Background
The common cold is an acute respiratory tract infection (ARTI) characterized by mild coryzal symptoms, rhinorrhea, nasal obstruction, and sneezing. Although the incidence of ARTI cannot be clearly defined because of seasonal and locational variability, it is estimated to vary from 3-6 cases per person per year in the United States. Children younger than 1 year have experienced an average of 6-8 episodes of ARTI. This figure decreases to 3-4 episodes per year by adulthood. Although the list of agents that cause the common cold is large, 66-75% of cases are due to 200 antigenically distinct viruses from 8 different genera. The most common of these are the rhinoviruses (25-80% of cases), followed by coronaviruses (10-20%), influenza viruses (10-15%), and adenoviruses (5%).
Rhinoviruses are members of the Picornaviridae family, which includes the human pathogens enteroviruses and hepadnaviruses (notably, hepatitis A). Rhinoviruses are small, nonenveloped, positive (sense) stranded RNA viruses. Their structure is an icosahedral capsid of 12 pentamers containing the 4 viral proteins. A deep cleft is involved in viral attachment. Attachment to cellular receptors can be blocked by a specific antibody. More than 100 different subtypes exist in 3 major groups and are categorized based on receptor specificity: intercellular adhesion molecule-1 (ICAM-1), low-density lipoprotein (LDL) receptors, and sialoprotein cell receptors.
Rhinoviral infections are chiefly limited to the upper respiratory tract but may cause otitis media and sinusitis. Rhinoviral infections may exacerbate asthma, cystic fibrosis, chronic bronchitis, and serious lower respiratory tract illness in infants, elderly persons, and immunocompromised persons. Although infections occur year-round, the greatest incidence occurs in the fall and spring. Of persons exposed to the virus, 70-80% have symptomatic disease.
Pathophysiology
Rhinoviruses are transmitted to susceptible individuals by direct contact or by aerosol particles infecting both ciliated areas of the nose and nonciliated areas of the nasopharynx through receptors, most frequently ICAM-1 (found in high quantities in the posterior nasopharynx). Few cells are actually infected by the virus, and the infection involves only a small portion of the epithelium. Symptoms develop 1-2 days after viral infection, peaking 2-4 days after inoculation, although reports have described symptoms as early as 2 hours after inoculation with primary symptoms 8-16 hours later.
Detectable histopathology that causes the associated nasal obstruction, rhinorrhea, and sneezing is lacking, which leads to the hypothesis that the host immune response plays a major role in rhinovirus pathogenesis. Infected cells release interleukin-8 (IL-8), which is a potent polymorphonuclear (PMN) chemoattractant. Concentrations of IL-8 in secretions correlate proportionally with the severity of common cold symptoms. Inflammatory mediators, such as kinins and prostaglandins, may cause vasodilatation, increased vascular permeability, and exocrine gland secretion. These, together with local parasympathetic nerve-ending stimulation, lead to cold symptoms.
Deficient interferon-beta production by asthmatic bronchial epithelial cells has been proposed as a mechanism for increased susceptibility to rhinoviral infections in individuals with asthma.
Viral clearance is associated with the host response and is due, in part, to the local production of nitric oxide. Serotype-specific neutralizing antibodies are found 7-21 days after infection in 80% of patients. Although these antibodies persist for years, providing long-lasting immunity, recovery from illness is more likely related to cell-mediated immunity. Persistent protection from repeat infection by that serotype appears to be partially attributable to immunoglobulin A (IgA) antibodies in nasal secretions, serum immunoglobulin G (IgG), and, possibly, serum immunoglobulin M (IgM).
The virus grows in a limited temperature range (33-35°C) and cannot tolerate an acidic environment. Thus, finding the virus outside of the nasopharynx is unlikely because of the acidic environment of the stomach and the increased temperature in both the lower respiratory and gastrointestinal tracts.
Epidemiology
Frequency
United States
The frequency of rhinoviral infection averages 1 episode every 1-2 years per person. Rhinoviruses cause up to 80% of colds during the autumn months in temperate climates.
International
Rhinoviruses have been found in all countries, even in remote areas such as the Kaluhi Islands and the Amazon. In Brazil, rhinoviruses reportedly cause 46% of ARTIs.
Mortality/Morbidity
Although not associated with fatal disease, rhinoviruses are associated with significant morbidity. ARTIs, predominantly rhinoviral infections, are estimated to cause 30-50% of time lost from work by adults and 60-80% of time lost from school by children. Complications of rhinoviral infections include otitis media, sinusitis, chronic bronchitis, and exacerbations of reactive airway disease in children and adults. These viruses are possibly involved in lower respiratory tract infections in elderly persons, infants, persons with cystic fibrosis, and immunosuppressed patients. The true impact of lower respiratory tract infection is not clear. Recovery of rhinovirus in these patients may be a marker of an underlying disease process or a precursor to a bacterial infection.
Race
No difference in susceptibility to infection or disease course has been described among different races.
Sex
Some reports indicate a male predominance of infection in children younger than 3 years, which switches to a female predominance in children older than 3 years. No difference in rates of infection in adults is apparent.
Age
Rhinoviral infection is most common in children, with decreasing incidence as they approach adulthood. Children are instrumental in transmission of infection, commonly passing infection to family members after contracting the virus in nurseries, daycare facilities, and schools.
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