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!
Saturday, February 20, 2021
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
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
Sunday, January 17, 2021
The virus mutates
The Boston Globe sent out a flash bulletin, clearly intended to worry its readers: “State health officials Sunday announced the first case of a more transmissible COVID-19 variant involving a Boston woman who developed symptoms after returning from the United Kingdom earlier this month. The woman, who is in her 20s, had traveled to the UK and became ill the day after she returned to Massachusetts, the department said.”
Be afraid. Be very afraid! Or not?
A key point to remember is that viruses mutate, particularly RNA viruses like the coronavirus and influenza virus. You are urged to get an annual flu vaccination not because your immunity has disappeared since last year’s shot but because the virus that circulates each winter is usually different than the one infecting people the prior year.
Mutations occur frequently; whether they become the prevailing strain depends on whether they give the mutated virus an advantage over the existing strains. Mutations that allow the virus to spread more easily, to reproduce faster or to be harder for the host immune response to destroy will have a selective advantage and soon become the dominant strain. Early in the pandemic, a mutation in the part of the viral RNA coding for the spike protein emerged and soon became the major strain. This was later found to be due to its higher transmissibility. The outbreak in Danish mink was due to a mutation that allowed the virus to better attach to receptors in the animal’s respiratory tract.
The most recent concern has been a new variant, called B.1.1.7, that appeared in the United Kingdom and which rapidly became common there. By the end of December, this strain had gone from undetected to causing 28% of all cases in the kingdom. Its “selective advantage” is clear: it spreads 56% more rapidly than the original strain. Similar but different mutations have been found in South Africa and Brazil, but as of this date seem confined to those countries.
The “UK strain,” however, has been detected in small numbers in at least 10 U.S. states as of Friday according to the CDC – and now 11 per the Globe report.
First the good news: this strain, while it spreads more rapidly, does not appear to cause more severe disease. Another piece of good news is that small studies done by Pfizer found that the neutralizing antibodies produced by their vaccine work on the B.1.1.7 variant virus.
The bad news is that because this variant spreads more easily, it is likely to become the dominant strain in the U.S. by March, and the increased transmissibility may lead to many more cases.
What does that mean for us? It adds urgency to the need to get as many people vaccinated as possible, and it means we cannot let down our guard. Basic hygiene measures: masks, social distancing, isolation and quarantine and hand washing must be maintained until a large majority have been vaccinated. So, don’t be afraid, but be sensible and cautious.
Prescription for Bankruptcy. Buy the book on Amazon
Be afraid. Be very afraid! Or not?
A key point to remember is that viruses mutate, particularly RNA viruses like the coronavirus and influenza virus. You are urged to get an annual flu vaccination not because your immunity has disappeared since last year’s shot but because the virus that circulates each winter is usually different than the one infecting people the prior year.
Mutations occur frequently; whether they become the prevailing strain depends on whether they give the mutated virus an advantage over the existing strains. Mutations that allow the virus to spread more easily, to reproduce faster or to be harder for the host immune response to destroy will have a selective advantage and soon become the dominant strain. Early in the pandemic, a mutation in the part of the viral RNA coding for the spike protein emerged and soon became the major strain. This was later found to be due to its higher transmissibility. The outbreak in Danish mink was due to a mutation that allowed the virus to better attach to receptors in the animal’s respiratory tract.
The most recent concern has been a new variant, called B.1.1.7, that appeared in the United Kingdom and which rapidly became common there. By the end of December, this strain had gone from undetected to causing 28% of all cases in the kingdom. Its “selective advantage” is clear: it spreads 56% more rapidly than the original strain. Similar but different mutations have been found in South Africa and Brazil, but as of this date seem confined to those countries.
The “UK strain,” however, has been detected in small numbers in at least 10 U.S. states as of Friday according to the CDC – and now 11 per the Globe report.
First the good news: this strain, while it spreads more rapidly, does not appear to cause more severe disease. Another piece of good news is that small studies done by Pfizer found that the neutralizing antibodies produced by their vaccine work on the B.1.1.7 variant virus.
The bad news is that because this variant spreads more easily, it is likely to become the dominant strain in the U.S. by March, and the increased transmissibility may lead to many more cases.
What does that mean for us? It adds urgency to the need to get as many people vaccinated as possible, and it means we cannot let down our guard. Basic hygiene measures: masks, social distancing, isolation and quarantine and hand washing must be maintained until a large majority have been vaccinated. So, don’t be afraid, but be sensible and cautious.
Prescription for Bankruptcy. Buy the book on Amazon
Wednesday, December 30, 2020
Coffee with that?
Tired of reading about Covid-19? Me too. I will not blog about the novel Coronavirus until there is something new and important to say. (And, no, I do not think that a few serious but very rare allergic reactions fit that description. If they did, we would have to take penicillin and many other important drugs off the market.)
Coffee has a fascinating history. Legend has it that it was discovered by a goat herder in Ethiopia when he noticed that after his goats ate berries from a specific tree, they became so energetic they did not want to sleep at night. From Ethiopia, coffee spread throughout the Arabian peninsula, and coffee houses soon became a staple of social life in the Muslim world. (Based on our travels, this is still true.) European travelers to the Middle East brought back stories of this unusual black beverage, and by the early 17th century, coffee had made its way to Europe. Initially condemned by the clergy as Satanic, coffee got a new lease on life when Pope Clement VIII tasted it, liked it and gave it papal blessing.
While there are numerous chemicals in coffee that lead to differences in aroma, color and taste, the main active ingredient is caffeine. It is caffeine that makes us more energetic and alert (good) and can also make us jittery and unable to sleep (bad). The caffeine in your cup reaches peak levels in your blood some 30 to 60 minutes after you drink it and has a “half-life” of 3 to 5 hours, meaning that some its effect can persist for 10 hours or longer.
In the United States, some 85% of adults consume caffeine daily, most commonly from coffee, but also from tea, chocolate, energy drinks, colas or in tablet form. The estimated average daily consumption of caffeine is 135 mg/day, the amount in about 1.5 8 ounce cups of coffee.
What about health risks and benefits of coffee? The science is less than robust, because most studies are based on comparing differences between people based on their self-reporting of how much coffee they drink. We have, or at least should have, learned that such “observational studies” can suggest possible benefits and harms but cannot prove them. People who drink 2-3 cups of coffee a day may not be like people who do not touch coffee. They may smoke more (or less), exercise more (or less) or may be more (or less) obese. Hence, take everything I say below as hypothesis or conjecture, not Truth.
Caffeine clearly increases alertness, reduces fatigue and reduces reaction time. It improves vigilance in performing tasks that require a long time with minimal stimulation, such as flying aircraft, driving long distances or working on an assembly line. It contributes to pain relief when added to common pain killers such as aspirin or acetaminophen (Tylenol). Caffeine also delays falling asleep and reduces sleep quality. Particularly at higher doses, it can cause or increase anxiety. These effects vary widely between different individuals. I have friends who drink a strong cup of coffee routinely at bedtime and drop off “like a log.” When I eat dinner out (remember those days?), I will ask the server for a cup of decaf “and your phone number, so I know who to call when I am awake at 3 AM.”
What about coffee’s effects on overall health? While consuming pure caffeine chronically has been shown to modestly elevate blood pressure, coffee does not appear to do this. Unfiltered coffee contains a compound that lowers the “good” cholesterol, HDL. This is not true for instant or filtered coffee, so if you are concerned about your lipids, avoid French press or Turkish coffee. There is no evidence that consuming as much as six cups of coffee daily increase the risk of heart attack or stroke.
There have been isolated reports of severe cardiovascular reactions, including sudden death, in people who took very large quantities of “energy drinks,” particularly when taken for weight loss or prior to gym work-outs.
The effects of coffee on cancer are, if anything, beneficial. Many cancers are less frequent in coffee drinkers, including liver, prostate, endometrial, skin and breast. A study published in November of 2020 found a lower risk of progression of metastatic colon cancer in coffee drinkers. Coffee drinkers also have fewer gallstones and kidney stones. Caffeinated (but not decaf) coffee appears to be protective against the development of Parkinson’s disease.
There is controversy about coffee consumption in pregnancy. A study published in the British Medical Journal claimed that maternal caffeine consumption was associated with increased risk of miscarriage and low birth weight. Both the British and American obstetric societies reviewed the study and disagreed with its recommendation that pregnant women avoid caffeine. The best advice seems to be to limit intake to the equivalent of 2 cups of coffee a day.
Several studies have found an association of drinking 2-5 cups of coffee daily with reduced mortality, and none have shown an increase.
A gentle reminder to older readers: caffeine is a diuretic - it will make you go more.
Bottom line: enjoy your morning Cup of Joe, guilt-free, but don’t overdo it.
Prescription for Bankruptcy. Buy the book on Amazon
Coffee has a fascinating history. Legend has it that it was discovered by a goat herder in Ethiopia when he noticed that after his goats ate berries from a specific tree, they became so energetic they did not want to sleep at night. From Ethiopia, coffee spread throughout the Arabian peninsula, and coffee houses soon became a staple of social life in the Muslim world. (Based on our travels, this is still true.) European travelers to the Middle East brought back stories of this unusual black beverage, and by the early 17th century, coffee had made its way to Europe. Initially condemned by the clergy as Satanic, coffee got a new lease on life when Pope Clement VIII tasted it, liked it and gave it papal blessing.
While there are numerous chemicals in coffee that lead to differences in aroma, color and taste, the main active ingredient is caffeine. It is caffeine that makes us more energetic and alert (good) and can also make us jittery and unable to sleep (bad). The caffeine in your cup reaches peak levels in your blood some 30 to 60 minutes after you drink it and has a “half-life” of 3 to 5 hours, meaning that some its effect can persist for 10 hours or longer.
In the United States, some 85% of adults consume caffeine daily, most commonly from coffee, but also from tea, chocolate, energy drinks, colas or in tablet form. The estimated average daily consumption of caffeine is 135 mg/day, the amount in about 1.5 8 ounce cups of coffee.
What about health risks and benefits of coffee? The science is less than robust, because most studies are based on comparing differences between people based on their self-reporting of how much coffee they drink. We have, or at least should have, learned that such “observational studies” can suggest possible benefits and harms but cannot prove them. People who drink 2-3 cups of coffee a day may not be like people who do not touch coffee. They may smoke more (or less), exercise more (or less) or may be more (or less) obese. Hence, take everything I say below as hypothesis or conjecture, not Truth.
Caffeine clearly increases alertness, reduces fatigue and reduces reaction time. It improves vigilance in performing tasks that require a long time with minimal stimulation, such as flying aircraft, driving long distances or working on an assembly line. It contributes to pain relief when added to common pain killers such as aspirin or acetaminophen (Tylenol). Caffeine also delays falling asleep and reduces sleep quality. Particularly at higher doses, it can cause or increase anxiety. These effects vary widely between different individuals. I have friends who drink a strong cup of coffee routinely at bedtime and drop off “like a log.” When I eat dinner out (remember those days?), I will ask the server for a cup of decaf “and your phone number, so I know who to call when I am awake at 3 AM.”
What about coffee’s effects on overall health? While consuming pure caffeine chronically has been shown to modestly elevate blood pressure, coffee does not appear to do this. Unfiltered coffee contains a compound that lowers the “good” cholesterol, HDL. This is not true for instant or filtered coffee, so if you are concerned about your lipids, avoid French press or Turkish coffee. There is no evidence that consuming as much as six cups of coffee daily increase the risk of heart attack or stroke.
There have been isolated reports of severe cardiovascular reactions, including sudden death, in people who took very large quantities of “energy drinks,” particularly when taken for weight loss or prior to gym work-outs.
The effects of coffee on cancer are, if anything, beneficial. Many cancers are less frequent in coffee drinkers, including liver, prostate, endometrial, skin and breast. A study published in November of 2020 found a lower risk of progression of metastatic colon cancer in coffee drinkers. Coffee drinkers also have fewer gallstones and kidney stones. Caffeinated (but not decaf) coffee appears to be protective against the development of Parkinson’s disease.
There is controversy about coffee consumption in pregnancy. A study published in the British Medical Journal claimed that maternal caffeine consumption was associated with increased risk of miscarriage and low birth weight. Both the British and American obstetric societies reviewed the study and disagreed with its recommendation that pregnant women avoid caffeine. The best advice seems to be to limit intake to the equivalent of 2 cups of coffee a day.
Several studies have found an association of drinking 2-5 cups of coffee daily with reduced mortality, and none have shown an increase.
A gentle reminder to older readers: caffeine is a diuretic - it will make you go more.
Bottom line: enjoy your morning Cup of Joe, guilt-free, but don’t overdo it.
Prescription for Bankruptcy. Buy the book on Amazon
Thursday, December 17, 2020
Enter Moderna
As you are doubtless aware, the FDA scientific advisory board today voted to recommend approval of Moderna’s Covid-19 vaccine under Emergency Use Authorization, and it is expected that the FDA will grant this on Friday, adding tens of millions of potential vaccine doses to our supply.
What is the difference between the two now-approved vaccines? While there is no peer-reviewed publication for Moderna’s entry as there was for Pfizer’s, the FDA did release the 54- page application the company provided, which I have reviewed. Spoiler alert! Not much.
The Moderna and Pfizer vaccines use almost identical technology: RNA coding for the “spike protein,” in lipid nanoparticles to allow entry into body cells. Both conducted large Phase 3 trials; Pfizer’s was slightly larger, about 18,800 people in each arm of the trial compared to 13,900. Both showed roughly 95% efficacy in preventing symptomatic Covid-19. Both also showed reduction in severe cases, with the edge here perhaps to Moderna. In the Pfizer study, after the first dose, there were 9 severe cases in placebo recipients and 1 in the vaccine group. In the Moderna study, the numbers were 11 and zero.
Side effects were similar in both studies, and I will not repeat these.
One possible advantage to Pfizer was that efficacy seemed similar across all age groups, while the Moderna study showed lower efficacy in subjects over 65: 95.6% in those 18-64, 86.4% in those 65 or older.
An obvious advantage to Moderna is that its vaccine can be stored at less demanding conditions: it should be stored at -13 to 5 degrees F, while Pfizer’s needs temperatures of -70C (-94F). Buy dry ice!!
How about Bell’s palsy, which was in the news? In the Moderna study, there were four cases of this condition, in which there is paralysis on one side of the face, usually (but not always) temporary, 3 in the vaccine group and 1 in the placebo group. To put this in perspective, Bell’s palsy is a common condition. With 30,000 people followed for 2-3 months, you would expect 2-3 cases, so while this needs to be watched for, it is not a major concern. Bottom line: very similar, and either seems both effective and safe.
Prescription for Bankruptcy. Buy the book on Amazon
What is the difference between the two now-approved vaccines? While there is no peer-reviewed publication for Moderna’s entry as there was for Pfizer’s, the FDA did release the 54- page application the company provided, which I have reviewed. Spoiler alert! Not much.
The Moderna and Pfizer vaccines use almost identical technology: RNA coding for the “spike protein,” in lipid nanoparticles to allow entry into body cells. Both conducted large Phase 3 trials; Pfizer’s was slightly larger, about 18,800 people in each arm of the trial compared to 13,900. Both showed roughly 95% efficacy in preventing symptomatic Covid-19. Both also showed reduction in severe cases, with the edge here perhaps to Moderna. In the Pfizer study, after the first dose, there were 9 severe cases in placebo recipients and 1 in the vaccine group. In the Moderna study, the numbers were 11 and zero.
Side effects were similar in both studies, and I will not repeat these.
One possible advantage to Pfizer was that efficacy seemed similar across all age groups, while the Moderna study showed lower efficacy in subjects over 65: 95.6% in those 18-64, 86.4% in those 65 or older.
An obvious advantage to Moderna is that its vaccine can be stored at less demanding conditions: it should be stored at -13 to 5 degrees F, while Pfizer’s needs temperatures of -70C (-94F). Buy dry ice!!
How about Bell’s palsy, which was in the news? In the Moderna study, there were four cases of this condition, in which there is paralysis on one side of the face, usually (but not always) temporary, 3 in the vaccine group and 1 in the placebo group. To put this in perspective, Bell’s palsy is a common condition. With 30,000 people followed for 2-3 months, you would expect 2-3 cases, so while this needs to be watched for, it is not a major concern. Bottom line: very similar, and either seems both effective and safe.
Prescription for Bankruptcy. Buy the book on Amazon
Monday, December 14, 2020
What do we know about the recently-approved Pfizer vaccine?
As you almost certainly know, the FDA gave emergency use authorization (EUA) late Friday for the Covid-19 vaccine produced by Pfizer and BioNTech, and initial supplies have been shipped. The trial data that persuaded the FDA Advisory Committee to vote in favor of EUA was also published online by the New England Journal of Medicine, giving me and everyone else the opportunity to go beyond the companies’ press release which led to massive hype.
The trial was large enough to be credible. 43,548 volunteers were randomized, and 43,448 received injections. 21,720 got the vaccine and 21,728 got a placebo injection. At the time of the report, 18,556 had gotten both doses of vaccine, 18,530 two doses of placebo and been followed for 2 months.
The two groups were followed for the development of symptoms consistent with Covid-19 and a positive PCR test. There was a clear separation between the two groups beginning at 14 days after the first dose, with many fewer cases in vaccinated people. The pre-defined measure was the difference between vaccine and placebo starting seven days after the second dose, and this was dramatic: 172 cases in the placebo group and 9 in the vaccinated group. This is what led to the widely reported 95% efficacy rate.
Side effects were common, but generally mild. Some 80% of younger vaccine recipients (16-55) had pain at the injection site, as did 68% of those over 55. Fewer than 10% had redness or swelling. Fatigue was seen somewhat more often after the first dose and in over half the subjects after the second. Headache was barely more frequent in vaccine recipients than in the placebo group after the first dose but was 2-3 times more common after the second. Chills and muscle pain were less common but were clearly more common after the vaccine. There were no ”major” adverse events. Two vaccine recipients died, as did four who got placebo, and none of these deaths were felt by independent experts to be vaccine related.
So, over a short period, the vaccine clearly works, and over a short period its side effects are no worse than those for widely accepted vaccines such as the shingles vaccine. What don’t we know? There are still unanswered questions.
First, does it work in children? All study participants were 16 years or older. Studies are now being done in younger adolescents, but not yet in younger children.
Is it safe for pregnant women? Pregnant women were excluded from the trial. The American College of Obstetricians and Gynecologists has offered guidance on vaccinating pregnant and lactating women. The group notes that women should not be required to undergo pregnancy tests before receiving the vaccine and say that vaccines shouldn't be withheld from pregnant women who are eligible for vaccination based on priority groups outlined by the Advisory Committee on Immunization Practices. In addition, vaccination should be offered to lactating women based on their priority group. As with all “expert opinion” that is not supported by data, you must accept this as helpful but inconclusive advice.
How long will immunity last? The study followed patients for a median of two months at the time of reporting. The vaccine used a new technology. A study I referenced in my prior post gave hope that immunity would last, but even that one only had several months’ experience.
What happens if you miss the second dose? As with all clinical trials, this one had a remarkably good follow-up: 98% of those who got dose 1 also got dose 2. In the real world, I would bet house and home that this will not be replicated, though every effort will be expended to try to get people back. It is somewhat reassuring that there was at least some evidence of protection by 14 days after dose 1, a week before the second dose. How much benefit and for how long it lasts are unknown.
Does the vaccine prevent asymptomatic or mild infections? People in the study were only tested if they developed symptoms consistent with Covid-19. We know that even now, many people can carry the virus and pass it to others without being obviously sick. It is certainly possible that vaccinated individuals could catch the virus, not get sick but pass it to others. This is important information that I hope the FDA will demand from on-going studies.
Finally, while the vaccine's safety appears to be acceptable, with mostly annoying side effects, it is too early to declare the vaccine free of serious side effects.
Am I going to get the vaccine? Absolutely, as soon as it is available for me.
Prescription for Bankruptcy. Buy the book on Amazon
The trial was large enough to be credible. 43,548 volunteers were randomized, and 43,448 received injections. 21,720 got the vaccine and 21,728 got a placebo injection. At the time of the report, 18,556 had gotten both doses of vaccine, 18,530 two doses of placebo and been followed for 2 months.
The two groups were followed for the development of symptoms consistent with Covid-19 and a positive PCR test. There was a clear separation between the two groups beginning at 14 days after the first dose, with many fewer cases in vaccinated people. The pre-defined measure was the difference between vaccine and placebo starting seven days after the second dose, and this was dramatic: 172 cases in the placebo group and 9 in the vaccinated group. This is what led to the widely reported 95% efficacy rate.
Side effects were common, but generally mild. Some 80% of younger vaccine recipients (16-55) had pain at the injection site, as did 68% of those over 55. Fewer than 10% had redness or swelling. Fatigue was seen somewhat more often after the first dose and in over half the subjects after the second. Headache was barely more frequent in vaccine recipients than in the placebo group after the first dose but was 2-3 times more common after the second. Chills and muscle pain were less common but were clearly more common after the vaccine. There were no ”major” adverse events. Two vaccine recipients died, as did four who got placebo, and none of these deaths were felt by independent experts to be vaccine related.
So, over a short period, the vaccine clearly works, and over a short period its side effects are no worse than those for widely accepted vaccines such as the shingles vaccine. What don’t we know? There are still unanswered questions.
First, does it work in children? All study participants were 16 years or older. Studies are now being done in younger adolescents, but not yet in younger children.
Is it safe for pregnant women? Pregnant women were excluded from the trial. The American College of Obstetricians and Gynecologists has offered guidance on vaccinating pregnant and lactating women. The group notes that women should not be required to undergo pregnancy tests before receiving the vaccine and say that vaccines shouldn't be withheld from pregnant women who are eligible for vaccination based on priority groups outlined by the Advisory Committee on Immunization Practices. In addition, vaccination should be offered to lactating women based on their priority group. As with all “expert opinion” that is not supported by data, you must accept this as helpful but inconclusive advice.
How long will immunity last? The study followed patients for a median of two months at the time of reporting. The vaccine used a new technology. A study I referenced in my prior post gave hope that immunity would last, but even that one only had several months’ experience.
What happens if you miss the second dose? As with all clinical trials, this one had a remarkably good follow-up: 98% of those who got dose 1 also got dose 2. In the real world, I would bet house and home that this will not be replicated, though every effort will be expended to try to get people back. It is somewhat reassuring that there was at least some evidence of protection by 14 days after dose 1, a week before the second dose. How much benefit and for how long it lasts are unknown.
Does the vaccine prevent asymptomatic or mild infections? People in the study were only tested if they developed symptoms consistent with Covid-19. We know that even now, many people can carry the virus and pass it to others without being obviously sick. It is certainly possible that vaccinated individuals could catch the virus, not get sick but pass it to others. This is important information that I hope the FDA will demand from on-going studies.
Finally, while the vaccine's safety appears to be acceptable, with mostly annoying side effects, it is too early to declare the vaccine free of serious side effects.
Am I going to get the vaccine? Absolutely, as soon as it is available for me.
Prescription for Bankruptcy. Buy the book on Amazon
Saturday, December 5, 2020
Vaccine for Covid-19: Can I get one? Should I get one?
As regular readers of these posts know, I consider vaccines to be one of, if not THE, major achievements of medical science. Vaccination has literally saved millions of lives over the years. Diseases such as polio, whooping cough and measles that killed children around the world should now be of historic interest only. [Insert drum roll and consign the “anti-vaxxers” to the deepest levels of Hell.] Can they save us from Covid-19?
The traditional approach to vaccination has been a slow process. There are two major ways vaccines have been produced. Measles, mumps and rubella vaccines use a weakened form of the virus – close enough to the real thing that the body builds up defenses against it but so modified as to not cause a serious infection. Flu and polio vaccines and others use killed virus particles that cannot cause infection but which still enable the body’s immune system to later recognize the virus if it tries to infect you and fight it off. New vaccines typically take up to 10 years from conception through wide distribution, with lengthy trials proving that they are both effective and safe. The current pandemic, which has killed millions and damaged economies around the world, did not give us the luxury of many years of development and testing.
National labs and pharmaceutical companies, large and small, have rushed to develop vaccines. As of August 20, a report found 30 vaccines in clinical trials and over 100 at earlier stages of development. As you are probably aware, the two that are furthest along are vaccines from Pfizer (working with a small German biotech firm, BioNTech SE). and Moderna, which has worked closely with the U.S. National Institutes of Health. Both these groups are using a relatively new technology. They are injecting messenger RNA (mRNA) into the body. The mRNA tells the body’s cells to produce a protein, in this case the “spike protein” that is a distinctive part of the coronavirus, which then causes the body to build up an immune response. Note that in one sense this is not that different than the use of weakened live virus: the body’s own cells are tricked into producing a “foreign” substance that induces development of immunity. A different approach has been used by AstraZeneca working with Oxford University. They use a genetically altered adenovirus that carries a Covid-19 protein to develop the immune response. (This technology is also being used by Johnson and Johnson in its attempt and is the basis of the vaccine being distributed in Russia before any testing.)
How well do the Covid-19 vaccines work? A MAJOR WARNING: everything that I and most people know about these vaccines comes not from published peer-reviewed scientific papers but from press releases. The British National Health Service, which hopefully had access to full data, approved the Pfizer vaccine last week for emergency use, and the U.S. FDA is to review their application this week. Moderna is set to apply for emergency use authorization later this month. Based on the data that has been made available, both vaccines are remarkably effective, in the range of 95%. The Moderna/NIH trial enrolled over 30,000 U.S. participants, including 7000 over 65, 5000 under 65 but with high risk chronic diseases, and included 37% black and Hispanic: all high-risk groups. The AstraZeneca trial has been viewed skeptically because of a strange result. Several thousand participants were accidentally given a half dose for their first shot and full dose for their second. After this was noted, all subsequent participants got the intended series of two full doses. The study found that the vaccine seemed 90% effective in the group getting the half dose first shot but only 60% in the rest. This seems biologically implausible and is currently under study.
How safe are the vaccines? This is the $64 question for a substance that may be given to billions of people around the world. The good news is that the preliminary trials have not identified any serious side-effects, though 10-15% did experience soreness at the injection site, fever, chills and muscle aches that last 1-2 days. Whether more important side effects turn up months or years later is at this point not known.
How long will the immunity last? Again, a question impossible to answer. A recent report in the New England Journal of Medicine was encouraging: people enrolled in the very early (Phase 1) trial of the Moderna vaccine still had good levels of immunity in their blood several months after the second dose. A “real life” experiment adds to the optimism. A fishing trawler with a crew of 122 tested all the crew before they went to sea, both by nasal swab and antibodies. Even though all tested negative for the virus, one got sick with Covid and almost the entire crew subsequently fell ill. The only three who did not develop Covid were the three whose earlier antibody tests showed antibodies to the coronavirus.
When will a vaccine be available? Assuming the FDA grants approval, Pfizer and Moderna expect to deliver some 40 million doses by the end of the year. Since all current vaccines require two doses to confer immunity, this means some 20 million people can be vaccinated by late January/early February. The Advisory Committee on Immunization Practices, whose advice is usually followed, said that first priority should go to front-line health care workers, nurses and doctors working with acutely ill patients, some 21 million, and the 3 million residents of long-term care facilities, who have suffered the worst of the effects of the pandemic. Next in line would be those over 75 and such essential workers as teachers, police, fire and EMTs. By May, supplies should be much larger, particularly if vaccines from AstaZeneca and Johnson and Johnson are approved, and the entire population could be vaccinated by the summer.
Will people accept the vaccine? Vaccine skeptics abound, and the politicization of the vaccine development program certainly feeds into these feelings. A recent poll found that more than a third of Massachusetts residents were unlikely to get vaccinated, even though 90% supported requirements to wear masks, 64% were somewhat or very worried about catching Covid-19 and 66% knew someone who had been diagnosed with it. The acceptance rate is critically important, as so-called “herd immunity” will only keep the pandemic at bay if 80-90% of us are immune. Hopefully by the time there is sufficient supply for the general public, enough time will have elapsed from the early use that safety concerns will be addressed. It will also be very important for the doctors, nurses and others giving the vaccine to warn people about the potential for short-term annoying side-effects and reassure them that this shows that the vaccine is working, and ensure they come back for their second shot.
Prescription for Bankruptcy. Buy the book on Amazon
The traditional approach to vaccination has been a slow process. There are two major ways vaccines have been produced. Measles, mumps and rubella vaccines use a weakened form of the virus – close enough to the real thing that the body builds up defenses against it but so modified as to not cause a serious infection. Flu and polio vaccines and others use killed virus particles that cannot cause infection but which still enable the body’s immune system to later recognize the virus if it tries to infect you and fight it off. New vaccines typically take up to 10 years from conception through wide distribution, with lengthy trials proving that they are both effective and safe. The current pandemic, which has killed millions and damaged economies around the world, did not give us the luxury of many years of development and testing.
National labs and pharmaceutical companies, large and small, have rushed to develop vaccines. As of August 20, a report found 30 vaccines in clinical trials and over 100 at earlier stages of development. As you are probably aware, the two that are furthest along are vaccines from Pfizer (working with a small German biotech firm, BioNTech SE). and Moderna, which has worked closely with the U.S. National Institutes of Health. Both these groups are using a relatively new technology. They are injecting messenger RNA (mRNA) into the body. The mRNA tells the body’s cells to produce a protein, in this case the “spike protein” that is a distinctive part of the coronavirus, which then causes the body to build up an immune response. Note that in one sense this is not that different than the use of weakened live virus: the body’s own cells are tricked into producing a “foreign” substance that induces development of immunity. A different approach has been used by AstraZeneca working with Oxford University. They use a genetically altered adenovirus that carries a Covid-19 protein to develop the immune response. (This technology is also being used by Johnson and Johnson in its attempt and is the basis of the vaccine being distributed in Russia before any testing.)
How well do the Covid-19 vaccines work? A MAJOR WARNING: everything that I and most people know about these vaccines comes not from published peer-reviewed scientific papers but from press releases. The British National Health Service, which hopefully had access to full data, approved the Pfizer vaccine last week for emergency use, and the U.S. FDA is to review their application this week. Moderna is set to apply for emergency use authorization later this month. Based on the data that has been made available, both vaccines are remarkably effective, in the range of 95%. The Moderna/NIH trial enrolled over 30,000 U.S. participants, including 7000 over 65, 5000 under 65 but with high risk chronic diseases, and included 37% black and Hispanic: all high-risk groups. The AstraZeneca trial has been viewed skeptically because of a strange result. Several thousand participants were accidentally given a half dose for their first shot and full dose for their second. After this was noted, all subsequent participants got the intended series of two full doses. The study found that the vaccine seemed 90% effective in the group getting the half dose first shot but only 60% in the rest. This seems biologically implausible and is currently under study.
How safe are the vaccines? This is the $64 question for a substance that may be given to billions of people around the world. The good news is that the preliminary trials have not identified any serious side-effects, though 10-15% did experience soreness at the injection site, fever, chills and muscle aches that last 1-2 days. Whether more important side effects turn up months or years later is at this point not known.
How long will the immunity last? Again, a question impossible to answer. A recent report in the New England Journal of Medicine was encouraging: people enrolled in the very early (Phase 1) trial of the Moderna vaccine still had good levels of immunity in their blood several months after the second dose. A “real life” experiment adds to the optimism. A fishing trawler with a crew of 122 tested all the crew before they went to sea, both by nasal swab and antibodies. Even though all tested negative for the virus, one got sick with Covid and almost the entire crew subsequently fell ill. The only three who did not develop Covid were the three whose earlier antibody tests showed antibodies to the coronavirus.
When will a vaccine be available? Assuming the FDA grants approval, Pfizer and Moderna expect to deliver some 40 million doses by the end of the year. Since all current vaccines require two doses to confer immunity, this means some 20 million people can be vaccinated by late January/early February. The Advisory Committee on Immunization Practices, whose advice is usually followed, said that first priority should go to front-line health care workers, nurses and doctors working with acutely ill patients, some 21 million, and the 3 million residents of long-term care facilities, who have suffered the worst of the effects of the pandemic. Next in line would be those over 75 and such essential workers as teachers, police, fire and EMTs. By May, supplies should be much larger, particularly if vaccines from AstaZeneca and Johnson and Johnson are approved, and the entire population could be vaccinated by the summer.
Will people accept the vaccine? Vaccine skeptics abound, and the politicization of the vaccine development program certainly feeds into these feelings. A recent poll found that more than a third of Massachusetts residents were unlikely to get vaccinated, even though 90% supported requirements to wear masks, 64% were somewhat or very worried about catching Covid-19 and 66% knew someone who had been diagnosed with it. The acceptance rate is critically important, as so-called “herd immunity” will only keep the pandemic at bay if 80-90% of us are immune. Hopefully by the time there is sufficient supply for the general public, enough time will have elapsed from the early use that safety concerns will be addressed. It will also be very important for the doctors, nurses and others giving the vaccine to warn people about the potential for short-term annoying side-effects and reassure them that this shows that the vaccine is working, and ensure they come back for their second shot.
Prescription for Bankruptcy. Buy the book on Amazon
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