A "cure" for Covid-19?

When a new disease appears, doctors must try unproven remedies based on things that “might” work, based on test tube data or what seem like logical extrapolations from similar conditions. As time goes on, better data allows them to change their approach. In an ideal world, all therapeutic decisions are based on scientifically valid trials in which different therapies are compared in similar patients, the so-called “controlled clinical trial.”

When Covid-19 swept the world, there was no proven therapy, and patients were dying. A variety of remedies were tried and, in some cases, seemed to work. These results were posted on-line and rapidly adopted even when the evidence was sketchy. We now have good trials of many different agents, and I can summarize by saying that none of them are a magic bullet.

First out of the gate: hydroxychloroquine, an anti-malaria drug that is also used to treat lupus, and which appeared to have anti-viral effects in the test tube. KILL IT! Put a stake through its heart! There are now good trials that show that hydroxychloroquine has no benefit when used preventively in health care workers or spouses of Covid-positive patients or in moderately ill patients. A World Health Organization-sponsored trial in hospitalized patients found higher mortality in patients receiving the drug.

On the caveat emptor front, I saw a news item recently indicating that the state of Oklahoma is trying to get the wholesaler to take back 1.2 million hydroxychloroquine pills the governor insisted on buying, none of which were used. (This is the same governor who has refused calls for a mask mandate.)

Next up were antibodies, the chemicals our immune system makes to help fight off invading microorganisms. The whole basis of vaccines is to get the body to produce these antibodies before it is invaded by the virus, so that we can promptly mount a defense. It made sense to give transfusions of plasma from patients who had recovered from Covid-19 and who had high levels of antibodies to the virus to patients now sick, Like many things that “make sense,” giving convalescent plasma to hospitalized patients was of no benefit. A well-conducted trial in Argentina did find that this treatment given to older adults within 72 hours of their developing mild symptoms cut in half the number who went on to develop severe disease (16% vs 31%).

We have also seen trials of synthetic, laboratory-produced antibodies. Using these avoids the risk of infusing plasma from possibly unmatched donors and having a transfusion reaction. A “cocktail” of bamlanivimab plus etesevimab given to patients with mild to moderate disease showed a modest reduction in the amount of virus excreted and reduced the combination of ER visits plus hospitalizations from 5.8% to 1.5%. There were no deaths in either group. Another synthetic antibody, toclizumab, given to sicker patients who needed oxygen, showed no benefit and a trend toward worsening.

How about vitamins? These have the great virtue of safety. One trial of IV Vitamin C shortened hospital stays but had no benefit in reducing deaths or the need for ventilators. Vitamin D has had a lot of buzz, largely because of published data showing that patients deficient in Vitamin D were more likely to die. My take on this is that low Vitamin D levels are a marker of poorer overall health. There is no evidence that low Vitamin D patients are more likely to catch the coronavirus, but they are more likely to die, as are frail elders and those with other serious diseases. No trials have shown benefit from giving Vitamin D, but it clearly falls in the category of “it cannot hurt,” and I would support routinely giving it to patients. Note: one newly published study found that a single large oral dose had no benefit.

The one FDA-approved treatment for Covid-19 is remdesivir, an anti-viral drug. Patients receiving it showed fewer complications and less need for ICU care, but there is little mortality benefit.

For decades, doctors have used cortisone-like drugs as a “hail Mary” treatment for severely ill patients with a variety of conditions. These are potent anti-inflammatory agents, and the sickest Covid patients seem to have an over-reaction of the body’s inflammatory system, so again it “made sense.” The best evidence we have is that use of corticosteroids reduces mortality in very sick patients but increases mortality in less sick patients. The best guidance we have suggests that patients who require oxygen or ventilators to breath should receive these drugs while they should be avoided in the majority.

The latest on the scene, and a spin on the anti-inflammatory angle, is colchicine. This ancient drug has been used for centuries to treat gout and more recently to treat other inflammatory diseases such as pericarditis. A large well-controlled Canadian trial showed that giving oral colchicine to non-hospitalized patients with proven Covid-19 reduced the combined endpoint of hospitalization or death from 6% to 4.6%. The only adverse effect was increased diarrhea in the colchicine group, which is a known side-effect of the drug.

My main takeaway? Don’t count on cure. Prevention is much better. Get vaccinated as soon as you can – any vaccine is better than none – and continue to wear a mask and practice social distancing.

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