Health
Science
Vaccines
Pandemic
Antiviral Drugs
Disease Severity
Omicron variant
Reinfections
Boosters
Spread
Just published. My long story on Omicron for @livemint with 1. everything we know 2. everything we can predict 3. and everything we can expect to know soon regarding:
reinfections, vaccines and boosters, spread, antiviral drugs, and disease severity.
livemint.com
reinfections, vaccines and boosters, spread, antiviral drugs, and disease severity.
livemint.com
Key points:
1. 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 is unknown.
1. 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 is unknown.
2. 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, P681X, N501Y. But, the wholesale effect can only be predicted now.
("Nature" papers published recently below)
("Nature" papers published recently below)
3. 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.
4. 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 definitely have biological significance.
5. 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.
6. 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.
7. If neutralizing antibody amounts decline a lot with Omicron, one option is to offer a booster of the earlier vaccine at the same dose or even at 2X dose to βtop-upβ antibody levels above the threshold for protection.
Vaccine makers are already testing this out.
Vaccine makers are already testing this out.
8. 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
9. Vaccine-makers are working on
a) booster doses,
b) modified vaccines tweaked to variant genetic sequences,
c) bivalent vaccines that work on multiple variants,
d) super-vaccines that work on multiple coronaviruses that recognize highly-conserved parts of the spike protein.
a) booster doses,
b) modified vaccines tweaked to variant genetic sequences,
c) bivalent vaccines that work on multiple variants,
d) super-vaccines that work on multiple coronaviruses that recognize highly-conserved parts of the spike protein.
10. Pfizer can get out a modified RNA vax 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.
11. 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.
12. 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).
13. Merckβs 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).
14. 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.
15. 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.
16. Pfizer's combo uses an antiviral previously used for HIV, ritonavir, and ties it up with a new small molecule that originated in Pfizerβs own laboratories. If approved, this could serve as a line of defense against Omicron as well as other variants. Efficacy looks good.
17. Dexamethasone will continue to work in limited cases where needed. Convalescent plasma will continue to not work in anyone. And monoclonal antibodies will probably need to be updated because the epitopes have changed.
18. What about reports from South Africa that the disease with Omicron is milder? Too soon to say anything. Infections with SARS-CoV-2 range from asymptomatic to critical/death based on age, comorbidities, and immune status (prev infected/vaccinated). Impossible to parse out yet.
19. South Africa has 25% vaxxed, previous multiple waves, and a young population. And the detected numbers of Omicron are still low compared to previous variants. Possibly milder but caution against making too much of this refrain until more is known. (/END)
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