Trends in Viral Respiratory Culture: Impacts of the SARS-CoV-2 Pandemic

Abstract Introduction Due to the increasing ease and availability of molecular assays, viral culture is rarely employed for the diagnosis of respiratory illnesses. Despite lower sensitivity than molecular techniques, viral culture may detect a wider array of viral pathogens at a lower cost relative to multiplex molecular panels. In this study, we examined the effects of the SARS-CoV-2 pandemic on viral respiratory culture ordering and trends in the rates of pathogen detection. Methods Viral respiratory culture results from Jan 1st, 2017 to February 28th, 2022 were analyzed for changes in the number of monthly orders, positivity rate, and incidence of individual pathogens. To determine changes in seasonal incidence and viral etiology, a comparison was made between winter (Dec-Feb) and summer (June-Aug) months as well as acute (Influenza A/B, RSV) and chronic (HSV, CMV) infections. Given SARS-CoV-2’s classification as a BSL-3 pathogen, our viral culture assay was not designed to detect this virus. As a surrogate method to measure rates of SARS-CoV-2 in viral culture specimens, we performed NAAT testing with the ThermoFisher TaqPath COVID-19, Flu A/B, RSV assay on negative specimens. Results Following the pandemic, testing volume decreased by 46.7% with the overall positivity rate decreasing from 6.67% to 4.85%. Among the 46 states for which more than ten orders were placed, monthly testing decreased in 38 states. Of the eight states with increased average monthly testing, the greatest increases were seen in Rhode Island, Nevada, and Montana. During the pre-pandemic timeframe, acute respiratory pathogens demonstrated a typical winter peak with low summer detection. Post-pandemic, there was an atypical increase of acute respiratory pathogens, driven primarily by RSV. The positivity rate for chronic viral infections increased from 3.43% pre-pandemic to 4.09% post-pandemic. Following the pandemic, HSV has replaced influenza as the most commonly detected pathogen during winter months. Molecular studies of 229 negative viral culture specimens identified 36 (15.7%) samples positive for SARS-CoV-2, 9 (3.9%) for RSV, and none for influenza A or B. Median cycle threshold values for SARS-CoV-2 samples were 21.3 (range: 9.1-36.5). Conclusions Following the SARS-CoV-2 pandemic, the number of respiratory virus cultures ordered significantly decreased. There has also been a statistically significant decrease in the positivity rate driven by the absence of acute viral respiratory pathogens, including influenza A/B and RSV. We also observed an offseason increase of RSV during the summer months of 2021. Detection rates of chronic viral pathogens including CMV and HSV have remained relative stable. The presence of SARS-CoV-2 in negative specimens raises concerns for inappropriate test utilization. While less sensitive than molecular methods, viral culture has the potential to offer a lower cost alternative for monitoring a broad range of viral pathogens.