hours, peaks in 36 hours and crashes in 17 hours. CRP qualitative test strip test like diabetes costs Rs 10 and glucometer like tests cost Rs 60. The market cost has increased from Rs 150 to Rs 1000 because of shortage. Qualitative test only tells if CRP is less than or more than 6.

Sutra 11: In this Covid time, train people to do self-test CRP at home and aim at making it negative.

Day 1 is the first day of symptom or the day of diagnosis. Overdiagnoses, over treat and over prevent in the present scenario.

Sutra 12: Do CRP, CBC first and then PCR to prevent CPR.If CRP is positive, steroids, aspirin and anticoagulant on Day 1.

Sutra 13: In view of the very high rates of vaccine and infection, high risk individuals should consider taking the second dose as soon as permissible to prevent post-vaccine Covid. Everybody should get at least one dose of the vaccine in the present circumstances.

Sutra 14: Post- vaccine Covid: Wait for 8-12 weeks before taking the vaccine after testing negative.Sutra 15: Post-vaccine cough and throat pain cannot be due to vaccine; rule out Covid in such patients. Post-vaccine Covid can be primary infection or breakthrough infection (after 14 days of vaccine): more contagious, lower Ct value, early incubation period, high fever, lungs are often spared, very high CRP, cough and cold/GI symptoms, children are also affected and as spreaders, R0 value is high. Pattern: Very high CRP by Day 1-3, rising d-dimer by day 2-3, falling platelets by day 4-5 and then resolving (in most cases). CRP is a surrogate marker for IL-6 and fibrinogen.

CME INDIA Comments on these Sutras – While some points are scientific, many have no scientific basis to recommend

Dr Awadhesh K. Singh, DM Endo., Kolkata: This expert consensus, lack scientific background and are extremely harmful and doctors should be held equally guilty for playing with science. Majority of Sutra’s are concocted and unproven. BTW what is sublingual Antidiabetic drugs?? Ask them please!

I think there is large communication gap with regard to the use of steroid in Covid amongst treating physicians. RECOVERY trial did not report outcome based on mild- moderate- or severe based on either radiological lung findings or laboratory markers but rather based on falling saturation or oxygen requirements (either requiring no O2 supplementation or O2 supplementation or mechanical ventilation). And this study found no benefit in group not requiring O2 irrespective of laboratory markers. Based on these findings it can be assumed that people requiring O2 had some sort of lung involvement. If you deeply dissect the supplementary appendix of Recovery trial it suggests that benefit happened only in those who were symptomatic for more than 7 days. There was no benefit or possibly harm with steroid those took within 7 days of symptoms. This suggest that early institution of steroid in Covid is not useful and possibly harmful unless they are having lung involvement requiring O2 supplementation. Hope this clears some confusion

Dr Ambrish Mithal, DM Endo, Delhi: Oho. This is quite random. Can create a lot of confusion. Please refrain from following unsubstantiated advice. This can be dangerous in a pandemic

Dr Apoorv Jain, Nephrologist, Agra: Even with so much scientific material available trials / meta-analysis, hypotheses like these are promoted. Poor science will always return as catastrophe.

Any attempt to control this pandemic will always start from bench, bedside skills can always act as stopgap arrangement

6. EVMS guidelines are very much popular, no recent updates, Last updated was on 27th December 2020 – Available here

Key Concepts of the I-MASK and MATH+ Treatment Protocols

This is an extraordinarily complex disease; many of the mysteries are still unravelling. However, a number of concepts are key to the management of this “treatable disease; they include.

1. Patients transition through a number of different phases (clinical stages). The treatment of each phase is distinct… this is critically important.

2. Antiviral therapy is likely to be effective only during the viral replicative phase whereas anti-inflammatory therapy is expected to be effective during the pulmonary phase and possibly the post-COVID-19 phase.

While Remdesivir is a non-specific antiviral agent that targets RNA viruses, it is likely that agents specifically designed to target SARS-CoV-2 will be developed.

3. The SARS-CoV-2 PCR remains positive for at least 2 weeks following detection of whole virus (by culture). Patients who progress to the pulmonary phase are usually PCR positive despite cessation of viral replication (and are therefore less likely to be infectious).

4. Due to the imperfect sensitivity of the PCR test as many as 20% of patients who progress to the pulmonary phase will be PCR negative (even on repeat testing). At symptom onset PCR will be positive in approximately 60% of patients; maximal positivity rate is on day 8 (post infection) when 80% of patients will be positive

5. Symptomatic patients are likely to be infectious during a narrow window starting 2–3 days before the onset of symptoms and to up to 6 days after the onset of symptoms

6. It is important to recognize that COVID-19 patients present with a variety of phenotypes, likely dependent on inoculum size and viral load, genetic heterogeneity mutations and polymorphisms, biotypes, blood type, sex and androgen status, age, race, BMI (obesity), immunological and nutritional status, and co-morbidities.

The phenotype at presentation determines the prognosis and impacts the optimal approach to treatment. It is noteworthy that obesity and increasing BMI are critical prognostic factors. This may be related to the fact that there are more ACE-2 receptors in visceral fat than in the lung.

7. The pulmonary phase is characterized by immune dysregulation a pulmonary microvascular injury (vasculopathy), with activation of clotting and a pro-coagulant state together with the characteristics of an organizing pneumonia.

8. Endothelial damage and an imbalance of both innate and adaptive immune responses, with aberrant macrophage activation, plays a central role in the pathogenesis of the severe COVID-19 Disease.

9. As patients, progress down the pulmonary cascade the disease becomes more difficult to reverse. The implications of this are twofold:

• a. Early treatment (of the pulmonary phase) is ESSENTIAL to a good outcome.
• b. Treatment in the late pulmonary phase may require escalation of the dose of corticosteroids as well as the use of salvage methods (i.e., plasma exchange). However, patients who present in the late pulmonary phase may have progressed to the irreversible pulmonary fibroproliferative phase.

10. The pulmonary phase of COVID-19 is a treatable disease; it is inappropriate to limit therapy to “supportive care” alone. Furthermore, it is unlikely that there will be a single “silver bullet” to treat severe COVID-19 disease. Rather, patients will require treatment with multiple drugs/interventions that have synergistic and overlapping biological effects.

11. The radiographic and pathological finding of COVID-19 lung disease are characteristic of a Secondary Organizing Pneumonia (and not ARDS).

12. THIS is NOT ARDS (at least initially), but rather an organizing pneumonia. The initial pulmonary phase neither looks like, smells like nor is ARDS.The ground glass infiltrates are peripheral and patchy, [346] and do not resemble the dependent air space consolidation (sponge/baby lung) seen with “typical ARDS”. Treating patients as if they ARDS is an extremely dangerous approach. The hypoxia is due to an organizing pneumonia with severe ventilation/perfusion mismatch likely due to the microvascular narrowing, thrombosis and vasoplegia.

13. The core principles of the pulmonary phase (MATH+) is the use of anti-inflammatory agents to dampen the “cytokine storms” together with anticoagulation to limit the microvascular and macrovascular clotting and supplemental oxygen to help overcome the hypoxia.

14. Ivermectin has emerged as a highly effective drug for the prophylaxis and treatment COVID-19. Ivermectin inhibits viral replication and has potent anti-inflammatory properties. Emerging clinical data (including RCT’s) suggest that ivermectin may have an important clinical benefit across the spectrum of phases of the disease, i.e., pre-exposure prophylaxis, postexposure prophylaxis, during the symptomatic phase and during the pulmonary phase.

Update: Systematic Review Published. Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review/https://link.springer.com/article/10.1007/s40264-021-01066-y.A meta-analysis of 19 studies (6 retrospective cohort studies, 7 RCTs, 5 nRCTs, 1 case series) and 8754 unique patients with multiple stages of COVID-19 later. Conclusions: Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.

Symptomatic patients at home (I-MASK+ EARLY Treatment Protocol)

This guideline is the king in options:

• Ivermectin 0.2 mg/kg on day 1 and day 3 (repeat on day 5 and 7 if poor response).
• Vitamin C 500 mg BID and Quercetin 250–500 mg BID.
• Zinc 75–100 mg/day (elemental zinc).
• Melatonin 10 mg at night (the optimal dose is unknown).
• Vitamin D3 2000–4000 IU/day. Calcifediol 0.2 mg is an alternative.
• ASA 81–325 mg/day (unless contraindicated). ASA has anti-inflammatory, antithrombotic, immunomodulatory and antiviral effects. Platelet activation plays a major role in propagating the prothrombotic state associated with COVID-19.
• B complex vitamins.
• Optional: Famotidine 40 mg BID (reduce dose in patients with renal dysfunction) [103-109].
• Optional: Vascepa (Ethyl eicosapentaenoic acid) 4g daily or Lovaza (EPA/DHA) 4g daily; alternative DHA/EPA 4g daily. Vascepa and Lovaza tablets must be swallowed and cannot be crushed, dissolved, or chewed. Omega-3 fatty acids have anti-inflammatory properties and play an important role in the resolution of inflammation. In addition, omega-3 fatty acids may have antiviral properties.
• Optional: Interferon-α/β s/c, nasal spray or inhalation.  It should be noted that Zinc potentiates the effects of interferon.
• In symptomatic patients, monitoring with home pulse oximetry is recommended (due to asymptomatic hypoxia). The limitations of home pulse oximeters should be recognized, and validated devices are preferred. Multiple readings should be taken over the course of the day, and a downward trend should be regarded as ominous. Baseline or ambulatory desaturation < 94% should prompt hospital admission.

The following guidance is suggested:

• Use the index or middle finger; avoid the toes or ear lobe.
• Only accept values associated with a strong pulse signal.
• Observe readings for 30–60 seconds to identify the most common value.
• Remove nail polish from the finger on which measurements are made.
• Warm cold extremities prior to measurement.

Not recommended: Hydroxychloroquine (HCQ). The use of HCQ is highly controversial. The best scientific evidence to date suggests that HCQ has no proven benefit for post exposure prophylaxis, for the early symptomatic phase and in hospitalized patients.

Not recommended: Systemic or inhaled corticosteroids (budesonide). In the early symptomatic (viral replicative phase), corticosteroids may increase viral replication and disease severity. An Open SAFELY analysis in patients with COVID-19 demonstrated a higher risk of death in COPD and asthmatic patients using high dose ICS. The role of ICS in the pulmonary phase is unclear as patients require systemic corticosteroids to dampen the cytokine storm, with ICS having little systemic effects.

NOTE: Latest AIIMS guideline included Inhaled Budesonide. Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/fulltext Published April 9, 2021).

Not recommended: Azithromycin.

7. IDSA Covid-19 Guidelines – Last updated April 14, 2021 – Available here

Recommendation 1: Among hospitalized patients with COVID-19, the IDSA guideline panel recommends against hydroxychloroquine plus azithromycin. (Strong recommendation, Low certainty of evidence)

• Remark: Chloroquine is considered to be class equivalent to hydroxychloroquine.

Recommendation 2: Among hospitalized patients with COVID-19, the IDSA guideline panel recommends against the use of the combination lopinavir/ritonavir. (Strong recommendation, Moderate certainty of evidence).

Recommendation 3: Among hospitalized critically ill patients with COVID-19, the IDSA guideline panel recommends dexamethasone rather than no dexamethasone. (Strong recommendation, Moderate certainty of evidence).

• Remark: If dexamethasone is unavailable, equivalent total daily doses of alternative glucocorticoids may be used. Dexamethasone 6 mg IV or PO for 10 days (or until discharge) or equivalent glucocorticoid dose may be substituted if dexamethasone unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.

Recommendation 4: Among hospitalized patients with severe, but non-critical, COVID-19, the IDSA guideline panel suggests dexamethasone rather than no dexamethasone. (Conditional recommendation, Moderate certainty of Remark: Dexamethasone 6 mg IV or PO for 10 days (or until discharge) or equivalent glucocorticoid dose may be substituted if dexamethasone unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg. **Severe illness is defined as patients with SpO2 ≤94% on room air, including patients on supplemental oxygen.

Recommendation 5: Among hospitalized patients with non-severe COVID-19 without hypoxemia requiring supplemental oxygen, the IDSA guideline panel suggests against the use of glucocorticoids. (Conditional recommendation, Low certainty of evidence)

Non-severe illness is defined as patient with a SpO2 > 94% not requiring supplemental oxygen.

Recommendation 6: Among hospitalized adults with progressive severe or criticalCOVID-19 who have elevated markers of systemic inflammation, the IDSA guideline panel suggests tocilizumab in addition to standard of care (i.e., steroids) rather than standard of care alone. (Conditional recommendation, Low certainty of evidence)

• Remarks: Patients, particularly those who respond to steroids alone, who put a high value on avoiding possible adverse events of tocilizumab and a low value on the uncertain mortality reduction, would reasonably decline tocilizumab.
• In the largest trial on the treatment of tocilizumab, criterion for systemic inflammation was defined as CRP ≥75 mg/L.

Recommendation 7: Among patients hospitalized with COVID-19, the IDSA guideline panel suggests against COVID-19 convalescent plasma. (Conditional recommendation, Low certainty of evidence).

Recommendation 8: Among ambulatory patients with mild-to-moderate COVID-19, the IDSA guideline panel recommends COVID-19 convalescent plasma only in the context of a clinical trial. (Knowledge gap).

Recommendation 9: In hospitalized patients with severe COVID-19, the IDSA panel suggests Remdesivir over no antiviral treatment. (Conditional recommendation, Moderate certainty of evidence) IDSA panel suggests treatment with five days of Remdesivir rather than 10 days of Remdesivir. (Conditional recommendation, Low certainty of evidence).

Recommendation 10: In patients with COVID-19 admitted to the hospital without the need for supplemental oxygen and oxygen saturation >94% on room air, the IDSA panel suggests against the routine use of Remdesivir. (Conditional recommendation, Very low certainty of evidence).

Recommendation 11: Among hospitalized patients with severe COVID-19, the IDSA panel suggests against famotidine use for the sole purpose of treating COVID-19 outside of the context of a clinical trial. (Conditional recommendation, Very low certainty of evidence).

Recommendation 12: Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, the IDSA guideline panel suggests bamlanivimab/etesevimab or casirivimab/imdevimab rather than no neutralizing antibodies. (Conditional recommendation, low certainty of evidence).

Recommendation 13: Among hospitalized patients with severe COVID-19, the IDSA guideline panel recommends against bamlanivimab monotherapy. (Strong recommendation, Moderate certainty of evidence).

Recommendation 14: Among hospitalized patients with severeCOVID-19 who cannot receive corticosteroids because of a contraindication, the IDSA guideline panel suggests use of baricitinib with remdesivir rather than remdesivir alone. (Conditional recommendation, Low certainty of evidence

• Remark: Baricitinib 4 mg daily dose for 14 days (or until hospital discharge). The benefits of baricitinib plus remdesivir for persons on mechanical ventilation are uncertain. See the remdesivir section for dose and duration.

Recommendation 15: Among hospitalized patients with COVID-19, the IDSA guideline panel recommends treatment with baricitinib plus remdesivir plus corticosteroids only in the context of a clinical trial. (Knowledge gap).

Recommendation 16: In hospitalized patients with severe COVID-19, the IDSA panel suggests against ivermectin use outside of the context of a clinical trial. (Conditional recommendation, very low certainty of evidence).

Recommendation 17: In outpatients with COVID-19, the IDSA panel suggests against ivermectin use outside of the context of a clinical trial. (Conditional recommendation, very low certainty of evidence).

8. All states and Institutions have their own protocol.

Dr. Priya Sampath Kumar, Director, Infectious ds, Mayo Clinic:

(Shared and endorsed by Dr. A. K. Singh MD, DM Endo., Kolkata)

CME INDIA Tail Piece

“If what you are doing ain’t working, change what you are doing” – Phillip C. McGraw.

Dr Noni G Singha Dibrugarh, Assam:

• Ivermectin is still in AIIMS guideline for managing Mild Covid-19. So, confusion again.
• I feel instead of looking to the West we Indians should have our own concrete recommendation. We have enough number of cases to get some viewpoints or study or review.
• There is a big confusion in timing of using steroid in Covid-19. Many are following it – Recovery trial – were starting steroids when patient needs Oxygen therapy. But that was the story of wild Covid virus (first wave) but as we all know these mutant viruses behave differently (second wave), once need of oxygen few succumb or deteriorates very fast and hardly giving time for steroid to act. We need to think differently.

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