Discussion

Based on real-world testing data from over 250 hospitals, we observed a shift in practice from clinical use of predominantly large multiplex NAAT respiratory panels prepandemic to small panels later in the pandemic after a transient disruption in use of panels of all sizes during the early pandemic period. This study represents the largest to date to examine patterns of respiratory NAAT testing across multiple hospitals, and our findings likely match the lived experience of most frontline clinicians. Use of small multiplex NAAT respiratory panels has become much more common in clinical care.

Multiple factors may drive implementation and clinical use of diagnostic testing, and we were unable to evaluate why specific tests were performed. During the early pandemic period, decision-making about which tests to implement was likely driven by the availability of supplies and staff. ¹³ We observed decreased use of respiratory panels of all sizes consistent with testing shortages during this period. Later in the pandemic, after disruptions in the supply chain began to ease, increased use of small panels may have reflected growing familiarity with and acceptance of point-of-care testing. ^{Reference Babic, Garner and Hirschhorn20} However, beyond what tests are available, real-world data can reveal the preferences of laboratorians, hospital administrators, and clinicians on which multiplex NAAT respiratory panels have the highest relative clinical value and utility. We suspect that the observed trends in testing reflect the perceived relative value and utility of different respiratory panels. For instance, we suspect that the observed shift from predominantly large panel use prepandemic to predominantly small panel use postpandemic was at least partially driven by the difference in cost of large and small panels. ^{Reference Baghdadi, O’Hara and Johnson3} Issues related to cost are exacerbated by more selective coverage for the large panels by health insurance.

However, the postpandemic shift toward increased use of small panels may also be attributable to the higher relative clinical utility of small panels. The potential appeal of large NAAT respiratory panels is that they test “for everything.” ^{Reference Schreckenberger and McAdam21} In practice, this approach means that large panels tend to include pathogens that clinicians are either less aware of or less concerned about, such as human rhinovirus, metapneumovirus, or bocavirus. Small panels, on the other hand, are typically limited to viral pathogens that clinicians care about, either because the results will inform antiviral treatment, as with COVID-19 or influenza, or because of important related clinical syndromes, as with RSV. Thus, small panels may be perceived as providing greater value both in terms of clinical yield and costs.

Some diagnostic tests, such as NAATs for SARS-CoV-2, produce meaningful results even when negative. But most clinicians do not perform respiratory panel testing with the intention of ruling out disease due to seasonal coronavirus HKU1. Testing for this viral pathogen, like most of the viral pathogens included on large respiratory panels but excluded from small respiratory panels, is only meaningful when positive. Human coronavirus HKU1 is “marginal” both in the sense that it is less clinically important and the sense that testing for it is a marginal benefit offered by larger respiratory panels. For marginal pathogens, the rate of test positivity can be considered an indirect measure of clinical utility. Thus, the observation that multiplex NAAT respiratory panels are rarely positive for marginal pathogens further supports our inference that large respiratory panels do not provide much marginal utility over small panels.

When considering the relative value and utility of each pathogen included on a respiratory panel, atypical bacteria represent a special case. Classically, M. pneumoniae, C. pneumoniae, and Legionella, were believed to cause 10-20% of all cases of community-acquired pneumonia. ^{Reference Bartlett and Mundy22} More recent studies have estimated the incidence of these pathogens as closer to 1%–3%. ^{Reference Schreckenberger and McAdam21,Reference Jain, Self and Wunderink23} When including all patients tested by respiratory panel, the incidence in our sample was <1%. Theoretically, tests for atypical bacteria should be meaningful even when negative, because a negative test can support appropriate discontinuation or de-escalation of antibiotics. However, multiple studies have demonstrated that respiratory panel testing does not influence antibiotic use by clinicians in practice among adult patients. ^{Reference Hatzileris, Holder and Braun24–Reference Brendish, Malachira and Armstrong26} Indeed, many clinicians are not even aware many respiratory panels include atypical bacteria. ^{Reference Baghdadi, Yang and Lynen27} Thus, our finding that respiratory panels are almost never positive for atypical bacteria supports the inference that large respiratory panels are less useful than small ones. If a clinician’s reason for testing with a large respiratory panel is to evaluate for atypical bacterial infection, they might as well not bother.

This study is subject to the limitations of an analysis of administrative discharge data. We ascertained the composition and size of respiratory panels based on the way groups of NAATs were collected and reported, rather than based on a test order or panel name. Thus, though our method may not capture the true composition of every panel, it does reflect the way each panel was reported to clinicians on the treatment team. Further, we were unable to account for why testing was being performed. We likely captured testing that was performed both for clinical diagnosis and testing performed for surveillance and infection prevention. Though we are unable to understand why specific tests or groups of tests were ordered, the observed trends in testing may generate hypotheses related to clinical utility of respiratory panels of different sizes.