Rhinovirus (RV) Infection (Common Cold)

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Practice Essentials

Rhinoviruses (RVs) are the most common cause of the common cold. They chiefly cause upper respiratory tract infections (URTIs) but may also infect the lower respiratory tract. Potential complications of infection include otitis media, sinusitis, chronic bronchitis, and exacerbations of reactive airway disease (eg, asthma). Although rhinovirus infections occur year-round, the incidence is highest in the fall and the spring (see the image below).



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Seasonal variations in frequency of selected upper respiratory tract infection pathogens. PIV = parainfluenza virus; RSV = respiratory syncytial virus....

Signs and symptoms of rhinovirus infection

Manifestations of rhinovirus infection typically appear after an incubation period of 12-72 hours and last 7-11 days, but may persist for longer. Signs and symptoms include the following:

Age-related differences in presentation are as follows:

Physical examination findings

Complications

See Clinical Presentation for more detail.

Diagnosis of rhinovirus infection

If findings from a thorough history and physical examination are consistent with a viral etiology and no complications are noted, an aggressive workup is rarely necessary. Common laboratory tests (eg, WBC, CBC, ESR) have little value. Because of the prolonged time to obtain positive culture findings, rhinovirus culture has rarely been found useful in clinical settings. PCR testing of respiratory specimens may be useful in evaluating severely immunocompromised patients.

See Workup for more detail.

Management

Rhinovirus infections are predominantly mild and self-limited; thus, treatment is generally focused on symptomatic relief and prevention of person-to-person spread and complications. The mainstays of therapy are as follows:

Other conventional supportive care for the common cold includes the following:

Pharmacologic treatment

See Treatment and Medication for more detail.

Background

Rhinoviruses (RVs) are members of the Picornaviridae family, which includes the human pathogens enterovirus and hepatovirus (notably, hepatitis A virus). More than 100 different subtypes exist in 3 major groups, categorized according to receptor specificity: intercellular adhesion molecule-1 (ICAM-1), low-density lipoprotein (LDL) receptors, and sialoprotein cell receptors.

Rhinovirus infections are chiefly limited to the upper respiratory tract but may cause otitis media and sinusitis; they may also exacerbate asthma, cystic fibrosis, chronic bronchitis, and serious lower respiratory tract illness in infants, elderly persons, and immunocompromised persons.[1, 2] Although infections occur year-round, the incidence is highest in the fall and the spring. Of persons exposed to the virus, 70-80% have symptomatic disease. Most cases are mild and self-limited.

The common cold is an acute respiratory tract infection (RTI) characterized by mild coryzal symptoms, rhinorrhea, nasal obstruction, and sneezing. 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. Rhinoviruses are the most common of these (25-80% of cases), followed by coronaviruses (10-20%), influenza viruses (10-15%), and adenoviruses (5%).

Although the incidence of acute RTI cannot be clearly defined, because of seasonal and locational variability, it is estimated to range 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 acute RTI. This figure decreases to 3-4 episodes per year by adulthood.

Pathophysiology

Viral transmission

Rhinovirus possesses various transmission modes and can infect a huge population at any given time. Most commonly, they are transmitted to susceptible individuals through direct contact or via aerosol particles. The primary site of inoculation is the nasal mucosa, though the conjunctiva may be involved to a lesser extent. The virus attaches to respiratory epithelium and spreads locally. Rhinovirus species A and B bind to the major human rhinovirus receptor, ICAM-1 (found in high quantities in the posterior nasopharynx).[3, 4, 5] Rhinovirus C (RV-C) binds to cadherin-related family member 3 receptor (CHDR-3). Viral particles are usually transmitted via inoculation into the eye or the nose from contact with the fingers that harbor the virus, especially since rhinoviruses are capable of surviving on hands for hours.[6, 7, 8]

Highly contagious behavior includes nose blowing, sneezing, and physically transferring infected secretions onto environmental surfaces or paper tissue. Contrary to popular belief, behaviors such as kissing, talking, coughing, or even drooling do not contribute substantially to the spread of disease.

Infection rates approximate 50% within the household and range from 0% to 50% within schools, indicating that transmission requires long-term contact with infected individuals. Brief exposures to others in places such as movie theaters, shopping malls, friends’ houses, or doctors’ offices are associated with a low risk of transmission. Because children produce antibodies to fewer serotypes, those who attend school are the most common reservoirs of rhinovirus infection.

Pathogenesis of rhinovirus infection

The attachment of the virus to its receptors (ICAM-1, CHDR-3, low-density lipoprotein receptor [LDLR]) in susceptible individuals elicits an innate immune response leading to airway inflammation and remodeling.

Few cells are actually infected by rhinovirus, 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, though reports have described symptoms as early as 2 hours after inoculation with primary symptoms 8-16 hours later.[9] Viremia is uncommon.

A local inflammatory response to rhinovirus in the respiratory tract can lead to nasal discharge, nasal congestion, sneezing, and throat irritation. The nasal epithelium is not damaged.[10, 11] Various polymorphisms in cytokine genes have been shown to impact the severity of infection, suggesting a genetic predisposition.[12] Detectable histopathology causing the associated nasal obstruction, rhinorrhea, and sneezing is lacking, which leads to the hypothesis that the host immune response plays a major role in the pathogenesis.

Infected cells release interleukin (IL)–8, which is a potent chemoattractant for polymorphonuclear (PMN) leukocytes. 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 production of interferon beta by asthmatic bronchial epithelial cells has been proposed as a mechanism for increased susceptibility to rhinovirus 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. Rhinovirus is shed in large amounts, with as many as 1 million infectious virions present per milliliter of nasal washings. Viral shedding can occur a few days before cold symptoms are recognized by the patient, peaks on days 2-7 of the illness, and may last as long as 3-4 weeks.

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).

Clinical studies indicate sinus involvement in common colds. Abnormal computed tomography (CT) findings (eg, opacification, air-fluid levels, and mucosal thickening) are present in adults with common colds that resolve over 1-2 weeks without antibiotic therapy.

Despite what is reported in folklore, no good clinical evidence suggests that colds are acquired by exposure to cold weather, getting wet, or becoming chilled.

Etiology

Rhinoviruses are small, nonenveloped, positive (sense) stranded RNA viruses of the Picornaviridae family. More than 100 different serotypes have been identified, categorized into 3 major groups on the basis of specificity for particular receptors: ICAM-1, LDL receptors, and sialoprotein cell receptors. 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.

Rhinovirus grows efficiently only within a limited temperature range (33-35°C), and it cannot tolerate an acidic environment. Thus, it is rarely found outside the nasopharynx, because of the acidic environment of the stomach and the increased temperature in both the lower respiratory tract and the gastrointestinal (GI) tract.

Transmission occurs with close exposure to infected respiratory secretions, including hand-to-hand contact, 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 the hands and nasal mucosa.

One study assessed the transfer of virus to surfaces by 15 adults with rhinovirus infection; each of the 15 stayed overnight in a hotel room, and afterward, 10 commonly touched sites in each room were tested for viral contamination.[13] The investigators determined that the virus could be recovered from 35% of these sites and found that the virus could be transferred back from inanimate objects to fingertips in many cases.

Higher rates of transmission occur in humid, crowded conditions such as are 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.

Risk factors

Factors that increase the risk and severity of rhinovirus infection include the following:

Epidemiology

United States statistics

Common colds are most frequent from September to April in temperate climates. Rhinovirus infections, which are present throughout the year, account for the initial increase in cold incidence during the fall (causing as many as 80% of colds in this period) and for a second incidence peak at the end of spring. Colds that occur from October through March are caused by the successive appearance of numerous viruses (see the image below). Adenovirus infections occur at a constant rate throughout the season.



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Seasonal variations in frequency of selected upper respiratory tract infection pathogens. PIV = parainfluenza virus; RSV = respiratory syncytial virus....

The incidence of the common cold is highest in preschool- and elementary school–aged children. An average of 3-8 colds per year is observed in this age group, and the incidence is even higher in children who attend daycare and preschool. Because of the numerous viral agents involved and the multiple serotypes that several of these agents (especially rhinovirus) have, it is not unusual for younger children having new colds every month during the winter. Adults and adolescents typically have 2-4 colds per year.

International statistics

Internationally, rhinovirus is a significant cause of RTI,[15, 16, 17, 18, 19, 20, 21, 22, 23] as well as a minor cause of bronchiolitis.[24] 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 acute RTIs. A seasonal increase in incidence during the winter months is observed worldwide.

Age-related demographics

Because antibodies to viral serotypes develop over time, the incidence of rhinovirus infection is highest in infants and young children and falls as children approach adulthood. Young children are more likely to have the frequent, close, personal contact necessary to transmit the virus; they commonly pass the infection to family members after acquiring the virus in nurseries, daycare facilities, and schools. Children may also be more contagious by virtue of having higher virus concentrations in secretions and longer duration of viral shedding.

Sex-related demographics

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. In adults, no difference in rates of infection between men and women is apparent.

Race-related demographics

No differences among different races with respect to susceptibility to rhinovirus infection or disease course have been described. In general, Native Americans and Eskimos are more likely to develop the common cold and appear to have higher rates of complications such as otitis media. These findings may be explained as much by environmental conditions (eg, poverty and overcrowding) as by ethnicity.

Prognosis

The prognosis for rhinovirus infection is excellent. The most common manifestation of infection, the common cold, is mild and self-limited. Complete recovery is usually observed within 7 days for adolescents and adults and within 10-14 days for children. Occasionally, a child’s cough and congestion linger for 2-3 weeks.

Although rarely associated with fatal disease, rhinoviruses are associated with significant morbidity. Acute RTIs, predominantly rhinovirus infections, are estimated to cause 30-50% of time lost from work by adults and 60-80% of time lost from school by children. Severe respiratory disease, including bronchiolitis, asthma exacerbations, and pneumonia ,[25, 26] can occur, particularly in infants and young children.[27] Preterm infants are also at high risk for severe infection.[28]

Rhinovirus is a predominant pathogen in lower respiratory tract infections (LRTI) in very low birth weight infants[22] and shares predominance in LRTI among young infants with respiratory syncytial virus (RSV).[29, 30] They may also be involved in LRTIs in elderly persons, persons with cystic fibrosis, and immunosuppressed patients. The true impact of LRTI is not clear. Recovery of the virus in these patients may be a marker of an underlying disease process or a precursor to a bacterial infection.

A retrospective analysis of a prospective cohort of 728 hospitalized elderly patients with rhinovirus infection in Hong Kong revealed a significantly higher 90-day mortality rate than their counterparts (1218 patients) with influenza infection. The rhinovirus group developed pneumonia complications, required oxygen therapy, and had longer hospital stays.[31]

Patient Education

Because spread of secretions by contact with hands is a major route of transmission, encourage parents and patients to wash their hands frequently. In addition, emphasize other environmental measures to control infections, such as avoiding finger-to-eye and finger-to-nose contact and coughing and sneezing into the crook of the elbow.

Reassure families and patients that frequent colds are common at certain times of the year. Inform parents that 6-12 colds per year can be normal for young children, especially if they attend daycare or preschool. Explain that frequent self-limited colds do not indicate a problem with a child’s immune system and do not warrant antibiotic treatment and that patients with common colds need not be excluded from daycare or preschool settings.

Advise patients to return if fever exceeds 102°F, if significant respiratory distress develops, or if symptoms do not resolve in 10-14 days. Remind patients and families that purulent nasal discharge is commonly observed after the first few days of the infection and does not indicate a bacterial infection or the need for antibiotics.

Some clinicians have advocated supplementation with vitamin C. Although large doses of vitamin C have been used for prevention and treatment of colds, controlled trials reveal minimal therapeutic benefit and no preventive qualities.[32] In any case, high doses in children are not recommended.

History

Rhinoviruses (RVs) cause or predispose to various upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs), which are less common. The most common manifestation of infection is the common cold. Rhinovirus 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. Symptoms generally last 7-11 days, though they may persist for up to 2 weeks in roughly 25% of patients. Rarely, patients complain of lingering symptoms that last more than 30 days.

Nasal dryness or irritation may be the first symptom of rhinovirus infection. A sore throat or throat irritation is also a common initial symptom and 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. Nasal secretions typically become thicker and colored after the first few days of illness. Nasal obstruction can interfere with sleep and feeding.

Other associated complaints include headache, facial and ear pressure, and loss of smell and taste. About 30% of infected individuals develop a cough, and 20% develop hoarseness, both of which may persist for up to 1 week, though they seldom become bothersome until nasal symptoms improve. Posttussive vomiting can occur. Irritability or restlessness is common.

Systemic signs and symptoms, such as fever and malaise, are unusual. If they are present, consider an alternative diagnosis. When fever is present, it is typically low-grade. Infants and preschoolers are more likely to experience fevers, which are often 38-39°C.

Infants and toddlers may display only nasal discharge. However, Calvo et al reported that among infants younger than 2 years with viral respiratory tract infection requiring hospitalization in Spain, rhinovirus infections are second only to respiratory syncytial virus (RSV) infections in terms of frequency.[33]

School-aged children usually complain of nasal congestion, cough, and runny nose. These symptoms persist for an average of at least 10 days.[34]

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 obstructive pulmonary disease (COPD; see Complications).

People who smoke do not appear to have more frequent rhinovirus infections; however, their infections are more severe, and their symptoms last longer.

Physical Examination

The physical examination findings in patients with rhinovirus infections are typically less severe than the symptoms reported by the patients themselves.

Fever is not common, though temperatures of 38-39°C are possible in younger children.

A red nose with a profuse, dripping nasal discharge may be present. The discharge can be clear and watery or mucopurulent (yellow or green). Purulent secretions are common after the first few days of illness because a large number of white blood cells (WBCs) migrate to the site of viral infection. Such secretions should not be taken as implying bacterial infection unless they persist for more than 10-14 days.

The nasal mucous membranes have a glistening, glassy appearance, usually (though not always) without obvious erythema or edema. Despite the sore throat, the pharynx typically appears normal, without any erythema, exudate, or ulceration. 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).

Mildly enlarged, nontender cervical lymph nodes are present. Auscultation of the chest may reveal rhonchi.

Complications

Complications of rhinovirus infection include otitis media, sinusitis, chronic bronchitis, and exacerbations of reactive airway disease in children and adults.

Otitis media

Rhinoviruses have been suggested both as rare primary pathogens and as co-pathogens with bacteria in the etiology of otitis media. It is believed that by causing respiratory mucosal inflammation that leads to eustachian tube obstruction, they potentially allow secondary bacterial infection.

Respiratory viruses are found in either the middle ear fluid or the nasopharynx in approximately 40% of patients with otitis media. In particular, as many as 24% of these patients have rhinovirus in nasopharyngeal secretions; rhinovirus has also been obtained from middle ear fluid. Patients whose symptoms are refractory to treatment with antibiotics are more likely to have positive viral cultures from the middle ear.

Sinusitis

Infection of the sinus mucosa with rhinovirus leads to alterations of sinus cavities, resulting in obstruction and entrapment of bacteria (eg, Streptococcus pneumoniae and unencapsulated strains of Haemophilus influenzae) and giving rise to bacterial sinusitis. The maxillary sinuses are involved most frequently.

Acute infectious episodes in patients with chronic bronchitis

Although rhinoviral invasion of the bronchial tree is unclear, alterations in ventilation and exacerbations of bronchitis have been described with rhinovirus infections.

Exacerbation of reactive airway disease

In general, people with asthma develop more viral respiratory tract infections than people without asthma. Viral URTI is a common trigger for asthma exacerbations in children of all ages. In children younger than 5 years, rhinovirus and respiratory syncytial virus (RSV) are the most commonly implicated pathogens. Rhinovirus is the most commonly implicated pathogen in older children.

Rhinovirus infection has been implicated in asthma exacerbations and refractory wheezing.[35] In a rhinovirus challenge model, exacerbation of wheezing was shown in a minority of adults, and only 20% had a 10% or greater decrease in forced expiratory volume in 1 second (FEV1).[36] In children at high risk for allergies and asthma, rhinovirus infection during infancy is the most significant risk factor for symptomatic wheezing.[37] More specifically, human rhinovirus 1B infection affects airway epithelial tight-junction expression, increasing epithelial permeability.[38]

Recently, evidence has shown that the virus induces the release of the chemokine CCL5, which causes airway smooth-muscle chemotaxis, influencing airway remodeling in persons with asthma.[39] Rhinovirus also induces T-helper-2 and T-helper-17 responses, leading to both eosinophilia and mucus hypersecretion during asthma exacerbations.[40]

Rhinovirus C has been implicated in apparent life-threatening events in infants,[41, 42, 43] and certain species are associated with hospitalization for severe respiratory tract infection.[44, 45] The role of rhinovirus infection early in life as a precursor to asthma later in life has been proposed.[37, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63]

Adults with COPD may experience exacerbations attributable to rhinoviruses. One study noted that 20% of all exacerbations could be traced to concomitant rhinoviral infection and found that bacterial colony counts and levels of proinflammatory cytokines were also more elevated when rhinoviruses were present.[64]

Rhinovirus is the implicated virus in as many as 57% of respiratory exacerbations in patients with cystic fibrosis.

Lower respiratory tract infection

Deep respiratory tract infections have been described in immunosuppressed patients, elderly persons, and infants and children with cystic fibrosis; however, determining the true impact of the virus is difficult because it may be either a marker of disease severity or an inciting event for other infectious processes. Rhinovirus may cause both pneumonia[65] and bronchiolitis in infants.[66]

In the Etiology of Pneumonia In the Community (EPIC) study, data from 2,638 children hospitalized because of pneumonia in the United States were analyzed. Eighty-nine percent had radiographically confirmed pneumonia, and 81% had a pathogen identified: 66% virus, 8% bacteria, and 7% both. Rhinoviruses were the second most commonly identified pathogen (27%) after RSV (28%).[67]

Other complications

Data suggest that antecedent rhinovirus infection circulating in the community predisposes children younger than 5 years to subsequent invasive pneumococcal disease.[68]

The virus may cause laryngotracheobronchitis in infants.

The virus is an uncommon cause of acute nasopharyngitis; common colds, by definition, are not characterized by objective evidence of pharyngeal irritation. Acute nasopharyngitis is most commonly caused by adenovirus, enteroviruses, influenza, and parainfluenza.

Rhinovirus C (RV-C), which includes rhinovirus C15 (RV-C15), has been associated with severe infections that usually require hospitalization in young children, particularly those with asthma. Rhinovirus C can also lead to serious respiratory problems in adults.[69]

Colds and other minor infections may increase stroke risk in children

Findings from a study by Hills and colleagues suggest that the strong effect of minor infections on the risk of stroke in children is short-lived. The risk appears to be highest during the three days following a doctor’s visit for an infection, after which it rapidly diminishes.[70, 71]

The researchers used the Kaiser Pediatric Stroke Study, which represents about 2.5 million children enrolled between 1993 and 2007 in Kaiser Permanente Northern California (KPNC). In a retrospective study of medical records, they identified 102 children who had sustained an arterial ischemic stroke and 306 control children without stroke. The total number of doctor visits during the 2 years before a stroke during which a diagnosis of 1 or more minor infections was made were included in the analysis.[71]

A total of 74 cases (73%) and 187 controls (61%) had at least 1 visit for infection during the 2-year observation period. The most common infection reported was upper respiratory tract infection representing 49% of infections in the cases and 45.4% of infections in the controls over the 2-year period.[71]

The rate of infection before the stroke or index date was greater for cases than controls in each of three time periods: within 3 days, 4 to 7 days, and 8 to 30 days. After adjustment for these periods, sex, immunologic, hematologic, and cardiac disease, and head and neck trauma in the preceding month, a diagnosis of infection 3 days before a stroke conferred a 12-fold increased risk for arterial ischemic stroke (odds ratio, 12.1; 95% confidence interval, 2.5 - 56.7; P = .002). The risk rapidly diminished after those 3 days, with no increased risk for stroke beyond 1 week.[71]

Approach Considerations

Clinical signs and symptoms of the common cold, by definition, are similar regardless of the infectious etiology. Accordingly, if findings from a thorough history and physical examination are consistent with a viral etiology and no complications are noted, an aggressive workup is rarely necessary. Differentiation of one virus from another or one rhinovirus (RV) serotype from another on the basis of clinical presentation is difficult.

In general, the white blood cell (WBC) count has little value in the diagnosis of the common cold, though in some cases, peripheral WBC counts may be elevated during the first 2-3 days of the infection. Other common laboratory tests, such as the complete blood count (CBC) and the erythrocyte sedimentation rate (ESR), are of virtually no benefit in managing rhinovirus infections.

Because of the prolonged time to obtain positive culture findings, culture of rhinovirus has rarely been found useful in clinical settings. Identity is confirmed by the acid sensitivity of the isolate. Specialized laboratories can identify serotypes by antibody neutralization, which requires a large battery of antisera. However, with more than 100 different serotypes of rhinovirus alone, assisting the diagnosis by means of serologic methods is economically impractical.

Although respiratory tract aspirations, brushings, and biopsies have been used in research protocols to identify etiologies of infections, these tests are of limited value in individual patients.

A 2009 study determined that rapid multiviral testing in the emergency department (ED) did not significantly affect treatment but could result in a reduction of antibiotic prescription in the community after discharge.[72] Rapid respiratory panel, which included a test for adenovirus, also shortened the duration of antibiotic use, length of hospital stay, and time in isolation in a similar study in 2015.[73]

Viral Testing

If a specific viral diagnosis is desired, the virus can be cultured from nasal secretions; nasal washings are more sensitive than throat specimens. Virus can be cultured on M-HeLa and human embryonic lung cells with typical cytopathic effect observed after culture, at 33-35°C on roller drums, for 2-6 days. Culture occasionally takes up to 14 days. Direct antigen tests are routinely available for influenza virus and respiratory syncytial virus (RSV). Some centers offer direct antigen tests for parainfluenza and adenovirus.

Increasingly, microarray[74] and real-time polymerase chain reaction (PCR) assays are being used to detect rhinovirus in respiratory specimens.[75, 76, 77] PCR assay is faster and more sensitive than culture. Real-time PCR has been shown to be a rapid and effective way of detecting the virus and has been proposed as the clinical detection method of choice. In clinical settings, PCR testing has been most useful in evaluating patients who are severely immunocompromised, such as bone marrow transplant recipients.

The results of PCR testing must be interpreted carefully.[78] One study reported persistent positive results for 5-6 weeks after admission of children for illnesses determined to be secondary to rhinovirus infection; furthermore, the use of nested PCR techniques has resulted in as many as 20% of illnesses being attributed to more than 1 organism.[79]

Current commercially available multiplex PCR assays cannot reliably differentiate rhinovirus from enterovirus, so results are reported as rhinovirus/enterovirus. In addition, detected rhinovirus may be related to a past infection rather than a current infection since prolonged viral shredding is known to occur. Among children younger than 1 year, viral shredding beyond 30 days is uncommon.[80]

Other Studies

Consider bacterial throat culture or rapid strep testing to identify the presence of group A streptococci if oropharyngeal examination suggests streptococcal infection.

Chest radiography is seldom needed and should be obtained only if another lower respiratory tract infection (eg, pneumonia) is suspected.

Sinus films or computed tomography (CT) scanning of the sinuses may be useful in cases of suspected sinusitis, though such imaging cannot differentiate viral processes from bacterial processes. More than 85% of patients with a common cold have sinus abnormalities on CT. A diagnosis of bacterial sinusitis is unlikely if the duration of symptoms is less than 10-14 days.

Approach Considerations

Rhinovirus (RV) infections are predominantly mild and self-limited; thus, treatment is generally focused on symptomatic relief and prevention of person-to-person spread and complications. The mainstays of therapy include rest, hydration, first-generation antihistamines, and nasal decongestants. In adults, evidence has shown that zinc decreases the duration of symptoms and severity. Antibacterial agents are not effective unless bacterial superinfection occurs. No antiviral agents are available to treat infections. Development of a vaccine is nearly impossible, because of the large number of rhinovirus serotypes.

Inpatient care is rarely required. Persons with rhinovirus infections are almost universally treated as outpatients. Referral to an allergist is appropriate if the patient has chronic rhinitis that is unresponsive to environmental and pharmacologic intervention.

Patients may limit their activity during the course of the infection, with clinical improvement occurring 48-72 hours after the prodrome of symptoms. Patients can reassured that the usual course of illness is 6-10 days.

Supportive Care

Most treatment approaches involve supportive measures for symptoms of respiratory illness. Conventional treatments for the common cold include the following:

Heated humidified air (40 L/min at 40-44°C in the nostrils) has been used for decades in efforts to alleviate symptoms due to rhinovirus infections. The rationale is based on the observation that increased temperatures inhibit rhinovirus replication in vitro. However, this treatment has never been shown to improve objective outcome measures.[82] In fact, a Cochrane review of 6 trials concluded that heated and humidified air did not improve outcomes.[83]

Hot chicken soup is often recommended on the grounds that it causes a temperature increase that accelerates nasal drainage. Be alert for possible hypernatremia.

Some practitioners have considered the use of aroma rubs,[84] homeopathic or herbal remedies, and ultrafine high-volume filtration systems. However, these treatment options have yet to be studied.

Pharmacologic Therapy

Symptomatic treatment

Symptomatic treatment with analgesics, decongestants, antihistamines, and antitussives is currently the mainstay of therapy. These over-the-counter (OTC) preparations are likely to benefit older children and adolescents[85] but should be avoided for children younger than 6 years (see below).[81] In 2004-2005, an estimated 1500 children younger than 2 years were treated in US emergency departments (EDs) for adverse events (including overdoses) associated with cough and cold medications.[86] In adults, antihistamines improve overall symptoms and rhinorrhea only in the short term (first two days of therapy), but not on the long term, according to a 2015 Cochrane review.[87]

Antibacterial therapy

Antibacterial agents are not effective unless bacterial superinfection occurs. Development of effective antiviral medications has been hampered by the short course of these infections. Because peak symptom severity occurs at 24-36 hours after inoculation, antivirals have only a narrow window within which to have a positive effect on infection. In addition, the common cold is not always caused by rhinovirus. Therefore, rapid and accurate diagnostic tests would be needed if a specific antiviral therapy were to be developed.

Zinc therapy

Zinc has been studied extensively as a treatment for the common cold. The exact mechanism of zinc’s antiviral effect remains uncertain, although in vitro studies have demonstrated that zinc can inhibit viral replication and has activity against respiratory viruses including rhinovirus and respiratory syncytial virus (RSV).[88] Ionic zinc reduces the level of intracellular adhesion molecule-1 (ICAM-1), increases IFN-γ levels by 10-fold, and assists in the protection of cell plasma membranes, which is thought to explain its therapeutic effectiveness for common colds.[89] In addition, zinc seems to inhibit rhinovirus from binding to ICAM-1 in the nasal mucosa while also inhibiting viral replication by preventing the formation of rhinovirus capsid proteins. Zinc also reduces symptoms by inhibiting proteolysis during the rhinovirus cell cycle, blocking facial nerve and trigeminal nerve conduction and decreasing nasal congestion and sneezing. It also stabilizes cell membranes and prevents the release of histamine. Lastly, zinc is able to inhibit prostaglandin metabolism.[90, 91, 92]

Multiple meta-analyses have investigated the role of zinc in the treatment and prevention of the common cold. A 2013 Cochrane review assessed 13 therapeutic trials involving 966 patients. Oral zinc taken within 24 hours of onset of common cold symptoms reduced duration of illness in adults when high doses (at least 75 mg of elemental zinc per day) were used. Unfortunately, the same benefit was not seen in the subgroup analysis among children, nor in trials that used low doses of zinc. In addition, zinc has also been associated with faster resolution of nasal congestion, nasal drainage, and sore throat, as well as improvement of cough (in terms of cough score).[92] Although heterogeneity was high among the trials included in the review, the findings were consistent with those reported in another systematic review of 17 trials involving 2121 participants.[88] Overlap of included studies was noted and methodological limitations have been raised against the two reviews. Still, in an illness that is considered a high-burden disease (with children experiencing 6-12 colds a year and adults having 2-4 episodes annually, accounting for 40% of time lost from work),[92, 91] "even an only partially effective medication could markedly reduce morbidity and economic losses."[93]

Multiple zinc preparations are available; 75 mg of elemental zinc per day should be used to treat the common cold in adult patients so that the benefits of reduction of symptom duration and severity can be achieved. Zinc acetate is composed of 30% elemental zinc; zinc gluconate, 14.3%; zinc sulfate, 23%; and zinc oxide, 80%.[94]

When administered for at least 5 months, zinc reduces the incidence of colds. However, zinc may have side effects, and the recommended dosing, formulations, and duration are difficult to establish without further studies. For most pediatric patients, zinc lozenges are not practical, because of their metallic taste.

Because of the large number of rhinovirus serotypes and the inaccessibility of the conserved region of the viral capsid (the most likely effective site for targeting a vaccine), no rhinovirus vaccine is on the horizon.

Steroid therapy

Steroids have been examined as a therapeutic modality in rhinovirus infection but have not been shown to confer a substantial benefit. In one study, children who experienced wheezing during infection and were treated with prednisolone experienced fewer wheezing episodes than untreated individuals in the subsequent 2 months; however, time to discharge was unchanged.[95] A Cochrane review of three poor-quality trials also did not recommend the use of intranasal steroid for the relief of common colds symptoms.[96]

Investigational agents

Numerous agents have been investigated or are being investigated for the treatment of viral infections. These include the following:

Pleconaril inhibits approximately 92% of rhinovirus serotypes. Susceptibility to pleconaril depends on the viral capsid surface protein VP1. A double-blind, randomized, placebo-controlled trial of pleconaril 400 mg given orally 3 times daily for 5 days, initiated within 24 hours of symptom onset, resulted in a decrease in the duration of symptoms by 1 day.[97] However, safety concerns, which included menstrual disorders in women taking pleconaril and oral contraceptives and the report that two women became pregnant while taking pleconaril and oral contraceptives, prompted the FDA advisory committee to reject the manufacturer’s application.[98]

Pirodavir, a substituted phenoxypyridazinamine, possesses broad antipicornavirus activity. Clinical studies demonstrate no decrease in viral shedding or symptoms.

Overall, although capsid binders are attractive and potent early-stage inhibitors of rhinovirus replication in vitro, problems in pharmacodynamics, in vivo efficacy, and resistance development were reported.

WIN 54954, a methylisoxazole derivative, has not been found to have any significant antiviral or clinical effects.

Interferon (IFN)–alfa is effective for cold prevention but has limited efficacy against for established symptomatic illness.[99] When administered via nasal spray (typically at dosages of 5 million U/day or higher), it can prevent as many as 80% of secondary rhinovirus colds. It has also been given in conjunction with ipratropium, chlorpheniramine, and ibuprofen. Unfortunately, IFN-alfa is not cost-effective, and significant adverse effects have been reported.

On the other hand, IFN-beta (but not IFN-gamma) has been shown to counter the permissiveness of mast cells for rhinovirus replication and release. This may be a novel mechanism by which rhinovirus-associated asthma exacerbations can be prevented in the future.[100] However, other bench researchers have also noted that IFN-gamma antagonizes type 2 innate lymphoid cells expansion and gene expression. This blocks the development of an asthma phenotype in baby mice.[101]

Virus receptor blockers are believed to prevent replication by blocking virus internalization. Tests of antireceptor antibodies have not demonstrated any decreases in infection frequency.

Tremacamra, a recombinant soluble ICAM-1 administered intranasally 6 times per day either 7 hours before or 12 hours after rhinovirus challenge was analyzed in a randomized, double-blinded study; neither timing strategy affected the incidence of infection, but combining the results from the 2 treatment groups demonstrated a 23% decrease in clinical colds, a 45% decrease in total symptom score, and a 56% decrease in total nasal secretion weight.[102]

3C protease inhibitors (eg, rupintrivir) are being evaluated in human trials. In a phase II study, rupintrivir delivered as a nasal spray was well tolerated, decreased positive viral culture results, and improved symptom scores; however, it did not decrease the frequency of colds.[103] 3C protease inhibitors act by interfering with the cleaving of a single large polyprotein that produces individual structures and enzymatic proteins of the virus.

Rhinoviruses are sensitive to low pH. In one study, citrate/phosphate buffers were administered intranasally, decreasing viral shedding but failing to decrease symptomatology.[104]

Protein kinase D (PKD) inhibitors are being studied for their novel antiviral action, since PKD appears to regulate viral replication. The specific mechanism of action of PKD inhibitors is still unknown.[105]

Bench research on alpha-1 antitrypsin has shown that it appears to prevent cigarette smoke–induced increases in rhinovirus infection incidence and may be an area of continued research that may be beneficial in smokers who are infected.[106]

When compared with itraconazole suspension, itraconazole microemulsion formulation delivered intranasally was considered a promising candidate for the treatment of rhinovirus infection, since the latter led to significantly less inflammatory markers in the lungs in mouse models, which may be related to the significant increase in drug released in the microemulsion formulation group.[107] Similar results in a murine model study also showed that itraconazole reduced virus replication and reduced immune cells (granulocytes and monocytes) in bronchoalveolar lavage fluid, which seemed to be related to the decreased pro-inflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid. In addition, the same study also noted that intranasal itraconazole may also be effective in the prevention of infection.[108]

Liposomes of phosphatidylserine have also been studied as a potential prototype treatment modality to reduce rhinovirus-associated inflammation. The liposomes did not induce cell death but appeared to markedly reduce inflammation as a response to infection, despite a nonsignificant increase in replication.[109]

The bark extract Ficus religiosa L, considered a "sacred tree" in South Asia, is another material that has been shown to possess antiviral activity in human rhinovirus (and respiratory syncytial virus) in vitro but will need further studies with regard to in vivo activity.[110]

Special considerations in children

Remind parents that treatment of rhinovirus infection in children younger than 6 years should be supervised by a physician. These children should receive analgesics, cough suppressants, decongestants, and antihistamines only on the advice of a physician.

The US Food and Drug Administration (FDA) does not recommend the use of cough and cold medications in very young children (age < 2 years). In January 2008, the FDA completed its review of information regarding the safety of OTC cough and cold medicines in children younger than 2 years. This review resulted in a new recommendation that these drugs should not be used to treat children in this age group, because serious and potentially life-threatening adverse effects can occur.

In October 2008, the pharmaceutical industry voluntarily changed the labeling for OTC pediatric cough and cold drugs to include that a statement these drugs should not be used in children younger than 4 years. This action was in response to dosing errors, misuse, and overuse of OTC pediatric cough and cold medications. Each year, nearly 7000 visits to EDs in the United States by children younger than 11 years are associated with cough and cold medicines.

Healthcare providers should emphasize to parents and caregivers that although OTC medications are available without a prescription, that does not mean that they are harmless. Providers should discuss the merits of hydration, rest, and humidification as initial treatment options. Most important, parents should seek specific instructions from their child’s physician if cough or cold medications are warranted and should give only the exact amount of medication that is prescribed.

To prevent overdose, it is vital that parents and caregivers be carefully instructed not to add other cough and cold medications to the regimen. Adverse effects, including deaths, have occurred as a consequence of unintentional overdose when different OTC or prescription medications that contain the same ingredients (eg, pseudoephedrine, dextromethorphan, an antihistamine, or an analgesic or antipyretic) have been combined.

For more information, see the following sources:

Diet

Dietary supplements have been touted as possible therapeutic or preventive measures. These include vitamin C and echinacea (3 species of plants used medicinally for their reported nonspecific stimulation of the immune system). For information on zinc, see Pharmacologic Therapy.

Vitamin C

Some clinicians have advocated supplementation with vitamin C. Although large doses of vitamin C have been used for prevention and treatment of colds, controlled trials reveal minimal therapeutic benefit and no preventive qualities.[32] In any case, high doses in children are not recommended.

A Cochrane review of 29 trials failed to demonstrate that vitamin C reduced the incidence of common colds or shortened illness duration.[111]

Vitamin C in combination with zinc has also been studied. In 2 preliminary, double-blind, randomized, placebo-controlled trials of vitamin C 1000 mg plus zinc 10 mg in patients with the common cold, a nonsignificant reduction of rhinorrhea duration was seen. In pooled analyses of the 2 studies, vitamin C plus zinc was significantly more efficient than placebo at reducing rhinorrhea over 5 days of treatment (this, despite the lower doses of zinc in the combined preparation, as opposed to the higher doses of zinc in the previous section). Symptom relief was also found to be quicker and the regimen well tolerated.

Echinacea

Echinacea purpurea has been studied for the prevention of experimental colds but did not reduce rates of infection or severity of illness when compared with placebo.[112] Although reports of improved symptoms have been described, validation and standardization of products is necessary.

Echinacea angustifolia has also been evaluated for the prophylaxis and treatment of experimental rhinovirus infection. Neither the rate of infection nor the severity of symptoms was significantly affected when E angustifolia was used either prophylactically or at the time of rhinovirus challenge.[113]

In contrast, a meta-analysis of echinacea indicated that in properly designed studies, patients receiving placebo were 55% more likely to experience cold symptoms than patients taking echinacea.[114] The most striking part of this meta-analysis was that 231 of 234 articles identified were excluded because they did not control for the type of viruses causing the colds.

In a randomized, controlled trial assessing the potential benefits of echinacea pills as a treatment for the common cold in 719 patients (713 of whom completed the protocol), illness duration and severity did not differ significantly between patients taking echinacea and those taking placebo.[115]

Prevention

Because infection is spread by hand-to-hand contact, autoinoculation, and, possibly, aerosol particles, it is crucial to emphasize appropriate handwashing, avoidance of finger-to-eyes or finger-to-nose contact, and use of nasal tissue. One study suggested that hand cleansers with salicylic acid and pyroglutamic acid prevent the transmission of rhinovirus and reduce the number of patients who become clinically infected.[116]

When a child has a viral illness, aspirin administration should be avoided to prevent Reye syndrome (though this is rare).

Medication Summary

Drugs used in symptomatic treatment of rhinovirus (RV) infection include nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, and anticholinergic nasal solutions. These agents have no preventive activity and appear to have no impact on complications. The combined effect of NSAIDs and antihistamines often relieves nasal obstruction; therefore, decongestion therapy is rarely needed. Oral decongestants (pseudoephedrine) and topical decongestants (oxymetazoline and phenylephrine) are commonly used for symptomatic relief.

First-generation antihistamines reduce rhinorrhea by 25-35%, as do topical anticholinergics and ipratropium bromide. Second-generation or nonsedating antihistamines appear to have no effect on common cold symptoms. Corticosteroids may actually increase viral replication and have no impact on cold symptoms.

In adults, evidence shows that zinc decreases the duration of symptoms and severity.

Diphenhydramine (Aler-Cap, Q-Dryl, Benadryl)

Clinical Context:  Diphenhydramine is an oral H1-blocker used in the treatment of allergic conjunctivitis and rhinitis, angioedema, pruritus, and urticaria. It causes occasional drowsiness and is suitable for use on a day-to-day basis.

Chlorpheniramine (Chlor-Trimeton, Aller-Chlor, Allergy Relief)

Clinical Context:  Chlorpheniramine competes with histamine for H1-receptor sites on effector cells in blood vessels and the respiratory tract.

Brompheniramine (Respa-BR, J-Tan PD)

Clinical Context:  Brompheniramine is an oral H1-blocker used in the treatment of allergic conjunctivitis and rhinitis, angioedema, pruritus, and urticaria. It is available in various formulations, including long-acting preparations, chewable, suspension, and prescription infant drops. It does not tend to cause drowsiness and is suitable for use on a day-to-day basis.

Class Summary

Antihistamines relieve runny nose, watery eyes, or other allergylike symptoms. They act by competitive inhibition of histamine at the H1 receptor. This mediates wheal-and-flare reactions, bronchial constriction, mucous secretions, smooth muscle contraction, edema, hypotension, central nervous system (CNS) depression, and cardiac arrhythmias. First-generation antihistamines are generally more sedating and have stronger anticholinergic side effects (eg, blurred vision, urinary retention) than second-generation antihistamines do. Still, the first-generation antihistamines are recommended over second-generation antihistamines because the latter appear to have no effect on common cold symptoms.

Cetirizine (Zyrtec)

Clinical Context:  Cetirizine is a H1-receptor antagonist and is also available as an over-the-counter (OTC) product.

Desloratadine (Clarinex)

Clinical Context:  Desloratadine is a long acting oral H1-receptor antagonist used for seasonal and perennial allergies and chronic idiopathic urticaria.

Fexofenadine (Allegra)

Clinical Context:  Fexofenadine is a selective peripheral H1-receptor antagonist known to inhibit bronchospasms and nasal congestion due to allergic rhinitis.

Levocetirizine (Xyzal)

Clinical Context:  Levocetirizine is an oral H1-receptor antagonist used for relief of symptoms associated with allergic rhinitis and uncomplicated urticaria.

Loratadine (Claritin)

Clinical Context:  Loratadine is an oral H1-receptor antagonist that temporarily relieves symptoms due to hay fever or other respiratory allergies.

Class Summary

Antihistamines relieve runny nose, watery eyes, or other allergy like symptoms. They act by competitive inhibition of histamine at the H1 receptor. Second-generation antihistamines are also known as nonsedating antihistamines. Although they are not void of sedative properties in all individuals, they are often better tolerated and have less anticholinergic effects. Second-generation antihistamines appear to have no effect on common cold symptoms, and so are not the antihistamines of choice for the common cold.

Ipratropium intranasal (Atrovent)

Clinical Context:  Ipratropium is chemically related to atropine. It comes in 2 strengths of nasal spray: (1) 0.03%, for treatment of rhinorrhea associated with allergic and nonallergic perennial rhinitis, and (2) 0.06%, for treatment of rhinorrhea associated with the common cold.

Class Summary

Anticholinergic agents have antisecretory properties and, when applied locally, inhibit secretions from the serous and seromucous glands lining the nasal mucosa.

Naproxen (Aleve, EC Naprosyn, Anaprox, Anaprox DS, Naprosyn)

Clinical Context:  Naproxen is used for relief of mild to moderate pain and reduction of fever; it inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.

Ibuprofen (Advil, Motrin IB)

Clinical Context:  Ibuprofen is used for relief of mild to moderate pain and reduction of fever; it inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis. Ibuprofen is one of the few NSAIDs indicated for reduction of fever.

Class Summary

Analgesic and antipyretic agents are used for relief of pain, discomfort, or fever. They inhibit central synthesis and release of prostaglandins that mediate effect of endogenous pyrogens in hypothalamus; thus, they promote return of set-point temperature to within the reference range. Other mechanisms also may exist (eg, inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions).

Acetaminophen (Tylenol)

Clinical Context:  Acetaminophen reduces fever by directly acting on hypothalamic heat-regulating centers, thereby increasing dissipation of body heat via vasodilation and sweating.

Class Summary

Acetaminophen is commonly used for analgesia or fever reduction. It may be used in alternation with NSAIDs.

Pseudoephedrine (Sudafed, Oranyl)

Clinical Context:  Pseudoephedrine stimulates vasoconstriction by directly activating alpha-adrenergic receptors of respiratory mucosa. It also induces bronchial relaxation and increases heart rate and contractility by stimulating beta-adrenergic receptors.

Class Summary

Decongestants relieve congestion of nasal passages or sinuses.

Phenylephrine nasal (Neo-Synephrine Nasal, 4-Way Fast Acting)

Clinical Context:  Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity; it produces vasoconstriction of arterioles, which decreases congestion.

Class Summary

Nonsystemic decongestants may be used temporarily to relieve congestion without causing systemic effects. Use for more than 3 days may result in rebound congestion.

Dextromethorphan (Robitussin, Delsym, Creo-Terpin, Nycoff)

Clinical Context:  Dextromethorphan is an antitussive-expectorant that is supplied as a single entity or in various combinations in cough and cold preparations.

Codeine

Clinical Context:  Codeine is used for symptomatic relief of cough. It is helpful for alleviating the pain of the intercostal muscle strain associated with cough. Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways and altering perception of and response to pain.

Class Summary

Antitussive agents act centrally or peripherally (or both) on the cough reflex. Centrally acting agents increase the threshold of the cough center in brain to incoming stimuli, whereas peripherally acting agents decrease the sensitivity of receptors in the respiratory tract.

Ascorbic acid (Cenolate, Vita-C, Acerola)

Clinical Context:  The effect of ascorbic acid on cold severity and duration is still controversial. Vitamin C comes in various formulations.

Class Summary

Vitamin C may decrease the severity and duration of colds (large doses are not recommended for children).

Zinc

Clinical Context:  The exact mechanism of the antiviral effect of zinc remains uncertain, although in vitro studies have demonstrated that zinc can inhibit viral replication and has activity against respiratory viruses including rhinovirus and respiratory syncytial virus.

Multiple zinc preparations are available; 75 mg of elemental zinc per day should be used to treat the common cold in adult patients so that the benefits of reduction of symptom duration and severity can be achieved. Zinc acetate is composed of 30% elemental zinc; zinc gluconate, 14.3%; zinc sulfate, 23%; and zinc oxide, 80%.

Author

Joseph Adrian L Buensalido, MD, Clinical Associate Professor, Division of Infectious Diseases, Department of Medicine, Philippine General Hospital, University of the Philippines Manila College of Medicine; Specialist in Infectious Diseases, Private Practice

Disclosure: Nothing to disclose.

Coauthor(s)

Jose Carlo B Valencia, MD, Medical Specialist III, Department of Medicine, Cagayan Valley Medical Center, Philippines

Disclosure: Nothing to disclose.

Chief Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

Disclosure: Nothing to disclose.

Additional Contributors

Michael Rajnik, MD, Associate Professor, Department of Pediatrics, Program Director, Pediatric Infectious Disease Fellowship Program, Uniformed Services University of the Health Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Duane R Hospenthal, MD, PhD Professor of Medicine, Uniformed Services University of the Health Sciences; Physician, Infectious Disease Service, San Antonio Military Medical Center (formerly Brooke Army Medical Center)

Duane R Hospenthal, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Society for Human and Animal Mycology, International Society for Infectious Diseases, International Society of Travel Medicine, and Medical Mycology Society of the Americas

Disclosure: Nothing to disclose.

James D Korb, MD Program Director, Department of Pediatrics, Children's Hospital of Orange County

Disclosure: Nothing to disclose.

Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Clinton Murray, MD

Program Director, Infectious Disease Fellowship, San Antonio Uniformed Services Health Education Consortium

Clinton Murray, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Association of Military Surgeons of the US, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Mai Ngoc Nguyen, MD

Staff Physician, Department of Pediatrics, Mattel Children's Hospital, University of California at Los Angeles

Mai Ngoc Nguyen, MD is a member of the following medical societies: American Academy of Pediatrics, and American Medical Association

Disclosure: Nothing to disclose.

José Rafael Romero, MD Director of Pediatric Infectious Diseases Fellowship Program, Associate Professor, Department of Pediatrics, Combined Division of Pediatric Infectious Diseases, Creighton University/University of Nebraska Medical Center

José Rafael Romero, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Gregory William RuteckiMD Professor of Medicine, University of South Alabama Medical School

Gregory William Rutecki is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Nephrology, National Kidney Foundation, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Gordon L Woods, MD Consulting Staff, Department of Internal Medicine, University Medical Center

Gordon L Woods, MD is a member of the following medical societies: Society of General Internal Medicine

Disclosure: Nothing to disclose.

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Seasonal variations in frequency of selected upper respiratory tract infection pathogens. PIV = parainfluenza virus; RSV = respiratory syncytial virus; MPV = metapneumovirus; Group A Strept = group A streptococcus.

Seasonal variations in frequency of selected upper respiratory tract infection pathogens. PIV = parainfluenza virus; RSV = respiratory syncytial virus; MPV = metapneumovirus; Group A Strept = group A streptococcus.

Seasonal variations in frequency of selected upper respiratory tract infection pathogens. PIV = parainfluenza virus; RSV = respiratory syncytial virus; MPV = metapneumovirus; Group A Strept = group A streptococcus.