Etiology

Human rhinoviruses are members of the Picornaviridae family (“pico” = small; “rna” = RNA genome). Traditional methods of virus typing using immune antiserum have identified ≈ 100 serotypes, classified into HRVA and HRVB species on the basis of genetic sequence similarity. A novel group of HRVs designated HRVC has been detected by reverse transcriptase PCR (RT-PCR) but has not yet been cultivated. Virus gene sequence analysis demonstrates that HRVC are a genetically distinct species. The increased proportions of HRV reported in recent PCR-based studies may partly be due to detection of these previously unknown HRVC viruses in addition to improved detection of known HRVA and HRVB strains.

Epidemiology

Rhinoviruses are distributed worldwide, and there is no proven correlation between serotypes and epidemiologic or clinical characteristics. Multiple serotypes may circulate in a community simultaneously, and particular HRV strains may be isolated during consecutive epidemic seasons, suggesting persistence in a community over an extended period. In temperate climates the incidence of HRV infection peaks in fall, with another peak in spring, but HRV infections occur year-round. Rhinoviruses are the major infectious trigger for asthma among young children, and numerous studies have described a sharp increase in asthmatic attacks in this age group when school opens in the fall. Peak HRV incidence in the tropics occurs during the rainy season, from June to October.

Rhinoviruses are present in high concentrations in nasal secretions and can be detected in the lower airways. Rhinovirus particles are nonenveloped and quite hardy, persisting for several hours in secretions on hands or other surfaces such as telephones, light switches, doorknobs, and stethoscopes. Transmission occurs when infected secretions carried on contaminated fingers are rubbed onto nasal or conjunctival mucosa. Rhinoviruses are present in aerosols produced by talking, coughing, and sneezing. Children are the most important reservoir of the virus.

Pathogenesis

The majority of HRVs infect respiratory epithelial cells via intercellular adhesion molecule-1 (ICAM-1), but some HRV strains utilize the LDL (low-density lipoprotein) receptor. Infection begins in the nasopharynx and spreads to the nasal mucosa and in some cases to bronchial epithelial cells in the lower airway. Rhinoviruses do not appear to cause significant direct cellular damage, so it is thought that many of the pathogenic effects are produced by the host immune response. Rhinovirus infection of bronchial epithelial cells in vitro induces the secretion of many inflammatory chemokines and cytokines. Both innate and adaptive immune mechanisms are important in HRV pathogenesis and clearance. HRV-specific nasal immunoglobulin (Ig) A can be detected on day 3 after infection, followed by the production of serum IgM and IgG after 7-8 days. Neutralizing IgG to HRV may prevent or limit the severity of illness following re-infection. Cross protection between antibodies to different HRV serotypes is limited in breadth and duration. Both allergen exposure and elevated IgE values predispose patients with asthma to more severe respiratory symptoms in response to HRV infection. Abnormalities in the host cellular response to HRV infection that result in impaired apoptosis and increased viral replication may be responsible for the severe and prolonged symptoms in individuals with asthma.

Clinical Manifestations

Most HRV infections produce clinical symptoms, but approximately 15% are asymptomatic. Typical symptoms of sneezing, nasal congestion, rhinorrhea, and sore throat develop following an incubation period of 1-4 days. Cough and hoarseness are present in one third of cases. Fever is less common with HRV than with other common respiratory viruses, including influenza virus, RSV, and HMPV. Symptoms are frequently more severe and last longer in children, with 70% of children still reporting symptoms by day 10, compared with 20% of adults. Virus can be shed for as long as 3 wk.

HRVs are the most prevalent agents associated with acute wheezing, otitis media, and hospitalization for respiratory illness in children and are an important cause of severe pneumonia and exacerbation of asthma or chronic obstructive pulmonary disease (COPD) in adults. HRV-associated hospitalizations are more frequent in young infants than in older children and in children with a history of wheezing or asthma. HRV infection in immunocompromised hosts may be life threatening.

Diagnosis

Culturing HRV is labor intensive and relatively low yield. Sensitive and specific diagnostic methods based on RT-PCR are commercially available. An important caveat of HRV detection is the fact that HRV infection can be asymptomatic, and thus the presence of the virus does not prove causality in all cases. Serology is impractical owing to the great number of HRV serotypes. Presumptive clinical diagnosis based on symptoms and seasonality is not specific, because many other viruses cause similar clinical illnesses. Bacterial culture or antigen testing may exclude streptococcal pharyngitis. Rapid detection techniques for HRV might lessen the use of unnecessary antibiotics or procedures.

Complications

Possible complications of HRV infection include sinusitis, otitis media, asthma exacerbation, bronchiolitis, pneumonia, and, rarely, death. HRV-associated wheezing during infancy is a significant risk factor for the development of childhood asthma. This effect appears to remain until adulthood, but the mechanisms have not been elucidated.

Treatment

Supportive care is the mainstay of HRV treatment. The symptoms of HRV infection are commonly treated with analgesics, decongestants, antihistamines, or antitussives. Data are limited on the effectiveness of such over-the-counter cold medications for children. If bacterial superinfections are highly suspected or diagnosed, antibiotics may be appropriate. Antibiotics are not indicated for uncomplicated viral upper respiratory infection. Vaccines have not been successfully developed because of the numerous HRV serotypes and limited cross protection between serotypes.

Prevention

Good handwashing remains the mainstay of prevention of HRV infection and should be reinforced frequently, especially in young children, the predominant “vectors” for disease.