Hello! How are you?
Cases of Omicron have been spreading all across the world. We have been told to be concerned, but not to panic. I hope you have set the dial on your anxiety-meter to that specific setting.
Just like you, I’m done with this virus and its myriad variants.
But I have a little more gas in the tank to talk about it for now. I’ve had a bit more time to formulate my thoughts, since I wrote my last newsletter one week ago.
Omicron is an I-told-you-so moment
We don't know where and how Omicron arose yet, but it is possible to make an educated assumption on the most plausible route of emergence. Given what we know about how massively mutated variants arise and the paucity of resources in parts of the world to fight the virus, the emergence of Omicron was expected.
I also have written my thoughts on the emergence of Omicron for Hindustan Times here. This my thirtieth weekly column and a milestone for me. If are a subscriber, please do let me know what you think. If you’re not- what are you waiting for? Quality content costs, money and if you’re not paying for it, then you’re the product. ;-)
Ok, no more unsolicited gyan except on Omicron.
Where did Omicron come from?
It's possible that the virus spread in many people before getting picked up or infected animals and mutated before reinfecting people. In fact, a few evolutionary biologists think that there are animal reservoirs where the virus is mutating right now. But the theory that most infectious disease experts think is most plausible based on the limited evidence we have now is this—
There have been multiple, well-documented cases of variants emerging in immunosuppressed patients. These variants have a large number of mutations that have been seen in Alpha, Beta, Gamma, Delta and most recently in Omicron.
It is likely that Omicron arose in an immunosuppressed individual who suffered from a long bout with the virus.
Vaccination of immunocompromised individuals (with added doses as needed) should be have been prioritized. Unfortunately, western nations prioritized booster doses for healthy, low-risk individuals in their own countries over first doses for high-risk individuals in other countries.
I tweeted this back in March. So did many others.
Unless the world collectively gets its act together we should not be surprised if more variants of concern arise after Omicron.
What else do we know or can we predict about Omicron?
I wrote a long-story for Mint with most of my thoughts on Omicron. I encourage you to read it here. Here are a few observations—
WHO designated Omicron a variant of concern out of an abundance of caution on very little actual data on spread or reinfections. The biggest concern is the possible effect of the large number of mutations in the spike protein. But the actual effect of these mutations is still unknown.
Why are the mutations in Omicron concerning?
Omicron is highly mutated, which means that it has many changes to its genetic material compared to the original SARS-CoV-2 virus identified in Wuhan, China. It also has many more mutations than prevailing variants of concern. Some of them almost certainly have biological significance.
Some mutations in the spike have been shown to enhance the transmission and disease-causing ability of other variants like Alpha and Delta. Take for example, Q498R and N501Y. Research on individual mutations is being published every week in leading journals like Nature But, the wholesale effect that all of these mutations have on Omicron can only be predicted until we have further data. Like Maggi Hot & Sweet Tomato Chili Sauce, this variant really is different.
As Omicron is detected in many countries, those in South Africa and neighboring countries feel that they have been singled out for punitive action. Travel bans are contentious because a travel restriction instituted after community spread has been identified locally is like shutting the barn door after the horse has already bolted.
How well will vaccines work?
You may have seen the following headlines and have become confused.
Well, never fear. I’m here to clarify things for you.
The vaccines will likely work to prevent severe disease with a drop-off against transmission and infection-preventing capabilities. It depends on how you measure success and how you define immunity.
This particular tweet of mine brought out a lot of antivaxxers who I had to swat away with the block button. Heh.
The vaccines currently used were created to elicit an immune response against the virus identified in Wuhan. As viruses mutate, the features recognized by antibodies generated after infection or vaccination change.
But Omicron is NOT vaccine-proof (the same way that some bacteria become antibiotic resistant). A new vaccine should just as well for it, as the existing ones do against the Wuhan lineage.
Researchers are testing how well antibodies from blood samples of those who have been vaccinated with earlier vaccines are capable of neutralizing Omicron. it is certain that antibodies will show reduced neutralization ability against Omicron. How low is the crucial question. We don’t know yet. But we will know in the next few weeks.
If neutralizing antibody amounts decline a lot with Omicron, one option is to offer a booster of the earlier vaccine to “top-up” antibody levels above the threshold for protection. Vaccine makers are already testing this out. These studies err on the side of caution. They don't account for cell-mediated immunity which kicks in to prevent severe disease. If antibodies are the army of the immune system, you also have a navy and an air force. Vaccinated folks won't be completely susceptible to Omicron.
Vaccine-makers are working on the following—
booster doses
modified vaccines tweaked to variant genetic sequences
bivalent vaccines that work on multiple variants
super-vaccines that work on multiple coronaviruses that recognize highly-conserved parts of the spike protein
Pfizer can get out a modified RNA vaccine in 100 days if needed. The mRNA vaccines are easy to adapt since the delivery mechanism remains the same. Viral-vectored vaccines (such as Oxford/AstraZeneca/Covishield) are easy to design, but require a bit more work to modify at scale.
We've focused on the spike protein, but I'm incredibly interested in reinfection rates and clinical severity after natural infection and after Covaxin shots. The virus has over two dozen proteins. I wonder if immune responses to other epitopes can prevent severe disease.
What about drugs?
Drugs will likely fare no worse against Omicron as they do against other variants because drugs have a different mode of action that does not target the spike protein. (Other proteins are also changed a bit, so this will be tested of course).
Merck’s molnupiravir is an oral drug that thwarts the viral replication process. The drug is a dummy for a key piece that the virus needs to insert into genetic material as it makes copies inside cells. The target is the same as remdesivir (but is instead an oral drug). Molnupiravir just got recommended by the FDA advisory panel through a split vote. It hasn't lived up to its early promise in late-stage trials in either India or in the US. But whatever the actual efficacy, it is not expected to drop further because of Omicron.
Pfizer has a brilliant antiviral combo drug that targets a protein called the main protease (this chops up a viral master-protein). The main protease is an enzyme that coronaviruses need to infect cells, so it is a great drug target. This should work well against Omicron. Pfizer's combo uses an antiviral previously used for HIV, ritonavir, and ties it up with a new small molecule that originated in Pfizer’s own laboratories. If approved, this could serve as a line of defense against Omicron as well as other variants. Efficacy looks good.
Dexamethasone will continue to work in limited cases where needed.
Convalescent plasma will continue to not work in anyone. And monoclonal antibodies may need to be updated if the epitopes have changed.
What’s the clinical picture?
What about reports from South Africa that the disease with Omicron is milder?
As with many other aspects of Omicron, it is too soon to say anything.
Infections with SARS-CoV-2 range from asymptomatic to critical/death based on age, comorbidities, and immune status South Africa has around 25% (43% if you could adults who have received at least one dose), previous multiple waves, and a young population. And the detected numbers of Omicron are still low compared to previous variants.
It takes a few weeks for the most critical patients to be hospitalized and face the worst outcomes. It is still too soon to know about clinical severity.
What about reinfections?
South Africa's serosurveys indicated ~60% of the urban adult population has been exposed to SARS-CoV-2 during the first two waves of infection. In a podcast interview with the New England Journal of Medicine, Dr. Salim Abdool Karim, one of South Africa’s leading infectious diseases researchers mentioned that the number of people exposed to the virus might reach 70%.
If Omicron continues to spread rapidly in a population with prior exposure, it will provide indirect evidence for significant reinfections.
That’s it for now. Take care,
Anirban
Dear Sir, thank you for your guidance and valuable insight as always.
Thank you for sharing the information about Omicron. A question. Is it advisable to take antibody test before booster dose? When it will be available in India one doesn't know. Though privately they are easily available. I read somewhere that if you have taken covishield, take Covaxin as a booster dose and vice versa. Is that true?