RSV and Rhinovirus Coinfections: Amplifying or Mitigating Disease Severity?

To the Editors: We read the study by Mrubata et al1 with great interest, particularly as it aligns closely with our ongoing investigation into the impact of respiratory syncytial virus (RSV) coinfections on disease severity and progression. Among hospitalized patients with RSV, the most common coinfecting viruses during the prepandemic period were human rhinovirus (hRV; 9.3%) and influenza (4.9%). During the pandemic period, hRV (10.8%) and human bocavirus (10.8%) were frequently detected as coinfections, whereas, in the postpandemic period, hRV (9.1%) and coronavirus (9.7%) were most identified. In up to 50% of episodes, a second virus was detected, with hRV being the most frequently codetected virus alongside RSV.2,3 This high coinfection rate is likely driven by the overlapping seasonal distribution and the elevated incidence of both viruses, particularly during December, January and February (Fig. 1). In addition, codetection may reflect sequential infections, given the prolonged viral shedding period associated with hRV.4FIGURE 1.: The percentage of positive cases with RSV and hRV at hospital-based surveillance. The data demonstrate an annual seasonal pattern by yearly averaging the percentage of positive cases with RSV and other respiratory viruses over a 7-year period, encompassing prepandemic (2017, 2018 and 2019), pandemic (2020 and 2021) and postpandemic (2022 and 2023). The percentage of positive cases was determined based on biweekly surveillance.In our cohort, which included patients infected with only hRV (n=596), only RSV (n=276) and those coinfected with RSV and hRV (n=37), the median age (interquartile range) of the patients was 43 (15–99), 4 (1–22) and 6 (2–38) months, respectively, with statistically significant differences (P < 0.001). Respiratory symptoms and clinical findings, including crackles, wheezing and decreased oxygen saturation, were most prevalent among patients with RSV-only infections, followed by those with RSV-hRV coinfections, and were least common in hRV-only cases (P < 0.001). Bronchiolitis was exclusively observed in RSV-only infections (10.9%), whereas it was absent in the other groups. In contrast, lower respiratory tract infections were significantly more common in coinfected patients (89.2%), followed by RSV-only cases (80.1%) and hRV-only cases (52.9%; P < 0.001). Notably, the requirement for respiratory support was the highest among patients with RSV only (71.0%), followed by coinfected patients (56.8%) and those with hRV-only infections (27.5%; P < 0.001). Importantly, no mortality was observed among patients coinfected with RSV and hRV, whereas infection-related deaths were reported in 1.1% of RSV-only cases and 0.8% of hRV-only cases. Multivariate logistic regression analysis identified neurologic and oncologic comorbidities, along with elevated C-reactive protein levels, as significant predictors of the need for respiratory support. While univariate models indicated a higher risk of requiring respiratory support in patients with coinfections and RSV-only infections, this association was not sustained in multivariate models. Resch et al5 previously reported that viral coinfections with RSV, particularly involving influenza virus, adenovirus and hRV, were associated with more severe disease outcomes. Our findings corroborate the hypothesis that RSV amplifies the severity of hRV infections, while hRV appears to attenuate the severity of RSV infections. This interaction diverges from the dynamics described between SARS-CoV-2 and RSV in the study by Mrubata et al.