Future Proofing Immunity: Spotting new viruses before next pandemic

Back in the summer, Dr. Michael Mina made a deal with a cold storage company. With many of its restaurant clients closed down, the firm had freezers to spare. And Dr. Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, had a half-million vials of plasma from human blood coming to his lab from across the country, samples dating back to the carefree days of January 2020. 

The vials, now in three hulking freezers outside Dr. Mina’s lab, are at the center of a pilot project for what he and his collaborators call the Global Immunological Observatory. They envision an immense surveillance system that can check blood from all over the world for the presence of antibodies to hundreds of viruses at once. That way, when the next pandemic washes over us, scientists will have detailed, real-time information on how many people have been infected by the virus and how their bodies responded. 

It might even offer some early notice, like a tornado warning. Although this monitoring system will not be able to detect new viruses or variants directly, it could show when large numbers of people start acquiring immunity to a particular kind of virus. 

The human immune system keeps a record of pathogens it has met before, in the form of antibodies that fight against them and then stick around for life. By testing for these antibodies, scientists can get a snapshot of which flu viruses you have had, what that rhinovirus was that breezed through you last fall, even whether you had a respiratory syncytial virus as a child. Even if an infection never made you sick, it would still be picked up by this diagnostic method, called serological testing. “We’re all like little recorders,” keeping track of viruses without realising it, Dr. Mina said. This type of readout from the immune system is different from a test that looks for an active viral infection. The immune system starts to produce antibodies one to two weeks after an infection begins, so serology is retrospective, looking back at what you have caught. Also, closely related viruses may produce similar responses, provoking antibodies that bind to the same kinds of viral proteins. That means carefully designed assays are needed to distinguish between different coronaviruses, for example. 

But serology uncovers things that virus testing does not, said Derek Cummings, an epidemiologist at the University of Florida. With a large database of samples and clinical details, scientists can begin to see patterns emerge in how the immune system responds in someone with no symptoms compared to someone struggling to clear the virus. Serology can also reveal before an outbreak starts whether a population has robust immunity to a given virus, or if it is dangerously low. 

“You want to understand what has happened in a population, and how prepared that population is for future attacks of a particular pathogen,” Dr. Cummings said. 

The approach could also detect events in the viral ecosystem that otherwise go unnoticed, Dr. Cummings said. For example, the 2015 Zika outbreak was detected by doctors in Brazil who noticed a cluster of babies with abnormally small heads, born seven to nine months after their mothers were infected. “A serological observatory could conceivably have picked this up before then,” he said. 

Serological surveys are often small and difficult to set up, since they require drawing blood from volunteers. But for several years Dr. Mina and his colleagues have been discussing the idea of a large and automated surveillance system using leftover samples from routine lab tests. “Had we had it set up in 2019, then when this virus hit the U.S., we would have had ready access to data that would have allowed us to see it circulating in New York City, for example, without doing anything different,” Dr. Mina said. 

Although the observatory would not have been able to identify the new coronavirus, it would have revealed an unusually high number of infections from the coronavirus family, which includes those that cause common colds. It might also have shown that the new coronavirus was interacting with patients’ immune systems in unexpected ways, resulting in tell-tale markers in the blood. That would have been a signal to start genetic sequencing of patient samples, to identify the culprit, and might have provided grounds to shut down the city earlier, Dr. Mina said. (Similarly, serology would not be able to spot the emergency of a new virus variant, like the contagious coronavirus variants that were discovered in South Africa and England before spreading elsewhere. For that, researchers must rely on standard genomic sequencing of virus test samples.) 

The observatory would require agreements with hospitals, blood banks and other sources of blood, as well as a system for acquiring consent from patients and donors. It also faces the problem of financing, noted Alex Greninger, a virologist at the University of Washington. Health insurance companies would be unlikely to foot the bill, since serology tests are usually not used by doctors to treat people. 

Dr. Mina estimated that the observatory would cost about $100 million to get off the ground. He pointed out that, according to his calculations, the federal government has allocated more than twice that much to diagnostics company Ellume to produce enough rapid Covid tests to cover the American demand for only a handful of days. A pathogen observatory, he said, is like a weather forecasting system that draws on vast numbers of buoys and sensors around the globe, passively reporting on events where and when they arise. These systems have been funded by government grants and are widely valued. 

The predictive power of serology is worth the investment, said Jessica Metcalf, an epidemiologist at Princeton and one of the observatory team members. A few years ago, she and her collaborators found in a smaller survey that immunity to measles was ominously low in Madagascar. Indeed, in 2018 an outbreak took hold, killing more than 1,000 people. Now, the half-million plasma samples in Dr. Mina’s freezers, collected by the plasma donation company Octapharma from sites across the country last year, are starting to undergo serological tests focused on the new coronavirus, funded by a $2 million grant from Open Philanthropy. Testing had to wait for the researchers to set up a new robotic testing facility and process the samples, but now they are working through their first batches. 

The team hopes to use this data to show how the virus flowed into the US, week by week, and how immunity to Covid has grown and changed. They also hope it will spark interest in using serology to illuminate the movement of many more viruses. “The big idea is to show the world that you don’t have to spend huge dollars to do this kind of work,” Dr. Mina said. “We should have this happening all the time.”