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Physicians around the world have suggested the Omicron variant may cause milder illness than other forms of the coronavirus. But actually understanding Omicron’s severity is an open question, experts caution — one that requires more patient data and more time to answer.

The South African physician Angelique Coetzee told the BBC this weekend, for example, that the cases she and colleagues were seeing weren’t serious. “We haven’t admitted anyone,” she said. In Israel, one doctor told Haaretz that, “if it continues this way, this might be a relatively mild illness compared to the Delta variant.”

But sussing out a change in severity in a pathogen — particularly if it’s a small change — can be difficult, in part because so many other factors influence outcomes. There’s the changing virus, but there’s also the age range of the people in a certain place, their rates of underlying conditions that make them more vulnerable to Covid-19, vaccination coverage, access to treatments, and what local health systems look like. Different hospitals have different practices for how sick a patient has to be to be admitted, for example, and when hospitals are overwhelmed with Covid patients, their outcomes can be worse.

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There is a normal range in symptoms among people infected by the coronavirus, from none to severe, so it takes a large set of people to get the full picture.

“I don’t think right now there’s any reason to expect that this virus is less or more severe than any other circulating variants,” said vaccinologist Florian Krammer of Mount Sinai’s Icahn School of Medicine. “The base assumption that we should have is that it behaves like other SARS-CoV-2 variants and we need to figure out, over time, if it’s more severe, if it’s less severe. But to assume right now that it might be attenuated in some kind of way I think would be problematic.”

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Notably, many of the Omicron cases reported in South Africa have been in younger people, so it’s not clear how the virus will behave if it infects people with health conditions or older adults. Many of the other cases have been identified in travelers, and as Natalie Dean, a biostatistician at Emory University, noted, that means those people were feeling well enough to get on a plane.

“Since there haven’t been that many cases, and they’re only now being identified, that’s going to be one thing that limits our ability to make general statements,” Dean said.

So far, the rising hospitalization count in South Africa — particularly in Gauteng province, which has had the largest Omicron outbreak — matches the proportion of people hospitalized in past waves, the Wall Street Journal reported. Joe Phaahla, South Africa’s health minister, has also said that the majority of hospital admissions continue to be among people who were not vaccinated, a hopeful sign that the shots are maintaining their protection.

Why, and how, do viruses mutate? Alex Hogan/STAT

There is another possible reason Omicron infections might be milder in more people: The hosts the virus is infecting — meaning people — are better equipped to fend it off and minimize its damage.

South Africa has had several massive Covid-19 waves, so, combined with vaccination, there’s lots of existing immunity in the population. If many of the people doctors are seeing now were previously infected, that remaining immunity could protect them from developing serious disease even if it couldn’t block the infection. In fact, if that winds up partially explaining why some of these infections appear milder, that would be a good sign that immune protection can stand up to this variant to at least some extent. It wouldn’t answer, however, how severe the virus is in people who remain unprotected either because they haven’t been infected previously or immunized.

The question of disease severity is one of several pressing unknowns about Omicron, along with whether it is more transmissible than the dominant Delta variant, what might give it that transmissibility boost, and how well immune responses are protecting against the variant.

One reason it’s challenging to compare how virulent different versions of a virus are is because they encounter different landscapes. The original SARS-2 virus entered into populations where essentially everyone was “naive” — meaning they had no prior exposure to the coronavirus — but each subsequent variant has arrived at a time when more people had some amount of protection, from past infections or vaccinations. With Omicron, it might be hard to isolate its virulence in naive people.

The ideal way to study two variants’ virulence would be to analyze the outcomes of patients within the same population with similar ages and health conditions at similar health care systems, at a time when both variants are circulating. The real-life changing circumstances of a pandemic don’t always allow for such apples-to-apples comparisons, however.

Even now, experts are still divided about whether Delta is more likely to cause severe disease in people. A few studies showed an increased hospitalization rate among people infected during countries’ Delta waves, and many health care workers reported younger people getting sicker faster from Delta. But other studies found no such difference in hospitalization rates from Delta, and some experts argue that Delta waves were so massive that enough young people got sick to account for the large number of serious cases among them.

There’s a notion that, over time, viruses evolve to become more transmissible (whether because they’re inherently better at spreading or because they can circulate among people with immune protection) and also to become less severe. But the latter doesn’t always hold true, experts say.

“That’s not a rule,” said Ramón Lorenzo-Redondo, a molecular virologist at Northwestern University’s Feinberg School of Medicine. “These are complex systems with a lot of randomness.”

There is a correlation between transmissibility and virulence — if a virus kills someone really quickly, it won’t be successful at spreading, for example — but only to a point, experts say. While many viruses do evolve to cause less severe disease over time, there’s not necessarily an evolutionary advantage in doing so, and some viruses have become more virulent.

Still, through regular exposure to the virus — whether through infection or vaccines — our immune systems get better equipped to stave off, at least most of the time, the serious outcomes. That’s how a pandemic virus becomes endemic.

Helen Branswell contributed reporting.

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