Neglected respiratory viruses rival influenza and RSV in blood cancer patients

For adults undergoing treatment for cancers of the blood and immune system, a viral infection of the lower respiratory tract is far more than a bad cold. Weakened by chemotherapy, neutropenia, and impaired cellular immunity, these patients face a real risk that a respiratory virus will descend from the upper airway into the lungs, triggering pneumonia, intensive care admission, and sometimes death. Influenza and respiratory syncytial virus, or RSV, have long been recognized as the dominant threats in this population, and they are the viruses against which new antivirals and vaccines are typically benchmarked. A new systematic review now argues that two far less studied pathogens, parainfluenza virus and human metapneumovirus, deserve a place in that same conversation, because their clinical outcomes in this vulnerable group appear broadly comparable to those of the better-characterized viruses.

The review, published in BMC Infectious Diseases by a team of Iranian researchers led by Majid Torabi and Zary Nokhodian of Isfahan University of Medical Sciences, set out to compare the clinical burden of what the authors call the neglected respiratory viruses against influenza and RSV pneumonia in adults with hematologic malignancies. Parainfluenza virus, or PIV, is an enveloped, single-stranded RNA virus of the family Paramyxoviridae, and human metapneumovirus, or hMPV, is a closely related paramyxovirus first identified in 2001. Both are common causes of seasonal respiratory illness in the general population, usually producing nothing worse than a cough or croup-like illness in children. But in patients whose cellular immunity has been dismantled by chemotherapy for leukemia, lymphoma, or multiple myeloma, these viruses can establish persistent, progressive lower respiratory tract infection, and unlike influenza, they have no widely deployed antiviral therapy or licensed vaccine.

To assemble the evidence, the researchers followed PRISMA 2020 reporting guidelines and registered their protocol prospectively on PROSPERO. They searched four databases from their inception to October 2025 for observational studies that directly compared clinical outcomes of PIV or hMPV lower respiratory tract infection with RSV or influenza pneumonia in adults receiving chemotherapy for hematologic malignancies. The primary outcomes of interest were all-cause mortality, intensive care unit admission, mechanical ventilation, and length of hospital stay. Study selection, data extraction, and quality assessment were each performed by two independent reviewers, and methodological quality was judged with the Newcastle-Ottawa Scale, a standard instrument for appraising non-randomized studies. Because the underlying evidence consisted of observational cohorts rather than randomized trials, the authors conducted a narrative synthesis rather than a meta-analysis, a choice that reflects the heterogeneity of the available data.

The screening funnel was wide but the yield was narrow. From 1,071 records screened, only 12 studies met the inclusion criteria, encompassing a total of 4,841 patients. Eleven of the twelve studies were rated as good quality on the Newcastle-Ottawa Scale, which lends credibility to the individual findings, but the small number of comparative studies is itself a telling result. It means that for a question with direct consequences for how clinicians triage and treat infected patients, the literature offers barely a dozen relevant analyses, most of them small single-center cohorts. Data on mechanical ventilation were particularly scarce, and notably absent altogether for PIV and influenza, leaving one of the four primary outcomes essentially unmeasurable for two of the four viruses.

The central quantitative finding concerns mortality, and it is striking for what it does not show. All-cause mortality ranged from 0 to 16 percent for PIV and stood at 1.4 percent for hMPV in the available data, while influenza pneumonia carried mortality of 2.2 to 33.3 percent and RSV ranged from 0 to 25 percent. In other words, the neglected viruses were not associated with higher death rates than the well-studied ones, and in some comparisons their reported mortality was considerably lower. The authors are careful to note that these ranges are highly variable and overlapping across all four viruses, which means that no single virus can be confidently ranked as the deadliest based on the existing evidence. The variability itself is informative, reflecting differences in patient mix, diagnostic methods, timing of treatment, and institutional practice across the source studies.

Intensive care unit admission rates told a similar story of variability and overlap. Across the included studies, ICU utilization was highly variable for every virus, with rates for the neglected viruses falling within the same broad ranges as those reported for influenza and RSV. This pattern suggests that the decision to admit a patient to intensive care in this population is driven less by which virus caused the infection than by patient-specific factors such as the degree of immunosuppression, the stage of the underlying malignancy, and the presence of bacterial coinfection. From a virological standpoint, this is a plausible result, since all four pathogens cause disease through similar mechanisms: direct cytopathic injury to the respiratory epithelium, inflammatory infiltration of the lung parenchyma, and in immunocompromised hosts, prolonged viral shedding that sustains tissue damage over weeks rather than days.

One finding stood out from the rest of the synthesis. In a single study, patients with PIV lower respiratory tract infection had a substantially prolonged median length of hospital stay of 28 days, compared with 18 days for RSV, 9 days for hMPV, and 10 to 13 days for influenza. The authors emphasize that this result derives from a single, small-cohort study and therefore requires independent validation before any firm conclusion can be drawn. But the magnitude of the difference is hard to dismiss. If PIV infection truly doubles or triples the median hospital stay relative to the other viruses, the morbidity and resource implications would be considerable, since prolonged hospitalization in immunocompromised patients carries its own cascade of risks, including nosocomial infection, antifungal and antibacterial toxicity, deconditioning, and delayed resumption of cancer-directed chemotherapy.

The biological basis for a prolonged PIV course is an open question, but several mechanisms are candidates. PIV establishes persistent infection in immunocompromised hosts, with viral shedding documented for weeks to months, and the virus is less reliably cleared by the recovering immune system than influenza, which typically produces a more self-limited course even in compromised patients. There is also no licensed antiviral with proven efficacy against PIV, whereas influenza has oseltamivir and baloxavir and RSV has emerging options such as nirservimvir, so clinicians managing PIV pneumonia have historically been limited to supportive care and reduction of immunosuppression where feasible. hMPV, by contrast, showed the shortest median stay in the comparative data, a reminder that the two neglected viruses may have distinct clinical profiles rather than a shared one.

The review’s conclusions carry practical weight for how the field allocates attention and resources. The authors argue that their findings challenge the perception of PIV and hMPV as uniformly less severe than influenza and RSV, and they call for prospective studies to guide optimized management and resource allocation. In an era when multiplex molecular panels routinely detect all four viruses in a single nasal swab, the diagnostic bottleneck has largely disappeared; what remains is an evidence bottleneck, with treatment decisions for the neglected viruses resting on extrapolation from other pathogens and small uncontrolled case series. The authors also note that the absence of ventilation data for PIV and influenza means that the full spectrum of severity, from ward-based pneumonia to prolonged mechanical ventilation, cannot yet be compared across viruses.

For clinicians caring for adults with hematologic malignancies, the message is that every respiratory virus detected in this population warrants serious attention, regardless of how familiar it is. For vaccine and antiviral developers, the review identifies a gap: the neglected paramyxoviruses cause a burden of disease in immunocompromised adults that is comparable in mortality to influenza and RSV, yet they lack the therapeutic and preventive pipeline that the better-studied viruses enjoy. The authors’ call for prospective, adequately powered studies is a recognition that the current evidence base, built from a dozen observational cohorts, cannot answer the questions that matter most, including whether early antiviral intervention, targeted immunoprophylaxis, or preemptive reduction of chemotherapy can alter the course of PIV and hMPV pneumonia in this uniquely vulnerable group.

Subject of Research: Outcomes of ‘neglected’ respiratory viruses (PIV, hMPV) vs. Influenza and RSV lower respiratory tract infections in hematologic malignancies: a systematic review

Article Title: Outcomes of ‘neglected’ respiratory viruses (PIV, hMPV) vs. Influenza and RSV lower respiratory tract infections in hematologic malignancies: a systematic review

Article References: Torabi, M., Mohammadzadeh Rostami, F., Hakamifard, A., Ataei, B., & Nokhodian, Z. (2026). Outcomes of ‘neglected’ respiratory viruses (PIV, hMPV) vs. Influenza and RSV lower respiratory tract infections in hematologic malignancies: a systematic review. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14629-0

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14629-0

Keywords: Outcomes, neglected, respiratory, viruses, hMPV, Influenza, lower, tract, infections, hematologic, malignancies, systematic