Researchers at Children’s Hospital of Philadelphia (CHOP) have found that circadian rhythms, the body’s internal biological clocks, can affect how patients recover from influenza infections. The study, published in the Journal of Clinical Investigation, suggests that aligning clinical care with these natural rhythms could help improve outcomes for patients with respiratory viral infections.
Circadian rhythms operate on a roughly 24-hour cycle and help organisms adapt to environmental changes. While it is commonly known that disruptions like shift work or jet lag can affect alertness and sleep, it is less widely recognized that these rhythms also influence how the body responds to infections. The researchers believe that understanding and utilizing these patterns could help clinicians time interventions more effectively.
The study examined how external cues such as light exposure and meal timing—known as “zeitgebers”—help synchronize circadian rhythms in organs and cells. Previous research by the team indicated that certain times of day are linked to better immune responses against viruses like influenza. However, whether ongoing exposure to rhythmic cues after infection could maintain this protection was not previously understood.
“Since influenza affects patients over a period of several days, we were able to test how zeitgebers like light influence this time-of-day-specific protection even after the host sustains the infection,” said senior study author Shaon Sengupta, MBBS, MPH, an attending neonatologist in CHOP’s Division of Neonatology. “We suspected that sustaining exposure to these rhythmic external cues helps maintain this level of protection after an infection.”
Using preclinical models, the researchers discovered that disrupting normal lighting schedules during a critical window eliminated the protective effect seen at specific times of day. This led to an abnormal immune response and increased inflammation in the lungs during upper respiratory infection. However, keeping a regular meal schedule reduced some negative effects caused by disrupted light cycles. This finding suggests that certain external cues can compensate when other aspects of the body’s clock are disturbed.
“Our findings are of particular relevance for hospitalized patients, since circadian disruption due to erratic light-cycling or meal timing are rather prevalent in such settings,” Sengupta said. “Our data suggest that circadian health of the host is a critical determinant of outcomes and may be modified by well-timed environmental cues with potential to drive outcomes in severe respiratory viral infection. Beyond mechanistic insights, our study calls for incorporating circadian-sensitive practices on hospital floors and intensive care units. These may include, but are not limited to, light-cycling and meal-timing interventions as strategies to bolster immune response and hasten recovery.”
The research received support from National Institutes of Health grants R01HL155934-01A1 and NHLBI R01HL147472 as well as funding from the Raine Medical Research Foundation.
Paul et al., “Effect of external cues on clock-driven protection from influenza A infection.” J Clin Invest. Online November 17, 2025. DOI: 10.1172/JCI193133.
