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The Omicron Story: The Winter of Our Discontent, Part 3

Part 3: What’s Next for SARS-CoV-2?

Larry Corey, Professor of Medicine
February 25, 2022

This is the third of a three-part series.

As the Omicron surge wanes, what’s next for the SARS-CoV-2 virus?

I think it’s hubris to feel confident that we know all of the virus’s immune-evasion strategies or all of its ways to increase its infectivity. Predicting Omicron’s future moves is speculative. We have to recognize that the virus has learned to select itself against many of the immune responses we currently possess. The one host immune response that we can test is evasion of antibodies, but not the other factors that slow virus replication. Escape from host non-antibody immune responses is less predictable.

One strategy that must be pursued is to improve our vaccines so they prevent people from acquiring infection in the first place. That means no sickness, no breakthroughs, no hospitalizations, no complications, no anything. The monoclonal antibody work suggests that at really high neutralization titers, we appear to prevent people from acquiring the virus. We have some early evidence that when the vaccine matched the ancestral strain it decreased acquisition nearly 40% of the time. My own bias is that if we could make vaccines that achieve the level of neutralization we see in the monoclonals, which is currently 10 times higher than we presently achieve, we might be able to prevent acquisition and truly reduce the widespread dissemination of disease we see now.

‘We must do more than write about our observations. We need to take action.’

There are a lot of people who will say I’m naïve. But I’ve always been an optimist. Conceptually, it helps in research to ask if our current technologies can push our antibody titers to the circulating strain up a log. That’s tenfold, so let’s say from 800 to 8,000. I can’t guarantee it, but I can feel pretty comfortable that if I can maintain a level of 8,000 for a long period of time, I would take that over 800. And it would be harder for a viral escape to occur, since as we’ve seen, the escapees generally originate in the immunocompromised population, which has low antibody and cellular responses. So, I do think it would help. It may require augmenting current vaccines with a mucosal vaccine delivered by drops or spray – technologies that currently exist. They just need to be developed and administered.

We must do more than simply write about our observations. We need to take action – especially as it relates to the large parts of the world that have no access to vaccines.

I wrote about immunosuppressed people being a source of new variants and that we need better medical monitoring to flag those variants as they emerge, which could occur anywhere in the world. There are no greater amounts of immunosuppressed people than those with HIV. And in sub-Saharan Africa, that’s up to 20% of the population. This is twice the number of immunosuppressed people in Europe or the United States. Is it surprising then that the Beta and Omicron variants emerged from sub-Saharan Africa where just 20% of the adult population is fully vaccinated? The consequences of lack of vaccine access and of intensive vaccine implementation in low- and middle-income countries result in the high likelihood of many people developing variants.

We haven’t proven that vaccinating people will help reduce the emergence of Variants of Concern, but it’s a logical assertion. It certainly could not hurt and probably would help. And if that is not true, then we should at least try and prove it one way or the other. Health services have gone down in low- and middle-income countries due to the COVID-19 pandemic. Most would argue that there is an 80% likelihood vaccination would decrease the percent of people with persistent COVID-19 and, hence, the milieu for generating multi-mutational Variants of Concern.

And, there is not yet proof that developing vaccine strategies for HIV-infected people would alter the emergence of variants. But, again, it’s a logical assumption and I wish I had raised our collective awareness about the issue sooner. True, suggesting an idea in summer 2021 would not have changed what happened in November 2021. But there is momentum for everything that leads to a call to action. It is this reflection that leads to my personal “winter of discontent.”

Larry Corey, Professor of Medicine

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.