The past winter was a heavy one for respiratory viruses, dominated by surges of RSV, influenza, and Covid-19. But just as it was winding down, a little-known virus that causes many of the same symptoms – a lower lung infection, hacking cough, runny nose, sore throat, and fever – was just picking up steam.
Cases of human metapneumovirus, or HMPV, spiked this spring, according to US Centers for Disease Control and Prevention's respiratory virus surveillance systems. It filled hospital intensive care units with young children and seniors who are the most vulnerable to these infections. At its peak in mid-March, nearly 11% of tested specimens were positive for HMPV, a number that's about 36% higher than the average, pre-pandemic seasonal peak of 7% test positivity.
Most people who caught it probably didn't even know they had it, however. Sick people aren't usually tested for it outside of a hospital or ER. Unlike Covid-19 and the flu, there's no vaccine for HMPV or antiviral drugs to treat it. Instead, doctors care for seriously ill people by tending to their symptoms.
An underestimated threat
Studies show that HMPV causes as much misery in the US each year as the flu and a closely related virus, RSV. One study of patient samples collected over 25 years found that it was the second most common cause of respiratory infections in kids behind RSV. A study in New York conducted over four winters found that it was as common in hospitalized seniors as RSV and the flu. Like those infections, HMPV can lead to intensive care and fatal cases of pneumonia in older adults.
Leigh Davidson caught human metapneumovirus during a family celebration in early April. Two weeks later, she was coughing so violently, she couldn't talk on the phone.
"I couldn't get out more than a couple of words," said Davidson, 59, an entertainment lawyer in Baltimore. "I would go into violent, violent coughing to the point where I was literally almost throwing up."
Her cough was so constant and deep, she was convinced she had finally caught the coronavirus after managing to avoid it throughout the pandemic. But she took six rapid tests for Covid-19, and all came back negative.
Davidson is immunocompromised, so she has been cautious throughout the pandemic. Concerned about pneumonia, she got a X-ray from a radiology clinic near her home and was told it was clear.
Her doctor wasn't satisfied, however, and sent her to an emergency room for more testing. Blood tests determined that she had HMPV.
"I was like, 'what?' Because it sounds really dire," Davidson said. "I've never heard of it."
Human metapneumovirus was discovered by Dutch virus hunters in 2001. They had 28 samples from children in the Netherlands with unexplained respiratory infections. Some of the children had been very ill and required mechanical ventilation, but they didn't test positive for any known pathogens.
The researchers cultured the samples in various types of cells from monkeys, chickens, and dogs, and then they looked at the cultures under an electron microscope. They saw something that seemed structurally related to the paramyxoviridae family, a group of viruses known to give people respiratory diseases like measles, mumps, and respiratory syncytial virus, or RSV.
A closer look at the virus' genes showed a close relative: avian metapneumovirus, which infects birds. The new virus was dubbed human metapneumovirus. Scientists believe it probably jumped from birds to humans at some point and evolved from there.
When the researchers tested blood samples from 72 patients that had been stored since 1958, all showed evidence of exposure to the mystery virus, indicating that it had been circulating in humans, undetected, for at least the previous half-century.
Doctors and patients in the dark
Respiratory infections are the leading cause of death for children around the world and the No. 1 reason kids are hospitalized in the United States, but scientists don't know what causes a good chunk of them, says Dr. John Williams, a pediatrician at the University of Pittsburgh who has spent his career researching vaccines and treatments for HMPV.
Williams says there were sweeping epidemiological studies conducted in the 1950s and '60s, looking into the causes of respiratory infections.
"Basically, they could only identify a virus in people about half the time. And so the question was, 'OK, what about that other half?' " he said. Human metapneumovirus doesn't account for all the unknown viruses, but it's a significant proportion – about as many cases as RSV or influenza.
But no one knows about it. Williams calls it "the most important virus you've never heard of."
"Those are the three major viruses," he said. "Those are the big three in kids and adults, the most likely to put people in the hospital and cause severe disease, most likely to sweep through nursing homes and make older people really sick and even kill them."
Because testing for HMPV is rarely done outside hospitals, it's hard to know the true burden of the disease.
Blood tests indicate that most children have had it by the age of 5.
A 2020 study in the Lancet Global Health estimated that among children younger than 5, there were more than 16 million HMPV infections in 2018, more than 600,000 hospitalizations and more than 16,000 deaths.
The infection generates weak or incomplete immune protection, however, and humans get reinfected throughout their lives.
Companies are working on vaccines against it. Covid-19 vaccine maker Moderna just finished an early study of an mRNA vaccine against HMPV and parainfluenza, according to the website clinicaltrials.gov.
The CDC recommends that doctors consider testing for HMPV in the winter and spring, when it tends to peak.
Doctors don't test for it mostly because of a lack of awareness of the virus, Williams said, but also because a test probably wouldn't change the care they would give a patient. It would help them rule out other causes that do have dedicated treatments, like Covid or the flu.
Davidson said HMPV gave her a serious bout of bronchitis. She was admitted to the hospital briefly for observation. She eventually got better, but she was sick for a month.
She's had respiratory infections before, of course, but she's particularly glad to be on the other side of human metapneumovirus, she said – "This was really kind of the worst I'd ever experienced."
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