CME INDIA Presentation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh, India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.

In India, we are recording significantly high number of Covid cases now. About 81% cases have been reported from Maharashtra, Kerala, Delhi and Karnataka. ICMR says “it’s wrong to say 4th wave is coming.” ICMR emphasized to examine district-level data. Many people believe that we are admits to fourth wave without any panic and restrictions.

Happening Now

  • Wild virus D614, G614, Alpha, Delta BA.1 Omicron BA.2 spread every nook and corner of the world even at a time of Lockdowns when there were no national or international flights.
  • But BA.4 and BA.5 the evolved versions of Omicron remain restricted to US and Europe and created havoc. India remained largely free of BA.4 and BA.5.
  • And this happened at a time when world had adopted Open Air policy and number of National and international flights operation, masks had started dropping.

Why? Only one difference: Vaccines

  • Vaccines used against Covid have trifurcated the World.

1. India

  • Whole virus killed vaccine Covaxin or Vector based Covishiled vaccine produce long lasting immunity and wider immunity protecting against evolving strains because they have multiple epitopes.
  • Delta ran through Indians in Second wave giving inherent Immunity more than 70% people.
  • Ethnically Indians might have better immunity though only ethnic prevalence data of BA.4 and BA.5 could prove or disprove the fact.

2. Western World – US, Europe

  • Primarily used mRNA vaccines which seem to be turning in effective in protecting against Evolving Virus.
  • Extremely specific Spike protein epitope in mRNA vaccines served good purpose in initial phase but proved futile once virus changed.
  • These vaccines require repeated booster after booster to maintain efficiency.
  • Now German American vaccine needs to be tweaked vaccine for Omicron.

Lesson: Old is Gold

3. 3rd Section of world

  • China also used killed virus vaccine but they were poor quality vaccines and secondly China followed Zero Covid depriving people of natural immunity.
  • So, China continues to face virus surge in different cities now and then.

Lesson – Virus can’t be chased. You need to just have a strong back.

CME INDIA Discussion

Dr. Shashank Joshi, DM Endo, Mumbai:

  • We very much have both BA4 and BA5 and INSACOG has reported it from across India.
  • INSACOG confirms presence of Omicron BA.4 and BA.5 sub-lineages.
  • INSACOG confirms presence of BA.4, BA.5 Omicron variants in India.
  • A quick update on BA4 & BA5 variants reported in India so far:
  • Maharashtra – 64 (One BA4 case reported today/19/7/22).
  • Karnataka – 42 (04 BA4 and 38 BA5).
  • BA 2.75 is the chase, but fundamentally I agree that we have large exposure to virus and vaccine both plus genes and generalized immunity which is keep current omicron stains asymptomatic or mild and very low in severity or mortality.

Dr. S. K. Gupta:

  • Fully agree with you that BA.4 and BA.5 cases have been reported in India.
  • But the real question which is worth highlighting is that unlike USA and France India did not have a ferocious 4th Wave despite Open Air policy.
  • Only difference in the post 2021 world is the vaccines used which leading to different surges in different parts of World.
  • This is one analysis which Americans agree in principle.

Dr. Shashank Joshi, DM Endo, Mumbai:

  • We have better hybrid immunity, large exposure to virus and vaccine, BCG vaccinated and possibly better genes and general immunity against microbes in general.

Dr. S. K. Gupta:

  • If you are anticipating that BA.4 and BA.5 will take over and push BA.2.75 from India – only time would tell. That’s exactly I wanted to convey. Plus, Better Vaccine, which made the difference over and above / To inherent genetics.

Dr. Shashank Joshi, DM Endo, Mumbai:

  • Our Genomic testing is low, we have active virus in circulation but it’s predominantly asymptomatic or mild so we really, we never know unless we have Genomic testing available like a rapid test. currently unless we don’t have a new voc, we r doing well over all. Only concern is if any spill over accident happens or a virulent strain comes up which is low probability as of now.
  • So, India over all is a global case study I agree mRNA platform was over hyped and never was robots enough and I feel old is gold is correct. we have done well despite all all adversities and resource limitations so I agree with you.
  • Surge of the BA.5 Omicron subvariant sweeps Europe, North and South America, Japan –

CME INDIA Tail Piece

Dr. Suresh Kubavat, Ahmedabad:

Should favipiravir be used instead of Molnupiravir in the continuing Fourth wave?

Dr. Ravi Doshi, Pulmonologist, Professor – Sri Aurobindo Medical College Institute, Indore:

  • Over 300 treated this wave you can manage very well without both.
  • In a high-risk group patient, Molnupiravir definitely gives an advantage of early viral load reduction.

Dr. Rajkamal Chaudhary, Asso Prof Med, Bhagalapur:

  • What are the Indications of Paxlovid in Corona? When it is suggestive of giving it?
  • Most of the Patients which are coming they go away within 3 to 5 Days of Admission. Patients with IHD, CKD, Liver Disease and Patients with Oncology conditions and usually from 60 to 80 years are dying. Two whom should we give?
  • I am definitely going to try its Efficacy in High-Risk Cases.

Dr. N K Singh:

  • The EPIC-HR trial demonstrated:
    • Starting ritonavir-boosted nirmatrelvir treatment in nonhospitalized adults with mild to moderate COVID-19 within 5 days of symptom onset reduced the risk of hospitalization or death through Day 28 by 89% compared to placebo.
    • This efficacy is comparable to remdesivir (87% relative reduction) and greater than the efficacy reported for molnupiravir (30% relative reduction).
  • Ritonavir-boosted nirmatrelvir is expected to be active against the Omicron (B.1.1.529) variant and its BA.2 subvariant.
  • There is currently a lack of data on the clinical efficacy of ritonavir-boosted nirmatrelvir against this variant and subvariant.
  • MUST BE REMEMBERED- because of the potential for significant drug-drug interactions with concomitant medications, this regimen may not be the optimal choice for all patients
  • Drug-drug interactions with ritonavir-boosted nirmatrelvir may lead to serious or life-threatening drug toxicities.
  • The recommended treatment course of ritonavir-boosted nirmatrelvir for COVID-19 is 5 days.
  • After the last dose is administered, most of the interaction potential resolves within 2 to 3 days, although resolution may take longer in elderly adults.
  • Do not give Ritonavir-boosted nirmatrelvir within 2 weeks of administering a strong CYP3A4 inducer (e.g., St. John’s wort, rifampin). Ritonavir-boosted nirmatrelvir is contraindicated in this setting ineffective against SARS-CoV-2. Alternative treatment for COVID-19 should be prescribed.
Evolving Omicron 4th Wave - How India is Likely to Turn the Tide?


Dr. Shailesh Trivedi, Chairman RSSDI, Gujrat:

  • We are hopeful that Pfizer’s anti-Covid oral drug Paxlovid, which is expected to be available this week in India, is likely to play a key role if Covid19 cases rise in India due to the new Omicron sub-lineage.
  • Hyderabad-based Hetero has already received the DCGI approval to launch the drug in India on April 21.
  • Drug is likely to be be available soon.

CDC Guidance:

  • How should you assess a patient for “high risk for progression to severe COVID?
    • Patients in the authorized population with risk factor for progression to severe COVID-19 are eligible for Paxlovid under the EUA even if they are fully vaccinated.
    • Patients do not have to have more than one risk factor to be considered “high risk.

Summary of Conditions with High Risk

  1. Higher risk for severe COVID-19 outcomes is defined as an underlying medical condition or risk factor that has a published meta-analysis or systematic review.
Cerebrovascular disease
Chronic kidney disease*
Chronic lung diseases limited to: Interstitial lung disease. Pulmonary embolism. Pulmonary hypertension Bronchiectasis COPD (chronic obstructive pulmonary disease)
Chronic liver diseases limited to:

Non-alcoholic fatty liver disease.
Alcoholic liver disease.
Autoimmune hepatitis.
Cystic fibrosis
Diabetes mellitus, type 1 and type 2*‡

Attention-Deficit/Hyperactivity Disorder (ADHD).
Cerebral Palsy.
Congenital Malformations (Birth Defects).
Limitations with self-care or activities of daily living.
Intellectual and Developmental Disabilities.
Learning Disabilities.
Spinal Cord Injuries.  
Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
HIV (human immunodeficiency virus)
Mental health disorders limited to:

Mood disorders, including depression.
Schizophrenia spectrum disorders.
Neurologic conditions limited to dementia‡
Obesity (BMI ≥30 kg/m2 or ≥95th percentile in children) *‡
Primary Immunodeficiencies
Pregnancy and recent pregnancy
Physical inactivity
Smoking, current and former
Solid organ or hematopoietic cell transplantation
Use of corticosteroids or other immunosuppressive medications
  1. Suggestive higher risk for severe COVID-19 outcomes is defined as an underlying medical condition or risk factor that neither has a published meta-analysis or systematic review
    • Overweight (BMI ≥25 kg/m2, but <30 kg/m2)
    • Sickle cell disease
    • Substance use disorders
    • Thalassemia
  2. Mixed evidence is defined as an underlying medical condition or risk factor that has a published meta-analysis or systematic review
    • Alpha 1 antitrypsin deficiency
    • Bronchopulmonary dysplasia
    • Hepatitis B
    • Hepatitis C
    • Hypertension

Is dose adjustment of Paxlovid in moderate renal impairment?

  • Needed.
  • Paxlovid is now supplied in two different dose packs, one for standard dosing and one for moderate renal impairment dosing.
In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of Paxlovid is 150 mg nirmatrelvir (one 150 mg tablet) and 100 mg ritonavir (one 100 mg tablet) twice daily for five days.
Patients with mild renal impairment (eGFR ≥60 to <90 mL/min) should receive the standard dose of 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together orally twice daily for five days.
Paxlovid is not recommended at this time in patients with severe renal impairment (eGFR <30 mL/min).


  1. Kompaniyets L, Pennington AF, Goodman AB, Rosenblum HG, Belay B, Ko JY, et al. Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020–March 2021. To learn more, visit the Preventing Chronic Disease article:

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