The Common Cold

Ronald B. Turner

Keywords

antihistamine; antitussive; coronavirus; decongestant; Echinacea; metapneumovirus; respiratory syncytial virus; rhinovirus; zinc

The term common cold refers to a syndrome of upper respiratory symptoms that may be caused by a variety of viral pathogens. References to these illnesses in ancient writings attest to the long association of colds and human health. Early observers noted that colds waned in frequency during sea voyages and then reappeared when social contact was reestablished, suggesting that these illnesses were transmitted from person to person. This observation was confirmed in human transmission studies conducted in the early 20th century. These studies established that transmission of colds was due to a “filterable agent” present in nasal secretions.¹ Epidemiologic studies begun by Dingle and co-workers² in the 1940s, among families in Cleveland, demonstrated the role of the family in the spread of colds and emphasized the greater incidence among children than adults. The pathogens responsible for the common cold syndrome were not identified, however, until the development of cell culture systems for detection of viral infections.

The clinical significance of the common cold derives primarily from the frequency of these illnesses in the general population. Although generally mild and self-limited, these illnesses are associated with an enormous economic burden both in lost productivity and in expenditures for treatment. Viral respiratory tract infection accounts for approximately 21 million days of school absence and 20 million days of work absence in the United States annually.³ Each year there are approximately 110 million physician visits, and patients purchase almost $3 billion worth of over-the-counter cough and cold medications for treatment of common cold symptoms.⁴ In recent years, particularly since the widespread use of the polymerase chain reaction (PCR) for detection of viral pathogens, there has been an increasing appreciation of the morbidity associated with the common cold viruses and the complications of these illnesses.

Etiology

The pathogens most frequently associated with common cold symptoms are the rhinoviruses that cause approximately half of all colds (Table 58-1). Other important pathogens include the coronaviruses and respiratory syncytial virus (RSV). Influenza, parainfluenza, and adenoviruses may be associated with cold symptoms; however, these agents frequently cause lower respiratory or systemic symptoms in addition to the upper respiratory symptoms characteristic of the common cold. Recent data suggest that the prevalence of different viruses may be different in an urban compared with a suburban environment.⁵

TABLE 58-1

Viruses Associated with the Common Cold

VIRUS GROUP	ANTIGENIC TYPES	PERCENTAGE OF CASES
Rhinoviruses	>100 types	40-50
Coronaviruses	5 types	10-15
Parainfluenza virus	5 types	5
Respiratory syncytial virus	2 types	5
Influenza virus	3 types*	25-30
Adenovirus	57 types	5-10
Metapneumovirus	2 types	5
Other viruses: enteroviruses, bocavirus

^* Multiple subtypes.

Knowledge of the pathogens associated with the common cold is based primarily on studies that relied on cell culture isolation for detection of virus. Systematic studies of common cold epidemiology using more sensitive diagnostic methods have not been done, although studies using PCR techniques in selected study populations and over limited time periods have generally confirmed the cell culture findings.⁶ The use of the more sensitive techniques, however, has permitted detection and characterization of previously unrecognized pathogens. Metapneumovirus, first detected in 2001, appears to be the cause of approximately 5% of common cold illnesses (see Chapter 161).⁷^,⁸ Bocavirus, a human parvovirus discovered in respiratory secretions in 2005, has since been detected in a small proportion (≈5%) of children with respiratory disease (see Chapter 149).⁹^,¹⁰ This virus is frequently detected in patients who are coinfected with previously recognized respiratory pathogens or who are asymptomatic; thus, the role of bocavirus as a common cold pathogen has not been established.¹¹^,¹² The use of PCR assay has also revealed that coinfection by multiple viral pathogens is frequent during a common cold illness.¹³^,¹⁴

Epidemiology

Seasonal Incidence

In temperate climates, colds occur year-round but have a decreased incidence during the summer months. The “respiratory virus season” in the northern hemisphere begins with an increase in rhinovirus infections in August or September and ends after the spring peak of rhinovirus infections in April or May.¹⁵^–¹⁷ Although rhinovirus continues to circulate at lower levels throughout the winter months, the season bracketed by these rhinovirus peaks consists of sequential and relatively discrete outbreaks caused by different viral pathogens.¹⁶^,¹⁸ The seasonal incidence for parainfluenza viruses usually peaks late in the fall and late in the spring, and for RSV and influenza viruses, it is highest between December and April.¹⁶^,¹⁹ An increased incidence of common cold symptoms is associated with each of these outbreaks. However, pathogens other than rhinovirus or coronavirus are generally associated with the occurrence in the community of other clinical syndromes, such as croup or bronchiolitis, that are more characteristic of an epidemic pathogen. In tropical climates, the common cold is prevalent throughout the year, and the incidence has little correlation to climatic changes, although outbreaks of influenza and parainfluenza may be associated with rainy seasons.²⁰^,²¹

Attack Rate

The average incidence of the common cold in preschool children is 5 to 7 per year but 10% to 15% of children will have at least 12 infections per year.²^,²²^,²³ The incidence of illness decreases with age and averages 2 to 3 per year by adulthood. The incidence of common colds is increased by contact with children in the home or extensive contact with children outside the home, as in child care centers. Children cared for in out-of-home daycare centers during the first year of life have 50% more colds than children cared for only at home.²⁴^–²⁶ The difference in the incidence of illness between these groups of children decreases as the length of time spent in daycare increases. However, the incidence of illness remains higher in the daycare group through at least the first 3 years of life.²⁵

Transmission

In general, respiratory viruses are spread by three mechanisms: small-particle aerosols, large-particle aerosols, and direct contact.²⁷ Small-particle aerosols form droplet nuclei that do not settle and can be transmitted over relatively long distances by airflow. When inhaled, these aerosols may reach the lower airway. Large-particle aerosols refer to droplets generated from the airway that settle rapidly and are transmitted only over relatively short distances. These particles are generally filtered by the upper respiratory tract and are not deposited in the lower respiratory tract. Direct contact refers to contact with contaminated fomites as well as direct person-to-person contact. Studies of experimental and natural rhinovirus colds in human volunteers suggest that transmission may occur by both direct contact and by large-particle aerosols.²⁸^,²⁹ The transmission of the other pathogens associated with colds is less well studied. RSV appears to require close contact for spread and, under experimental conditions, has been spread by direct contact with contaminated fomites.³⁰ In contrast to rhinovirus and RSV, influenza appears to spread from person to person predominantly by small-particle aerosols.³¹ Regardless of the mechanism of transmission, initiation of a common cold illness requires that the pathogen come in contact with, and infect, the nasal epithelium.

Immunity and Factors Predisposing to Infection or Illness

Infection with the respiratory viruses reliably produces an adaptive immune response. The risk of infection on subsequent exposure to the virus appears to be related to the presence or absence of specific antibody to the pathogen. The frequency of infection with these viruses is due to the various mechanisms that the pathogens have evolved to avoid host defenses. Infections with rhinoviruses and adenoviruses result in the development of serotype-specific protective immunity. Repeated infections with these pathogens occur because there are a large number of distinct serotypes of each virus (see Table 58-1). Similarly, the influenza viruses behave as though there were multiple virus serotypes, by virtue of the changes of the antigens presented on the surface of the virus. The interaction of coronaviruses with host immunity is not well defined, but it appears that there are multiple distinct strains of coronavirus that are capable of inducing at least short-term protective immunity.³² In contrast, the parainfluenza viruses, metapneumovirus, and RSV each have a small number of distinct serotypes. Reinfection with these viruses occurs because complete protective immunity to these pathogens does not develop after an infection. Although reinfection is not prevented by the adaptive host response to these viruses, the risk of infection is decreased, and the severity of subsequent illness is moderated by preexisting immunity.

A number of putative interventions for prevention of the common cold claim to act by enhancing or supporting nonspecific immune function. Despite these claims, there is no evidence that nonspecific depression of immune function plays any role in the risk of acquisition of infection or the severity of illness. Several studies have suggested that genetic polymorphisms that result in decreased concentrations of mannose-binding lectin may increase susceptibility to viral respiratory infection, particularly in young children.³³^,³⁴ The data are not conclusive, however, and the importance of polymorphisms in this component of the innate immune system remains to be determined.³⁵

The effect of personality and stress on infection and illness associated with upper respiratory pathogens has also been evaluated. These studies suggest that stress is not a factor in the acquisition of infection but that chronic stress, in particular, is associated with the development of more severe symptoms.³⁶ Personality type may also impact symptom severity. Introverted individuals are reported to have more severe illness.³⁷ In contrast, a positive emotional style, characterized by a general attitude of vigor and well-being, is associated with a reduction in symptom severity.³⁸

Pathogenesis

Viral infection of the nasal epithelium may be associated with destruction of the epithelial lining, as with influenza viruses and adenoviruses; less extensive effects, as with coronavirus 229E;³⁹ or there may be no apparent histologic damage, as with rhinoviruses and RSV. Regardless of the histopathologic findings, infection of the nasal epithelium is associated with an acute inflammatory response characterized by release of a variety of inflammatory cytokines and infiltration of the mucosa by inflammatory cells. Although there is some variation in the specific pathways involved in the response to the different viral pathogens, this acute inflammatory response appears to be responsible, at least in part, for many of the symptoms associated with the common cold.

Information about the pathogenesis of specific symptoms of the common cold is limited. Nasal obstruction and rhinorrhea are the prominent symptoms of the cold. The nasal inflammatory response appears to be associated with pooling of blood in the capacitance vessels of the nose and increased nasal blood flow.⁴⁰ The important contribution of these changes to nasal obstruction is demonstrated by the substantial decongestant effect associated with the use of topical vasoconstrictors.⁴¹ Increased vascular permeability with leakage of serum into the nasal mucosa and nasal secretions may also contribute to nasal obstruction.⁴²^–⁴⁴ Transudation of serum into the secretions is a major contributor to rhinorrhea early in the course of the cold.⁴²^–⁴⁴ The contribution of glandular secretions from the nose to rhinorrhea becomes more important later in the course of the illness.⁴³

Cough is a less common symptom in colds, but when it occurs, it is frequently reported as the most bothersome symptom. The pathogenesis of cough in colds is poorly understood and may be due to a variety of different mechanisms. Extension of viral infection into the lower respiratory tract appears to be associated with cough in some patients.⁴⁵ There is also evidence that in some patients cough is triggered by neural reflexes as a result of stimulation of sensitized upper airway receptors.⁴⁶^,⁴⁷ Throat irritation associated with postnasal drip may be associated with voluntary “throat-clearing” that appears to be a distinct mechanism of cough.⁴⁸

The sore throat that is characteristic of rhinovirus colds may be produced by elaboration of bradykinin as a part of the inflammatory response. Increased concentrations of bradykinin are found in nasal secretions during rhinovirus colds, and challenge of normal volunteers with bradykinin produces sore throat symptoms.⁴⁹^,⁵⁰

Clinical Manifestations

The onset of common cold symptoms typically occurs 1 to 3 days after viral infection.⁵¹ The first symptom noted is frequently a sore or “scratchy” throat, followed closely by nasal obstruction and rhinorrhea. The sore throat usually resolves quickly, and by the second and third day of illness, nasal symptoms predominate. Cough is associated with approximately 30% of colds and usually begins after the onset of nasal symptoms. Systemic symptoms are uncommon in colds, but influenza viruses, RSV, and adenoviruses are more likely than are rhinoviruses or coronaviruses to be associated with fever and other constitutional symptoms. The usual cold persists about 1 week, although 25% last 2 weeks.⁵²^,⁵³ Recent data suggest that coinfection by multiple pathogens may be associated with prolonged illnesses.¹³ Virus shedding persists after the resolution of symptoms, and virus may be cultured from 10% to 20% of subjects for 2 to 3 weeks after infection.⁵⁴^,⁵⁵

The physical findings of the common cold are limited to the upper respiratory tract. Increased nasal secretion is frequently obvious to the examiner. A change in the color or consistency of the secretions is common during the course of the illness and is not indicative of sinusitis or bacterial superinfection. Examination of the nasal cavity may reveal swollen, erythematous nasal turbinates, although this finding is nonspecific and of limited diagnostic usefulness.

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