In late November 2021, scientists reported the emergence of a new variant of SARS-CoV-2, the virus that causes COVID-19. In a matter of weeks, the variant, dubbed Omicron, spread around the globe.
Today, the Omicron variant accounts for about 98 percent of all COVID-19 cases in the United States, and case counts and hospitalizations are spiking at all-time highs in many places. At the same time, recommendations are constantly shifting about how to prevent COVID-19, and when to isolate or quarantine. Across both social media and mainstream media outlets, conflicting opinions are being raised about what Omicron means for the future of the COVID-19 pandemic.
This week, three virologists at Gladstone Institutes—Warner Greene, MD, PhD, director of the Michael Hulton Center for HIV Cure Research; Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology; and Nadia Roan, PhD, associate investigator—discussed what people should know about Omicron, home testing, and more.
Roan: When this variant first emerged from South Africa, scientific studies revealed an alarming number of mutations, including those that could evade antibody immunity. Such evasion was consistent with observations of Omicron spreading rapidly in South Africa, which had built up immunity from their Beta variant surge. Omicron’s increased transmissibility is now clear and is causing high numbers of infections globally—not only in the unvaccinated but also in the vaccinated, although the variant leads to much less severe disease in the latter. On the bright side, Omicron does seem to be milder than Delta, meaning it does not result in as much severe disease or death. Whether that’s a result of the existing immunity in the human population, or the virus itself, is a little bit hard to untangle. It’s probably a mix of both.
Interestingly, Omicron replicates better in the cells of the upper respiratory tract but less well in the lungs, which can potentially help explain both why it is more transmissible and less severe. The localized infection in the upper respiratory tract cells such as those in the throat may potentially produce a lot of copies of the virus that can more easily aerosolize out of your body to infect someone else. Omicron’s diminished ability to replicate well in the lung can limit damage to this crucial organ and limit the chances the virus will spread to the rest of the body.
Greene: The average time between Omicron infection and symptoms is 2 to 3 days, compared to 3 to 5 days with prior SARS-CoV-2 variants. In general, Omicron doesn’t cause as much severe disease—in part because it tends to remain localized in the upper airway where infection is more limited and clears out more rapidly. This is particularly true in vaccinated individuals.
Because of this rapid clearance, the CDC changed their guidelines to allow individuals with no symptoms to return to work after Day 5. However, many scientists and clinicians pushed back on this recommendation arguing for rapid antigen testing on Day 5 to identify individuals who are continuing to shed virus and thus should not return to the workplace. The CDC has since modified their guidelines suggesting rapid antigen testing could be performed on Day 5 if available.
Roan: The reasons the CDC changed their isolation guidelines to 5 days are complex, and were driven by the need to keep our hospitals and society running during this surge. With so many health care workers testing positive, many hospitals are understaffed at the moment, and the idea was to allow them to return when they are likely no longer infectious.
But it’s a very difficult question as to what is the perfect number of days someone should isolate after testing positive, because how long a person is infectious or symptomatic varies so much between people. Generally speaking, one is less likely to be infectious after a full 10 days than 5 days, so I’d say if you want to play it safe, follow the prior 10-day guidelines.
Ott: PCR remains the gold-standard test for detecting whether someone is infected with COVID-19. But antigen tests are also a valuable tool right now; they give you a snapshot of whether a person is infectious at that moment.
One of the issues arising is that there is a time delay between when a PCR test can detect Omicron and when an antigen test can detect it. The good news is that we don’t think people are actually infectious and spreading Omicron in that interval before the antigen test shows up positive. That means a home rapid test can still do a great job telling you if you’re infectious, even if it’s not positive at the very earliest moment you’re infected.
Roan: The thought is that based on tests performed in the lab, the virus may be replicating particularly well in the throat and bronchus, so we may find more virus there. There are anecdotal reports on social media and other platforms about people testing positive when swabbing both the throat and nasal cavity, when they had tested negative by nasal swab alone.
However, the FDA is recommending sticking to nasal swabbing for at-home antigen tests. I test regularly and I don’t swab my throat (admittedly because I think it’s a bit gross). If for whatever reason I’m concerned about a false negative (e.g., I think I may have been exposed), I go for the more sensitive PCR test.
Greene: Where to swab has been an ongoing question, particularly given the discomfort induced by deep nasal swabbing. Several studies have shown throat swabs are highly effective. Many testing centers are now performing both nasal (less deep mid-turbinate sampling) and throat swabbing.
Roan: Getting an N95 or a KN95 mask right now is going to be your best strategy; I’d say if possible, replace those cloth masks with these masks, which are most effective at filtering particles. For people with children who can’t be vaccinated yet, minimize their exposure to unvaccinated people, and have visitors wear masks. We’re not going to need to mask forever, but we’re in the midst of this really, really bad surge with the Omicron variant. So right now, I would highly encourage people to just put on a mask—even outdoors—if you’re around a bunch of other people.
Ott: I want to emphasize that masking helps. We’re very lucky here at Gladstone that everyone has complied and remained masked during the course of the pandemic; even when we’ve had COVID-19 cases, we haven’t been able to document any community spread within the building. That means masking is successful in reducing transmission. I know everyone is sick of masks, but I think we should use them to their fullest potential, especially during this surge.
Greene: Vaccination is absolutely our best defense against COVID-19 and our clearest path out of this pandemic. The recent arrival of Omicron has set back the timetable for when the pandemic will wane. This variant is hyper-infectious (2 to 3 times more infectious than the highly infectious Delta variant), plus it has mutations that allow partial escape from neutralizing antibodies. These properties allow Omicron to reinfect previously infected people and to produce breakthrough infections in partially or fully vaccinated individuals. That said, booster shots can certainly help and have been shown to provide 70 percent protection from symptomatic infection. However, within 10 weeks of boosting, this protection drops to 45 percent.
I believe it’s time for us to stop using prevention of infection as our benchmark for vaccine effectiveness. Almost all of our current vaccines do not protect us from infection by the targeted pathogen—instead the vaccines have trained our immune response to intercept the pathogen after infection, but before it induces disease. Frankly, we have been spoiled by the remarkable ability of the RNA vaccines (like the ones from Pfizer-BioNTech and Moderna) to prevent infection, but we now understand these infection-preventing effects are short-lived and hard to maintain even with boosting when variants like Omicron are in wide circulation.
Greene: Going forward, I believe the general population will be safely protected after receiving a three-shot RNA vaccine. Further boosting in this population will not be necessary until evidence of reduced protection from COVID-19 hospitalization emerges. However, high-risk groups like the elderly, immunocompromised individuals, and people with underlying medical conditions merit special consideration. These groups have poorer clinical outcomes when infected, so boosting in this situation makes sense. Ideally, boosting will be performed with an RNA vaccine incorporating Spike from both the Delta and Omicron variants.
Ott: An Omicron Spike booster certainly helps boost our existing immunity and might help us move toward more broad protection against future variants, especially those that derive from omicron. A number of scientists are looking at a multivalent vaccine strategy, where viral proteins from different variants are included in order to provide as broad protection as possible.
Roan: While additional booster shots will likely be important for immunocompromised individuals who may not mount a full immune response after the first few shots, I don’t think it’ll be absolutely crucial for young, immunocompetent, healthy individuals. The original vaccines and the current recommended booster are still doing a very good job at protecting us against severe COVID-19 (their primary purpose), even in the face of Delta and Omicron. This is likely due in part to their ability to elicit long-lived memory cells, such as B and T cells.
That being said, additional boosting of the general population can help decrease chances of getting symptomatic COVID-19, and can make the course of infection milder (like the annual flu shot can do for flu), but I anticipate it will not be necessary to prevent a surge of severe COVID-19.
Roan: Even if you’re a healthy person who’s vaccinated and boosted, and therefore very unlikely to personally get severe COVID-19, you can still get long COVID. We don’t know a lot about these persistent symptoms and their underlying causes yet, but it’s clear that long COVID can occur even after mild infection.
And then you need to think about the vulnerable people out there, including the immunocompromised, and the kids who still can’t get vaccinated. Do you want to be responsible for infecting someone who might get very severe disease? I understand the pandemic fatigue and the need to get back to pre-pandemic life, but we are in the midst of the biggest surge yet in terms of cases, and everyone doing their little bit right now can help keep our hospitals from being overwhelmed, not to mention help decrease the chances of the next scary variant emerging. As a community, we need to work together, which will help end the pandemic sooner.
Ott: We anticipate this is going to be a short, but brutal surge. Everyone is watching the hospitals, not so much because patients are filling their ICUs, but because more health care workers are being removed from their workplace when they test positive themselves. The good news is that viral detection in our sewage system is going down, indicating that we might have peaked, and case numbers will hopefully follow soon.
Greene: Our ability to peer into a COVID-19 crystal ball and predict the future course of the pandemic has been disappointing at best. The virus is consistently winning the arms race against its human host by spinning off new variants that transmit better and partially elude immunity elicited by natural infection or vaccination. Will we see yet another variant creating a new surge? Unclear. But I do think the virus may have more cards to play. We should be arming ourselves by moving swiftly to get the world vaccinated. Then, if a new, highly transmissible variant emerges, virus-induced disease and death will be effectively quelled. And then, we can finally transition out of pandemic mode and start learning how to live with SARS-CoV-2 as simply another circulating endemic respiratory virus like influenza.
Roan: The projections are saying this surge is going to peak soon, at least for the San Francisco Bay Area, and recent sewage data suggests we may already be peaking. I think after this Omicron surge passes, we’ll have pretty good immunity at the population level and things will seem calmer and more normal.
The question is, how long will that last? Some encouraging observations are that memory cells including T cells, which are important fighters against viruses, can persist for long periods of time after COVID-19. Also, persisting T cells have been observed 17 years later in patients who were infected with SARS-CoV-1 in the early 2000s. If that holds true with SARS-CoV-2, it means that vaccination or infection with COVID-19 could convey quite long-term protection against severe infection, even if we still see transmission. That could potentially, at some point, turn COVID-19 into a kind of endemic common cold.
Roan: What endemic means is that the virus is with us and it’s never going away, but it’s at lower prevalence and not affecting us the way it currently is in these overwhelming surges. There’s no clear definition of the exact transition point between a pandemic and an endemic virus. I think eventually, COVID-19 will become endemic—but we’re not there yet. Each surge will hopefully be a little bit less overwhelming, milder, and affect fewer people, and eventually it won’t be causing so much disease and death.
I certainly hope that Omicron is the beginning of the end, and I think it’s possible that it is. But if this pandemic has taught us anything, it’s that viruses can do very unexpected things.
Improvements in the cell analysis technique known as flow cytometry are helping Gladstone researchers make discoveries in immunology, stem cell biology, cardiology, and neuroscienceGladstone Experts Flow Cytometry Core Neurological Disease Alexanian Lab Roan Lab