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 Kaluhi Islands
and the Amazon. In Brazil, rhinoviruses reportedly cause 46% of ARTIs.

Mortality/Morbidity

Although not associated with fatal disease, rhinoviruses are associated with significant
morbidity. ARTIs, predominantly rhinoviral infections, are estimated to cause 30-50% of time
lost from work by adults and 60-80% of time lost from school by children. Complications of
rhinoviral infections include otitis media, sinusitis, chronic bronchitis, and exacerbations of
reactive airway disease in children and adults. These viruses are possibly involved in lower
respiratory tract infections in elderly persons, infants, persons with cystic fibrosis, and
immunosuppressed patients. The true impact of lower respiratory tract infection is not clear.
Recovery of rhinovirus in these patients may be a marker of an underlying disease process or a
precursor to a bacterial infection.

Race

No difference in susceptibility to infection or disease course has been described among different
races.

Sex
Some reports indicate a male predominance of infection in children younger than 3 years, which
switches to a female predominance in children older than 3 years. No difference in rates of
infection in adults is apparent.

Age

Rhinoviral infection is most common in children, with decreasing incidence as they approach
adulthood. Children are instrumental in transmission of infection, commonly passing infection to
family members after contracting the virus in nurseries, daycare facilities, and schools.

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.

Treatment
Medical Care

Rhinoviral infections are predominately 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, antihistamines, and nasal decongestants.

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 to positively affect a rhinoviral infection. In addition, the cause of the common
cold is not always rhinoviral infection. Therefore, rapid and accurate diagnostic tests would be
needed if a specific antiviral therapy were developed.
 • Because of the large number of rhinovirus immunotypes 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.
• Because infection is spread by hand-to-hand contact, autoinoculation, and,
possibly, aerosol particles, emphasize appropriate hand washing, avoidance
of finger-to-eyes or finger-to-nose contact, and use of nasal tissue.
• Heated humidified air has been used for decades for the alleviation of
symptoms due to rhinoviral infections but has never been shown to improve
objective outcome measures.34
• Numerous agents are under investigation for the treatment of viral infections.
o 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 PO tid for 5 days, initiated within 24 hours of symptom onset,
resulted in a decrease in the duration of symptoms by 1 day.14
o Steroids have been examined as a therapeutic modality and have
shown little effect with rhinoviruses. One recent article noted that
children who experienced wheezing during a rhinoviral infection and
were treated with prednisolone experienced fewer wheezing episodes
than untreated individuals in the subsequent 2 months. However, no
change in time to discharge was noted.18
o A blinded, placebo-controlled trial using intranasal interferon-alpha-2b
and ipratropium with oral naproxen started within 24 hours of
rhinovirus inoculation decreased viral shedding, geometric mean virus
titers, and symptoms in the treatment group. Similar findings were
reported with the use of intranasal interferon-alpha-2b,
chlorpheniramine, and ibuprofen. Recombinant interferon-alpha-2b
applied topically to the nose at 5 million U or more per day prevented
experimental infections. Unfortunately, the effect of this agent on
symptomatic illness was limited.11
o A recombinant soluble intercellular adhesion molecule-1 (ICAM-1)
administered intranasally 6 times per day and beginning either 7 hours
before or 12 hours after rhinovirus challenge was analyzed in a
randomized, double-blinded study. Neither strategy affected the
incidence of infection, but combining results from both treatment
groups found a 23% decrease in clinical colds, a 45% decrease in total
symptom score, and a 56% decrease in total nasal secretion weight.50
o 3C protease inhibitors are currently being evaluated in human trials,
but no data are currently available. A phase II study found that
ruprintrivir, a 3C protease inhibitor, delivered as a nasal spray was well
tolerated and decreased positive viral culture results and improved
symptom scores but did not decrease the frequency of colds.15 These
drugs act by interfering with the cleaving of a single large polyprotein
that produces individual structures and enzymatic proteins of the virus.
o Rhinoviruses are sensitive to low pH. In one recent study,
citrate/phosphate buffers were administered intranasally, decreasing
viral shedding but failing to decrease symptomatology.48

Diet
Dietary supplements have been touted as possible therapeutic or preventive measures.

• 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.33
• Zinc has been found to inhibit rhinovirus replication in vitro, but no proven
benefit has been shown in vivo on virus activity or immune modulation.
• The genus Echinacea consists of 3 species of plants used medicinally for their
reported nonspecific stimulation of the immune system.
o Echinacea purpurea has recently been studied and did not show any
differences in rates of infection or severity of illness when compared
with placebo. Although reports of improved symptoms have been
described, validation and standardization of products is necessary.36
o Echinacea angustifolia has also been examined in the prophylaxis and
treatment of experimental rhinoviral infection. Neither the rate of
infection nor the severity of symptoms were found to be statistically
significantly affected when E angustifolia was used either
prophylactically or at the time of challenge.39
o In contrast, a recent 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.
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. Echinacea extracts will continue to
be evaluated.32

Activity

Patients may limit their activity during the course of the infection, with clinical improvement
occurring 48-72 hours after the prodrome of symptoms.

Medication
Drugs used in the symptomatic treatment 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 (pseudoephedrine) and topical (oxymetazoline and phenylephrine) decongestants 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.

Antihistamines
These agents act by competitive inhibition of histamine at the H1 receptor.

Diphenhydramine (Benylin, Benadryl)

Occasional drowsiness and is suitable for use on a day-to-day basis. Oral H1-blocker used in the
treatment of allergic conjunctivitis and rhinitis, angioedema, pruritus, and urticaria.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

25-50 mg PO q6-8h prn; not to exceed 400 mg/d

10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d

Pediatric

12.5-25 mg PO tid/qid, or 5 mg/kg/d, or 150 mg/m2/d divided tid/qid; not to exceed 300 mg/d
5 mg/kg/d IV/IM or 150 mg/m2/d, divided qid; not to exceed 300 mg/d

• Dosing
• Interactions
• Contraindications
• Precautions

Potentiates effect of CNS depressants; because of alcohol content, do not administer syrup
dosage form to patients taking medications that can cause disulfiram-like reactions

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; MAOIs

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract

obstruction; xerostomia may occur

Chlorpheniramine (Telachlor, Chlo-Amine, Chlor-Trimeton, Aller-Chlor)

Competes with histamine or H1-receptor sites on effector cells in blood vessels and respiratory
tract.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

10-20 mg IV/IM/SC once; not to exceed 40 mg/d

4 mg PO q4-6h; not to exceed 24 mg/d or 8-12 mg SR q8-12h; not to exceed 24 mg/d

Pediatric

<2 years: Not established

2-6 years: 1 mg PO divided q4-6h; not to exceed 6 mg/d
6-12 years: 2 mg PO q4-6h; not to exceed 12 mg/d or 8 mg SR PO hs
>12 years: Administer as in adults

• Dosing
• Interactions
• Contraindications
• Precautions

CNS toxicity increases with coadministration of other CNS depressants, tricyclic antidepressants,
MAOIs, and phenothiazines

• Dosing
• Interactions
• Contraindications
• Precautions
Documented hypersensitivity; asthma attacks; narrow-angle glaucoma; symptomatic prostate
hypertrophy; bladder-neck obstruction; stenosing peptic ulcer

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause significant confusional symptoms; not for administration to premature or full-term
neonates

Brompheniramine maleate (Bromphen, Nasahist B, Dimetane Extentabs)

Does not tend to cause drowsiness and is suitable for use on a day-to-day basis. Oral H1-blocker
used in the treatment of allergic conjunctivitis and rhinitis, angioedema, pruritus, and urticaria.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

Capsule/elixir: 4-8 mg PO q6-8h prn

Extended-release form: 8 mg PO q8-12h or 12 mg PO q12h prn; not to exceed 24 mg/d

Pediatric

<2 years: Not established

2-5 years: 1 mg PO q4-6h prn; not to exceed 6 mg/d
6-11 years: 2-4 mg PO q6-8h prn; not to exceed 12 mg/d
>12 years: Administer as in adults

• Dosing
• Interactions
• Contraindications
• Precautions
MAOIs and beta-blockers increase the effects of sympathomimetics; may reduce
antihypertensive effects of methyldopa, mecamylamine, reserpine, veratrum alkaloids; alcohol
and other CNS depressants may have an addictive effect

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; severe hypertension; severe coronary artery disease; current or

within 14 days of MAOI use; narrow-angle glaucoma; urinary retention; peptic ulcer disease;
during an asthma attack

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Caution in patients with hypertension, heart disease, diabetes, or thyroid disease; antihistamines
may cause drowsiness

Anticholinergics

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

Ipratropium intranasal (Atrovent)

Two strengths of nasal spray: 0.03% for treatment of rhinorrhea associated with allergic and
nonallergic perennial rhinitis and 0.06% for treatment of rhinorrhea associated with common
cold. Chemically related to atropine.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

Rhinorrhea common cold 0.06% nasal solution: 2 sprays (42 mcg/spray) per nostril tid/qid
Rhinorrhea allergic/nonallergic perennial rhinitis 0.03% nasal solution: 2 sprays (21 mcg/spray)
per nostril bid/tid

Pediatric

Administer as in adults

• Dosing
• Interactions
• Contraindications
• Precautions

Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol may
increase effects

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with narrow-angle glaucoma, prostatic hypertrophy, or bladder-neck

obstruction

Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of
action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other
mechanisms also may exist (eg, inhibition of leukotriene synthesis, lysosomal enzyme release,
lipoxygenase activity, neutrophil aggregation, various cell membrane functions).
Naproxen (Anaprox)

For relief of mild to moderate pain and antipyretic action; inhibits inflammatory reactions and
pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin
synthesis.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

550 mg PO q12h or 275 mg PO q6-8h prn

Pediatric

<2 years: Not established

>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d

• Dosing
• Interactions
• Contraindications
• Precautions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects;
probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect
of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and
thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk
of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal

insufficiency

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary
necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk
acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during
therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further
evaluation and may require discontinuation of drug

Ibuprofen (Ibuprin, Motrin)

For relief of mild to moderate pain and antipyretic action; inhibits inflammatory reactions and
pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin
synthesis.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d

Pediatric

<6 months: Not established

6 months to 12 years: 4-10 mg/kg/dose PO tid/qid
>12 years: Administer as in adults