CME INDIA Presentation by Dr. Rajeev Jayadevan, MD, DNB, MRCP, ABIM (Med) ABIM (Gastro), NY. Vice Chairman, Kerala state IMA Research Cell. Member, National IMA Task Force on Corona Epidemic, Cochin.
A Cyclical Disease.

- It is easy to see now COVID-19 is not the only cyclical viral disease.
- By the way, there is a difference between seasonal and cyclical.
- The common cold and influenza are SEASONAL. They arrive at the same time every year.
- But SARS-CoV-2 virus is a CYCLICAL disease, not necessarily tied to season or specific month.
- That being said, in countries that have distinct seasons, there is a tendency for COVID-19 waves to arrive in winter, followed by a rise in spring.
- In South Africa, waves have been separated by EXACTLY 6 months so far. (Therefore, next wave is due in May, if the trend continues)
- Other countries have other patterns.
- The pandemic graph of India (a really large geographic region, hence can’t really be boxed into one pattern) shows ABSOLUTELY no seasonal pattern, it is ALL CYCLICAL.
Why is it cyclical?
- The birth of a successful variant in any part of the world can drive waves in other parts.
- A new variant can take off from any branch of the genomic tree. In other words, new variants are not like iPhone upgrades, one doesn’t lead to the other. E.g. Omicron is not the daughter of Delta.
- Typically, it happens when the virus lives for several months in an immune compromised person, where it accumulates numerous mutations at once, after carefully studying that person’s antibodies. (A short stay in a healthy person does not allow enough time for the virus to study everything)

Let’s now look at some other factors that drive the pandemic
- Towards the southern end of India is the state of Kerala, which shows a different wave pattern from northern parts of India.
- But Kerala’s pandemic curve is very similar to Sri Lanka’s. Why?
- Kerala is physically close to Sri Lanka, (only 226 miles away), and practically has the same tropical humid warm weather, rainfall and identical geographic conditions.
- The wave timing is remarkably similar, with each wave in Sri Lanka (South by Latitude) coming a few days after Kerala. See the graph I have annotated.

(For some reason, if we look at the graph, Omicron spike in Sri Lanka was lower though. Maybe Sri Lanka did not test much in 2022)
Note: The pandemic control measures in these two regions are obviously completely different.
- These observations suggest that the regional spread pattern also depends on weather trends in each area. For instance, Tamil Nadu weather is quite different from that of Kerala.

Weather influence on pandemic spread makes biological sense.
Why?
- Survival of aerosol (droplets <5 microns in diameter, which helps them remain suspended in air endlessly) depends on humidity, temp, wind speed and evaporation rate. The virus travels from person to person in these droplets. Think of it like seeds or soap bubbles being dispersed in the wind.
- Longer droplet survival and the farther the distance travelled by these droplets, the more efficient the spread of virus.

Learning points
- The pandemic is a cyclical disease. The next wave can occur as soon as the next successful variant is born, and spreads just enough to break out.
- Further spread in each region depends on crowd behaviour, immunity levels, use of masks, weather conditions.
What about immunity?
- Mucosal immunity against respiratory viruses was never permanent. These viruses are built to reinfect. They have multiple entry visas.
- In contrast, Polio and Measles have (mostly) single entry visas.
- Vaccinated people have:
- Lower overall death rates in each adult age category.
- Lower overall infection rates, compared to the unvaccinated.
Birth of variants
- “Births” of new variants are random events. Can’t predict in what country, and whether the accumulated mutations make it faster than the existing variant, and what other biological properties it comes loaded with. All this occurs by natural selection. We don’t (can’t) control it beyond reducing total number of infected people.
How fast can it travel?
- For man to travel the world, it takes less than a day now.
- We know that Omicron took only 43 days from its discovery in South Africa, to cover 99% of UK.
- The next variant will invariably be a faster one, as we saw in history.
- What else it is capable of doing inside the human body, what tissues it is able to infect, we will only know then. Maybe it will be innocuous. Maybe not.
- It was never a smart thing to term this pandemic as over – and declaring that further waves won’t come. We saw people predict pandemic was over repeatedly since 2020, each time with huge fanfare. Science is not the same as wishful thinking.
- Staying prepared (and humble) will reduce damage, and also eliminate the need for lockdowns.
CME INDIA Tail Piece
(By Dr. Rajeev Jayadeven)

- Recombination does not necessarily generate a new variant.
- Recombination is a method that viruses use to generate diversity (see my earlier tweets, linked below) – one way of rolling the dice, if you will.
- Imagine Delta and BA.1 trapped within the same cell.
- Parts of RNA get interchanged: XD is born (France), or XF (UK). That’s a virus with mixed properties of both variants.
- But there is no need to worry, because mutations do not work like 1+1 = 2.
- In fact, sometimes it can be 1+1 = 1 or even 1+1 = 0 (it is called epistasis when some mutations cancel each other out).
- Recombination has been recorded not just between Delta and Omicron, but also between two sublineages of Omicron (BA.1 and BA.2, officially called XE now)
- Japan NIID had reported recombination between Alpha and Deta too.
What do these findings imply?
- We don’t have any data yet whether these isolates have any extra capability (or less).
- Chances are they have been occurring all the time during this pandemic, as in the case of other viruses, as part of virus adaptation to host/evolution.
What exactly is recombination?
- Recombination is a process by which two different viruses can exchange large segments of genetic material by being present in the same organism at the same time.
- A successful recombination event will lead to a “gain in the function” of the virus, e.g. a change which leads to faster spread or immune evasion.
- Recombination is different from mutation, which involves one change at a time.
- If the genetic code of a virus was a novel, a mutation is a single spelling mistake.
- Whereas recombination is shuffling of its chapters – with another novel of similar genre
Reference:
- https://smw.ch/article/doi/smw.2020.20224
- Gorbalenya AE. bioRxiv, 2020;2020.02.07.937862.
- WHO Emergency Committee. Statement on the second meeting of the international health regulations (2005) emergency committee regarding the outbreak of novel coronavirus (2019-ncov). 2020. Available at: https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov).

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