Pfizer vaccine deemed safe and effective by the FDA, and a question for readers

December 8, 2020 • 8:45 am

Ripped from the headlines of CNN!  Click on the screenshot to read:

Many of us know that the FDA is meeting Thursday to decide whether to approve the Pfizer vaccine for general use. If the approval occurs, vials of vaccine will be making their way across the U.S., ready for immediate transfer into the arms of Americans.

Now, judging by the headline above, it looks almost certain that the FDA will indeed approve the vaccine in two days, and the first ranks of Americans will start getting vaccinated. Who gets it first appears to vary from state to state, but, rightly, healthcare workers and nursing-home patients (and their carers) will almost always be the first in line—and that’s what the FDA recommended as well.  After all, if the vaccine is safe and effective, why wouldn’t it be approved?

The good news gets even better: it appears that some immunity is conferred even after the first dose, which appears by itself to be 50% effective (two are required for the 95% effectiveness). Flu vaccine—the single shot we should all have gotten already this year, is only between 40% and 60% effective. “Effectiveness” is the reduction of risk that you get when you are vaccinated.

From CNN:

An advisory committee to the US Food and Drug Administration on Tuesday released a briefing document detailing data on Pfizer and BioNTech’s Covid-19 vaccine candidate, which will be considered this week for emergency use authorization in the United States.

The document confirms that the vaccine’s efficacy against Covid-19 was 95%, occurring at least seven days after the second dose – an efficacy that had been previously reported by Pfizer. The proposed dosing regimen for the vaccine is to administer two 30-microgram doses 21 days apart.

However, the document also notes that the vaccine, called BNT162b2, appears to provide “some protection” against Covid-19 following just one dose.

The document describes the efficacy of Pfizer’s vaccine in the time between the first and second dose as 52.4%, but the document notes that “the efficacy observed after Dose 1 and before Dose 2, from a post-hoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the time of observation is limited by the fact that most of the participants received a second dose after three weeks.”

In other words, “the trial did not have a single-dose arm to make an adequate comparison.”

The document goes on to detail the safety profile of the vaccine as “favorable” and notes that the most common adverse reactions to the vaccine have been reactions at the injection site, fatigue, headache, muscle pain, chills, joint pain and fever.

Severe adverse reactions occurred in less than 4.6% of participants, were more frequent after the second dose and were generally less frequent in older adults as compared to younger participants, according to the document. The document adds that swollen lymph nodes also may be related to vaccination.

That’s good enough for me, and I’ll be taking the shots as soon as my doc recommends it—which I presume will be as soon as I’m permitted to get them.

A STAT-Harris Poll published last month, however, showed that the proportion of Americans willing to get vaccinated depends on the vaccine’s efficacy, but only weakly.  Below are those data in graphic form.  What’s disturbing is that if the vaccine were 50% effective, only 60% of Americans would be likely to get the shots. And even with over 90% effectiveness, which is the case with all the vaccines about to hit the market, the willingness rises to only about 63%—a pathetically low figure. I’ve heard that the acquisition of herd immunity in the U.S. to coronavirus requires that 70% of Americans have immunity; even counting those who were infected, the figures on willingness to get vaccinated doesn’t give us that level of immunity. However, it will protect those smart people who get the shots.

So here’s the question: assuming you can get the shots because you don’t have a condition that bars them, are you going to get vaccinated? (I’m assuming that the Pfizer vaccine, or one with similar effectiveness, is the one on offer.) If not, why not?

Thanks to an American Catholic bishop, the pandemic gets a boost

November 20, 2020 • 9:00 am

I was going to say “the Catholic Church gives the pandemic a shot in the arm,” but that would have been confusing. Reader Bill sent me this link to the Los Angeles Times about a faith-soaked Catholic bishop (click on screenshot) who’s bad-mouthing coronavirus vaccines because they’re supposedly made using embryonic tissue from aborted fetuses or from surplus embryos used during in vitro fertilization (IVF) that are eventually discarded.

An excerpt:

Citing ethical concerns about the use of fetal cells in vaccine development, Bishop Joseph Brennan of the Diocese of Fresno is urging Catholics not to “jump on the COVID-19 vaccine bandwagon.”

In a video shared by the diocese this week, Brennan said that some of the researchers racing to produce a coronavirus vaccine have made use of cells derived from an aborted fetus, and perhaps other “morally objectionable” materials.

“I try to maintain a joyful spirit, so I don’t like to rain on anyone’s parade,” Brennan said. “But I’m going to rain on a parade today: the vaccine parade.”

In his message, Brennan said the use of fetal cells at any stage of a vaccine’s development means Catholics cannot avail themselves of its scientific results.

“I won’t be able to take a vaccine, brothers and sisters, and I encourage you not to, if it was developed with material from stem cells that were derived from a baby that was aborted, or material that was cast off from artificial insemination of a human embryo,” he said. “That’s morally unacceptable for us.”

. . . Brennan said he is not opposed to vaccines in general, and noted that he has received vaccines for the flu and pneumonia, but said he is specifically opposed to vaccines derived from babies “whose lives were taken.”

This is one example of the hypocrisy of Catholicism. Even if vaccines were made using fetal or embryonic tissue, that tissue would eventually be discarded. Why not use it to save lives? Further, even if you think that discarding unused IVF embryos, or aborting fetuses, is “murder,” there is no evidence that women will undergo these procedures in order to help create vaccines.  Bishop Brennan has a bizarre kind of calculus in which tissue already available cannot be used to save other lives. Note that he is in general expressing the position of the Catholic church, though I don’t think the Pope has yet weighed in on this.

But are the vaccines really made using this kind of tissue? Nope—not one mentioned by Brennan during his video homily:

He cited the Pfizer vaccine by name, which — along with another vaccine from Moderna — has been roundly celebrated as a breakthrough in the fight against the coronavirus.

Brennan did not explain why he singled out Pfizer’s COVID-19 vaccine for criticism. There is no indication that it was developed using either fetal cells or human embryonic stem cells.

“Not a single stage has had it,” Pfizer spokeswoman Jerica Pitts said Thursday.

The Pfizer and Moderna vaccine candidates are made with a snippet of the coronavirus’ genetic code, and both are estimated to be roughly 95% effective.

You think the good bishop would have done his homework, for how many Catholics that heard his homily are going to check for themselves?

It is true that some vaccines are made using fetal tissue:

The Charlotte Lozier Institute, an antiabortion organization, has flagged five COVID-19 vaccine candidates that were developed with the help of fetal cells. One of them, developed by Oxford University and AstraZeneca, is in late-stage testing. So is another developed by Johnson & Johnson.

If Catholics are worried about burning in hell if they take a vaccine developed this way, all they have to do is take the Pfizer or Moderna vaccine. But I repeat: even if you equate abortion or unused IVF embryos as “murder”, what is the moral objection to using that tissue to save further lives? It’s not as if women get IVF and abortions for the purpose of creating vaccines, or get paid to do so. Those abortions or IVF procedures would take place with or without a vaccine being developed.

All I can say is that it’s a good thing that at least some vaccines are being developed without use of fetal or embryonic material, because otherwise pious Catholics wouldn’t be able to get vaccinated, and more people would die in the name of a senseless “morality”.

Allow me to regale you with details of my operation

November 4, 2020 • 9:45 am

Yesterday I had a redo of inguinal hernia surgery, which I originally had in August of 2019. When there was a swelling at the site later, I assumed it was a seroma (an accumulation of fluid at the site), and since seromas often take a while to go away, I wasn’t worried. But it didn’t go away, so I had an ultrasound, revealing that the damn hernia had recurred. My surgeon, who’s top notch, was really peeved at this, as he said that in his entire career he’d never had such a recurrence, and had no idea why. (He added that yesterday’s operation would reveal the cause.)  Inguinal hernias are the maladaptive result of our having evolved as quadrupeds and then become bipedal, but their status as “vestigial pathologies” doesn’t hearten me much.

I scheduled surgery at the U of C hospital as soon as possible, as I don’t want the damn thing there (it could get strangulated, which can kill you), and there’s always the possibility that they’d stop elective surgeries if the pandemic recurs big time.

So I went under the knife (actually three of them) yesterday.  Because my surgeon had a complicated procedure before taking me, I waited 3.5 hours in the lobby, and then, after I was moved into pre-op, where they put their initials on the hernia (to ensure they operate on the correct side), connect you to IVs, give you a slight tranquilizer, a blood thinner, and IV fluids, and make you take off all your clothes except for that damn gown that opens in the rear—I waited another two hours. Everyone was very nice, but I was bored to tears.

Finally came the moment of truth, when they wheeled the gurney into the operating room. That always gives me a perverse kind of thrill, as it reminds me of Ben Casey and Dr. Kildare, and I’m always curious to have a look at the operating room, which contained the giant laparoscopic robot, before they put me to sleep. It was crowded with people, and the big robot with its three giant cutting and manipulating arms loomed in the theater:

The surgeon sits at the console on the other side of the room as in the photo, manipulating the arms, which made three holes in my belly (they always do the middle as well as the non-hernia side to see if there’s any issues there). Robotic surgery is one of the more amazing and salubrious medical innovations of our time.

My original surgery was done by the robot, and the surgeon told me that the chances were very high that the redo would also involve minimally invasive cutting. But, he added, there was about a 15% chance that I’d have to have the “old” procedure, which involves a big incision and a much longer healing process. Fortunately, the robot did the trick this time.

Just before they wheeled me into the OR, they gave me an injection that, said the anesthesiologist, would make me forget stuff. I asked him why, and he said that many people don’t like to have memories of going into surgery. But I didn’t forget stuff: I remember every word said to me while they filled my lungs with oxygen and were preparing to knock me out. There were two men in the room and four women, including a female medical student (I had to give permission for the  student, which I did), but I realized that they were going to see me naked. This was brought home to me when I woke up almost completely shaved in the nether parts. Oy!.

I was particularly interested to experience the loss of consciousness. Would it be nearly instantaneous, like last time when everything went black at once? It was even faster this time! I remember the anesthesiologist approach me on the left side, and I asked him “Is this going to knock me out?” He replied “Get ready for the happy juice!” (What a card!). And that’s the last thing I remember; I don’t even remember losing consciousness. (By the way, the fact that consciousness is completely removed, even without dreams, with propofal—the “Michael Jackson drug”— and then restored within ten minutes after surgery, is strong evidence that consciousness is a purely physical phenomenon.)

I woke up almost instantly; the operation, I was told, took about two hours. I was groggy for a while, but just wanted to get my tuchas home. Within an hour a friend picked me up and I got back to my crib, lying in bed for a short while and then making some soup. When I felt more restored, I took this selfie of my shaved belly (trigger warning: shaved belly!) The curious thing is that I did forget things during post-op: I called several friends today to tell them I was all right, and a few informed me that I’d already called them last night.

Note that they shaved me bald (the depilation went much lower), and that there are three punchholes, all closed with a superglue-like material. That’s the only scarring, and when the hair grows back they’ll be invisible.

I had some slight pain during the night, but regular Tylenol took care of that. I had no prescriptions for antibiotics or other pain meds, as they also gave me an IV antibiotic in pre-op.

So, Ceiling Cat willing, that is the end of this procedure. I didn’t get to talk to the surgeon yet, though I’m just as curious as he was about why the damn thing recurred.

Thanks so much to all the kind people who took care of me, from pre-op through recovery. Special thanks to Dr. Vivek Prachand for his compassion, his willingness to answer questions, and his and steady hand at the robot. Like Dan Dennett, I say, “Thank goodness!”

Covid 19 may hijack pain receptors, reducing pain and increasing the spread of the virus: a possible result of natural selection

October 8, 2020 • 9:00 am

The paper below, which has just been published (click on screenshot to go to page, then click the “download” button to the left to get the pdf), has a unique twist that may say something about evolution in pathogens, but the evolutionary angle hasn’t been mentioned. It’s a complex and technical paper, using rat models (i.e., tissue and analyses), to study whether the Covid-19 virus has the ability to reduce pain.

There’s also a publicity piece from the University of Arizona that explains the results in simpler language, and a two-minute video below that dumb things down a bit, but gives the gist.

From the publicity piece:

SARS-CoV-2, the virus that causes COVID-19, can relieve pain, according to a new study by University of Arizona Health Sciences researchers.

The finding may explain why nearly half of all people who get COVID-19 experience few or no symptoms, even though they are able to spread the disease, according to the study’s corresponding author Rajesh Khanna, PhD, a professor in the UArizona College of Medicine – Tucson’s Department of Pharmacology.

Rajesh Khanna, PhD. (Photo: Kris Hanning/University of Arizona Health Sciences)“It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” said Dr. Khanna. “You have the virus, but you don’t feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that’s of enormous value.”

The paper, “SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia,” was published today in PAIN, the journal of the International Association for the Study of Pain.

. . .The U.S. Centers for Disease Control and Prevention released updated data Sept. 10 estimating that 50% of COVID-19 transmission occurs prior to the onset of symptoms and 40% of COVID-19 infections are asymptomatic.

“This research raises the possibility that pain, as an early symptom of COVID-19, may be reduced by the SARS-CoV-2 spike protein as it silences the body’s pain signaling pathways,” said UArizona Health Sciences Senior Vice President Michael D. Dake, MD. “University of Arizona Health Sciences researchers at the Comprehensive Pain and Addiction Center are leveraging this unique finding to explore a novel class of therapeutics for pain as we continue to seek new ways to address the opioid epidemic.”

In other words, the virus’s famous spike protein nullifies the effect of another protein, VEGF—one of the several proteins that normally causes pain. And that’s all ye need to know unless you work on this system.

But here’s where the evolution comes in. Remember, pain is an adaptation whose evolution was doubtlessly prompted by its ability to tell us that there’s something wrong, like “Hey, your hand is in the fire.” People who don’t feel pain, like those with Hansen’s disease (leprosy) and some rare neurological conditions, often incur severe damage to their bodies because they’re unaware of injuries. The reason Hansen’s sufferers lose their fingers and other bits is not because the bacteria eat away at those bits; rather, it’s because the bacteria numb feelings of pain, and so you start damaging your body without being aware of it. So pain is a good thing to have, even though it feels bad.

But if a virus that normally causes pain because it injures your innards can somehow block that pain, it might spread faster. This would be true for viruses like COVID-19, which is spread by human-to-human contact, and depends on its transmission for people going about and infecting others. If you take to bed because you’re in pain, the virus won’t spread as well.

And what that means is that mutant variants of the virus that reduce pain will spread faster than forms that cause pain. This differential would create natural selection for the mutants that reduce pain, and the virus “species” would evolve painlessness as one “symptom”.

As far as I can see, nobody in either the paper or the puff pieces have mentioned this possibility. Now we don’t know if this speculation is true, or if it’s just fortuitous that the spike protein blocks pain receptors. Further, while this might be an evolved property of the virus, it could also be an inherent property of the spike protein, evolved for other reasons, that simply allowed the virus to spread quickly.

I’m merely suggesting this as one possibility in a field called “Darwinian medicine,” which analyzes symptoms of diseases from an evolutionary viewpoint. Other suggestions from this area involve things like malaria. When you have a malaria outbreak, the malaise and fever put you flat on your back. And that facilitates the spread of the malaria pathogen (a protozoan), because that protozoan is transmitted by mosquitoes. When you’re prostrate in bed and sick, you’re not as liable to slap a biting mosquito as when you’re walking around, and so those protozoans that knock you flat will more readily find a mosquito vector. (This is all speculation, of course.)

Another suggestion involves the virus for the common cold. It doesn’t debilitate you, but rather makes you a bit grotty but still able to walk around—and transmit the virus to other people. If a common cold were to knock you out like malaria, the virus wouldn’t spread so well.

And so many of the symptoms that are caused by pathogens may well have evolved in those pathogens to facilitate their own transmission. This must certainly be true in some cases, but of course proving it is very hard to do. You couldn’t do experiments in humans, though I suppose you could in model animals like rats, but I wouldn’t be keen on hurting animals to test evolutionary hypotheses. (I even anesthetized all my fruit flies before killing them.) It is curious, though, that I haven’t seen this new and striking result mentioned as a possible example of natural selection in the virus.

Here’s the video, though you might not learn much if you’ve read what’s above.

h/t: Charles

Click to access 2020.07.17.209288.full.pdf

Nobel Prize for Physiology or Medicine goes to three for discovering the Hepatitis C virus

October 5, 2020 • 7:00 am

Knowing that the first Nobel Prize for science would be awarded today—in Physiology or Medicine—I made a contest in which readers were to guess just one winner of each of the three science prizes plus the winner of this year’s Literature Nobel.

Well, the first prize was awarded this morning, and the contest is already over. Everyone lost (see here and here).

Granted, this was not an easy one to guess. The award in fact went to three people—Harvey Alter, Michael Houghton, and Charles Rice—with each getting a third of the prize money. The award was given for the discovery of the virus that causes Hepatitis C.  Here’s part of the press release from the Nobel Prize site:

This year’s Nobel Prize is awarded to three scientists who have made a decisive contribution to the fight against blood-borne hepatitis, a major global health problem that causes cirrhosis and liver cancer in people around the world.

Harvey J. Alter, Michael Houghton and Charles M. Rice made seminal discoveries that led to the identification of a novel virus, Hepatitis C virus. Prior to their work, the discovery of the Hepatitis A and B viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives.

. . . The Nobel Laureates’ discovery of Hepatitis C virus is a landmark achievement in the ongoing battle against viral diseases (Figure 2). Thanks to their discovery, highly sensitive blood tests for the virus are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the world, greatly improving global health. Their discovery also allowed the rapid development of antiviral drugs directed at hepatitis C. For the first time in history, the disease can now be cured, raising hopes of eradicating Hepatitis C virus from the world population. To achieve this goal, international efforts facilitating blood testing and making antiviral drugs available across the globe will be required

Here’s the video of the award with details about the winners, and giving some scientific background; the action starts at 12:50. It’s worth listening to the 20 minutes of science, as you’ll learn a lot. There’s also an interview with the Secretary of the Prize Committee beginning at 34:34.

I guess the prize for CRISPR-Cas9 will have to wait for another year.

A good article on Covid-19 testing, a way forward, and where we screwed up

October 2, 2020 • 1:45 pm

I commend to your attention this article in The Atlantic on Covid-19.  The authors, Robinson Meyer and Alexis Madrigal (staff writers on science and technology), discuss the best ways to stem the pandemic, the advantages and disadvantages of various tests for infection, and how the U.S. screwed up in its response. Click on the screenshot to read:

It’s very good and clear on the science, though I can’t judge the efficacy of their plan, which involves continual “spit testing”, a very quick but not completely accurate way of diagnosing the virus through its antigens, like the spike protein. PCR tests are much more accurate, but are expensive and take time, yet if we do continual antigen testing, the errors tend to go away, and we could get results in 15 minutes on a strip of paper. You could do this before flights, before entering restaurants, and so on.

The problems with PCR tests are numerous, the most serious being that it can’t distinguish between a new infection, which is contagious, and one that’s a month old, which isn’t contagious. And they’re much more expensive to distribute and more time-consuming to diagnose. The authors discuss “pooling”, a cute way to cut down on money and time by bundling together swab results (or spit) from a bunch of people. If there’s no positive in the mix, you needn’t go further. If there is, you subdivide, and so on.

The main reason we screwed up is, of course, Trump. In this case the authors indict him for failing to invoke the Defense Production Act, a wartime regulation, still on the books, that allows the government to force companies to mass-produce things in case of a national crisis, like this one. One excerpt:

. . . the Trump administration has addressed the lack of testing as if it is a nuisance, not a national-security threat. In March and April, the White House encouraged as many different PCR companies to sell COVID-19 tests as possible, declining to endorse any one option. While this idea allowed for competition in theory, it was a nightmare in practice. It effectively forced major labs to invest in several different types of PCR machines at the same time, and to be ready to switch among them as needed, lest a reagent run short. Today, the government cannot use the Defense Production Act to remedy the shortage of PCR machines or reagents—because the private labs running the tests are too invested in too many different machines.

Because of its trust in PCR, and its assumption that the pandemic would quickly abate, the administration also failed to encourage companies with alternative testing technologies to develop their products. Many companies that could have started work in April waited on the sidelines, because it wasn’t clear whether investing in COVID-19 testing would make sense, Sri Kosaraju, a member of the Testing for America governing council and a former director at JP Morgan, told us.

The Trump administration hoped that the free market would right this imbalance. But firms had no incentive to invest in testing, or assurance that their investments would pay off. Consider the high costs of building an automated testing factory, as Ginkgo is doing, said Stuelpnagel, the Illumina co-founder. A company would typically amortize the costs of that investment over three to five years. But that calculation breaks down in the pandemic. “There’s no way that we’re doing high-throughput COVID testing five years from now. And I hope there’s not COVID testing being done three years from now that would require this scale of lab,” he said. Companies aren’t built to deal with that level of uncertainty, or to serve a market that would dramatically shrink, or disappear altogether, if their product did its job. Even if the experimentation would benefit the public, it doesn’t make sense for individual businesses to take on those risks.

So nothing happened—for months. Only in the past few weeks has the federal government begun to address these concerns.

Even if you don’t see the use of mass antigen testing as a big step forward until (and if) we get an effective vaccine, this article will teach you a lot.

Dr. Alex’s latest advice on Covid 19, and a chance to ask questions

August 25, 2020 • 9:00 am

From time to time, my primary care physician Dr. Alex Lickerman posts articles on his website from about what’s going on with the pandemic, concentrating on the scientific research and what it means. The latest post on the website, below, “lays out the evidence for wearing masks, talks about the development of a vaccine, and answers questions about the validity of the rapid nasal swab test.” You can read it as a whole, or skip to the “bottom line” in each section. I’ll simply list the sections (Q&A’s) and the bottom lines.

Alex has kindly volunteered to answer readers’ questions about the pandemic, about vaccinations, about masks, and anything to do with the virus and how we should deal with it as individuals and as a society. So feel free to put your questions in the comments, and Alex will answer them as he has time.

Click on the screenshot to read the post:

.

The sections and “bottom lines” (quotes are indented). Any take I have will be flush left, and of course each section below is followed in Alex’s post by an extensive discussion of the medical/scientific data.

Question: Will the wearing of masks in appropriate circumstances slow the pandemic?

Answer:  Probably.

BOTTOM LINE: The only way we’ll ever know for certain if mask-wearing by asymptomatic people, in the right circumstances, will reduce the spread of SARS-CoV-2 would be to prospectively assign a region (e.g., a city) to wear masks and compare its rates of infection over the same time to another region where people were assigned not to wear masks (and measure the compliance of each). The impossibility of conducting such a study at this point is obvious. Therefore, we’ll likely never be able to conclude with 100 percent certainty that mask-wearing in the right circumstances will slow the progression of the pandemic. But when we consider the sum of the evidence above, we conclude that mask-wearing by asymptomatic people, in the right circumstances, is likely to slow the progression of the pandemic.

***********

Question: Who should wear masks, then?

Answer: Everybody.

. . . .When you consider this data together, you have what seems on the surface to be a good argument for not wearing masks to reduce the spread of COVID-19 if you’re asymptomatic.

BOTTOM LINE: But it’s not. Here’s why: a 21 percent prevalence of asymptomatic SARS-CoV-2 infection represents 57.9M people infected. If each of those 57.9M infected people has a 0.33 percent chance of spreading the infection without wearing a mask and does so, it would amount to roughly 191,070 transmitted infections! (Even if our estimate of the number of asymptomatic infections is off by a factor of 10, this would still amount to 19,107 infections.) We don’t know to what degree wearing a mask will decrease the risk down from 0.33 percent, but even a small amount would translate into a large number of people. Thus, while the impact of one asymptomatically infected person not wearing a mask is small, the impact of all asymptomatically infected people not wearing masks may be large. The logic of collective action requires that individuals act as if their contribution is greater than it is because only that way do enough individuals act in such a way that yields the protection society needs. We all need to tolerate inconvenience to contribute to the greater good.

Alex also discusses which masks are best. So far there are data only for which masks keep you from spreading viruses through respiratory droplets. For this N95s are the gold standard, but plebes like us can’t easily get them. He recommends using surgical masks to prevent infecting others, though most other masks seem to be about as good. And the best masks to protect YOU are probably the best masks for protecting others against you, though this isn’t 100% certain. Avoid knitted masks and single-layer cloth masks. I covered some research on this in a post a few weeks ago.

***********

To me, this is the most depressing part, but I can’t quarrel with the argument:

Question: Will we have a safe, effective vaccine for COVID-19, and if so, when?

Answer: Probably. But likely not until the Summer of 2021 at the very earliest.

BOTTOM LINE: Currently, there are over 140 COVID-19 vaccines in development. Given the statistics we quoted above, that means we should end up with 14 viable vaccines. There’s one RNA vaccine being tested in a Phase III trial right now with 30,000 volunteers being given the vaccine. But we predict it will take us at least until mid- or late-2021 to determine if it’s a winner because it will take at least that long to make sure the vaccine is safe and effective. Remember, the risk of adverse reactions to vaccines needs to be substantially lower than the risk of adverse reactions to medications. This is because: 1) the number of people vaccinated will be much greater than the number of people given a medication (medications for diseases are given to at most millions of people; a vaccine for COVID-19 will be given to billions of people), so even small risks of harm can mean harm is done to millions of people, and 2) the vaccines are given to healthy people, not people already suffering from a disease. Thus, the risk of adverse events from the vaccine must be compared to the risk of not just contracting the disease but of experiencing a severe adverse outcome (i.e., severe, chronic morbidity or death). So, in the case of COVID-19, if we’re considering immunizing a 12-year-old child, for example, whose risk of dying from COVID-19 is literally only 0.022 percent, the risk of a severe adverse reaction to the vaccine needs to be far below that.

Unfortunately, the history of vaccine development is replete with stories of harm. One vaccine developed against respiratory syncytial virus (RSV) in the 1960s actually caused a form of immune enhancement where the disease was worse in vaccinated children, even killing two who’d been vaccinated. In 1955, Cutter Laboratories, a small pharmaceutical company that manufactured a polio vaccine, released vaccines contaminated with fully live virus due to manufacturing errors and poor government oversight, resulting in an estimated 40,000 children being infected with polio. Two hundred victims were permanently paralyzed, and ten of them died.

We mention these cautionary tales not to add fuel the anti-vaccine movement fire, but to highlight the importance of doing the science correctly, of not rushing inadequately tested vaccines to market. The reason vaccines are among the safest of medical interventions available is because they undergo such long and rigorous safety testing. As candidates come off the pipeline, we’ll review their efficacy and safety data and make recommendations about them.

This section has a good precis on how vaccines are both developed and tested. There’s also a nice graph in this section showing the reduction of nine childhood diseases after vaccination was introduced—good ammunition against antivaxers. Alex concludes: “Immunization is one of the most effective—and safest—public health measures that exist. The prevalence of infections from diseases for which we now vaccinate children has declined by ninety percent (see chart below of effectiveness of routine childhood vaccinations). There are literally no other interventions in medicine that are as effective as vaccination.”

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Question: Are rapid tests worth doing, especially because the results are returned so much more rapidly

Answer: Only if the rapid test comes back positive can you believe it.

BOTTOM LINE: We don’t recommend people get a rapid test. Even though results take longer with the PCR test, a negative PCR test is more likely to be accurate. We know only one rapid test with a zero false-positive rate. Other rapid tests may not perform nearly as well.

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This is the tenth in Alex’s series of posts on coronavirus and the pandemic; you can see all the links at the bottom of this post. There’s a lot more to read if you’re interested.

So, if you have questions—my latest one, which I asked Alex yesterday, was “is it safe to get a haircut, and how should ensure that the experience is the safest possible?”—put them in the comments below and then check back in a while to see if they’ve been answered.

Thanks to Alex for offering his analyses and advice to the readers.

Trump administration places severe restrictions on fetal tissue research, impeding medical progress

August 6, 2020 • 9:00 am

Let me make this clear from the outset: fetal tissue used for research is taken from abortions that women elect to undergo.  The tissue has shown enormous promise for medical research, including its past use in developing the polio vaccine, as well as making useful advances in AIDS research, birth defects, Down Syndrome, spinal cord injuries, organ transplants, diabetes, and many other conditions. The reason fetal tissue is used rather than, say, adult tissue from cadavers is because fetal tissue retains an ability to transform itself into various types of tissue, and also grows faster than adult tissue. Further, because fetal tissue doesn’t elicit nearly as strong an immune response as does adult tissue (you can imagine why this is the case; think pregnancy), you can create strains of mice that have a weakened immune system and also carry fetal tissue in them, facilitating experimental work. (These are known as “humanized mice” and reader Simon has an explanation below the fold about how they’re made and what they’re good for.)

Over the years, conservatives, especially religious ones, have objected to the use of fetal tissue in research because it’s seen as parts of dead babies (i.e., humans with “souls”), with some hinting darkly that allowing the work could actually promote abortions. But if that tissue can save future adult lives, and comes from dead fetuses whose tissue would be otherwise destroyed, what kind of inhumane calculus would forbid its use? Further, I can’t imagine that a single woman who wanted to have her baby would volunteer to have an abortion instead so that the fetal tissue could be used in research. That idea is insane. There is no rational objection to the use of fetal tissue in research save that its use undergoes the same kind of ethics vetting as other use of human tissue, which it already does.

But now, after more than twenty years when government-funded agencies like the National Institutes of Health (NIH) permitted such research, the Trump administration is putting clamps on it, as reported by the article below in the Washington Post (click screenshot to read it). They add that “officials say the president made the final decision.”

The impediments to research come in the form of requiring all government-funded work on fetal tissue to be approved by a new ethics committee beyond the vetting normally used in such research. The kicker is that the committee hasn’t yet been constituted, and may not be for a long time to come. The result is that nobody is writing government grants to do work on fetal tissue. Further, every grant approved by this perhaps-to-be-constituted-someday committee must also be approved by Health and Human Services Secretary Alex Azar, who has the final say. Finally, the new rules require that any research using fetal tissue document that the tissue come with an assurance from the provider that the donating woman provided informed consent, which brings up questions of privacy, both of the women and of the clinics and tissue banks who provide the material.

The ethics panel, if it actually materializes, will meet only once a year, far less often than the number of NIH deadlines.

Current NIH grants using the tissue can continue till they expire, but no future grants are being written, and research on fetal tissue within the NIH has already been halted, as have training grants that use the tissue. Private companies can continue the work, but the big majority of fetal-tissue work is funded by the government, and even for private companies the cost of using “humanized mice” without government support will be prohibitively expensive.

Some researchers are investigating replacement material, like using “deprogrammed” adult tissue, but nothing so far has proven as useful in research as the fetal tissue.

For a vigorous argument by two researchers on the value of using fetal tissue, and what progress has come from it, click on the screenshot below to read an article in Stem Cell Reports:

Again, there is no rationale—beyond the religious view that somehow fetal tissue is sacred—to support this new decision. Without the research, the fetuses would be disposed of normally, and that doesn’t mean burial. So, under pressure from the religious Right, Trump and his administration have slowed down medical research, possibly sacrificing lives that could be saved, and for no good reason. Even Francis Collins, head of the NIH and an evangelical Christian, favors the use of fetal tissue in research.

Once again we see a conflict between faith and fact, with faith impeding not just the discovery of important facts, but ones that could save lives. What kind of tradeoff are these religious crazies making?

h/t: Bat

Click “read more” if you want to learn how “humanized mice” are made. Continue reading “Trump administration places severe restrictions on fetal tissue research, impeding medical progress”

My emergency-room bill

June 3, 2020 • 11:45 am

On May 6, as I reported, I ripped my ear open on a jagged tree branch while running between the ponds. I didn’t show the picture of the carnage here as it was extremely bloody. I sent a photo to my GP, as it wouldn’t stop bleeding, and he told me to go to the emergency room in the time of the cornavirus, for I’d need stitches. He added, which was true, that it would be pretty much empty because people were afraid to get the virus, even in the ER. But I had to remove my mask during the stitching, as it was around my ear.

As I reported, the ER had a lot of precautions, including taking your temperature, socially distancing you in the chairs (only one other guy was waiting, along with three cops who had a professional interest in being there), and ensuring that everyone wore masks.

I was in there for about 5 hours, most of that time spent waiting. Finally, a nice resident in ENT came down and sewed me up, tossing the bloody gauzes on the floor during the long process, so that the floor looked like a MASH unit when we were done. It took about 11 stitches, and was very painful despite the anesthetic—and I consider myself pain-resistant. At any rate, I’m better now, and the stitches fell out, as they were supposed to.

I just got the bill, along with my portion not covered by insurance, which was larger than usual because it was an ER visit. For those of you who are blessed with single-payer medical care, and pay nothing or very little beyond your taxes, here’s my bill:

Actually, it was about $200 more than this because of some other charge. I paid about $200 total. $6,412 is a lot of dosh, but more or less what I expected.

Hydroxychloroquine and chloroquine are not only useless in treating Covid-19, but very harmful

May 22, 2020 • 10:30 am

UPDATES: The discussion of this paper has gone back and forth, and the cause is that neither Alex nor I read the paper carefully. I just skimmed it, and Alex read it quickly but paid most of his attention to the tables. That led to this first update in which he concluded (and I agreed) that the study wasn’t very useful at all:

UPDATE 1:

In two comments below, my own physician, Dr. Alex Lickerman, who carefully read the study I describe below  (see his first comment and his second), noted that the sickest patients were the ones more likely to be given the chloroquine drugs, and were also the patients with the highest comorbidities—factors like heart disease that would tend to make them sicker. In other words, as Alex notes,

So–was it the drugs that were responsible for their increased likelihood of death or the risk factors already known to increase the likelihood of death? We simply can’t tell from this study. This is the problem with the observational study design. We CAN almost certainly say that hydroxychloroquine and its ilk don’t improve survival in COVID-19, but whether or not they increase mortality in COVID-19 we don’t yet know.

This is only part of his analysis; read the whole thing in comment 1. He also notes in his second comment that there is no evidence that using hydroxychloroquine as a preventive has any benefit.

I am guilty of not having detected the flaws in the study, which are, I found, not even clearly pointed out by its authors in the traditional “here-are-some-weaknesses-in-this-study” part of the paper, and I thank Alex for the clarification. But even more culpable are the reviewers of that study, who did not insist on a clear outline of its limitations, as well as the medical/science journalists, who touted the study uncritically (like me!) Alex has helped me learn that many medical studies, even in journals as reputable as The Lancet, are pitifully weak or even fatally flawed.

UPDATE 2: In a very useful comment, reader BillyJoe noted that the paper does indeed say that the paper controlled to some extent for comorbidities, so its conclusions are stronger than we thought: we can have more confidence in its conclusions that hydroxychloroquine and chloroquine are positively dangerous when given to people sick with Covid-19.  Alex then said yes, he was wrong about the study not taking into account comorbidities, and has posted this comment in the thread:

Yikes! I’m guilty of the same criticism I made of others: not reading the trial carefully. You are absolutely correct that the authors made good-faith attempts to control for the inequalities/confounding variables between treatment groups. This is still a statistical adjustment, not a direct measurement as would be done in a randomized trial, so must be taken with a grain of salt, but to the authors’ credit, they address that.

The problem does remain that when you do the randomized trials, results are often different because of confounding variables the authors didn’t know about and therefore weren’t able to statistically adjust for—but also because sometimes their multivariate analysis (meant to adjust for known confounding variables)–also wasn’t adequate. So we still need a randomized trial to really know the answer definitively.

Nevertheless, I withdraw my criticism of the authors and the Lancet reviewers. I guess this is a good example of why science and statistics should always be done by more than one person! I’m quite embarrassed to have made this mistake. I apologize to readers and to our host, who must now fall on his sword with me.

___________________

 

Well, it’s official (I mean, of course, “provisional”): a new and large study published in the medical journal The Lancet (second link below; click screenshots to go to both articles) confirms that hydroxychloroquine and chloroquine not only don’t help patients seriously ill with Covid -19, but increases their mortality (in other words, kills them). Below is the CNN report, with a more layperson-y summary (my emphasis):

Researchers analyzed data from more than 96,000 patients with confirmed Covid-19 from 671 hospitals. All were hospitalized from late December to mid-April, and had died or been discharged by April 21.

Just below 15,000 patients were treated with the antimalarial drugs hydroxychloroquine or chloroquine, or one of those drugs combined with an antibiotic.

All four of those treatments were linked with a higher risk of dying in the hospital. About 1 in 11 patients in the control group died in the hospital. About 1 in 6 patients treated with chloroquine or hydroxychloroquine alone died in the hospital. About 1 in 5 treated with chloroquine and an antibiotic died and almost 1 in 4 treated with hydroxychloroquine and an antibiotic died. 

Researchers also found that serious cardiac arrhythmias were more common among patients receiving any of the four treatments. The largest increase was among the group treated with hydroxychloroquine and an antibiotic; 8% of those patients developed a heart arrhythmia, compared with 0.3% of patients in the control group.

Note that the mortality in the control group was about 9%, rising to about 16% with chloroquine or hydroxychloroquine alone, and 20-25% when either of the chloroquine drugs was supplemented with an antibiotic (remember, antibiotics kill bacteria, not viruses like Covid-19. Clearly, refraining from using these drugs is the wisest course of action.

Here’s The Lancet study that went online today, and the findings and summary, while more comprehensive, are the same (“macrolides”, as is meant here, refers to a class of antibiotics that includes erythromycin). If you can’t access the paper, a judicious inquiry will yield it.

 

Findings:

96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.

Interpretation:

We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
You know the upshot: DO NOT TAKE HYDROXYCHLOROQUINE as a Covid-19 drug, as it causes heart problems and, overall, is much worse than standard treatment, doubling your chance of dying. This also means that since there’s yet no evidence that the drug staves off the virus, the side effects on those taking it as a preventive (like Trump) will also include heart issues. That’s been known from earlier but smaller studies.

What Trump is doing is not only injurious to himself (I suspect his heart is a ticking time bomb given his weight and penchant for McDonald’s food), but sets a terrible example to the public. It’s a President flaunting quackery, and of course his supporters are more likely to dose themselves or ask for the drug if they get the virus. The saving grace is that no decent doctor will give an infected patient hydroxychloroquine.

But remember, Trump’s osteopath official physician, Sean Conley, in consultation with Trump, decided that the potential benefits outweighed the risks when prescribing Trump the drug as a preventive. That’s doubly shameful: a faux President being treated by a quack physician with a useless drug, and the President bragging about it and lying about the drug’s “benefits.” No wonder other countries look upon the U.S. with pity!