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‘Odds are, people are going to get sick this year,’”

In typical years, flu hospitalizes an estimated 140,000 to 710,000 people in the United States alone; some years, RSV can add on some 200,000 more. “Our baseline has never been great,” Yvonne Maldonado, a pediatrician at Stanford, told me. “Tens of thousands of people die every year.”

this time of year, on top of RSV, flu, and COVID, we also have to contend with a maelstrom of other airway viruses—among them, rhinoviruses, parainfluenza viruses, human metapneumovirus, and common-cold coronaviruses.

Illnesses not severe enough to land someone in the hospital could still leave them stuck at home for days or weeks on end, recovering or caring for sick kids—or shuffling back to work

“This is a more serious pathogen that is also more infectious,” Ajay Sethi, an epidemiologist at the University of Wisconsin at Madison, told me. In the past year, COVID-19 has killed some 80,000 Americans—a lighter toll than in the three years prior, but one that still dwarfs that of the worst flu seasons in the past decade.

Globally, the only infectious killer that rivals it in annual-death count is tuberculosis

Rivers also pointed to CDC data that track trends in deaths caused by pneumonia, flu, and COVID-19. Even when SARS-CoV-2 has been at its most muted, Rivers said, more people have been dying—especially during the cooler months—than they were at the pre-pandemic baseline.

This year, for the first time, millions of Americans have access to three lifesaving respiratory-virus vaccines, against flu, COVID, and RSV. Uptake for all three remains sleepy and halting; even the flu shot, the most established, is not performing above its pre-pandemic baseline.

COVID could now surge in the summer, shading into RSV’s autumn rise, before adding to flu’s winter burden, potentially dragging the misery out into spring. “Based on what I know right now, I am considering the season to be longer,” Rivers said.

barring further gargantuan leaps in viral evolution, the disease will continue to slowly mellow out in severity as our collective defenses build; the virus may also pose less of a transmission risk as the period during which people are infectious contracts

even if the dangers of COVID-19 are lilting toward an asymptote, experts still can’t say for sure where that asymptote might be relative to other diseases such as the flu—or how long it might take for the population to get there.

it seems extraordinarily unlikely to ever disappear. For the foreseeable future, “pretty much all years going forward are going to be worse than what we’ve been used to before,”

although a core contingent of Americans might still be more cautious than they were before the pandemic’s start—masking in public, testing before gathering, minding indoor air quality, avoiding others whenever they’re feeling sick—much of the country has readily returned to the pre-COVID mindset.

When I asked Hanage what precautions worthy of a respiratory disease with a death count roughly twice that of flu’s would look like, he rattled off a familiar list: better access to and uptake of vaccines and antivirals, with the vulnerable prioritized; improved surveillance systems to offer  people at high risk a better sense of local-transmission trends; improved access to tests and paid sick leave

Without those changes, excess disease and death will continue, and “we’re saying we’re going to absorb that into our daily lives,” he said.

And that is what is happening.

last year, a CDC survey found that more than 3 percent of American adults were suffering from long COVID—millions of people in the United States alone.

“We get used to things we could probably fix.” The years since COVID arrived set a horrific precedent of death and disease; after that, this season of n+1 sickness might feel like a reprieve. But compare it with a pre-COVID world, and it looks objectively worse. We’re heading toward a new baseline, but it will still have quite a bit in common with the old one: We’re likely to accept it, and all of its horrors, as a matter of course.

"If you want to make a new influenza vaccine using the traditional methods, you have to isolate the virus, learn how to grow it, learn how to inactivate it, and purify it. That takes months. With RNA, you only need the sequence,"

"When the Chinese released the sequence of the SARS-CoV-2 virus, we started the process of making RNA the next day. A couple weeks later, we were injecting animals with the vaccine."

Weissman's lab is now working on a universal coronavirus vaccine that would protect against Covid-19, SARS, MERS, coronavirus that cause the common cold -- and future strains.

"We started working on a pan-coronavirus vaccine last spring," Weissman said. "There have been three coronavirus epidemics in the past 20 years. There are going to be more."

Another obvious use for mRNA technology is to fight cancer. The human body fights off cancer every day, and using mRNA could help it do so even better.

Different tumor cell types have various, recognizable structures on the outside that the immune system can recognize. "You can imagine being able to inject someone with an mRNA that encodes an antibody that specifically targets that receptor," McLellan said.

"We identify mutations found on a patient's cancer cells," the company says on its website. Computer algorithms predict the 20 most common mutations. "We then create a vaccine that encodes for each of these mutations and load them onto a single mRNA molecule," Moderna says.

BioNtech has been working with academic researchers to use mRNA to treat mice genetically engineered to develop a disease similar to multiple sclerosis -- an autoimmune disease that starts when the immune system mistakenly attacks the myelin, a fatty covering of the nerve cells.In the mice, the treatment appeared to help stop the attack, while keeping the rest of the immune system intact.

The idea behind gene therapy is to replace a defective gene with one that works properly.

The mRNA approach promises to send instructions for making the healthy version of a protein, and Weissman sees special promise in treating sickle cell disease, in particular.

"It's gene therapy without the half a million dollar price tag," he added. "It should be just an IV injection and that's it."

"The idea there is if you are immune to tick saliva proteins, when the tick bites you, the body produces inflammation and the tick falls off," Weissman said.