| THE COMMON COLD Objectives |
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
Para influenza 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
Hand washing 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 combating 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.
Information provided by NIH & NIAID
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
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