SARS: Systematic review of treatment effects

The SARS virus set alarm bells ringing across the world when it first appeared in 2002, but now a review of the effectiveness of the treatments used against it has found no evidence that any of them worked.

The review was commissioned by the World Health Organization and has been published in PLoS Medicine.

Severe acute respiratory syndrome (SARS) is caused by a virus; the main symptoms are pneumonia and fever. The virus is passed on when people sneeze or cough. In 2003 there were over 8,000 cases and 774 deaths worldwide. The situation was alarming, because the first ever cases only appeared in 2002, in China, and so the best way to treat this new disease was unknown.

Not many drugs are effective against viruses and all doctors can usually do with a viral disease is to treat symptoms like fever and inflammation, and rely on the body's own immune system to fight off the virus. However, in recent years a number of antiviral drugs have been developed (for example, there are several in use against HIV/AIDS) and there was hope that some of them might be active against SARS. Steroids have also been used in SARS treatment to try to reduce the inflammation of the lungs. To find out which, if any, of the potential treatments were effective, a number of research studies were carried out, both during and since the outbreak.

The World Health Organization (WHO) established an International SARS Treatment Study Group, which recommended that a 'systematic review' of potential SARS treatments should be carried out. In particular, it was considered important to bring together all the available evidence on the use of certain antiviral drugs (ribavirin, lopinavir and ritonavir), steroids, and proteins called immunoglobulins which are found naturally in human blood. The WHO group wanted to know how these treatments affected the virus outside the body ('in vitro') and whether it helped the condition of patients and reduced the death rate, especially in those patients who developed a dangerous complication called acute respiratory distress syndrome.

Researchers conducted a comprehensive search for information from research studies that fitted carefully pre-defined selection criteria. They found 54 SARS treatment studies, 15 in- vitro studies, and three acute respiratory distress syndrome studies. Some of the in-vitro studies with the antiviral drugs found that a particular drug reduced the reproduction rate of the viruses, but most of the studies of these drugs in patients were inconclusive. Of 29 studies on steroid use, 25 were inconclusive and four found that the treatment caused possible harm.

From the published studies, it is not possible to say whether any of the treatments used against SARS were effective. It is now many months since any new cases have been reported, but it is possible that the same or a similar virus might cause outbreaks in the future. It is disappointing that none of the research on SARS so far is likely to be useful in helping to decide on the best treatments to use in such an outbreak. The authors examined the weaknesses of the studies they found and urge that more effective methods of research should be applied in any future outbreaks. Their recommendations mean that researchers should be better prepared to learn from potential future outbreaks.