Why Making a Diagnosis of Respiratory Syncytial Virus Should Matter to Clinicians

(See the Major Article by Ackerson et al on pages 197–203.) Respiratory syncytial virus (RSV) is an important cause of lower respiratory infections, with severe disease affecting primarily infants and older adults. RSV infections are common during the winter, occurring at an annual rate of 2%–10% in older adults; attack rates can exceed those of influenza in this population [1, 2]. In adults aged ≥60 years, there are an estimated 700000 to 2 million cases annually [2–5]. Moreover, approximately 12% of all medically attended acute respiratory illnesses (ARIs) in older adults [3, 6] and approximately 200000 hospitalizations annually are associated with RSV infection compared to 300000 hospitalizations secondary to influenza in the same population [7, 8]. The incidence of RSV-associated hospitalization increases with age; 1 study reported that 30% of hospitalizations of adults aged >75 years admitted for ARI were due to RSV infection [3, 8]. Like influenza, RSV mortality disproportionately affects the elderly, with 78%–82% of all RSV-associated deaths occurring in persons aged ≥65 years in the United States [4, 5]. Population-based reports estimate 6%–8% mortality or 11000–17000 RSV associated deaths in older adults each year in the United States [4–6]. Moreover, an estimated 1%–2% of all cardiopulmonary deaths are attributed to RSV [4, 5]. However, perhaps more significant than the limited mortality data is what we know about RSV-associated morbidity. First, RSV infection can exacerbate chronic underlying cardiac and pulmonary conditions, and antecedent RSV infection may be a trigger for hospitalization for these conditions [9]. Falsey et al estimated that among patients aged ≥65 years hospitalized with laboratory-confirmed RSV infection, RSV infection accounted for 11% of hospitalizations for pneumonia, 11% of hospitalizations for chronic obstructive pulmonary disease (COPD), 5% of hospitalizations for congestive heart failure (CHF), and 7% of hospitalizations for asthma [2]. In a recent study, 445 patients aged ≥50 years with COPD and/or CHF were followed prospectively; 22% were diagnosed with RSV infection over a 2–3 year period, suggesting higher attack rates in this population [10]. Other studies have also found a significant association between RSV infection and exacerbation of other cardiovascular conditions in older adults, demonstrating that when patients with underlying cardiac disease are infected with RSV, they generally have higher healthcare utilization and worse outcomes [11]. Despite these previously published findings, the burden of RSV infection in older adults may actually be underestimated for several reasons. First, RSV testing is not routinely performed. Second, low awareness of RSV infection in adults among providers leads to a low index of suspicion and clinical diagnosis. Third, RSV is either not suspected or may no longer be detectable when it results in an exacerbation of an underlying chronic cardiac or pulmonary condition. In a important new study from investigators at Kaiser Permanente Southern California, the investigators add to the body of literature and demonstrate the significant burden of RSV infection in older adults [12]. They correctly conclude that this is one of the largest studies to compare outcomes from infection with RSV to influenza in this population and astutely surmise that a comparison with a more widely recognized cause of severe morbidity and mortality may increase provider awareness of the potential of RSV to cause severe disease in older adults and trigger more routine testing for RSV. But why should clinicians be concerned about making a diagnosis of RSV in this patient population? Previous arguments in favor of routine testing for RSV and more comprehensive population-based characterization of infection and disease in older adults have included the support of antimicrobial stewardship efforts, the timely and appropriate isolation of infected patients in acute care settings, and the need to inform the evaluation of antiviral and vaccine candidates in development. However, there is an even more direct benefit to knowing if an elderly patient has an RSV infection, that is, to better care for the patient and understand their risk for, and perhaps prevent, serious clinical outcomes. In an observational retrospective cohort study conducted at the Kaiser Permanente southern California healthcare system, which provides care and access to 4.4 million patients at 15 large community hospitals, Ackerson et al [12]. were able to evaluate a wide range of clinical outcomes for adults hospitalized with RSV infection. During the study period, 645 adults aged ≥ 60 years were hospitalized with RSV and 1878 patients were hospitalized with influenza. Patients with RSV were slightly older, with a higher proportion of adults aged ≥85 years hospitalized compared to those with influenza. Interestingly and consistent with previous reports, patients with RSV were more likely to have CHF (35.3% vs 24.5%; P < .001), COPD (29.8% vs 24.3%; P = .006), or asthma (26.6% vs 18.6%; P = .12) than those with influenza. Patients with RSV were also more likely to have received oseltamivir prior to hospitalization, likely reflecting the failure of outpatient providers to recognize and diagnosis RSV infection, and were more likely to receive antibiotics and treatment with inhaled, oral, or intravenous steroids in the hospital. The latter findings can probably be explained by the higher incidence of complications related to the exacerbation of underlying cardiopulmonary disease in RSV patients compared to those with influenza. Other clinical outcomes in the recent Kaiser Permanente Study [12] included healthcare utilization measures such as length of stay, use of mechanical ventilation or other respiratory support, and intensive care unit (ICU) admission. Previously, healthcare utilization for older patients hospitalized with RSV had been reported to be similar or higher when compared to patients hospitalized with influenza. In 1 study at a single large academic institution, 94% of older adults diagnosed with RSV in the emergency department required hospitalization [13]. Increased disease severity has also been demonstrated for older adults by longer lengths of hospital stay (6 vs 3.6 days) and increased need for mechanical ventilation (16.7% vs 7.2%), resulting in mean adjusted costs for RSV hospitalizations more than double ($38828) those for influenza ($14519) [14]. Additionally, in a recent review of the epidemiology of medically attended RSV infection in older adults, 10%–30% of patients required ICU care and 3%–17% required mechanical ventilation [6]. Similarly, Ackerson and colleagues reported higher lengths of stay among patients with RSV compared to those with influenza (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.2–1.7), more frequent respiratory complications (OR, 2.7; 95% CI, 2.2–3.2), greater oxygen supplementation among other clinical parameters (OR, 1.6; 95% CI, 1.0–1.6), and higher incidence of ICU admission (OR, 1.3; 95% CI, 1.0–1.7). Perhaps the most consequently finding and novel information from the Ackerson study [12] pertain to and novel information pertain to long-term morbidity and mortality. The authors of this article report that one-third more adults infected with RSV required home health service after discharge compared to those with influenza (OR, 1.3; 95% CI, 1.0–1.6). Moreover, 1-year survival after admission was significantly lower in older adults hospitalized with RSV compared to those with influenza (74.2% vs 81.2%; P = < .001). This is the first study to assess the long-term impact of RSV hospitalization, and the conclusions are important. Not only can RSV infections result in severe, acute illnesses for older adults, but infections may also have a lasting and prolonged impact on long-term functional status and mortality. As the authors point out, this may reflect the ability of RSV to drive chronic inflammation associated with persistent and progressive pulmonary disease but may also be related to loss in functional status due to prolonged hospitalization that may, in part, result from the failure to recognize and diagnose RSV infection early. More than 50 therapeutic and vaccine agents are currently being developed making this an ideal time to conduct studies to collect data on the incidence of RSV infection in older adults and characterize the extent of RSV-associated complications and healthcare resource utilization. Ultimately, these data will help to prioritize and evaluate the benefits of RSV prevention and treatment strategies. The authors of this important new study [12] from the Kaiser Permanente Southern California network have provided an important update to what has previously been reported but more importantly demonstrate a significance finding on the long-term impact of RSV in this population. Awareness of the burden of RSV infection in older adults may be improving. Pastula and colleagues conducted a retrospective review of the National Inpatient Sample Data from 1997–2012 and noted increased RSV hospitalization rates from 0.5 to 4.6 per 100000 for older adults, likely due to increased testing and recognition [14]. Conversely, in a recent survey of the diagnostic testing practices for RSV of infectious disease physicians nationwide, 80% of physicians who cared for patients with ARI felt being able to diagnose RSV in adults was either very or somewhat important, but only 48% reported that they were likely to order RSV testing for older adult patients or those with COPD exacerbation [15]. The primary reason given for respondents who reported that diagnosing RSV was not very important was the lack of antiviral treatment or current vaccines, and 63% of physicians surveyed were not aware that RSV candidate vaccines for older adults were in development. While developing protective vaccines and effective antiviral agents is an important goal, I propose that making a diagnosis of RSV infection in older adults is, in itself, a worthwhile pursuit. RSV is not just one of the noninfluenza viral infections without a specific treatment, it is also a viral infection with serious potential long-term clinical consequences for a growing older population. Knowing that an elderly patient has RSV early in their hospital course might allow clinicians to implement early interventions such as chest physiotherapy, bronchodilators, and antiinflammatory treatments, as well as physical therapy, to get the patient moving and prevent deconditioning. Perhaps a diagnosis of RSV and an understanding of the potential functional decline associated with infection in older adults can be used to better counsel patients and their families about overall prognosis and the need for post-hospitalization rehabilitation services. For those reasons, making a diagnosis of RSV should be very important to all clinicians. Potential conflicts of interest.