Conference Coverage

Metapneumovirus infections clinically indistinguishable from flu, RSV



The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

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