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Severe acute respiratory syndrome (SARS) is a new infectious disease first
identified in humans in early 2003.
SARS is caused by a newly described coronavirus, called SARS-associated coronavirus
(SARS-CoV). Previously identified human coronaviruses (named for their spiky,
crown-like appearance) were known to cause only mild respiratory infections.
SARS typically begins with flu-like symptoms, including high fever that may
be accompanied by headache and muscle aches, cough, and shortness of breath.
Up to 20 percent of infected people may develop diarrhea. Most SARS patients
subsequently develop pneumonia. In the 2003 outbreak, there were more than
8,000 probable cases of SARS and 774 deaths (approximately 9 percent mortality),
according to the World Health Organization. Eight confirmed cases were identified
in the United States, with no deaths. For current information about SARS, visit
the Centers for Disease Control and Prevention (CDC) Web site at http://www.cdc.gov/ncidod/sars/.
The virus spreads primarily by close human contact. SARS-CoV-containing droplets
can be released into the air when an infected person coughs or sneezes. Some
specific medical procedures performed on SARS patients also can release virus-containing
droplets into the air. Touching a SARS-CoV-infected surface and subsequently
touching the eyes, nose, or mouth may also lead to infection.
Intensive and supportive medical care is the primary therapy, as no specific
treatment has yet been shown to consistently improve the outcome of the ill
person.
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The prompt recognition that SARS is caused by a new type of coronavirus is a
tribute to the dedication of and collaboration by the world's medical researchers
and public health experts. Much more research is needed, however, to develop
ways to identify, treat, and prevent this deadly illness. NIAID scientists, grantees,
and industry partners are working to better understand the different aspects
of SARS and the virus that causes it. Below are some recent accomplishments and
goals for future efforts.
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Using high-powered microscopes, blood tests, and other standard laboratory
techniques, NIAID-supported scientists in Hong Kong were the first to show
that SARS was caused by a virus. Within a few days, these scientists and others
from the CDC were the first to show that the virus was a new and deadly type
of coronavirus. These efforts subsequently sparked worldwide efforts to rapidly
develop SARS-CoV diagnostic tests, drugs, and vaccines.
The genetic material, RNA, contained in the SARS-CoV is very difficult to
manipulate in the lab. NIAID-funded researchers generated a form of SARS-CoV
that is easier to work with. Researchers will be able to use it to study the
structure and function of viral proteins, and use the information to develop
vaccine candidates.
An ongoing NIAID-funded program for conducting influenza surveillance in the
live bird markets of Hong Kong was expanded to search for animal carriers of
SARS-CoV. Researchers traveled to live animal markets in China and determined
that some of the samples taken from two animals, the palm civet and the raccoon-dog,
were positive for SARS-CoV. These results were the first report of isolation
of a SARS-like CoV from animals. Although it is not known if these animals
are a natural reservoir for SARS-CoV, live animal markets provide effective
opportunities for the spread of animal viruses directly to humans.
In the area of basic immunological research, NIAID is supporting work to determine
how the immune system responds to SARS-CoV and if there are human genetic variations
that affect how susceptible an individual is to SARS.
NIAID is supporting analyses of genes from human and animal coronaviruses,
including many strains taken from SARS patients. This work could lead to a
better understanding of where the virus came from and how it causes disease,
including the immune system response.
NIAID is encouraging grant applications on the immunopathology of SARS, including
studies on inflammation and airway hypersensitivity, and the ways in which
SARS-CoV may evade destruction by immune system cells.
NIAID scientists have developed a mouse model of SARS, which will allow the
study of both the course of SARS infection and potential vaccines against the
disease. This model will also be used by an NIAID contractor to evaluate the
safety and efficacy of experimental therapies.
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NIAID has developed a project to study and treat SARS patients, contacts,
and health care workers. Should the disease return, these clinical trials would
take place at the NIH Clinical Center and would include researching the disease
as well as evaluating antiviral and immune-based therapies.
NIAID, using its Collaborative Antiviral Study Group network of clinical trial
sites, is taking the lead in a collaborative effort with the National Heart,
Lung and Blood Institute of the NIH, the CDC, and academic and clinical investigators
from the United States and Canada to study experimental SARS therapies. One
of the experimental drugs to be evaluated for efficacy is alpha interferon,
a drug already approved by the FDA for the treatment of hepatitis B and C infections.
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NIAID is participating in a project to screen up to 100,000 antiviral drugs
and other compounds for activity against SARS-CoV. While several compounds
have shown antiviral activity, only alpha interferon is suitable for immediate
clinical evaluation. Several compounds that act by inhibiting the coronavirus
cysteine protease enzyme showed a dramatic amount of antiviral activity. These
compounds are undergoing preclinical safety evaluations to allow selection
of a single candidate for clinical study. Experimental compounds are provided
by large and small pharmaceutical firms, foreign and domestic academic scientists,
and members of the lay community.
As more is learned about the mechanisms of SARS-CoV infection, it will become
possible to design drugs specifically aimed at its weak points. NIAID-supported
researchers are engaged in this rational drug design. One such project is developing
an "entry inhibitor" that prevents SARS-CoV from infecting human cells.
In 2003, NIAID awarded a contract to develop humanized antibodies against
SARS-CoV. It is hoped that one of these antibodies could be used to prevent
infection from gaining hold in health care workers and others who are exposed
to SARS patients.
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Because the symptoms of SARS are similar to those of influenza, clinicians
must have fast, accurate tests to identify and, if necessary, isolate people
with SARS. NIAID-supported scientists in Hong Kong developed a test that is
able to detect the virus in respiratory aspirates (material taken from the
lungs and bronchial passages) and in fecal samples. Research is continuing
to improve the accuracy of this test.
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Since it is not known which type of vaccine will be most effective against
the SARS-CoV, NIAID scientists and grantees are pursuing several parallel approaches
in the search for a vaccine.
In 2003, NIAID awarded contracts to Baxter Healthcare and Aventis Pasteur
to produce experimental inactivated whole virus SARS vaccines, and awarded
a contract to Protein Sciences Corporation to produce a recombinant subunit
vaccine. Once these experimental vaccines are ready, NIAID plans to test them
in clinical trials conducted by its Vaccine Testing and Evaluation Units.
Scientists at NIAID's Vaccine Research Center in Bethesda, MD, have developed
an experimental SARS vaccine that prevents the SARS-CoV from replicating in
laboratory mice. They are seeking Food and Drug Administration approval to
begin early stage safety and immunology studies in people.
Through a grant to China's Center for Disease Control, NIAID plans to help
support the development of several separate vaccine programs, including a protein
vaccine made from select SARS-CoV proteins and a recombinant protein vaccine.
Scientists in NIAID's Laboratory of Infectious Diseases have developed a mouse
model for replication of SARS-CoV. They have also demonstrated that antibodies
produced by the mice block replication of SARS-CoV. These findings
will help researchers working on SARS vaccines. NIAID scientists continue to
work on other animal models, including rodents and non-human primates, to evaluate
vaccine candidates and strategies for immunotherapy.
NIAID and foreign scientists are collaborating to develop and test a variety
of vaccines including standard killed virus vaccines and molecularly designed
vaccines, some of which can be administered intranasally.
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To help the world's research community develop an agenda leading to effective
control measures for SARS, NIAID convened an international meeting of experts
in May 2003.
Soon after the genetic code for SARS-CoV was determined, NIAID provided interested
researchers with free SARS "gene chips" embedded with a reference strain of
the virus. With the chip, researchers can rapidly detect genetic variations
among SARS strains and could eventually determine which strains are the most
dangerous as well as gaining other information useful in developing antiviral
drugs.
NIAID has also developed synthetic fragments of key SARS-CoV proteins that
are available to SARS researchers. These protein fragments can be used to help
understand the immune response to the SARS-CoV.
NIAID is working to establish a SARS-CoV research reagent repository. Scientists
throughout the world performing basic SARS research or testing candidate vaccines
and drugs against SARS-CoV can access them as these reagents become available.
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