March 2004

NIAID Research on Severe Acute Respiratory Syndrome (SARS)

What is SARS?
NIAID Research on SARS and Coronaviruses
Understanding the virus and how it spreads
Studying SARS in the clinic
Developing drug treatments
Developing diagnostic tests
Developing vaccines
Providing resources to researchers

What is SARS?

• 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.

NIAID Research on SARS and Coronaviruses

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.

Understanding the virus and how it spreads

• 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.

Studying SARS in the clinic

• 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.

Developing drug treatments

• 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.

Developing diagnostic tests

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.

Developing vaccines

• 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. For more details, see this March 31, 2004, NIAID press release: http://www.niaid.nih.gov/newsroom/releases/sarsvax.htm.

• 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, described in a March 12, 2004, press release (http://www.niaid.nih.gov/newsroom/releases/sarsmouse2.htm), 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.

Providing resources to researchers

• 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. (http://www.niaid.nih.gov/sars_meeting.htm)

• 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. (http://www.niaid.nih.gov/newsroom/releases/SARSChip.htm)

• 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.

NIAID is a component of the National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

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

U.S. Department of Health and Human Services

Department of Health and Human Services

National Institutes of Health (NIH) Bethesda, Maryland 20892

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