Real-time lung function measurements of Syrian hamsters for SARS-CoV-2 research

In preclinical rodent models of respiratory viral infections, disease is frequently evaluated on virological, pathological and surrogate clinical parameters not directly associated with lung function. In humans, however, measurement of lung function is critical for the assessment of respiratory disease severity. To bridge the gap between preclinical and clinical readouts, we set up a whole-body plethysmography (WBP) system in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements have been investigated extensively for mice and rats in preclinical research, work in hamster models is underdeveloped. To address this, we performed a series of experiments aimed at measuring lung function via WBP in unrestrained SARS-CoV-2-infected hamsters. During our measurements, we obtained highly variable and contradictory values outside the normal physiological range. We hypothesized and confirmed by video surveillance that this was due to background noise created by normal movement/exploration of the hamsters. Importantly, however, we obtained reliable respiratory parameters when hamsters were at rest. We noted that the curiosity of hamsters in exploring the WBP chambers was not substantially reduced even after repeated acclimatization of several hours. We conclude that prolonged, video-supported measurements will be needed to obtain sufficient reliable datapoints during periods when the hamsters are at rest, an approach that is challenging and impractical under BSL-3 conditions. In summary, our experience shows that WBP data obtained from unrestrained Syrian hamsters may require methodic interpretation. We plan to investigate strategies to limit animal movement, which could aid in obtaining more reliable results within a feasible measurement window.