CME INDIA Presentation by Dr. N. K. Singh, MD, FICP, Diabetologist Physician, Director – Diabetes and Heart Research Centre (DHRC), Dhanbad, Chairman – RSSDI Jharkhand, Editor – CME INDIA.

Updated 03/01/2022

“Knee-jerk, draconian” reaction has put South Africa in mess and whole of world is in panic mode again. So far data from Omicron illness has been stated to be extremely mild and needs nothing more than observation and symptomatic medications like paracetamol and anti-allergic.

Still, it is perfect wisdom to be alert, monitor and know the science available so far.

What to perceive?

• Variant hunting is performed through whole genome sequencing of samples that have tested positive for the virus.
• This process involves checking every sequence obtained for differences compared to what we know is circulating so far.
• When we see multiple differences, this immediately raises a red flag. We investigate further to confirm – this is what happened in South Africa.
• Then Omicron as B.1.1.529 was born to blast the dynamics of world.

South Africa in trouble, not due to unmanageable Omicron but undue response of the West

Heavy transmission is the main feared factor

How Omicron case will come to you?

• Covid symptoms linked to the new omicron variant stated to be “extremely mild” by the South African doctor Dr. Angelique Coetzee who first broke the news.
• No sufficient data exists as on 01/12/2021. The WHO will take weeks to understand how the variant may affect diagnostics, therapeutics and vaccines.
• Feeling extremely tired for few days, body ache and  headache – these are usual presenting complains.
• Usually no sore throat, no cough or loss of taste or smell have been seen.
• It is better to follow “Watch List for all Variants (CDC)/ Symptoms may appear 2-14 days after exposure.”

Look for emergency warning signs

How to diagnose?

• The trick of diagnosing Omicron illness is to go for usual tests at present.
• The accuracy of existing molecular (PCR, NAAT) tests appears uncompromised by COVID-19 variant Omicron (B.1.1.529)
• Preliminary evidence suggests that this is also true for the accuracy of rapid antigen tests.
• Thus current SARS-CoV-2 PCR diagnostics continue to detect this variant.
• Several labs have indicated that for one widely used PCR test, one of the three target genes is not detected (called S gene dropout or S gene target failure) and this test can therefore be used as marker for this variant, pending sequencing confirmation.
• Using this approach, this variant has been detected at faster rates than previous surges in infection, suggesting that this variant may have a growth advantage. (WHO)
• The ability of diagnostic tests to detect the Omicron variant is critical to tracking its spread and putting in place measures to halt transmission.
• We must remember that although  analyses so far suggest that the rapid antigen (lateral flow) and gold-standard PCR tests should still detect the variant, we have to wait for further comprehensive verification which  is ongoing.
• Do RT-PCR-Look for S gene dropout.
• In India like South Africa, it is not possible to go for Genomic sequencing in all cases. S gene dropout gives you a SIGNAL to track the variant’s spread without genomic sequencing, which is usually only performed for a subset of PCR-positive samples (where capacity is available).
• A major issue is that we are still struggling with testing capacity for COVID-19, including genomic sequencing capacity.

• Thermo Fisher Scientific Inc (TMO.N) COVID-19 diagnostic tests:
  • As per company claim, it can accurately detect the new coronavirus variant Omicron. Thermo Fisher’s TaqPath COVID-19 assays can report accurate results even in the case where one of the gene targets is impacted by a mutation. This assay can be used not only to successfully detect COVID-19 but it can also be used as a proxy for the [Omicron] variant.
  • It is the only COVID-19 diagnostic test that is both authorized by the U.S. Food and Drug Administration and can be used to indicate if a case is caused by the Omicron variant.
• Roche Holding AG (ROG.S) and Abbott Laboratories (ABT.N)
• It can also be used to diagnose positive cases of COVID-19 caused by the variant, though only Thermo Fisher has so far confirmed that its test can be used to help identify the variant.
• However, the WHO has cleared that verification work with technical experts is going on to understand the potential impact of these tests.

How to Treat?

Treatment of Mild Cases (So far Omicron has been found causing extremely MILD symptoms)

Following are usual measures to tackle a Mild Case. Use these measures intelligently

• Rehydration.
• Antipyretic (Paracetamol) Take paracetamol tablet 650 mg every 4-6 hours if you have fever – not more than four times in 24 hours. If fever is more than 101 degrees F, do tepid sponging using tap water (not cold water or ice) or take a shower. Mefenamic acid 500mg tablet can be added if fever not subsiding with paracetamol provided renal function is normal.
• Nutritional support.
• No role of Azithromycin/ Doxycycline Note: Most of centers/experts use these drugs on personal experiences and have found them useful.
• Supportive: Anti-tussive SOS /Vitamin C 500 mg BD or 2 weeks/T. Zinc 50 mg OD for 2 weeks Vit D 2000 units once daily or 60000 IU once weekly for 4-8 weeks.
• Tab Melatonin or Clonazepam if needed to allay anxiety.
• Say No to HCQS.
• Ivermectin-Not useful. Do not use.
• Favipiravir No data. Do not use.
• Molinipiravir (Available now)- which also needs early use in first week of viral replication but better data is needed.Molnupiravir 800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY . This is at present available but one Paxlovid is avaiable,do prefer it.

• When to start? – Molnupiravir should be administered as soon as possible after a diagnosis of COVID-19, and within five days of symptom onset. It is stated to prevent progression of disease leading to hospitalization.
• Whom should it be given to? – We recommend only to give adult Covid-19 patients with Comorbidities like Diabetes, CKD, COPD Heart Disease,  COPD, immunocompromised states, Obesity within 5 days of symptom onset.
• Dose: Overall, the course has 40 pills. 800 mg (four 200 mg capsules) taken orally every 12 hours for five days, with or without food. Completion of the full five-day treatment course is important to maximize viral clearance and minimize transmission of SARS-CoV-2. Once started complete the course.

• Paxlovid: Nirmatrelvir 300 mg with ritonavir 100 mg (Paxlovid) orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg( not available in India). Caution – lot of drug interactions due to ritonavir. Not available now but expected soon.
• Steroids MUST NOT be used in patients with only mild disease. Concept of starting steroid on day 1 is detrimental and must be abandoned.
• Recently Budesonide Inhalation (given via DPI/MDI with Spacer at a dose of 800 mcg BD for 5 to 7 days) to be given if fever and respiratory symptoms are persistent beyond 5 days of disease onset or even early if in High-Risk Group (PRINCIPLE Trial).
• Prophylactic dose of LMWH ONLY if risk factor for thrombotic disease – Enoxaparin dose is 1mg/ kg OD not 40mg od for all or Inj Fondaparinux 2.5mg s/c OD. For Home, we prefer – Apixaban 2.5 mg BD Alternatively: Tab Aspirin 75 mg (or clopidogrel 75/ mg) in high-risk groups. (No data with Omicron).
• Anti-SARS-CoV-2 Monoclonal Antibodies: ( Present regn antibodies available in India is not effective against omicron and should not be used as such, this is the consensus opinion ). Approved molecules as Emergency use authorization (EUA):
  1. Casirivimab, 600 mg plus Imdevimab 600 mg: Antibody cocktail- now available in India.
  2. Bamlanivimab 700 mg plus etesevimab 1,400 mg: Now not recommended as use of bamlanivimab plus etesevimab has been found to increase in the proportion of the variants of concern (VOC) Gamma (P.1) and Beta (B.1.351). These VOCs have reduced susceptibility to both bamlanivimab and etesevimab.
  3. Single monoclonal antibody (sotrovimab).sotrovimab, It retains in vitro activity against the full known Omicron spike protein, the new SARS-CoV-2 variant (B.1.1.529). Sotrovimab 500 mg as a single IV infusion, administered as soon as possible and within 10 days of symptom onset in those aged ≥12 years and weighing ≥40 kg who live in areas with a high prevalence of the Omicron VOC. Neutralising antibodies against omicron are three times less but still can be effective. Not available in India at present.

(Casirivimab plus imdevimab and sotrovimab remain active against these variants).

We suggest the use of casirivimab/imdevimab in patients with mild to moderate COVID-19 who are at high risk for progression to severe disease.

Among hospitalized patients with severe COVID-19, we do not recommend this therapy.

But patients who are admitted to the hospital for reasons other than COVID-19, and who have mild-moderate COVID-19, may also receive this therapy. The NIH and CDC suggest that treatment decisions (including use of monoclonal antibody therapy) be made regardless of COVID-19 vaccination status.

This therapy must be initiated in highly selective high-risk patients only as per following table:

• When to start: Treatment should be started as soon as possible after the patient receives a positive result on a SARS-CoV-2 antigen test or a nucleic acid amplification test and within 10 days of symptom onset.
• How to give: The intravenous administration takes about 20 to 30 minutes. For the subcutaneous route, four syringes of 2.5 ml (2 each of Casirivimab & Imdevimab) need to be administered concurrently at four different sites on the abdomen or thigh. Patients should be monitored during the infusion and observed  at  least one hour after the completion of the infusion and 15–30 minutes after the subcutaneous injection.
• How supplied: Each pack of Antibody Cocktail (Casirivimab and Imdevimab) contains one vial of Casirivimab and one vial of Imdevimab totaling 2400 mg of the antibody cocktail (one vial of Casirivimab (1200 mg) and one vial of Imdevimab (1200 mg)). Each pack can treat two patients as the dosage per patient is a combined dose of 1200 mg (600 mg of Casirivimab and 600 mg of Imdevimab) administered by intravenous infusion or subcutaneous route. The vials need to be stored at 2°C to 8°C. If opened for the first patients’ dose, a vial can be used for the second patients’ dose within 48 hours if stored at 2°C to 8°C.
• How much priced: The price for each patient dose [a combined dose of 1200 mg (600 mg of Casirivimab and 600 mg of Imdevimab)] will be INR 59,750 inclusive of all taxes. The maximum retail price for the multidose pack (each pack can treat two patients) is INR 119,500 inclusive of all taxes.
• Alert: Receipt of a COVID-19 vaccine should be deferred for at least 90 days in those who have received anti-SARS-CoV-2 monoclonal antibodies.
• Remdesivir – 3 days course approved by CDC .Remdesivir 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg.

WHY REMDESIVIR IS BACK? – Surprisingly Remdesivir is back – basis is PINETREE trial which showed that 3 consecutive days of IV remdesivir resulted in an 87% relative reduction in the risk of hospitalization or death compared to placebo.

Order or preference as per CDC:

CDC Panel recommends using 1 of the following therapeutics (listed in order of preference):

1. Paxlovid

2. Remdesivir

3. Molnupiravir

Efficacy of above mentioned agents – Paxlovid – reduced the risk of hospitalization or death by 88% compared to placebo in non-hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. This efficacy is comparable to the efficacies reported for sotrovimab (i.e., 85% relative reduction), and remdesivir (i.e., 87% relative reduction) and greater than the efficacy reported for molnupiravir (i.e., 30% relative reduction).

CME INDIA Learning Points

• We are in the learning process. If symptoms are only extremely mild then all these dramatic measures and panic appear unfortunate.
• Science and politics go hand in hand.
• Diagnosing Omicron is a top priority, which is possible by SURROGATE MARKER. The missing S gene target can act as a surrogate marker for the new variant in tests, which target this gene, as the currently dominant Delta variant is S-gene positive on PCR.
• The S gene dropout has made possible timely screening for the Omicron variant.
• Treatment is entirely as with usual COVID Protocol.
• CAB (Covid Appropriate Behaviour) is the key of precautionary measures.

CME INDIA Tail Piece

Opportunity in disaster:

India has issued revised guidelines:

• This is for international travellers arriving from “at risk” countries, including the whole of Europe, South Africa and Brazil, mandating testing on arrival, home quarantine for seven days on a negative result, and a retest on the eighth day. Several states have imposed their own restrictions.

Dr. Rajkamal Chaudhary, Asso. Prof. Med., Bhagalapur:

My opinion about the Omicrons – As the virus becomes weaker chances of Mutations increases before being wiped out from the universe, this is similar to the Poliovirus in which the P2 virus before being out had Mutations and suddenly the P1 virus circulation was intense and when rounds of Monovalent P1 was taken for many years the Mutations and the VAPD started coming which was weak and suddenly again P3 virus was out in Bihar and UP and when P3 Polio rounds were taken everything finished.

It took 16 years to Finish Polio, and similarly the COVID-19 pandemic is going to become weaker and weaker and it will be wiped.

Dr. Vaibhav Agnihotri, Consultant and Incharge, Dept. of Paediatrics and Neonatology, Balaji Soni Hospital, Jaipur:

References:

1. https://www.who.int/groups/technical-advisory-group-on-sars-cov-2-virus-evolution
2. https://reliefweb.int/report/world/current-testing-tools-uncompromised-new-covid-19-variant-concern-omicron-b11529

Discover CME INDIA

• Explore CME INDIA Repository
• Examine CME INDIA Case Study
• Read History Today in Medicine
• Register for Future CMEs

Get CME INDIA Highlights

Curated articles in your inbox.

SUBSCRIBE!

You have Successfully Subscribed!