Human rhinovirus species and season of infection determine illness severity

Abstract

Rationale: Human rhinoviruses (HRVs) consist of approximately 160 types that cause a wide range of clinical outcomes, including asymptomatic infections, common colds, and severe lower respiratory illnesses.

Objectives: To identify factors that influence the severity of HRV illnesses.

Methods: HRV species and types were determined in 1,445 nasal lavages that were prospectively collected from 209 infants participating in a birth cohort who had at least one HRV infection. Questionnaires were used during each illness to identify moderate to severe illnesses (MSI).

Measurements and main results: Altogether, 670 HRV infections were identified, and 519 of them were solitary infections (only one HRV type). These 519 viruses belonged to 93 different types of three species: 49 A, 9 B, and 35 C types. HRV-A (odds ratio, 8.2) and HRV-C (odds ratio, 7.6) were more likely to cause MSI compared with HRV-B. In addition, HRV infections were 5- to 10-fold more likely to cause MSI in the winter months (P < 0.0001) compared with summer, in contrast to peak seasonal prevalence in spring and fall. When significant differences in host susceptibility to MSI (P = 0.004) were considered, strain-specific rates of HRV MSI ranged from less than 1% to more than 20%.

Conclusions: Factors related to HRV species and type, season, and host susceptibility determine the risk of more severe HRV illness in infancy. These findings suggest that anti-HRV strategies should focus on HRV-A and -C species and identify the need for additional studies to determine mechanisms for seasonal increases of HRV severity, independent of viral prevalence, in cold weather months.

Figure 1.

Prevalence of human rhinovirus (HRV) infection according to severity of illness. A total of 1,445 samples of nasal mucus collected from 209 infants in their first year of life between March 1999 and May 2001 were tested for common respiratory viruses. Viruses in the non-HRV category included respiratory syncytial virus A and B, coronaviruses NL63 and OC43, parainfluenza viruses 1 to 4, human metapneumovirus, influenza A and B, adenovirus B and C, enteroviruses, and bocavirus.

Figure 2.

Epidemiology of human rhinovirus (HRV) infections and illnesses. HRV infections were identified in 670 of 1,445 samples, and infection rates (per 100 child-days) were plotted according to the month of sampling (A). The seasonality of respiratory syncytial virus infections in the study is included for contrast. To examine the relationship between season and severity of illness, the percent of solitary HRV infections (n = 519) that caused moderate to severe illness (MSI) was estimated using mixed effects logistic regression models (B). Month of infection was strongly associated with the risk of MSI (P < 0.0001). Error bars represent 95% confidence intervals.

Figure 3.

Differential virulence of human rhinovirus (HRV) species and types. The species and types of the 519 solitary HRV infections were determined by partial genome sequencing. The probability of inducing moderate to severe illness (MSI) by each species (A) and type (B) was estimated using mixed effects logistic regression models. Error bars represent 95% confidence intervals.

Figure 4.

Risk of human rhinovirus (HRV) moderate to severe illness (MSI) depends on both susceptibility and virus type. Using mixed effects logistic regression models, we estimated the virulence (propensity to cause MSI) of the 93 different HRV types (x axis, ordered low to high), and the susceptibility to MSI for 219 study participants (y axis, ordered low to high). The graph illustrates the risk of MSI for all combinations of subject susceptibility and HRV type. The species of each type is indicated on the upper color bar (A = black; B = green; C = red).