Is Omicron Milder?

Posted by on December 22, 2021 6:30 am
Categories: Everything Else

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When Omicron appeared, scientists had three big questions.

First, would Omicron be more transmissible than previous variants? Judging from the nearly vertical charts of case growth in South Africa, Europe, New York City, and just about every other place Omicron has made an unwelcome appearance, the answer is yes. This may be the most transmissible strain of the coronavirus that we’ve ever seen.

Second, would Omicron evade some immune defense from our vaccines and prior infections? Here the evidence is also overwhelming: Yes. The skyrocketing daily cases in largely vaccinated regions are persuasive enough. For even more glaring examples, look at the hundreds of breakthrough cases in the NFL, NHL, and NBA, leagues with vaccination rates greater than 90 percent. Despite having mandated vaccines, Cornell had to shut down its campus after nearly 1,000 students tested positive.

Third, would Omicron cause more severe disease? This has been the most difficult to answer, in part because it has two components: an easy question and a hard question.

[Ashish K. Jha: Don’t panic about Omicron. But don’t be indifferent, either.]

The easy question is whether a typical vaccinated (or recently infected) adult faces the same individual risk of severe disease from Omicron that she faced from the original coronavirus in March 2020. The answer is, almost certainly, no. The U.S. has banked a lot of immunity through infection and vaccinations, and the Omicron variant doesn’t seem to evade all of that built-up protection. In the past month, we’ve learned that Omicron excels at breaking through the first layer of immunity, which is our neutralizing antibodies. But our next layer of protection, our T-cell response, seems to hold up much better against the variant. If you think of the vaccines as a castle-defense system, Omicron is like an invading army that can scale walls (i.e., bypass neutralizing-antibody protection) but not fight the knights within them (i.e., overcome T-cell protection). Boosted Americans are particularly well equipped against the Omicron variant, because the third shot increases the number and quality of our neutralizing antibodies, which effectively builds up our immunity wall.

Now for the harder question: How severe is the Omicron variant for people without immunity? Altogether, evidence from countries with big Omicron outbreaks and from studies points tentatively toward an optimistic answer. But even the optimistic answer for individuals could be bad news for the health-care system.


South Africa—pretty optimistic, but possibly misleading: The nation’s hospitalization rate has plunged in this wave, and for now cases seem to have already peaked. Within hospitals, doctors are reporting a decrease in the percent of people who need supplemental oxygen, which would predict a lower overall death rate. South Africans of all age groups have been less likely to die from Omicron; most cohorts have seen a 50 to 70 percent reduction in fatality rates compared with previous coronavirus strains, by one analysis. And the nation’s warp-speed wave might suggest the presence of many asymptomatic cases. This is all promising, compared with the most pessimistic scenario. But South Africa is a younger country than the U.S., with widespread exposure to previous waves of disease, so we should not expect every country to have the exact same experience.

The United Kingdom—less optimistic, but also very early: Hospitalizations are rising quickly in London and more moderately throughout England. But researchers can’t yet disentangle how much of the hospitalization increase is the result of a Delta resurgence and how much is due to the rise of Omicron. A widely shared headline from the Financial Times, which was summarizing a study from Imperial College London, claimed to find “no evidence” that Omicron is less severe than Delta. But the study’s authors were more careful than most journalists to point out that this finding was based on “very limited” hospitalization data. The U.K. is a better proxy than South Africa for America’s expected experience with Omicron, but for now it’s a worse source of high-quality data. This is a wait-and-see case.

Denmark—somewhat optimistic, but also very early: The Omicron case graph is basically vertical in Denmark, but the country’s Omicron hospitalization rate appears to be about 60 percent lower than for Delta, according to some measures, and the government reports that fewer than five patients diagnosed with Omicron are in the intensive-care unit. The daily deaths average remains unchanged, moreover. But it may well be too early to use deaths or even hospitalizations as an indicator, given the lag between case growth and fatalities.


South Africa—lots of evidence of milder disease, all with caveats: A real-world analysis by Discovery, South Africa’s largest health insurer, estimated that adults infected with Omicron were about 30 percent less likely to be hospitalized than were adults who’d been infected in other waves. (On Thursday, an early assessment published before peer review estimated that, compared with Delta infections, Omicron patients were 70 percent less likely to develop severe illness.) Most of South Africa’s Omicron hospitalizations—including more than 80 percent of its ICU admissions—have been unvaccinated people. The Discovery paper also found that two doses of the Pfizer vaccine, while only 30 percent effective at reducing transmission, was about 70 percent effective at reducing hospitalization.

Hong Kong—a possible mechanism for milder disease: One analysis from Hong Kong researchers studying viral samples in a dish concluded that, 24 hours after infection, Omicron multiplied 70 times faster than the Delta variant and the original virus in the bronchus, the airways that connect your windpipe to your lungs. But the study also found that Omicron is significantly less effective than previous strains at multiplying in the lower-lung tissue. This might suggest a different disease profile for Omicron. Upper-respiratory-tract infections typically cause colds and sore throats, while lower-respiratory infections are more likely to cause pneumonia. The finding might also suggest a mechanism for greater contagiousness: Virus particles in the upper lung region are less likely to cause severe disease but more likely to be expelled when people talk or sing or just breathe.

Cambridge—another possible mechanism for milder disease: Ravi Gupta, a professor of clinical microbiology at the University of Cambridge, co-authored a new report finding that the Omicron variant bypasses our neutralizing antibodies at the cost of less replication in our lungs—kind of like the invading medieval army that specializes in scaling castle walls but not in fighting the knights within them. Just like the Hong Kong study, the Cambridge study’s description of Omicron would be consistent with a virus that is more contagious but less likely to cause severe respiratory illness, such as pneumonia. (The study also independently concluded that a third dose of mRNA “rescues” neutralizing antibody levels in the short term, making infection and severe illness less likely.)

Before any evidence materialized, my assumption was that Omicron would be roughly as severe as Delta. At this point, based on the national data and lab studies, my best assessment is that it’s slightly less severe for an unvaccinated healthy adult without a prior infection—and significantly less severe for individuals with T-cell protection from previous infections or vaccination.

[Read: We know enough about Omicron to know that we’re in trouble ]

The arithmetic of pandemics is more complicated than the sum of individual experiences. Viruses are multiplication problems. A virus that’s 60 percent milder yet 300 percent more infectious is going to create more severe cases, overall. With an ongoing Delta wave that is already killing more than 10,000 people a week in the United States, any coincident variant—even one that is much milder—could risk overloading a health-care system that is already worn down.

What does all this mean for you? The tough thing about answering this question is that I don’t know who “you” are, what your T-cell protection is, or how you’re going to spend the holidays. The best way to think about total severity in the U.S. is to imagine four concentric circles, where the risk of illness increases as you fan outward.

In the center ring are boosted non-seniors. This group seems quite safe from severe illness and well protected against infection. One ring out are doubly vaccinated Americans under 65 without immune-system complications. This group is more at risk for breakthrough Omicron cases—and could spread Omicron cases to more vulnerable people—but seems fairly protected against severe illness thanks to T-cell immunity. (As for these groups’ long-COVID risk from Omicron, I don’t think we have any good information yet. But previous strains have been associated with months of labored breathing and impaired lung function.)

In the third ring are people who are vaccinated, or even boosted, but still at-risk. This group, which includes seniors and immune-compromised individuals, deserves special care. People in the center-most circles should be cautious about mixing households with seniors, because in the case of a breakthrough, we can’t be sure that older people’s T-cell protection will protect them against severe illness. Remember that, among boosted seniors, age still matters: According to the CDC, people older than 85 have a COVID fatality risk that is roughly five times higher than the typical 65-year-old.

Finally, the fourth circle represents the broader unvaccinated population, both in the U.S. and throughout the world. Omicron seems so contagious that, even with an overall milder course of disease, we should expect a surge of hospitalizations among the unvaccinated.

Fitting all the rings together, you can see why the question of severity is so hard. Individuals in rings one and two might not face much personal risk of severe infection from Omicron. But if they’re infectious while celebrating with people in rings three and four, they could spread the disease to significantly more vulnerable groups who could get really sick.

Please take precautions when mixing households this holiday season. Try to get your hands on rapid tests to ensure that you’re not contagious when spending time with older relatives. Omicron may be less severe than we feared. But we can be optimistic and careful at the same time.

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