Introduction
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.
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 KaluhiIslands 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.
Clinical
History
Rhinoviral infections are typically indistinguishable from colds of other viral etiologies. Individual patients exhibit a wide variety of signs and symptoms.
- The incubation period is 12-72 hours, averaging 8-16 hours after viral inoculation of the nose. Symptomatic complaints 2 hours after viral inoculation have been described.
- Illness initially begins with a sore throat, which is frequently the most bothersome of the early symptoms. This is followed by nasal discharge, nasal congestion, and sneezing, which intensify over the next 2-3 days.
- Other associated complaints include headache, facial and ear pressure, and loss of smell and taste.
- Thirty percent of infected individuals develop a cough, and 20% develop hoarseness, both of which may persist up to a week, although they seldom become bothersome until nasal symptoms improve.
- Systemic signs and symptoms, such as fever and malaise, are unusual. If they are present, consider an alternative diagnosis.
- Symptoms generally last 7-11 days, although they persist up to 2 weeks in a quarter of patients. Rarely, patients complain of lingering symptoms that last more than 30 days.
- Infants and toddlers may display only nasal discharge. However, Calvo et al recently reported that, among infants younger than 2 years with viral respiratory tract infection requiring hospitalization in Spain, rhinoviral infections are second only to respiratory syncytial virus infections in terms of frequency.46
- School-aged children usually complain of nasal congestion, cough, and runny nose. These symptoms persist for an average of at least 10 days.45
- Most patients have obstruction and mucosal abnormalities of sinuses, eustachian tubes, and middle ear, which causes a predisposition to secondary bacterial infection in up to 2% of patients.
- Infection may exacerbate underlying asthma and chronic pulmonary disease.
- People who smoke do not appear to have more frequent rhinoviral infections; however, their infections are more severe and their symptoms of longer duration.
Physical
The physical examination findings are typically less severe than those reported by the patient.
- Red nose with dripping nasal discharge may be present.
- Nasal mucous membranes have a glistening glassy appearance without obvious erythema or edema. Yellow or green nasal discharge does not indicate bacterial infection because a large number of white blood cells migrate to the site of viral infection.
- If marked erythema, edema, exudates, or small vesicles are observed in the oropharynx or if conjunctivitis or polyps in the nasal mucosa occur, consider other etiologies, including infection with adenovirus, herpes simplex virus, mononucleosis, diphtheria, coxsackievirus A, or group A streptococci (GAS).
- Auscultation of the chest may reveal rhonchi.
Causes
- Rhinoviral transmission occurs with close exposure to infected respiratory secretions, including hand-to-hand, self-inoculation of eyes or nose, and, possibly, large- and small-particle aerosolization. The virus has been cultured from the skin after up to 2 hours and after up to 4 days on inanimate objects in ideal conditions. Donors are typically symptomatic with a cold at the time of transmission, and virus is detected on their hands and nasal mucosa.
- One recent study assessed the transfer of virus to surfaces in 15 adults with rhinoviral infection. Each stayed overnight in a hotel room. Afterward, 10 commonly-touched sites in each room were tested for viral contaminants. They found that virus could be recovered from 35% of these sites. Furthermore, they found that virus could be transferred back from inanimate objects to fingertips in many cases.47
- Higher rates occur in humid, crowded conditions, as found in nurseries, daycare centers, and schools, especially during cooler months in temperate regions and the rainy season in tropical regions.
- The likelihood of transmission does not appear to be related to exposure to cold temperatures, fatigue, or sleep deprivation.
More on Rhinoviruses |
 Overview: Rhinoviruses |
| Differential Diagnoses & Workup: Rhinoviruses |
| Treatment & Medication: Rhinoviruses |
| Follow-up: Rhinoviruses |
| References |
| Next Page » |
References
Arola M, Ruuskanen O, Ziegler T, et al. Clinical role of respiratory virus infection in acute otitis media. Pediatrics. Dec 1990;86(6):848-55. [Medline].
Arruda E, Pitkaranta A, Witek TJ Jr, et al. Frequency and natural history of rhinovirus infections in adults during autumn. J Clin Microbiol. Nov 1997;35(11):2864-8. [Medline].
Dagher H, Donninger H, Hutchinson P, et al. Rhinovirus detection: comparison of real-time and conventional PCR. J Virol Methods. May 2004;117(2):113-21. [Medline].
Dick EC, Jennings LC, Mink KA, et al. Aerosol transmission of rhinovirus colds. J Infect Dis. Sep 1987;156(3):442-8. [Medline].
Douglas RG, Lindgren KM, Couch RB. Exposure to cold environment and rhinovirus common cold. Failure to demonstrate effect. N Eng J Med. 1968;279:742-7.
Ghosh S, Champlin R, Couch R, et al. Rhinovirus infections in myelosuppressed adult blood and marrow transplant recipients. Clin Infect Dis. Sep 1999;29(3):528-32. [Medline].
Goldmann DA. Transmission of viral respiratory infections in the home. Pediatr Infect Dis J. Oct 2000;19(10 Suppl):S97-102. [Medline].
Gwaltney JM Jr, Phillips CD, Miller RD, et al. Computed tomographic study of the common cold. N Engl J Med. Jan 6 1994;330(1):25-30. [Medline].
Gwaltney JM Jr, Hendley JO, Simon G, et al. Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl J Med. Dec 8 1966;275(23):1261-8. [Medline].
Gwaltney JM Jr, Hendley JO, Simon G, et al. Rhinovirus infections in an industrial population. II. Characteristics of illness and antibody response. JAMA. Nov 6 1967;202(6):494-500. [Medline].
Gwaltney JM Jr, Winther B, Patrie JT, et al. Combined antiviral-antimediator treatment for the common cold. J Infect Dis. Jul 15 2002;186(2):147-54. [Medline].
Halperin SA, Eggleston PA, Beasley P, et al. Exacerbations of asthma in adults during experimental rhinovirus infection. Am Rev Respir Dis. Nov 1985;132(5):976-80. [Medline].
Harris JM 2nd, Gwaltney JM Jr. Incubation periods of experimental rhinovirus infection and illness. Clin Infect Dis. Dec 1996;23(6):1287-90. [Medline].
Hayden FG, Herrington DT, Coats TL, et al. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Clin Infect Dis. Jun 15 2003;36(12):1523-32. [Medline].
Hayden FG, Turner RB, Gwaltney JM, et al. Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob Agents Chemother. Dec 2003;47(12):3907-16. [Medline].
Hendley JO, Gwaltney JM Jr. Mechanisms of transmission of rhinovirus infections. Epidemiol Rev. 1988;10:243-58. [Medline].
Jartti T, Lehtinen P, Vuorinen T, et al. Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children. J Med Virol. Apr 2004;72(4):695-9. [Medline].
Jartti T, Lehtinen P, Vanto T, et al. Evaluation of the efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus. Pediatr Infect Dis J. Jun 2006;25(6):482-8. [Medline].
Jennings LC, Anderson TP, Werno AM, et al. Viral etiology of acute respiratory tract infections in children presenting to hospital: role of polymerase chain reaction and demonstration of multiple infections. Pediatr Infect Dis J. Nov 2004;23(11):1003-7. [Medline].
Kirkpatrick GL. The common cold. Prim Care. Dec 1996;23(4):657-75. [Medline].
Ledford RM, Patel NR, Demenczuk TM, et al. VP1 sequencing of all human rhinovirus serotypes: insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds. J Virol. Apr 2004;78(7):3663-74. [Medline].
Lemanske RF Jr, Jackson DJ, Gangnon RE, et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. Sep 2005;116(3):571-7.
Makela MJ, Puhakka T, Ruuskanen O, et al. Viruses and bacteria in the etiology of the common cold. J Clin Microbiol. Feb 1998;36(2):539-42. [Medline].
Malcolm E, Arruda E, Hayden FG, et al. Clinical features of patients with acute respiratory illness and rhinovirus in their bronchoalveolar lavages. J Clin Virol. Apr 2001;21(1):9-16. [Medline].
McBride TP, Doyle WJ, Hayden FG, et al. Alterations of the eustachian tube, middle ear, and nose in rhinovirus infection. Arch Otolaryngol Head Neck Surg. Sep 1989;115(9):1054-9. [Medline].
Monto AS, Bryan ER, Ohmit S. Rhinovirus infections in Tecumseh, Michigan: frequency of illness and number of serotypes. J Infect Dis. Jul 1987;156(1):43-9. [Medline].
Monto AS, Ullman BM. Acute respiratory illness in an American community. The Tecumseh study. JAMA. Jan 14 1974;227(2):164-9. [Medline].
Naclerio RM, Proud D, Lichtenstein LM, et al. Kinins are generated during experimental rhinovirus colds. J Infect Dis. Jan 1988;157(1):133-42. [Medline].
Nicholson KG, Kent J, Hammersley V, et al. Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden. BMJ. Oct 25 1997;315(7115):1060-4. [Medline].
Rotbart HA, Hayden FG. Picornavirus infections: a primer for the practitioner. Arch Fam Med. Sep-Oct 2000;9(9):913-20. [Medline].
Sanders SP, Proud D, Permutt S, et al. Role of nasal nitric oxide in the resolution of experimental rhinovirus infection. J Allergy Clin Immunol. Apr 2004;113(4):697-702. [Medline].
Schoop R, Klein P, Suter A, et al. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clin Ther. Feb 2006;28(2):174-83. [Medline].
Schwartz AR, Togo Y, Hornick RB, et al. Evaluation of the efficacy of ascorbic acid in prophylaxis of induced rhinovirus 44 infection in man. J Infect Dis. Oct 1973;128(4):500-5. [Medline].
Singh M. Heated, humidified air for the common cold. Cochrane Database Syst Rev. 2004;CD001728. [Medline].
Smith CB, Kanner RE, Golden CA, et al. Effect of viral infections on pulmonary function in patients with chronic obstructive pulmonary diseases. J Infect Dis. Mar 1980;141(3):271-80. [Medline].
Sperber SJ, Shah LP, Gilbert RD, et al. Echinacea purpurea for prevention of experimental rhinovirus colds. Clin Infect Dis. May 15 2004;38(10):1367-71. [Medline].
Turner RB. The treatment of rhinovirus infections: progress and potential. Antiviral Res. Jan 2001;49(1):1-14. [Medline].
Turner RB, Biedermann KA, Morgan JM, et al. Efficacy of organic acids in hand cleansers for prevention of rhinovirus infections. Antimicrob Agents Chemother. Jul 2004;48(7):2595-8. [Medline].
Turner RB, Bauer R, Woelkart K, et al. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med. Jul 28 2005;353(4):341-8. [Medline].
Wark PA, Johnston SL, Bucchieri F, et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. Mar 21 2005;201(6):937-47. [Medline].
Wilkinson TM, Hurst JR, Perera WR, et al. Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD. Chest. Feb 2006;129(2):317-24.
Winther B, Brofeldt S, Christensen B, et al. Light and scanning electron microscopy of nasal biopsy material from patients with naturally acquired common colds. Acta Otolaryngol. Mar-Apr 1984;97(3-4):309-18. [Medline].
de Arruda E, Hayden FG, McAuliffe JF, et al. Acute respiratory viral infections in ambulatory children of urban northeast Brazil. J Infect Dis. Aug 1991;164(2):252-8. [Medline].
van Kraaij MG, van Elden LJ, van Loon AM, et al. Frequent detection of respiratory viruses in adult recipients of stem cell transplants with the use of real-time polymerase chain reaction, compared with viral culture. Clin Infect Dis. Mar 1 2005;40(5):662-9. [Medline].
Pappas DE, Hendley JO, Hayden FG, et al. Symptom profile of common colds in school-aged children. Pediatr Infect Dis J. Jan 2008;27(1):8-11. [Medline].
Calvo C, Garcia-Garcia ML, Blanco C, et al. Role of rhinovirus in hospitalized infants with respiratory tract infections in Spain. Pediatr Infect Dis J. Oct 2007;26(10):904-8. [Medline].
Winther B, McCue K, Ashe K, et al. Environmental contamination with rhinovirus and transfer to fingers of healthy individuals by daily life activity. J Med Virol. Oct 2007;79(10):1606-10. [Medline].
Gern JE, Mosser AG, Swenson CA, et al. Inhibition of rhinovirus replication in vitro and in vivo by acid-buffered saline. J Infect Dis. Apr 15 2007;195(8):1137-43. [Medline].
Miller EK, Lu X, Erdman DD, et al. Rhinovirus-associated hospitalizations in young children. J Infect Dis. Mar 15 2007;195(6):773-81. [Medline].
Turner RB, Wecker MT, Pohl G, et al. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA. May 19 1999;281(19):1797-804. [Medline].
Further Reading
Keywords
rhinoviruses, rhinovirus infection, cold, common cold, respiratory virus, RV, acute respiratory tract infection, ARTI, upper respiratory tract infection, URTI, otitis media, sinusitis, chronic bronchitis, lower respiratory tract illness, rhinoviral infection, rhinorrhea
