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Covid still packs a punch — and likely will for some time, experts say

Our tussle with Covid-19 — after a harrowing introduction and then wave upon wave of infections — seems to have settled into a persistent pattern. It may stay that way for a while.

While Covid is not nearly the threat it once was, transmission of the coronavirus remains at sky-high levels. At the same time, the death rate has dropped thanks to vaccinations and improved treatments, and the overwhelming majority of people in the United States have developed some level of protection, from shots, a previous infection, or some combination of the two.

In some ways, Covid is increasingly looking like other respiratory infections — mild in many people, but sometimes severe in certain high-risk populations.

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Ann Falsey, an infectious disease physician at the University of Rochester, is treating Covid patients who are generally elderly, have compromised immune systems, or have serious heart or lung conditions — the same types of people who get hospitalized from the seasonal bugs that most of us shake off.

“It doesn’t remotely look like Covid in someone who’s immunologically naive,” Falsey said, recalling how before vaccines were available people flooded hospitals with cases of widespread pneumonia that are far less common now.

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Falsey has studied other respiratory viruses for years, including the four seasonal coronaviruses that cause a decent chunk of common colds. In one 2013 paper focused on two of those viruses, OC43 and 229E, Falsey and colleagues noted that, while they often just caused mild or even asymptomatic infections, they could still occasionally result in hospitalization and death, particularly among the elderly.

In a best-case scenario, perhaps that’s the long-term impact of the SARS-CoV-2 virus.

What remains different for now, however, is that SARS-2 is still killing hundreds of Americans each day.

Average daily deaths have rarely dipped below 300 since last summer. More recently, as the latest Omicron subvariant BA.5 fueled another burst of transmission on top of an elevated plateau of cases, deaths have surpassed 400 a day (though the BA.5 wave appears to have crested). Such levels are far higher than those seen with other respiratory viruses, especially in the summer.

“It’s something that, because we’ve been in this pandemic for so long, we can easily get jaded to,” said Jonathan Abraham, an infectious diseases physician at Brigham and Women’s Hospital in Boston.

Perhaps more worrisome is the fact that many experts don’t foresee much change anytime soon. While there will be ups and downs, some forecasts project 100,000 annual Covid deaths, if not more, for the next several years. Ignoring seasonal variation, that’s some 275 deaths a day.

“It’s hard for me to see, barring any massive change in the way we’re treating the virus right now or trying to manage it, that anything inherent to the virus is really going to change much,” said Stephen Kissler, an epidemiologist at Harvard’s T.H. Chan School of Public Health. “We’re going to continue to see the emergence of variants, we’re going to continue to see spread outside the winter months, we’re probably going to see more spread in winter months in temperate regions — basically any time people are crowding indoors.”

What that means, Kissler said, is that going forward, Covid could generate two to three bad flu seasons’ worth of deaths each year.

That won’t necessarily be the case forever. Many experts see SARS-2 retreating to something more on par with the other human coronaviruses as we keep building up additional layers of immunity. But how long that process takes — three years? five years? 10 years? — remains an open question.

“What are we looking at and how long is this going to go on?” said Vineet Menachery, a coronavirus specialist at the University of Texas Medical Branch. “Is this just how we have to deal with it going forward or is there some relief in sight? I think the honest answer is, we just don’t know. We haven’t seen anything quite like this.”

Beyond deaths, the current level of illness is nothing to shrug off.  Mass infections are both disruptive to society and result in an untold number of cases of long Covid.

Experts note there’s room for improvement with available tools, both by vaccinating those who have not yet rolled up their sleeves and who still account for a sizable chunk of deaths, and by reaching more people with booster shots. U.S. health officials are also still trying to expand access to and uptake of Covid therapies — both those that are given to infected people, like the antiviral Paxlovid that President Biden took during his recent bout, and a treatment called Evusheld, which is given to immunocompromised people who aren’t infected to prevent illness.

But a key reason why the country is still recording several hundred Covid deaths a day is simply because so many infections are occurring. Though there have been regional ebbs and flows, national case counts since mid-May have been greater than 100,000 a day, increasing to 130,000 recently. This is also a massive undercount, given that surveillance efforts have been rolled back and many people either forgo tests or use them at home.

With hundreds of thousands of cases a day, even the small and shrinking percentage of them that result in deaths can add up to hundreds of deaths a day.

So why then, two and a half years into the pandemic, is transmission still so high?

First off, SARS-2 — especially its Omicron variants — has become an incredibly infectious virus, far more so than some other respiratory viruses. The mitigation measures that people carried well into last year, like masking and distancing, have also broadly been cast aside.

At the same time, prior infections don’t protect us from getting reinfected all that well. Neither do vaccinations, although these continue to provide robust protection against severe disease. This is a result of both waning immunity and the mutations different variants have picked up.

It’s not that recovering from an infection or getting a jab provides no protection against future infection. While some reinfections have been documented after just a few weeks, recent studies from Qatar, Portugal, and Israel have all underscored that, generally, people who had recent infections or shots were less likely to become infected. But that type of immunity doesn’t seem all that durable and doesn’t reduce the risk of infection to zero. Essentially, the virus is still finding plenty of people to infect.

All this can help fuel a nasty cycle, too: The more the virus is spreading, the higher the likelihood that better-spreading variants emerge, which can in turn only accelerate transmission.

Even with a virus as infectious as SARS-2, one that is going to burn through huge numbers of people each year, many experts still see us stabilizing into a better place over time.

Many of us, between infections and vaccines, have had three, perhaps four, maybe even five encounters with the virus or its spike protein. It could be that we need even more exposures to really tame the virus.

“If you get infected over and over again, and it seems like that’s going to be the case — in part because of viral evolution and in part because of waning immunity — that secondary, tertiary, quaternary, those repeated infections are probably not going to be as damaging,” said evolutionary biologist Katia Koelle of Emory University.

Those repeated exposures — especially to different variants — should elicit deeper and broader immunity, with a stronger arsenal of fighters like antibodies and T cells, Koelle said. We might still get infected by SARS-2 dozens of times over our lifetimes — just as with the coronaviruses that cause the common cold — but in most instances, it will cause only a case of the sniffles. (In rare events, subsequent infections may make people sicker than earlier cases.)

The repeated training of the immune system in the form of booster shots is particularly important for older people, who have a harder time building up an immune armamentarium against a novel pathogen and see their defenses wane faster than younger people. But over time, people will scale up their immunity when they are younger and carry that with them as they age. People who are 60 now may not be as vulnerable to Covid when they’re 75 as people who are 75 now.

Perhaps our deeper immunity will even extend to a more durable protection against infection, or make us less likely to further spread the virus. With the four seasonal coronaviruses, it’s thought that protection against infection lasts a year or two, though these viruses haven’t been as well studied as SARS-2.

“Is there a threshold amount of immunity that will protect you” against infection? Menachery said. “If you had asked me that two years ago, I would have thought a vaccine and an infection might have been enough. We’re seeing that that’s not enough at this point,” he said, though he added the reason for that is unclear. Is it that the virus has mutated enough to overcome the immune barriers we’ve been able to erect thus far?

All the experts STAT spoke to for this story stressed that predicting the future with SARS-2 is fraught. There are factors they know they can’t predict, such as how the virus will continue to evolve. Will future variants emerge from the drifting of Omicron like we’ve seen throughout 2022, or will something unexpected, like when Omicron appeared, undercut our immunity?

We, as the virus’s host, could also have a trick up our sleeves. The government is planning on rolling out updated Omicron-targeting booster shots this fall, specifically with a component of the BA.5 subvariant, which now accounts for 85% of U.S. infections. Even if some other Omicron sublineage becomes dominant by then, the shots could be a better match against what’s circulating than the original formulation — and could help bolster protection against infection, and in turn act as a drag on transmission.

The updated shot will combine the BA.5 component with the original vaccines that targeted the virus’s spike protein from early 2020. Training the immune system on two variants can lead to a broader response generally, said Meagan Deming, a virologist and infectious diseases physician at the University of Maryland. 

“Hopefully that breadth of immunity will cover whatever [variant] comes next,” Deming said. “And hopefully we can shut down transmission a little bit this fall. We’ll see.”

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