Clinical progression parameters associated with SARS-CoV-2, influenza, and respiratory syncytial virus infections

Mathematical and computational models are often used to forecast respiratory infectious disease burden, including to inform healthcare capacity requirements. We aimed to characterize pathways of clinical progression associated with SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) infections using data from patients in an integrated healthcare system, whose encounters were monitored across all levels of acuity spanning virtual, ambulatory, and inpatient care settings. Using parametric survival models, we estimated probabilities of progression and distributions of time to progression from each care setting to all higher-acuity settings on a cascade encompassing the following classes of events or healthcare encounters: symptoms onset; diagnostic testing; telehealth or other virtual care appointment; outpatient physician office visit; urgent care presentation; emergency department presentation; hospital admission; mechanical ventilation; and death. Our analyses included data from 59,668, 22,705, and 1,668 episodes associated with positive SARS-CoV-2, influenza, and RSV tests, respectively, between 1 April 2023 and 31 March 2024. First clinical encounters occurred in inpatient settings for only 4.7%, 3.4%, and 18.7% of SARS-CoV-2, influenza, and RSV episodes, respectively, with median times (interquartile range) of 6.8 (3.6-13.2), 6.6 (3.5-12.1), and 6.4 (3.8-10.6) days from symptoms onset to admission. Overall, 7.9% of SARS-CoV-2 episodes, 5.8% of influenza episodes, and 33.8% of RSV episodes resulted in inpatient admission, ventilation, or death. Between 40.4-62.1%, 71.6-87.3%, and 47.9-58.7% of SARS-CoV-2, influenza, and RSV infections, respectively, had encounters in lower-acuity virtual care, outpatient, or urgent care settings. For all three viruses, the proportions of cases receiving care at each level of acuity increased with older age and greater numbers of comorbid conditions. Median durations of hospital stay were 4.2 (2.6-7.3), 4.0 (2.3-6.8), and 4.3 (2.5-7.4) days for SARS-CoV-2, influenza, and RSV episodes resulting in admission. These estimates provide a basis for modeling real-world clinical care requirements and the progression of respiratory viral infections. AUTHOR SUMMARYModels of respiratory infections such as SARS-CoV-2, influenza, and RSV are used to forecast disease burden and plan the allocation of healthcare resources. Early healthcare system encounters--for instance, for receipt of care in virtual or outpatient settings--may provide a basis for anticipating higher-acuity care requirements as patients progress to more severe disease. However, limited data are available addressing patterns of healthcare utilization among patients with these infections. Using electronic healthcare records from an integrated healthcare system, we estimated probabilities and rates of progression from lower-acuity states, such as virtual or outpatient visits, to increasingly higher-acuity states including inpatient admission, ventilation, and death. We quantified associations of demographic and clinical risk factors with progression probabilities for each infection. We provide a databank containing fitted distributions for progression to inform infectious disease modeling.