Sneezing, scratchy throat, runny nose--everyone knows the first signs of a cold, probably the most common illness known to man. Although the common cold is usually mild, with symptoms lasting a week or less, it is a leading cause of doctor visits and of school and job absenteeism.

Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID) have made significant advances in understanding the structure and disease-causing mechanisms of the many viruses that can cause the common cold, with the goal of preventing and treating this troublesome and costly ailment.

The Problem

In the course of a year, individuals in the United States suffer 1 billion colds, according to some estimates.

Colds are most prevalent among children, and seem to be related to youngsters' relative lack of resistance to infection and to contacts with other children in day-care centers and schools. Children have about six to eight colds a year. In families with children in school, the number of colds per child can be as high as 12 a year.

Adults average about two to four colds a year, although the range varies widely. Women, especially those aged 20 to 30 years, have more colds than men, possibly because of their closer contact with children. On average, individuals older than 60 have fewer than one cold a year.

The economic impact of the common cold is enormous. The National Center for Health Statistics (NCHS) estimates that, in 1992, 65 million cases of the common cold in the United States required medical attention or resulted in restricted activity. In 1992, colds caused 157 million days of restricted activity and 15 million days lost from work, according to the NCHS.

The Causes

The Viruses. More than 200 different viruses are known to cause the symptoms of the common cold. Some, such as the rhinoviruses, seldom produce serious illnesses. Others, such as parainfluenza and respiratory syncytial virus, produce mild infections in adults but can precipitate severe lower respiratory infections in young children.

Rhinoviruses (from the Greek rhin, meaning "nose") cause an estimated 30 to 35 percent of all adult colds, and are most active in early fall, spring and summer. More than 110 distinct rhinovirus types have been identified. These agents grow best at temperatures of 33° Celsius [about 91° Fahrenheit (F)], the temperature of the human nasal mucosa.

Coronaviruses are believed to cause 10 to 20 percent of all adult colds. They induce colds primarily in the winter and early spring. Of the more than 30 isolated strains, three or four infect humans. The importance of coronaviruses as causative agents is hard to assess because, unlike rhinoviruses, they are difficult to grow in the laboratory.

Approximately 10 to 15 percent of adult colds are caused by viruses also responsible for other, more severe illnesses: adenoviruses, coxsackieviruses, echoviruses, orthomyxoviruses (including influenza A and B viruses), paramyxoviruses (including several parainfluenza viruses), respiratory syncytial virus and enteroviruses.

The causes of 30 to 50 percent of adult colds, presumed to be viral, remain unidentified.

The same viruses that produce colds in adults appear to cause colds in children. However, the relative importance of various viruses in pediatric colds is unclear because of the difficulty in isolating the precise cause of symptoms in studies of children with colds.

Does cold cause a cold? Although many people are convinced that a cold results from exposure to cold weather, or from getting chilled or overheated, NIAID grantees have found that these conditions have little or no effect on the development or severity of a cold. Nor is susceptibility apparently related to factors such as exercise, diet or enlarged tonsils or adenoids.

On the other hand, research suggests that psychological stress, allergic disorders affecting the nasal passages or pharynx, and menstrual cycles may have an impact on a person's susceptibility to colds. For example, NIAID-funded experiments showed individuals under high levels of psychological stress are more prone to infection with any of five cold-producing viruses and more apt to experience respiratory symptoms than people experiencing less stress.

The Cold Season

In the United States, most colds occur during the fall and winter. Beginning in late August or early September, the incidence of colds increases slowly for a few weeks and remains high until March or April, when it declines. The seasonal variation may relate to the opening of schools and to cold weather, which prompt people to spend more time indoors and increase the chances that viruses will spread from person to person.

Seasonal changes in relative humidity may also affect the prevalence of colds. The most common cold-causing viruses survive better when humidity is low--the colder months of the year. Cold weather also may make the nasal passages' lining drier and more vulnerable to viral infection.

Cold Symptoms

Symptoms of the common cold usually begin two to three days after infection and often include nasal discharge, obstruction of nasal breathing, swelling of the sinus membranes, sneezing, sore throat, cough and headache. Fever is usually slight but can climb to 102° F among infants and young children. Cold symptoms can last from two to 14 days, but two-thirds of people recover in a week. If symptoms occur often or last much longer than two weeks, they may be the result of an allergy rather than a cold.

Colds occasionally can lead to secondary bacterial infections of the middle ear or sinuses, requiring treatment with antibiotics. High fever, significantly swollen glands, severe facial pain in the sinuses, and a cough that produces mucus may indicate a complication or more serious illness requiring a doctor's attention.

How Cold Viruses Cause Disease

Viruses cause infection by overcoming the body's complex defense system. The body's first line of defense is mucus, produced by the membranes in the nose and throat. Mucus traps the material we inhale: pollen, dust, bacteria, viruses. When a virus penetrates the mucus and enters a cell, it commandeers the protein-making machinery to manufacture new viruses which, in turn, attack surrounding cells.

Cold symptoms: the body fights back. Cold symptoms are probably the result of the body's immune response to the viral invasion. Virus-infected cells in the nose send out signals that recruit specialized white blood cells to the site of the infection. In turn, these cells emit a range of immune system mediators such as kinins. These chemicals probably lead to the symptoms of the common cold by causing swelling and inflammation of the nasal membranes, leakage of proteins and fluid from capillaries and lymph vessels, and the increased production of mucus. Kinins and other mediators released by immune system cells in the nasal membranes are the subject of intensive research. Researchers are examining whether drugs to block these mediators, or the receptors on cells to which they bind, might benefit people with colds.

How Colds are Spread

Depending on the virus type, any or all of the following routes of transmission may be common:

• Touching infectious respiratory secretions on skin and on environmental surfaces and then touching the eyes or nose.
• Inhaling relatively large particles of respiratory secretions transported briefly in the air.
• Inhaling droplet nuclei: smaller infectious particles suspended in the air for long periods of time.

Research on rhinovirus transmission. Much of the research on the transmission of the common cold has been done with rhinoviruses, which are shed in the highest concentration in nasal secretions. Studies suggest a person is most likely to transmit rhinoviruses in the second to fourth day of infection, when the amount of virus in nasal secretions is highest. Researchers have also shown that using aspirin to treat colds increases the amount of virus shed in nasal secretions, possibly making the cold sufferer more of a hazard to others.

NIAID grantees have found that rhinoviruses from nasal secretions can be transferred easily from the hands of an infected person to those of another--by shaking hands, for instance--or to a surface such as a doorknob or telephone that is then touched by another person. By touching one's eyes or nose with the fingers, something most people do many times a day, the susceptible person can be "self-inoculated." Other studies suggest rhinovirus colds can be transmitted through the air.

Preventing Transmission

Handwashing is the simplest and most effective way to keep from getting rhinovirus colds. Not touching the nose or eyes is another. Individuals with colds should always sneeze or cough into a facial tissue, and promptly throw it away. If possible, one should avoid close, prolonged exposure to persons who have colds.

Because rhinoviruses can survive up to three hours outside the nasal passages on inanimate objects and skin, cleaning environmental surfaces with a virus-killing disinfectant might help prevent spread of infection.

A cold vaccine? The development of a vaccine that could prevent the common cold has reached an impasse because of the discovery of many different cold viruses. Each virus carries its own specific antigens, substances that induce the formation of specific protective proteins (antibodies) produced by the body. Until ways are found to combine many viral antigens in one vaccine, or take advantage of the antigenic cross-relationships that exist, prospects for a vaccine are dim. Evidence that changes occur in common-cold virus antigens further complicate development of a vaccine. Such changes occur in some influenza antigens and make it necessary to alter the influenza vaccine each year.

Treatment

Only symptomatic treatment is available for uncomplicated cases of the common cold: bed rest, plenty of fluids, gargling with warm salt water, petroleum jelly for a raw nose, and aspirin or acetaminophen to relieve headache or fever.

A word of caution: several studies have linked the use of aspirin to the development of Reye's syndrome in children recovering from influenza or chickenpox. Reye's syndrome is a rare but serious illness that usually occurs in children between the ages of three and 12 years. It can affect all organs of the body, but most often injures the brain and liver. While most children who survive an episode of Reye's syndrome do not suffer any lasting consequences, the illness can lead to permanent brain damage or death. The American Academy of Pediatrics recommends children and teenagers not be given aspirin or any medications containing aspirin when they have any viral illness, particularly chickenpox or influenza. Many doctors recommend these medications be used for colds in adults only when headache or fever is present. However, researchers also have found aspirin and acetaminophen can suppress certain immune responses and increase nasal stuffiness in adults.

Nonprescription cold remedies, including decongestants and cough suppressants may relieve some cold symptoms but will not prevent, cure or even shorten the duration of illness. Moreover, most have some side effects, such as drowsiness, dizziness, insomnia or upset stomach, and should be taken with care.

Antihistamines generally don't relieve cold symptoms, because the body makes inflammatory chemicals other than histamine when attacked by a cold virus.

Antibiotics do not kill viruses. These prescription drugs should be used only for rare bacterial complications, such as sinusitis or ear infections, that can develop as secondary infections. The use of antibiotics "just in case" will not prevent secondary bacterial infections.

Does vitamin C have a role? Many people are convinced that taking large quantities of vitamin C will prevent colds or relieve symptoms. To test this theory, several large-scale, controlled studies involving children and adults have been conducted. To date, no conclusive data has shown that large doses of vitamin C prevent colds. The vitamin may reduce the severity or duration of symptoms, but definitive evidence is lacking.

Taking vitamin C over long periods of time in large amounts may be harmful. Too much vitamin C can cause severe diarrhea, a particular danger for elderly people and small children. In addition, too much vitamin C distorts results of tests commonly used to measure the amount of glucose in urine and blood. Combining oral anticoagulant drugs and excessive amounts of vitamin C can produce abnormal results in blood-clotting tests.

Inhaling steam also has been proposed as a treatment of colds on the assumption that increasing the temperature inside the nose inhibits rhinovirus replication. Recent studies found that this approach had no effect on the symptoms or amount of viral shedding in individuals with rhinovirus colds. However, steam may temporarily relieve symptoms of congestion associated with colds.

Interferon-alpha has been studied extensively for the treatment of the common cold. Investigators have shown interferon, given in daily doses by nasal spray, can prevent infection and illness. However, interferon causes unacceptable side effects such as nosebleeds and does not appear useful in treating established colds. Most cold researchers are concentrating on other approaches to combatting cold viruses.

NIAID Research

In laboratories in Bethesda, Md., and at grantee institutions nationwide, NIAID supports basic research on the structure of viruses that cause colds and cold-like diseases, and on their disease-causing mechanisms. The institute provides rhinovirus research materials to investigators, and has made its nationwide network of Vaccine and Treatment Evaluation Units available for clinical studies of potential new treatments.

NIAID-supported researchers have pioneered the use of X-ray crystallography to look at the atomic structure of viruses. The ability to picture the rhinovirus at this level and study its three-dimensional structure has revolutionized the design and testing of new antiviral drugs.

The researchers have shown rhinoviruses all share a common structure--a rhinovirus canyon--required for attachment to susceptible cells. These canyons are not accessible to attack by antibodies. Investigators are using X-ray crystallography to develop new drugs that snugly fit into and change the shape of the rhinovirus canyon, making the virus non-infectious.

Also, scientists have identified the docking molecule on cells to which the rhinovirus canyon attaches. This molecule is known as the intracellular adhesion molecule-1 (ICAM-1). NIAID-supported studies suggest that ICAM-1, or ICAM-1 coupled to an antibody, might be used to disrupt rhinoviruses and prevent their replication.

NIAID-funded studies of kinins and other mediators released in the nasal membranes are underway to further illuminate the sequence of events that occur between infection with a cold virus and the onset of symptoms. Recently, for example, investigators found increased levels of interleukin-1 (IL-1) in the nasal secretions of people with experimentally induced rhinovirus colds. The researchers speculate that IL-1 could play a number of roles in the development of the common cold, including the recruitment of immune system cells to the nasal mucosa.

The Outlook

Thanks to basic research, scientists know more about the rhinovirus than almost any other virus, and have powerful new tools for developing antiviral drugs. Although the common cold may never be uncommon, further investigations offer the hope of reducing the huge burden of this universal problem.

NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases as well as allergies and immunology.

Prepared by:
Office of Communications
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

Public Health Service
U.S. Department of Health and Human Services
June 1996