SARS (Severe Acute Respiratory Syndrome)

• 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 people with SARS 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. Of the 774 deaths attributed to SARS, more than 50 percent occurred in people 65 years of age or older. Susceptibility decreased significantly with age, with children the least likely to acquire the disease. For current information about SARS, visit the Centers for Disease Control and Prevention (CDC)
• 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 also may 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.

• Using high-powered microscopes, blood tests, and other standard laboratory techniques, NIAID-supported scientists in Hong Kong were the first to show that SARS symptoms was caused by a virus. Within a few days, these scientists and others from CDC showed 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 opportunities for animal viruses to spread 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 a person 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, how it jumped from animals to humans, and how it causes disease, including the immune system response.
• NIAID is encouraging grant applications on the immunopathology of SARS disease , including studies on inflammation and airway hypersensitivity, and the ways in which SARS-CoV may evade destruction by immune system cells.
• NIAID scientists and collaborators at CDC have developed several animal models for SARS, including mouse, hamster, and non-human primate models. These models, will allow researchers to study the course of SARS infection, potential vaccines against the disease, and the safety and efficacy of experimental therapies

• 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 in Bethesda, Maryland, 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 NIH National Heart, Lung, and Blood Institute, CDC, and academic and clinical investigators from the United States and Canada to study experimental SARS therapies. One experimental drug to be evaluated for efficacy is alpha interferon, a drug already approved by the Food and Drug Administration for treating hepatitis B and C infections.

• NIAID is participating in a project to screen up to 100,000 antiviral drugs and other compounds for activity against SARS virus-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 being 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, NIAID-supported researchers are beginning to design drugs specifically aimed at its weak points. 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. Researchers hope 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.

• 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 Sanofi Pasteur to produce experimental inactivated whole virus SARS disease 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 and Treatment Evaluation Units.
• Scientists at NIAID's Vaccine Research Center developed an experimental SARS vaccine that prevents the SARS-CoV from replicating in laboratory mice. The vaccine was tested on 10 healthy volunteers to determine if it is safe in people and to examine the immune response stimulated (immunogenicity).
• 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 mouse, hamster and non-human primate models for replication of SARS-CoV. Researchers found the magnitude of SARS virus replication in hamsters to be much higher than that detected in other models, making it easier to measure the effectiveness of candidate vaccines. Studies in mice 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.