Saturday, February 20, 2021

Tell me about these new vaccines

In February 2021, the only Covid-19 vaccines available in the United States are the very similar mRNA-based vaccines from Pfizer and Moderna, both of which were reported to be 94-95% effective at preventing symptomatic Covid-19 in study participants who got the vaccine. A “real world” test, following the results of vaccinated people in Israel, has reassured us that the trial results were valid. Among 600,000 people who got the Pfizer vaccine, there was a 94% drop in symptomatic cases, only 4 severe cases and no deaths.

The problems with these vaccines are that there is simply not an adequate supply to vaccinate everyone in the U.S. soon enough, and that the price, need for two shots and the logistics of storing and transporting the vaccines limit how widely they can be used. Given the interconnectedness of the modern world, mass vaccination of the entire planet will be needed before any of us are truly safe. Happily, many other vaccines are well along in development.

A vaccine from Johnson and Johnson is closest to getting emergency use authorization in the U.S. This vaccine uses an adenovirus, a generally harmless virus, modified to carry the gene for the Coronavirus “spike protein” into human cells, which then produce this protein, which induces our immune system to recognize and fight off Covid-19 if we are exposed to it. This vaccine has many desirable qualities: it only requires one shot and it can be stored for months at normal refrigerator temperatures, making it much easier to distribute and administer.

You may have seen headlines indicating that it was only 66% effective at preventing symptomatic Covid-19, well below the efficacy of the mRNA vaccines. To some degree this is not a fair “apples to apples” comparison. The J&J vaccine was tested later than the mRNA vaccines, and it was tested in South America, Mexico and South Africa as well as in the U.S., while the Moderna vaccine was only tested in the U.S. The J&J shot thus had to contend with the new strains of virus, and we now know that the mRNA vaccines are less effective against these new strains than the original Coronavirus. Importantly, the J&J vaccine was 85% effective at preventing severe Covid-19, and there were no deaths in the vaccinated group.

Another candidate on the near horizon is from U.S. biotech firm Novavax. This vaccine combines a protein mimicking the virus’ spike protein with a “adjuvant,” a non-specific immune system stimulator. Preliminary trial results have shown 95% efficacy against the original SARS-CoV-2 virus and 86% against the B.1.1.7 (British) and 60% against the B.1.351 (South African) variants. Trials have been done in Great Britain and South Africa, and the vaccine requires two shots, 3 weeks apart, and can be stored at normal refrigerator temperature.

The Russian “Sputnik V” is another two-shot adenovirus-based vaccine. While the Russians were criticized for rolling out the vaccine before testing was complete, the preliminary trials have shown a 92% efficacy at preventing symptomatic Covid-19. Efficacy was similar across all age groups, and there were no severe cases in people who received both shots.

The Oxford/Astra Zeneca vaccine uses a modified adenovirus with DNA coding for the spike protein to generate an immune response. It got a lot of bad press when preliminary results showed better protection in those who had mistakenly gotten a lower dose than planned for their first dose followed by the planned second dose. This did not make biologic sense and put the trial into question. The larger trial has now shown 76% efficacy after one dose and 82% after a second. There were no Covid-19 hospitalizations in the vaccinated group. The vaccine has been approved for use in the United Kingdom.

Which vaccine should you get? To answer that question requires you to grasp one crucial fact: there have been essentially NO DEATHS from Covid-19 in people who got any of the available or soon to be available vaccines. We are not going to “wipe out” Covid-19. There have been and will continue to be coronaviruses circulating among us. What we need to get life back to normal is to eliminate deaths and markedly reduce hospitalizations from the SARS-CoV-2 virus. If Covid-19 can become just another cold that we catch and get over, we can go back to eating out, attending concerts and hugging each other.

So: take which ever vaccine you are offered!

Wednesday, February 3, 2021

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.

Prescription for Bankruptcy. Buy the book on Amazon