Risk Factors and Medical Resource Utilization of Respiratory Syncytial Virus, Human Metapneumovirus, and Influenza-Related Hospitalizations in Adults-A Global Study During the 2017-2019 Epidemic Seasons (Hospitalized Acute Respiratory Tract Infection [HARTI] Study)

Abstract

Background: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza are respiratory pathogens leading to hospitalization in adults. Our understanding of the disease burden is limited to data from single-center or 1-season studies in elderly patients. The HARTI study allows comparison of risk factors for progression to severe disease and medical resources utilization (MRU) during and post-hospitalization in adults diagnosed with influenza, RSV, or hMPV.

Methods: This was a prospective global study in adults hospitalized with acute respiratory tract infection (40 centers, 12 countries). Participants with influenza, RSV, or hMPV were enrolled in a substudy and followed for up to 3 months postdischarge.

Results: Overall, 366 influenza, 238 RSV, and 100 hMPV-infected participants enrolled in the substudy. RSV participants were older and had greater frequency of risk factors and longer duration of symptoms before hospitalization than influenza participants. The RSV and hMPV groups received more bronchodilators, corticosteroids, and oxygen supplementation. No significant differences in intensive care unit admissions or complications were observed. Readmission occurred in 20%-33% of patients within 3 months postdischarge, with the highest rates for RSV and hMPV. In-hospital death occurred in 2.5% of RSV, 1.6% of influenza, and 2% of hMPV participants. In multivariate analyses, length of stay was independently associated with country, renal disease, and increased age; probability of receiving supplemental oxygen was associated with pathogen (hMPV > RSV > influenza), abnormal chest x-ray, and increased age.

Conclusions: Although influenza is more frequent, the HARTI study demonstrates greater frequency of underlying risk factors and MRU for RSV and hMPV vs influenza in hospitalized adults, indicating a need for effective interventions.

Keywords: Influenza; RSV; global prospective study; hMPV; medical resource utilization.

Figure 1.

Study design schema. ^aWhen nasal swab collected as part of SOC, midturbinate swab (collected from opposite nostril than used for SOC test). ^bIf a participant was hospitalized for a short period (ie, <72 hours) or transferred to another ward, an early discharge assessment was performed on the day of discharge. Abbreviations: ADL, activities of daily living; ARTI, acute respiratory tract infection; EQ-5D-5L, EuroQol 5 Dimensions 5 Levels; hMPV, human metapneumovirus; IADL, instrumental activities of daily living; MRU, medical resource utilization; PCR, polymerase chain reaction; RiiQ, Respiratory Intensity and Impact Questionnaire; RSB, Respiratory Symptoms Bother and Change in Health Status Questionnaire; RSV, respiratory syncytial virus; SOC, standard of care.

Figure 2.

Flow diagram of participants at each study visit. Patients having a positive result for 2 or more respiratory pathogens between FLU, RSV, and hMPV are presented in the co-infections. All the percentages were calculated based on the total number of patients included for each pathogen. Missing patients at each study visit are not included in the diagram above. ^aIf a participant was hospitalized for a short period (ie, <72 hours) or transferred to another ward, an early discharge assessment was performed on the day of discharge. Abbreviations: hMPV, human metapneumovirus; FLU, influenza; RSV, respiratory syncytial virus.

Figure 3.

Multivariate accelerated failure time model results for the length of hospital stay. Acceleration factors and 95% CIs of the variable included in the final model are presented. Rows without estimates are the reference category for that variable. ^aAdditional underlying medical condition on top of ARTI. Abbreviations: AF, acceleration factor; ARG, Argentina; ARTI, acute respiratory tract infection; AUS, Australia; BRA, Brazil; CAN, Canada; DEU, Germany; FRA, France; FLU, influenza; hMPV, human metapneumovirus; JPN, Japan; KOR, Korea; MEX, Mexico; MYS, Malaysia; RSV, respiratory syncytial virus; USA, United States of America; ZAF, South Africa.

Figure 4.

Multivariate logistic regression model results for the probability of receiving supplemental oxygen during hospitalization. Odds ratios and 95% CIs of the variable included in final model are presented. Rows without estimates are the reference category for that variable. ^aAdditional underlying medical condition on top of ARTI. Abbreviations: ARG, Argentina; ARTI, acute respiratory tract infection; AUS, Australia; BRA, Brazil; CAN, Canada; DEU, Germany; FRA, France; FLU, influenza; hMPV, human metapneumovirus; JPN, Japan; KOR, Korea; MEX, Mexico; MYS, Malaysia; NEWS, National Early Warning Score; RSV, respiratory syncytial virus; USA, United States of America; ZAF, South Africa.