CME INDIA Presentation by Dr. Padmanabha Shenoy, MBBS, MD – Internal Medicine, DM Clinical Immunology and Rheumatology, Consultant Rheumatologist and Medical Director, CARE (Centre For Arthritis and Rheumatism Excellence), Nettoor, Cochin.

“There is consistent evidence that Omicron has a substantial growth advantage over Delta. It is spreading significantly faster than the Delta variant in countries with documented community transmission, with a doubling time between 1.5–3 days. Omicron is spreading rapidly in countries with high levels of population immunity and it remains uncertain to what extent the observed rapid growth rate can be attributed to immune evasion, intrinsic increased transmissibility or a combination of both. However, given current available data, it is likely that Omicron will outpace Delta where community transmission occurs.” – WHO (Enhancing Readiness for Omicron (B.1.1.529): Technical Brief and Priority Actions for Member States. 17 December 2021. Technical document)

Million-dollar Questions

• What do we know about Omicron till now and how is it going to impact the World, India and Kerala?
• How omicron is going to impact us depends on whether it will overwhelm the hospital capacity?

This in turn will depend on

1. How fast it spreads through the population (Rt-Effective Reproduction Number)
2. Severity: What percentage of the patients develop severe disease

Let’s consider one by one.

Effective reproductive number: depends on multiple factors

1. Transmissibility of the virus  
2. Susceptible population
3. Human behavior

Now it is settled

• It’s very clear that due to immune evasive properties of the omicron, population susceptible to omicron has remarkably increased. Order of susceptibility will be:
  • Unvaccinated >> Double dose vaccinated> Three dose vaccinated >> Hybrid (Infected + Vaccinated)
• What’s clear by now is that Omicron spreads thorough the susceptible population like wildfire, resulting in huge number of cases. Before we realize that omicron has started spreading, it has already resulted in a huge Tsunami.

Delmicron tsunami ahead?

• With omicron surge superimposing on ongoing steady delta wave most of European countries are having a “delmicron” tsunami of COVID.
• The effective reproductive number of Omicron in UK currently is above 5 while that of delta is below 1. This has resulted in a doubling of cases every 2-3 days.
• Not only UK, most European countries, which had created a reasonably strong predominantly vaccine-based immunity wall, are seeing huge surge in cases.  Human behavior in the form of crowding in indoor places and non-adherence to masking will accelerate this wave. 

Severity of Omicron

• Unlike in 2020, when the pandemic began, now a large chunk of population has acquired some form of immunity against the SARS COV 2 either by vaccination or by prior infection.
• It’s very likely that although omicron may evade the first line of defense (antibodies) the second line of defense (T cells) are likely to protect against development of severe disease.
• Early data suggests that because of the mutations, the ability of the omicron to multiply in the throat has increased manifold, its ability to multiply and destroy cells in lung has decreased to great extent. This may translate to less severe lung disease.

What is cool and assuring?

• In a nut shell, either because of the decreased virulence of the virus or because of the immunity acquired by the population, the proportion of positive people who will develop severe disease is going to be less.
• So, what we have understood is that on one side we have a more transmissible variant which is going to affect higher number of people. But the good thing is that the proportion of people becoming sick will be significantly less

So, does it means that we need not bother, let it spread?

• Answer is NO.
• Always remember that a small percentage of a big number is a big number. So, let’s assume that proportion of people developing severe disease with omicron is 50% less than delta.
• With delta, it was approximately 2%. With omicron let’s assume its 1%.
• With these assumptions if a country had 50,000 delta cases per day last winter, 2% of these (1000) will get severe disease per day and get admitted to hospital with a lag period of 10 days.
• As we know omicron is more transmissible, we may see 200,000 cases per day in the same population. Even if we assume that proportion of people becoming sick is half that of delta wave, 1% of 200,000 is 2000 or double that of the delta wave.
• So, if omicron is 4 times more transmissible with half virulence the impact on hospital admission is going to be higher.
• The most important question is how less severe is omicron wave vs delta wave? Is it half, 1/3rd or 1/20th. That’s a million-dollar question. The answer to this we will get in a couple of months. Lower the better.

How will Omicron affect India?

• India had a very large delta wave, with close to 3/4th of its population getting infected. Following which we had a successful vaccination program with 4/5th of eligible population getting first dose of vaccine.
• A single dose of vaccine following infection generates much higher immunity than even three doses of vaccines.
• This hybrid immunity will give India an edge against the omicron. But does it mean that we can forget Covid protocols. NO.
• If we don’t follow Covid appropriate behavior, we will be ultimately losing the advantage we have through hybrid immunity.
• So, let’s have all forms of defense ready against omicron. Hybrid immunity with universal Covid appropriate behavior will definitely help India make omicron wave lighter.

Kerala Story is different?

• Kerala has done reasonably well in terms of vaccination. But as only half of Kerala population got infected with Covid, the proportion of people having hybrid immunity is significantly less than other states of India.
• So, Kerala is at a higher risk of Omicron wave than rest of country. Hence, we need to mask better and avoid closed spaces.
• Till now, masking in Kerala is better than other parts of country. If we intensify the efforts to increase proper masking and double vaccinate at record pace, we will be definitely able to decrease the impact of omicron.

Will Paxlovid make huge difference?

• Oral antiviral Paxlovid appears to reduce chance of severe disease by 90%. We should ramp up production of this molecule – this will make a huge difference against Omicron.

CME INDIA Learning Points

• Paxlovid is a combination of Pfizer’s investigational antiviral PF-07321332 and a low dose of ritonavir, an antiretroviral medication traditionally used to treat HIV.
• The treatment disrupts the replication of SARS-CoV-2 in the body by binding to the 3CL-like protease, an enzyme crucial to the virus’ function and reproduction.
• According to an interim analysis, Paxlovid reduced the risk of Covid-19-associated hospitalisation or death by 89% in those who received treatment within three days of symptom onset.
• The drug was found to be very effective – just 1% of patients who received Paxlovid were hospitalised through day 28 compared to 6.7% of placebo participants (As per Phase II/III trial).
• Like molnupiravir, Paxlovid is administered orally, meaning Covid-19 patients can take the drug at home in the early stages of infection.

Important Updates

(doi: https://doi.org/10.1038/d41586-021-03614-z)

• Omicron’s rapid rise in South Africa is what worries as the variant could spark explosive increases in COVID-19 cases elsewhere.
• Based on the rise in COVID-19 cases and on sequencing data, Omicron can infect three to six times as many people as Delta, over the same time period. “That’s a huge advantage for the virus — but not for us,” – Wenseleers.
• Although genome sequencing is needed to confirm Omicron cases, some PCR tests can pick up a hallmark of the variant that distinguishes it from Delta.
• How well the variant spreads elsewhere might depend on factors such as vaccination and previous infection rates – Aris Katzourakis (Researcher on viral evolution at the University of Oxford, UK).
• If Omicron can dodge neutralizing antibodies, it does not mean that immune responses triggered by vaccination and prior infection will offer no protection against the variant. Immunity studies suggest that modest levels of neutralizing antibodies may protect people from severe forms of COVID-19 – Miles Davenport (Immunologist at the University of New South Wales in Sydney, Australia.)
• Third doses supercharge neutralizing-antibody levels, and it’s likely that this will provide a bulwark against Omicron’s ability to evade these antibodies – Bieniasz.
• “I think the severity question will be one of the last bits that we’ll be able to untangle – That’s how it happened with Delta” Çevik.
• More countries are detecting the Omicron variant. Importantly, the capacity to rapidly sequence viruses from positive COVID-19 tests is concentrated in wealthy countries, meaning that early data on Omicron’s spread will be skewed.

CME INDIA Comments

Dr. Shashank Joshi, DM, Endo., Mumbai (On Twitter):

• Lull Before the Storm? The striking discordance between lower death and severe illness in Omicron is indeed assuring. The Immune Escape, rapid transmission, explosive spread and dominance over Delta dent Indian Covid-19? math, Mask, Ventilation, Vaccine are the keys .
• “Delmicron” Twin spikes of Delta and Omicron in Europe and US have lead to a mini tsunami of cases and explosive number only warn India that we need to be very careful and cautious without panic. Behave RESPONSIBLY, Mask Completely, Vaccinate totally.

Dr. Pradeep Sahay, Physician, Giridih, Jharkhand:

• Till 19/12/21, 137.6 crore Covid vaccine doses have been administered. Our active caseload stands at 83,913. Active cases are less than 1% of total cases, currently 0.24%, the lowest since March, 2020. There were 7,081 cases with 264 deaths on 19/12/21 in spite of rise in Omicron cases.
• Of the total Omicron cases, 20.4% adults between 20 to 39 years (largest age group) are affected. Only 2.5% of Omicron cases occurred in the 60 to 89 years age group.
• Total COVID deaths on 19/12/21 were 264. Recovery rate stands at 98.38%. Although Omicron is spreading rapidly, the high rate of seropositivity is perhaps a factor for the mildness of the infection as compared to delta. Over 70% Indians have COVID antibodies. Masking, distancing and vaccination will keep Covid under control. So far, advanced countries including those with one tenth of our population have over 20,000 new cases per day as compared to our 8,000 or less fresh cases per day, but I believe Omicron will eventually spread, providing immunity against future infections. The true situation will be known by March ’22. Till then, I’m keeping my fingers crossed.

Dr. Prashant Gajbhare, Assistant professor medicine, GMC Nanded (Maharashtra):

• Omicron is spreading significantly faster than the Delta variant in countries with documented community transmission, with a doubling time between 1.5-3 days.

Dr. Manoj Rawal, MD, BPS GMCH, Kanpur:

• UK is full of Omicron wave – worse than us.
• Europe is in worse condition once again in spite of vaccination and infrastructure. Hope India doesn’t suffer from another wave. COVID IS NOT DONE YET.
• Hospitalizations have been touching 70-80% of worst wave so far in USA.
• 100-150K positive cases every day.

Dr. Anupama Ramkumar, Physician and Clinical Researcher, Ahmedabad:

• If 97% are delta and yet the infection surges – it’s time to reconsider the vaccine effectiveness rather than recommending boosters of what at best are experimental interventions.

Dr. Manoj Rawal:

• Vaccination is saving lives but ultimately human race will have to learn to live with in.
• We can’t pause the life each time there is new variant. It’s more a pressure strategy from vaccine companies for booster. What’s the surety that we will not require further boosters if some other variant comes in future?

Dr. Anupama Ramkumar:

• That’s exactly the point to ponder… countries that are most vaccinated are reeling and continents like Africa and SAARC countries after the initial onslaught are doing much better.
• Is there a writing on the wall we are being asked to ignore?
• All Pharma companies are now in a race to develop a treatment… For illnesses that have an effective vaccine – the drug development falls behind.
• That’s not happening here.

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