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On December 1, JAMA convened a panel of experts to discuss what’s known—and unknown—about Omicron, the newest SARS-CoV-2 variant of concern. JAMA Associate Editor Preeti Malani, MD, MSJ, a professor of medicine in the Division of Infectious Diseases at the University of Michigan Medical School and the university’s chief health officer, hosted the panel. Joining her were Adam Lauring, MD, PhD, an associate professor of medicine in the university’s Division of Infectious Diseases, and Carlos del Rio, MD, a distinguished professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine, a professor of epidemiology and global health at the Rollins School of Public Health, and a member of JAMA’s editorial board. The following is an edited version of their conversation.
Dr Malani:Omicron was designated as a variant of concern within just a few days of being identified. There’s been a lot of talk about this variant, in particular the large number of mutations.
Dr Lauring:I think the big thing that struck everyone was the sheer number of mutations in the spike protein. There are so many in Omicron’s spike, I think 35 or so. Mutations affect how well the virus spreads. Spike is also important as a target for our monoclonal antibodies and for the vaccines. So I think that raised alarm bells appropriately and is why we’re all paying attention to it.
Dr Malani:This was [first] sequenced in South Africa and it’s yet unknown where and how it emerged. One of the things being discussed is whether this variant emerged in someone whose immune system is otherwise not normal. Can you comment on that?
Dr del Rio:One of the theories is that a person with HIV and severe immune suppression who was infected for a prolonged period of time, maybe over 300 days, is where the evolution happened. As you’re unable to clear the virus, the virus is multiplying and continuously mutating in that environment. That could have led to this variant. But we have a lot of immunosuppressed patients throughout the world. We have patients who are transplant recipients. We have people that we immunosuppress with some of the drugs we use. So this emphasizes the importance of not only vaccinating immunosuppressed individuals, but also continuing NPIs [nonpharmaceutical interventions] for them.
Dr Lauring:To me, with so many mutations in spike, it’s clear that there’s been a lot of evolution and adaptation happening in that protein. I think there are 2 leading hypotheses. There’s this immunocompromised host idea, because with prolonged infection you can get enough time for that selection to happen and mutations to accumulate. The other one, which has received less attention, is the possibility of what’s called a reverse zoonosis. In that idea, SARS-CoV-2 has gone into other animals over time. It will evolve differently in an animal host than it will in a person. And it could then potentially enter back into the human population as a very different virus.Right now we don’t know which of those is more likely, but we do know that there’s been a lot of evolution happening in Omicron. I’ve always pushed back gently on immunocompromised host origin theories for these variants, not scientifically always, but because I do worry about stigmatizing these patients. I think we have to be very careful in talking about variants in these hosts and what to do about it, because it’s a really complicated issue.
Dr del Rio:But I think what we clearly understand for this variant is that it’s not like it was one strain that through subsequent transmissions to other individuals accumulated mutations. It’s pretty clear that all these mutations occurred in the same individual or in the same host.
Dr Lauring:Yes. Or at least the vast majority of them. It’s been evolving in some sort of environment for some time.
Dr del Rio:When you look at the phylogenetic trees, it’s really out there. This is really a very separate branch from many of the other variants we’ve seen in the past.
Dr Malani:What’s going to happen in the public health arena in the coming days, weeks, and months?
Dr del Rio:From a public health standpoint, I think the coronavirus task force and the CDC [Centers for Disease Control and Prevention] are focusing on several things. Number 1: the CDC has now authorized boosters for anybody over the age of 18. Only about 20% of Americans who’ve been vaccinated have been boosted. So we’ve got to get more of our patients, our families, our friends, ourselves boosted if we haven’t. Number 2: CDC needs to scale up testing and genomic sequencing. Normally about 5% to 7% of isolates get sequenced nationwide, and we need to scale that up quite a bit.We need to also establish good ways to look at [international] travelers. The US is requiring a SARS-CoV-2 negative test 72 hours before you board [a plane]. From the countries that have Omicron, they may move that to maybe 24 hours before departure. They’re talking about doing a test after you arrive in this country—maybe 2 to 3 days after—and following people that arrive from those countries carefully.
Dr Malani:What are some of the things happening right now in [clinical] labs?
Dr Lauring:At our health system, there’s a lot of discussion on how to shift testing programs to certain platforms that might provide an early alert for Omicron. Certain PCR [polymerase chain reaction] tests have a signature that can be used for screening of the Omicron variant.
Dr del Rio:The other thing that I like to remind people is that from all the indications we have, the rapid tests still pick up this variant very well. Most of the mutations are in spike and spike is not the antigen in the rapid test. But rapid tests are still very expensive and not available for the great majority of the population. The government needs to subsidize rapid testing so people can test themselves very actively.
Dr Malani:I agree with you on that. Now, let’s shift to therapeutics. How does Omicron affect the monoclonal antibody strategy?
Dr Lauring:We do have some clues based on the mutations. There are many within the targeted epitopes of these monoclonals, and it appears that some of them are going to probably have a loss of significant activity based on those mutations. It’s hard to know because you don’t know how these mutations interact together. They may not be the sum of their parts. So we’ll have to wait for the data.
Dr del Rio:At the end of the day, my worry about monoclonals is that we’re struggling to get them here. They’re totally unavailable in the great majority of the world. And it’s not a therapy that we can scale up in any significant way. In most of the world, talking about monoclonals is like talking about going to the moon. We need to find other therapies. What we really need is oral antivirals that we can scale up globally to treat people with SARS-CoV-2 infection.
Dr Malani:Let’s talk about vaccine effectiveness against Omicron.
Dr Lauring:As you know, it takes a while to do these studies well, and it takes a careful look at the data and controlling for all sorts of bias and confounders in an observational study. I’m sure we’re going to hear a lot early on about how many people were vaccinated who got Omicron and such, but it’s going to take a while to figure out. We’re still learning about Delta and vaccine effectiveness.That said, I suspect that circulating antibodies probably won’t neutralize Omicron as well as the original SARS-CoV-2. That’s pure prediction and speculation. And I wouldn’t be surprised if there might be some erosion in vaccine effectiveness against infection. I’m much more optimistic that vaccine effectiveness will be maintained against more severe disease.
Dr Malani:Let’s talk about one of the harder questions [about vaccines]. We’re experiencing a very large surge right now in Michigan. I’ve seen a lot of patients with severe COVID, almost all of whom were unvaccinated, and some were very, very vulnerable—organ transplants, very advanced age, severe lung disease. Earlier in the year, I would really push and have more conversations. I have to say I’ve gotten a bit discouraged. What can clinicians really do? My own efforts have moved toward trying to get people boosted who are already vaccinated, but we need to get first doses in people.
Dr del Rio:You’re absolutely right. Starting a vaccination series has really flattened in our country. We’re seeing an uptake on the boosting, but we have a population that has not been vaccinated. I think the first thing is we need to realize that it’s not one population, right? You have people that are anti-vaxxers and are not going to get a vaccine no matter what. But then you have a large number of individuals that I think are still in the hesitant stage, in the “wait and see.” A lot of them have been saying things like, “I’ll take them once they’ve been approved.” I remind people that the Pfizer vaccine, for people over the age of 18, now has full FDA [US Food and Drug Administration] approval.I think there are a lot of people out there not getting vaccinated not because of a lack of information, but because of excessive misinformation. And, therefore, combating misinformation, I think, is critically important. This myth going around that the vaccines impact your fertility, for example, is a big one that I hear from young individuals that don’t want to get vaccinated. Today, somebody sent me a clip of something that they saw on Facebook saying that the vaccine changes your DNA. We have to really tackle misinformation because it’s driving a lot of people to not get vaccinated.And then we have to use opportunities like Omicron. I’m hoping that Omicron, in the midst of all this conversation, is yet another opportunity to tell people, “Okay, you’ve been waiting for vaccine, now is the time to take it.” When people have said, “What can I do about Omicron?” I said, “Get vaccinated. And if you’ve been vaccinated, get boosted.”
Dr Malani:The misinformation, it’s really challenging to get at it.
Dr del Rio:We have to also hold our politicians accountable. Many politicians have actively spread misinformation and have fueled it. And if they haven’t fueled it, they haven’t counteracted it. This is not a Republican or a Democratic issue. We all need to come together. This is really an issue of health and national security.
Dr Malani:Looking ahead to 2022, what are you looking forward to and what gives you hope?
Dr del Rio:I’m hoping that we will come out of this pandemic with lessons. Probably the most important lesson out of the pandemic is that we need to address health disparities. This pandemic has highlighted what we have all known from HIV and from many other diseases—the enormous health disparities that exist in this country and globally. I’m hopeful that we will begin to really take inequality seriously. That we stop talking about it and really do something.
Dr Malani:Adam, what gives you hope for the new year?
Dr Lauring:I think we are going to get better at controlling COVID. I know that with Omicron it feels that everything has started over again. But we are so much farther than we were at the beginning of the pandemic. We’ve got highly effective vaccines. We’ve got drugs coming out. Even though there’s a lot of big problems to solve, we really have made tremendous improvements. It feels a long way away, but I think we’re going to get to that magic endemic point that everyone talks about. It may be late 2022, but we’re going to get there. We’re moving in that direction.
Dr Malani:We’re recording this on December 1. As we’re recording, we just got an alert that the CDC has [confirmed] the first case of Omicron in the United States. Any early reactions?
Dr del Rio:Well, I’m not surprised. If you look, you’re going to find it. We’re all interconnected.
Conflict of Interest Disclosures: Dr del Rio reported receiving grants from the National Institute of Allergy and Infectious Diseases (NIAID) Emory Vaccine and Treatment Evaluation Unit. Dr Lauring reported receiving personal fees from Sanofi as a consultant on oseltamivir and influenza and personal fees from Roche as a member of a steering committee for a clinical trial of baloxavir and influenza. Dr Malani reported serving on the NIAID COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated.
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This was a very useful article summarizing what is known and not known about the new Omicron variant. In discussing the risk factors and remedies the speakers could have highlighted that obesity is a primary factor in why the risks of COVID-19 are greater in the US than in many other countries, and in particular in Michigan (1). Why not add weight loss to the strategies recommended for combating COVID-19?
1. The Michigan Department of Health and Human Services (MDHHS)
Abbasi J. Omicron Has Reached the US—Here’s What Infectious Disease Experts Know About the Variant. JAMA. 2021;326(24):2460–2462. doi:10.1001/jama.2021.22619
Coronavirus Resource Center