"A Pretty Good Understanding" of SARS

Dr. Donald Low of Toronto says researchers now have reason to believe that their treatments are getting better

As an epidemic of a mystery virus sweeps from China and Hong Kong to the rest of the world treatment remains elusive. About 80% of those who get the illness, dubbed severe acute respiratory syndrome (SARS), seem to recover fully after a few weeks. But the rest get very sick. The worst symptom: Their lungs fill up with fluid, making it difficult to breathe -- and to get enough oxygen into their bodies. Respirators can help, but not always. Four percent of patients die (see BW, 4/14/03, "Deadly Virus").

That has touched off a frantic search to find a medicine or vaccine that can help. Dr. Donald E. Low of Mount Sinai Hospital in Toronto is at the forefront of that search, and he's at the center of the outbreak in Canada -- which began when an elderly woman brought the disease back from Hong Kong. Since then, he has treated dozens of patients. In fact, he has been exposed to the disease himself and is now under isolation in case he's infected.

Low says "we're now able to speculate about exactly what happened -- and we have a pretty good understanding of what's going on." The evidence suggests that somewhere in Southern China, a virus that normally infects animals jumped to a person -- "probably a farmer or someone in close contact with animals," says Low.


  The virus, he suggests, doesn't do all that well in people. That's why my most people manage to fight off the infection. But some people develop a very severe pneumonia. Why?

In Canada, Low and his colleagues have found two things that predict how hard the disease will strike. One is that virtually all of those who died were either elderly or had other, chronic diseases, or both. Those who are young and healthy appear to be far more capable of fighting off the virus. With one exception: Those who are exposed to a huge dose of the virus can die regardless of how strong and healthy there are.

Low points out that the elderly woman who brought the disease to Toronto had a 43-year old son, who helped care for her when she fell ill. Over the course of her illness, doctors speculate, the son got a huge dose of virus. "I bet he got a massive exposure," says Low. He soon became ill himself and died on Mar. 13, eight days after his mother passed away.


  Based on study of the disease so far, Low believes that his team has made progress in treating it. Scientists now think the fluid in the lungs is caused by a biochemical mechanism that involves chemical messengers in the immune system called cytokines. Somehow -- the exact mechanisms aren't yet known -- the virus triggers cells in the immune system to make far too many cytokines. The cytokines, in turn, cause the capillaries (small blood vessels) in lung tissue to leak fluid into the lungs.

Doctors thought there might be two ways to tackle this deadly chain of events. One is to try to knock the virus back directly with an antiviral drug like ribavarin. But Low says he has treated 20 patients with ribavarin "and I've not been impressed," he says. "It's not a great drug -- at least in the test tube" against this virus.

The other approach is to try to dampen the immune response just enough to keep the amount of cytokines (and thus the fluid in the lungs) from getting dangerously high. The drugs of choice: steroids. But steroids can be a double-edged sword. Even as they dampen the cytokine response, they may also dampen the immune system's ability to make antibodies against the virus. These antibodies are crucial to fighting off the microbe. And "steroids may allow more viral reproduction," Low explains.


  So the approach Low and others are now using combines both steroids and ribavarin. The hope is that the ribavarin, even though it's not very potent against the virus, might slow it down just enough to counteract the steroids' bad effects on the immune system. That way, the steroids' good effects -- reducing fluid in the lung -- can help patients live long enough for their antibodies to kick in, finally conquering the virus.

"In our more recent patients, we started ribavarin and steroids at the same time -- and they've done very well," says Low. But something else should work a lot better, he says. Ample evidence shows that the body's immune system can make antibodies against the virus. So what if doctors took those antibodies and gave them to sick people?

The idea "definitely warrants further investigation," says Low. The same approach has worked well in other dangerous infections, he says. "The challenge is to find patients who have recovered and to harvest antibodies from them," he says. But if that can be done, "it could be a very attractive treatment."


  Low believes that Canada and other countries with strong public-health systems will be able to control their outbreaks. But maybe not so in the rest of the world: "My big concern is that if it goes into countries with no resources, no expertise, [and] no infrastructure, it will become a pandemic," he says. That means it would keep spreading from person to person for years to come -- and periodically come back to haunt countries that managed to stamp it out this time around.

If that happens, Low hopes, at least by then doctors will be better equipped to handle it. "If we can control the outbreak in this country now, it will give us the lead time to get vaccines and better treatments, so we'll be more prepared when it comes back," he says. In the meantime, the research goes on.

By John Carey in Washington

Edited by Douglas Harbrecht

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