Covid-19 is still not done with humanity. Decorative gourd season is on the horizon, and with it, more cozy time indoors by the fire with friends, loved ones, and the latest set of SARS-CoV-2 variants. It means: We’re probably going to need to spend more time and money fighting the virus. But where should the money go?

We’ve already spent a lot of money on the pandemic. Like, really a lot, especially in the early days: health care spending increased by nearly 10 percent between 2019 and 2020, when it normally increases by only about 4 percent annually.

“We were really in desperate times,” said Arthur Caplan, a bioethicist at New York University’s Langone Health Center, “and that drove expenditures.” In 2020, the knowledge vacuum on how to treat Covid-19 led to huge costs, mostly in the form of public Medicaid dollars, accounting for nearly a third of the $4.1 trillion the US spent on health care in 2020. The nation also spent $18 billion on developing vaccines in Operation Warp Speed.

Two and a half years later, it’s hard not to wonder: At this point in the pandemic, how great are the returns on any of the Covid-19 investments American society could make? Which of our pandemic tools are most valuable now?

Investments today likely face diminishing returns. Today, at least 95 percent of Americans have some immunity to the virus. There are effective Covid-19 vaccines and treatments, and the American appetite for pandemic precaution has withered.

Importantly, the trillions of dollars in federal funds committed to pandemic response have largely been spent. Of the $4.5 trillion the US Congress has allotted to fight Covid-19, agencies have paid out $3.9 trillion — and there’s little enthusiasm among legislators to spend more.

The “what’s worth it now” question is difficult to answer, in part because neither the costs nor the benefits of each tool are easily quantifiable. Models have attempted to predict how effectively certain policies and programs save lives and prevent bad medical outcomes. But models can’t account for the “unknown unknowns” of the pandemic — the new variants, new beliefs, and logistical challenges that determine what the public will accept and, in the end, what actually works.

I asked six experts — among them academics and practitioners in public health and health policy, economics, security, and ethics — what’s worth investing in at this point in the pandemic. Our goal: understand how they’re thinking about the extraordinarily complex question of what our next big pandemic investment should be.

Two big areas stood out: Next-generation vaccines and air filtration.

Why next-generation vaccines are a critical part of the solution

Every expert I spoke to mentioned next-generation vaccines as a key intervention for reducing Covid-19’s impact going forward. The “next-generation” piece is important here: Experts use this term to refer to vaccines being developed with the goal of altogether preventing Covid-19 infection.

Although currently available vaccines do a great job at keeping people out of the hospital and alive, they no longer stop infections in their tracks. That matters because even when viral replication doesn’t lead to severe disease, it provides the SARS-CoV-2 virus with opportunities to evolve new variants and, potentially, to cause new cases of long Covid, an often-debilitating condition affecting one in 13 Americans, that involves a range of symptoms lasting weeks, months, or even years after an initial infection.

For this reason, experts eagerly await “not just strain updates,” like the bivalent vaccines likely to drop this fall, said Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security who focuses on emerging infectious diseases. What’s needed are “universal coronavirus vaccines, nasal vaccines, oral vaccines — something that provides more protection against infection than the current approved vaccines do.”

Although multiple universal vaccine candidates are in development, only one — developed by the US Army — is in the phase 1 clinical trial stage, which aims to assess a vaccine’s safety.

On an immunological level, what makes these candidates different from existing vaccines is their attempt to harness parts of the immune system other than neutralizing antibodies. Neutralizing antibodies target the virus’s spike protein, which is constantly evolving. These other responses — which include T-cells and memory B cells — could target other parts of the virus’s structure.

If universal vaccines can induce our immune systems to prevent viral replication — getting us to a state called “sterilizing immunity” — they could do enormous good, explained Adalja. “In general, the best way to reduce the impact of an infectious disease — any infectious disease — is to not get it,” he said.

Meanwhile, at least 12 nasal vaccine candidates are in clinical development. These vaccines, administered as nasal sprays, achieve high levels of protective antibodies in the parts of the nose and throat that first encounter the virus. These vaccines would shut the front door to the virus entering the body, while vaccines injected into the muscle deal with the virus once it’s already past the respiratory tract.

Jay Varma, a physician and epidemiologist who directs the Cornell Center for Pandemic Prevention and Response, noted it usually costs about a billion dollars to bring a new drug to market. While it’s unclear how much more it would cost to develop and distribute a universal coronavirus vaccine in the US, the ballpark is likely in the tens of billions of dollars. So far, only about $250 million has been committed to developing these new products.

If a next-generation vaccine really came through on a promise of sterilizing immunity, it would likely eventually be required for kids entering public schools, said Varma. In his mind, that would signal the true sunset of the pandemic: “Everybody gets vaccinated sometime between the ages of 3 and 5, and then you don’t have to worry about them arguing with you when they’re 20 years old about not getting vaccinated,” he said.

Adalja noted that if everyone who’d gotten at least one vaccine were to be vaccinated with a next-generation formulation, about 70 percent of Americans would have long-lasting protection from infection. That would have a meaningful impact on transmission, he said.

At a late-July White House summit on the future of coronavirus vaccines, experts discussed efforts to accelerate development of next-generation vaccines. But there’s no clear indication that any funder — least of all the US Congress — is planning a multibillion-dollar investment in next-generation vaccines.

Improving indoor air quality could dramatically reduce Covid-19 transmission without requiring behavior change — and have other wide-ranging benefits

Although investing in developing and buying vaccines may be the most important thing we can do to end the pandemic, any pandemic strategy that relies exclusively on vaccines has “a ton of limitations,” said Megan Ranney, an emergency physician and health services researcher at the Brown University School of Public Health.

Another important cornerstone of a path forward, she says, is improving air qualities in buildings. “That would be impactful, not just for Covid but for other droplet- or aerosol-borne illnesses, never mind allergies and pollution,” she said.

For decades, scientists have been aware of links between a variety of health problems and contaminated indoor air, but the pandemic has led to renewed interest and focus on the infection risks of inadequate filtration and ventilation.

In March, the White House announced a call to action urging building schools and state and local governments to use any of the $522 billion allotted as part of the American Rescue Plan to make indoor air quality improvements. (The caveat here is that those dollars can and likely will be used for other Covid-19-related expenditures.) The Environmental Protection Agency issued a Clean Air in Buildings Challenge with best practices for reducing the risk of transmitting airborne particles indoors.

Joseph Allen, an environmental scientist and air quality researcher who directs the Harvard Healthy Buildings Program, says one of the key advantages of pursuing these healthy building interventions is that they require no buy-in or even awareness from the majority of the people who benefit from them. “They don’t require behavior change,” he said. “It doesn’t require you to push masks on people or force them to test each day when they’re on a university campus.” For them, the intervention is as easy as breathing.

Achieving cleaner indoor air isn’t cheap. Compared with the nearly $5 billion price tag of the bivalent vaccines and even Operation Warp Speed’s much heftier budget, the costs of overhauling all of the schools, office buildings, and multifamily residential buildings in the US are likely much higher. Although government incentives can help induce building owners to refit existing HVAC systems, the funds to make these improvements don’t need to come from the federal government. Because upgraded buildings have higher market value, individual building managers may want to take retrofits upon themselves.

The up-front costs “could be balanced against the potential benefits not just in preventing Covid,” said Varma, “but in preventing other respiratory infections, and potentially, in certain areas, protecting against allergic conditions, pollution, etc.” Some older modeling studies suggest that investments made in improving air filtration and repairing buildings’ existing HVAC systems yield early returns, with some investments paying for themselves in energy savings or reduced respiratory illnesses in less than five years.

Experts favor strategies whose benefits would outlast the pandemic

One of the features that distinguishes next-generation vaccines and indoor air quality innovation from other strategies is that investments in both of these areas will keep on giving well after Covid-19 is (relatively) in the rearview mirror.

For example, the dividends of a breakthrough on a universal coronavirus vaccine would have “cascading benefits” on other areas of vaccine development, said Adalja.

The benefits of sustainably improving indoor air also extend beyond the realms of infectious disease and even public health, and into increased worker productivity.

Lower air quality reduces cognitive performance among workers, and improving air quality increases productivity and reduces absenteeism, which together increase a workplace’s profitability. Improving indoor air also holds potential benefits for climate change mitigation. Many of the changes Allen advocates would improve energy efficiency while also protecting people from the harmful effects of climate-related weather events like wildfires. “There’s so much magic that can happen when we pursue a healthy buildings strategy that goes so far beyond Covid,” he said.

It’s also worth noting that, despite what cost-effectiveness models say, none of the experts I spoke with favored masks or strategies with strong quarantine-and-isolation components. “Masking is probably the most cost-effective thing, but it’s the least acceptable thing” in terms of what the public is willing to do, said Varma. With Americans increasingly unwilling or unable to engage in some of the strategies that defined the early days of the response, perhaps the interventions most worth the investment are the ones that require no action on the part of the individual.

There are lots of right answers to this question

Although the experts I spoke with were generally in agreement on the important investments forward for the US as a whole, many of them told me that the right choices had a lot to do with who’s making them. “Who is ‘we’? Who’s making the decision?” said Lisa Robinson, deputy director of the Center for Health Decision Science at Harvard’s public health school.

Over and over again, experts told me that different decision-makers have wildly different resources, values, and liabilities, and these differences dramatically affect the kinds of decisions they can and will make. For example, a school district with a large number of low-income students — and many schools who favor vaccination requirements — might find a vaccine mandate to be a popular and low-cost way to protect students and staff. Meanwhile, a cafe owner in a town with low masking rates might find that the cheapest way to stay open while keeping staff safe is to expand its outdoor dining space.

Different leaders in the public and private sectors have different options and different budgets when they make these choices, and they answer to different constituencies. The size and the power of the group an intervention affects changes the stakes associated with choosing those interventions.

So does the timing and social context of decisions. When elected officials perceive their popularity as being tied to the popularity of their decisions, for example, they may be incentivized to delay — or rush — certain interventions.

“The most important thing isn’t really the method that you use” to fight the virus, Robinson said. “It’s being thoughtful about what might actually happen if you’ve implemented policy.”

Although I asked experts to choose one most promising investment aimed at reducing Covid-19’s impact, several pointed out that improving social welfare can also pay dividends in terms of public health. Under the patchwork structure of the US safety net, if people can’t work, their families may not eat — and if we don’t pay for people to get vaccinated, they’re more likely to get sick and be unable to work.

Alongside investments in next-generation vaccines and indoor air quality, said Ranney, investments in some of public health’s most basic functions — gathering data and communicating with the public — are critical to finding a way out of the pandemic. “The fact that we’re having to say, ‘this one thing over that one thing’ is a commentary on how underfunded and under-resourced our public health system is in general,” she said.

“We shouldn’t have to choose between vaccines and ventilation,” she said. “But it’s also kind of reality.”