Study Sheds Light On Virus That’s ‘Not on People’s Radar’

Among hospitalized children and teens, respiratory syncytial virus (RSV) mostly affects younger, otherwise healthy infants, while the lesser-known human metapneumovirus (HMPV) tends to affect older children, many of whom have preexisting health conditions, according to a study published in Pediatrics.

Researchers and other experts said the findings will hopefully promote the development of HMPV vaccines and affordable rapid diagnostic tests for the virus in outpatient settings.

“HPMV is not on people’s radar,” said John V. Williams, MD, chair of the Department of Pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin. “It was the largest prospective apples-to-apples comparison [on RSV and HMPV]; it has tremendous importance in that sense.”

The incidence of young children hospitalized because of HMPV is lower than RSV but similar to influenza and human parainfluenza type 3, according to the American Academy of Pediatrics. The virus accounts for roughly 10% of all respiratory infections in children.

With the introduction of vaccines to prevent RSV in recent years, no vaccines for HMPV are on the market in the US. Williams and his team sought to create a baseline for hospitalized children with either virus to later measure the effect of preventive products.

Williams and his colleagues analyzed data obtained from seven major US pediatric hospitals and emergency departments (EDs) from 2016 to 2020. The researchers tracked children younger than 18 years hospitalized with RSV (4398) or HMPV (931) and those seeking care at EDs due to RSV (2371) or HMPV symptoms (905). They also interviewed caregivers.

“The most surprising findings were the age differences,” Williams said.

Children with RSV were generally younger than those with HMPV, both when hospitalized and when seeking care at the ED (7 months vs 16 months when hospitalized; 15 months vs 22 months when in the ED).

They also found that children presenting to the ED with RSV were 68% more likely to be hospitalized than children with HMPV (adjusted odds ratio, 1.68; 95% CI, 1.50-1.87).

Among hospitalized children younger than 12 months, those with HMPV were more likely to have preexisting conditions than those with RSV (< 6 months: 7.8% [RSV] vs 19.9% [HMPV], P < .0001; 6-11 months: 18.2% [RSV] vs 31.7% [HMPV], P < .0001).

Children across most age groups hospitalized with RSV were also less likely to require mechanical ventilation than those hospitalized with HMPV (3.9% vs 5.9%, P = .006). Pneumonia diagnoses were twice as frequent among children hospitalized with HMPV than among those with RSV.

Timing also differentiated the viruses. Williams and his team found that while RSV typically peaked in December, other years showed spikes in cases in November and January. Cases of HMPV in the study most often peaked in March but ranged from October to June across the four years of the study.

The two viruses are genetically related and present very similarly, said Danelle Fisher, MD, a pediatrician at Providence Saint John’s Health Center in Santa Monica, California, who was not involved with the study. Both include symptoms of cough, nasal congestion, and fever. Most cases of HMPV are mild and self-limiting, but not always, as the study shows, she said.

Clinicians should send patients who are wheezing, struggling to breathe, or unable to drink to the ED, Fisher said. Fisher also said the only way to differentiate between the viruses is to test.

Williams said although immunofluorescent tests exist for HMPV, “there aren’t any FDA-cleared, truly sensitive, specific, and efficient rapid antigen tests designed to be used at the point of care or in the clinic.”

Most molecular polymerase chain reaction or other nucleic acid amplification tests for the virus are expensive and mainly used in hospitals or reference labs, he said.

“It would be helpful to have rapid diagnostic tests for HMPV in a pediatric clinic,” Williams said. “These childhood viruses are transmitted to older adults, and they make older adults really sick. Future interventions for HMPV are very likely to have significant benefits for high-risk adults.”

The study was supported by a cooperative agreement by the US CDC and a grant from the National Center for Advancing Translational Sciences.

Various authors of the study reported receiving funding, consulting for, and serving on advisory boards for Pfizer, Sanofi Pasteur, AstraZeneca, Merck, Luminex, and GlaxoSmithKline, among others.