Coronavirus news & views

Politics: A Risk Factor For Death From COVID?

What are you gonna believe, medical science or dubious talking heads?

In 2021 former Green Bay Packers quarterback, Aaron Rodgers, said he was “immunized” against COVID. He wasn’t. He claimed to have done “research” and learned how to get an infusion of antibodies and take some unproven ‘medicine.’ His ‘research’ was talking to radio pundit and hot-air purveyor, Joe Rogan. How many more people like Rodgers listen to the wisdom of the likes of Rogan or Tucker Carlson and think they know more than medical professionals and then rationalize their avoidance of COVID vaccines? And to what effect?

The Kaiser Family Foundation estimates that from June 2021 through March 2022 about 234,000 COVID deaths could have been prevented had the decedents been vaccinated against the SARS-CoV-2 virus. That protection was especially important during the more deadly Delta virus wave during the earlier stage of the pandemic, but it still extends into the Omicron era, which fortunately is not as deadly as Delta was, but still is not to be taken lightly. People are still dying from the virus.

How does politics come into this?

A 2022 study published in the journal, Lancet Regional Health-Americas, found higher COVID mortality rates in more conservative congressional districts across the US. And in another 2022 study using 2020 presidential election returns, researchers at the University of Maryland and the University of California at Irvine found that, through October 2021, Republican-majority counties across the US experienced nearly 73 additional COVID deaths per 100,000 people relative to majority Democratic counties.

These are correlations looking for a cause. A good causal candidate could be differences in vaccination rates between people who tend toward conservatism vs liberalism. The former are much less likely to get vaccinated than their left leaning neighbors. But, that connection needs to be made.

Sure enough, a July 2023 report by Yale researchers in the journal, JAMA Internal Medicine, compared COVID death rates in counties in Florida and Ohio that voted for Trump vs Biden before and after the vaccines came out. The bottom line was that after the vaccines rolled out, Trump voting counties saw 40% higher fatality rates per million residents. Before the vaccines, the COVID death rates were the same for all counties. Viral infection rates were similar for both types of counties throughout the period of analysis. Importantly, counties and individuals that went for Trump had lower vax rates than those that went for Biden.

That pretty much closes the circle on the causation. The greater reluctance of more conservative people to get vaccinated and boosted likely killed them at a greater rate.

Karma?

Now, don’t get me started on the conservative vs liberal attitudes on face masks and social distancing. Conservatives are wrong on these matters. I say this as a conservative myself. But, I also am a data driven scientist who believes data trumps partisanship.

How do you think SARS and MERS were stopped without a vaccine or anti-viral drugs? How do you think society stopped any epidemic such as small pox, influenza, bubonic plague, etc. throughout its history before modern medicine and effective vaccines? How do you think today we are handling Ebola for which there is no vaccine or drug? Non-pharmaceutical physical measures, like masks, gloves, sanitation, social distancing, etc. are effective ways to halt infectious diseases in lieu of vaccine and drug preventive measures.

Conservative resistance to these non-pharmaceutical physical protective measures also probably contributed to their higher death rates observed in the studies mentioned above.

Karma.

Don’t Forget The Drugs: An Update

In these pages last March, I reminded readers to be thankful for the vaccines that prevent COVID-19, but to not forget the antiviral drugs that are being developed that might treat the disease. Both vaccines and antivirals are part of the same quiver of weapons we have to fight the pandemic. In that blog post, I mentioned an experimental drug, molnupiravir that was being developed by Merck and Ridgeback Therapeutics. Well, they just posted an encouraging update. It continues to show success at preventing serious disease when given to high-risk people early after infection. Its only side effects were similar to the placebo, meaning it is very safe. In animal studies, the drug also was effective against different CoV-2 variants, including Delta, and against other coronaviruses including SARS and MERS. Molnupiravir is a “prodrug,” which means that it has no activity on its own; rather it is metabolized after ingestion to an active drug that was developed in the early 2000s to treat hepatitis C.

This is a significant step for being able to easily protect high-risk patients at home. The pill that patients take on their own cuts their risk of hospitalization or death by ~50%. The results were so encouraging that the study was halted after consultation with the FDA. Early termination of studies like this is only done when interim data analyses show such good efficacy of a treatment that it would be unethical to continue enrolling subjects, some of whom would receive placebo, thereby being denied an effective therapy.

The drug slows the spread of the virus in infected people by forcing the enzyme that copies the viral genetic material into making so many mistakes the virus cannot reproduce. That, in turn, reduces the patient’s viral load, shortening the infection and damping the type of over-exuberant immune response (cytokine storm) that causes serious problems in many COVID patients. It was not effective when given to already hospitalized, or advanced, patients. It is on track to be approved by the FDA by the end of the year, and would be the first proven and approved oral antiviral drug for treating COVID-19 (neither ivermectin nor hydroxychloroquine have been proven or approved).

The FDA has already cleared another antiviral drug, remdesivir, for treating COVID-19, but it is only used to treat advanced patients who are already hospitalized (interestingly remdesivir was also originally developed to treat hepatitis C and it is also used to treat Ebola). Several lab-produced monoclonal antibody treatments have also been approved by the FDA for treating mild to moderate COVID-19 and they are more successful than molnupiravir at preventing advanced disease. But both remdesivir and the antibody treatments require an intravenous infusion done in a health care setting, making them more complicated and more expensive than just taking a pill at home, which is a decided advantage of molnupiravir. Finally, one of the more effective approved drugs against COVID-19 is the steroid, dexamethasone, but that is only given to very sick patients since its side effects are significant. Therefore, there is much room in the anti-COVID quiver for effective, simple-to-administer drugs such as molnupiravir. Both Pfizer and Roche also have other antiviral drugs that block viral replication in advanced stages of development. Stay tuned.

As of October 5, 2021, the Milken Institute tracker shows that there are 331 “treatments” for COVID-19 in development worldwide. This effort recently got a $3.2 billion boost from the US Antiviral Program for Pandemics, which is a rejuvenated initiative that was started during the MERS outbreak in 2012, but was tabled after MERS fizzled out. Then there is the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program, also sponsored by NIH. These programs focus on developing non-vaccine therapies designed to treat not prevent the disease and they include studies of medicines currently used to treat other diseases (including ivermectin, which has yet to be proven effective) as well as studies of new drugs.

While the news about molnupiravir is encouraging, health experts are concerned that the news also could increase complacency regarding vaccines in the vax-hesitant. It is important to realize that prevention (vaccination) is almost always preferable to treatment (drugs).

Get the vax.

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

Vying With Viral Variants

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

The back story: There are four known CoV-2 variants in the US that are more transmissible than the parent strain. They are the UK variant, which is 70% more infectious and 60% more deadly than the original strain. There also are Californian and Brazilian variants that are more transmissible, but it is not yet known if they are more deadly. However, in Brazil, their variant is associated with a significant increase in infections and ICU stays for young, healthy, unvaccinated people. Fortunately, the current vaccines seem to be effective at preventing infection with these strains.

More worrisome is the South African variant that is 50% more transmissible. It is worrisome because the AstraZeneca vaccine is not very effective against this variant, and a very recent, but a small study out of Israel suggests that the Pfizer vax might have reduced efficacy against the S. African variant. It is not yet known if this strain causes more serious disease. These findings provide evidence that mutation can produce new viral strains that can evade the immune response to the viral spike protein.

Two other variants, the so-called New York variant, and a second Brazilian variant have early signs of being more infectious or even being able to reinfect people who previously had COVID-19. Data are still being collected in order to better understand the risk that these variants pose. Stay tuned.

You can follow the variants in the US here.

The bottom line is that the world is in a race to roll out vaccines faster than troubling virus variants can arise. The UK is expected to reach herd immunity​ early next week. Infections there dropped by 60% during March, with deaths dropping more rapidly, indicating that the vaccines are helping prevent severe illness and viral spread. Meanwhile, the US leads the world in total vaccines administered (175 million), with 43% of the adult population having received at least one shot. More than 700 million doses have been administered world-wide.

The major concern is that a too-slow vaccine distribution, such as what has happened in Brazil, will encourage more virulent variants to arise. If we don’t quickly achieve herd immunity across the world, it probably will just be a matter of time before a variant arose that renders the current vaccines useless, and we would have to start over.

What is a world to do? Besides increasing surveillance of viral variants, a couple more prevention initiatives are in the works. One is economic and the other scientific.

Economics of viral mitigation: The economic approach is detailed in an article by the Associated Press Economics Writer, Martin Crutsinger. Basically, the International Monetary Fund (IMF) proposes giving $650 million to support vulnerable countries struggling to deal with a global pandemic. Along with that, the Group of 20 major industrial countries issued a joint statement that announced a six-month moratorium on debt payments by 73 of the world’s poorest countries.

The rationale behind these actions is to ensure that poor countries, where vaccinations are lagging due to lack of resources and infrastructure, can pick up the pace of vaccination. Their lag in rolling out shots is a threat to the whole world, even while wealthy countries are approaching herd immunity. In order to beat the variants, vaccines are needed to quickly create herd immunity and stop viral spread before a variant that can avoid vaccine immunity appears. When countries lag in vaccinations, the virus continues to spread increasing the chance for an immune-avoiding variant to pop up. Such a variant can then spread to countries that are highly vaccinated, starting the pandemic over again because the current vaccines would be ineffective. We would be back at square one.

Science to the rescue: So far, all the vaccines, except one from China, which uses the whole virus, direct the immune response to the viral spike protein that is used to attach to receptors on the surface of cells in your body. The viral variants we are concerned about show mutations in the spike protein that allow them to become more infectious, and in one case, to be less affected by some of the vaccines. In addition to trying to  nip the virus in the bud by quickly building world-wide herd immunity, new vaccine strategies are being developed to quickly respond to newly arising CoV-2 variants, and even to respond to entirely new strains of viruses that will arise in the future.

• One way to do this is to begin developing booster shots as soon as a coronavirus variant becomes a significant concern. With the new mRNA, and adenovirus vaccine delivery technology, this is eminently possible. It just requires scientists around the world being vigilant for new variants. Pfizer, Moderna, AstraZeneca, and Johnson & Johnson have all said they’re starting work on developing booster shots to the known variants.

• Last week, the US government announced a pact with CureVac to tackle variants, pairing artificial intelligence to predict future mutations that can be quickly addressed with modern vaccine technology. London-based GlaxoSmithKline is also working with CureVac on mutant-quelling vaccines.

• Another strategy is to identify viral molecules other than the spike protein that the immune system can recognize. Efforts are underway to test the immunogenicity of what is called the CoV-2 nucleocapsid, or N protein, which wraps itself around the viral RNA. If successful, future vaccines could incorporate both the N and S (or spike) proteins, which would require the virus to mutate both of those genes in order to avoid vaccine-induced immunity, a greatly tougher task for the virus.

• Researchers at Moderna, Novavax, and the University of Oxford are designing multivalent vaccine strategies to protect against multiple CoV-2 variants with a single shot, and even against new viruses that might emerge in the future. A similar strategy is used with the annual flu vaccine, which usually incorporates four different influenza strains in one shot. It is also used with measles, mumps, and rubella vaccines. Some vaccines against pneumonia target as many as 23 variants of that pathogen.

• Finally, a wholly new vaccine technology has shown recent success in animal studies. It works by chemically attaching many short viral protein sequences from different CoV-2 variants, and even from completely different coronaviruses, to engineered nanoparticles that are then injected. In mice, this single vaccine induced an antibody response capable of neutralizing many different coronavirus strains. If successful, this could represent a universal vaccine capable of neutralizing CoV-2 and its variants, as well as other coronaviruses such as SARS and MERS with a single vaccine. And it can be easily modified to quickly respond to future viral epidemics caused by novel coronaviruses or other viruses that will certainly arise. The technology is being developed at Cal Tech using technology developed by collaborators at Oxford University. The nanoparticle platform is a “cage” made from 60 identical proteins. Each of those proteins has a small protein tag that functions like a piece of Velcro to which the viral protein sequences stick resulting in a vaccine nanoparticle with short protein sequences from four to eight distinct coronavirus strains on its surface. If successful, this could prevent infection and disease for several different viruses with a single shot.
  

 We are in a revolutionary era of vaccinology. BioX marches on.

In The Midst Of The Vaccine Frenzy, Let’s Not Forget Drugs

Why drugs? While there is palpable excitement over the great success of several vaccines against the CoV-2 virus, companies around the world also have been developing new anti-coronavirus drugs to treat infections. As of March 5, the Milken Institute tracker reports that 251 vaccines are still in development, and 323 anti-viral drugs also remain under development.

While vaccines have dominated our thoughts in recent weeks, drugs can still play a very important role too. For example, even though we have vaccines for influenza, we also have the drug Tamiflu that shortens and reduces the severity of the flu. The drug is useful when we guess wrong about the strains of flu to vaccinate against each year. It also is used as prophylaxis for people working with the flu virus in clinical and research labs since they often work with flu strains that are not included in the annual vaccines. Also, while we have not been able to develop vaccines against hepatitis C or HIV, due to the quirkiness of those viruses, we have been able to take advantage of their biochemical quirks to develop drugs that now cure hepatitis C and that have turned HIV into a manageable and mild chronic problem rather than a death sentence.

All of this begs two questions; why would vaccines be needed if we had an effective drug against the virus, and why would a drug be needed if we had an effective vaccine against the virus? The answer has to do with the difference between prevention vs treatment. Prevention (i.e., vaccination) is ideal, but it takes time to develop vaccines to novel pathogens; hence, the value of an effective anti-coronavirus  drug to treat novel species of the virus that will arise in the future. Treatment (i.e, with a drug) also is good, but it still is better to prevent disease than to respond to it after you get sick.

So, there definitely remains a significant role for an effective anti-coronavirus drug even while we have successful vaccines. First, some people cannot be vaccinated or they have a compromised immune system that would render a vaccine ineffective. These people need an effective anti-viral drug. Second, as we have seen over the last decade with SARS, MERS, and now CoV-2 and its variants, deadly coronaviruses are popping up that require a swift response by public health folks. Even though the vaccines to CoV-2 were developed in record time, the virus still killed a couple million people around the world and caused untold long-term health problems in millions more before we had the vaccines. Furthermore, the current vaccines very likely will not be effective against the next species of coronavirus that visits us. Current vaccines also might show reduced effectiveness against newly arising CoV-2 variants. In fact, the AstraZeneca vaccine has proven so ineffective against a novel CoV-2 strain that arose in South Africa, that that country no longer uses it. Therefore, having a drug that can be quickly distributed to meet a new coronavirus threat would go a long way to protect us against future outbreaks while vaccines are being developed.

The new anti-viral drugs: More than a year into the pandemic, we have very limited drug options. Hydroxychloroquine showed early promise, but controlled clinical trials showed it to be a bust, as was ivermectin, which the FDA recently disapproved for COVID-19 patients. Only remdesivir has been authorized for use in COVID-19 patients, and it only provides modest benefit in hospitalized patients, reducing their stays by a couple of days. However, recent encouraging, but preliminary, results suggest an effective anti-coronavirus drug might have been found. The pill, molnupiravir, which is being developed by Ridgeback Biotherapeutics and Merck, significantly reduced infectious virus in 182 subjects in a phase 2 clinical trial. After five days of treatment, no virus was detected in any of the treated volunteers, while subjects who received a placebo did show virus. The drug interferes with the biochemistry involved in viral reproduction inside cells, therefore it prevents viral spread. Further study of the new drug is under way.

And four other potential anti-viral drugs are in mid-to-late stage trials at NIH under the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. ACTIV is a public-private partnership program to coordinate research strategy that prioritizes and speeds development of promising COVID-19 treatments and vaccines, and was launched on August 4, 2020. Like the vaccines, these new antiviral drugs are being developed in record time.

The drugs include SNG001 developed by Synairgen; it is an inhalable beta interferon delivered by nebulizer. Beta interferon is a cytokine produced by virally infected cells as a first line defense against viral replication. There also is AZD7442, a long-acting monoclonal antibody combination (AstraZeneca), and Camostat mesilate, an orally administered enzyme inhibitor designed to block CoV-2 from entering cells (Sagent Pharmaceuticals). 

Eli Lilly has also reported positive results with a combination of two antibody drugs, bamlanivimab and etesevimab (who comes up with these names?), that cut COVID-19 hospitalizations and deaths by 70% in recently diagnosed patients. These are anti-CoV-2 antibodies produced in the laboratory and work by mimicking the body’s immune system to give infected patients a head start fighting the disease while their natural immune systems ramp up to deal with a new pathogen. These also were developed as part of the ACTIV program and have been approved by the FDA to treat mild to moderate COVID-19 in people at high risk for severe disease. The feds have purchased large quantities of these Lilly antibody drugs and is making them available to qualified patients at no cost.  Meanwhile, on January 5, 2021 Durham, NC biotech company, Brii Biosciences, launched an ACTIV study on two other investigational lab-produced antibodies designed to neutralize the CoV-2 virus

That leaves a bit over 300 more investigational anti-coronavirus drugs to go.

The Lesson Behind The Long Recovery From COVID-19 For A Young Physician Assistant

This is an update to a story published on March 10, 2020 by MedPageToday. You can read the original piece here.

In March, James Cai, a physician assistant and New Jersey's first COVID-19 patient, made headlines for warning the country that even young, healthy 32-year-olds like himself were vulnerable to the virus. He came down with the disease in early March and was admitted to the hospital on March 3. Because the disease was so new, he was worried that he wasn't getting the right treatment at the hospital, so he took his case to Twitter.

In the beginning, he was treated like he had a serious case of the flu. He received high-flow oxygen, chloroquine, and lopinavir/ritonavir (Kaletra), and was one of the first patients to receive remdesivir under compassionate use approval. He was able to connect with Chinese physicians who had experience with the disease, and a Chinese-American doctor translated the Chinese protocols into English for Cai's New Jersey doctors.

He was discharged on March 21, but still needed supplemental oxygen -- especially at night. A month after his discharge he went back to work as a physician assistant, but only virtually and half-time. But even by mid-summer, Cai was still seeing impairments in his oxygen saturation and activity levels. His O2 saturation was 97% during the day, which is good, but it dropped to 90% when he lay down to sleep, necessitating the oxygen supplement. He tired very easily and was unable to run and exercise like he did before. Through that time, he was taking dual anticoagulant therapy of Xarelto and aspirin.

In late summer, things started to look up. On August 21, he confirmed that he could sleep through the night without oxygen, but the results of his latest chest CT showed permanent fibrotic lung damage in his left lower lung. As of December, he was still testing positive for coronavirus antibodies.

We still do not know why some people, especially young, healthy people can be so hard hit by the virus while others are not. Why did Cai become so ill and suffer permanent lung damage, while a couple of my nearly 70 year old friends caught it and had milder, temporary symptoms? It will be a while before we understand this.

This story also illustrates the folly of just looking at mortality numbers when assessing COVID risk. The death rate for COVID-19  is low, about 1% or less of people who get infected die from the disease, so some folks cite that low death risk and take a cavalier approach and avoid social restrictions designed to slow the virus spread. By focusing on that simple statistic, they ignore the fact that COVID is now the leading cause of death in the US by far and has killed 10 times the number of people who are killed by seasonal flu. The devastating 1918 Spanish flu also had a very low death rate, but in just 24 weeks, it killed more people around the world than were killed in the 10 years of WWI and WWII combined!

And those people who cherry pick their statistics to justify their careless behavior ignore the greater number of people like Cai who survive the disease, but suffer long term and even permanent health problems. Is it really worth the risk of permanent lung damage to exercise your freedom to not wear a mask?

Nasal Spray To Prevent CoV-2 Infection?

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

A November 5 preprint showed that a nasal spray was 100% effective in preventing infection in an animal CoV-2 infection model. The spray contained a small piece of the SARS-CoV-2 spike protein designed to block the ability of the virus to enter human cells in the respiratory tract.

Ferrets were given the nasal spray and then placed in cages with an infected partner to see if the virus would transfer to the treated animal. After 24 hours, 100% of the animals that received a sham spray were infected while none of the animals that received the experimental nasal spray were infected. This not only shows that the spray seems to work, it also confirms that sinus exposure to the virus is the primary route of infection--at least in ferrets. It shows that saliva exchange, sharing food and water, etc., are not as important routes of infection.

While very encouraging, this also is very preliminary. We need to learn how long such protection lasts, whether it works early after infection, whether it works in humans, and assess its safety profile in humans.

Such a pre-exposure, or even early post-exposure prophylactic, would be very helpful to high risk people, front-line health care workers, teachers, nursing home residents, and many others. If it works, it could provide a relatively inexpensive and readily available prophylaxis and complement the vaccines that will likely be soon approved. Since it seems that only about 50% of the US are willing to get an anti-CoV-2 vaccine, which is not sufficient to confer herd immunity, a preventive measure like this nasal spray could go a long way in reducing the R₀ value for CoV-2 to <1.

SARS-CoV-2 vs Hepatitis C: SpaceX vs NASA: New vs Old

What does hepatitis C have to do with the coronavirus subject of this blog? More to the point, why in the world bring up SpaceX and NASA in a blog on the coronavirus? Let me make a couple of seemingly disparate points and then try to tie them together.

First point: American scientists Harvey J. Alter and Charles M. Rice, and British scientist Michael Houghton were just awarded the Nobel Prize for Medicine or Physiology for the discovery of the hepatitis C virus (HCV). Their work led to new diagnostic and treatment developments for HCV that have saved millions of lives. That research took almost four decades.

Second point: Let’s compare the NASA space shuttle to the SpaceX rocket that just took astronauts to the International Space Station.

• Flight control:
  • Shuttle--human drivers
  • SpaceX--totally autonomous. Humans not needed at all.
• Reusability:
  • Shuttle--only the shuttle was reusable. The launch vehicle was not.
  • SpaceX--totally reusable.
• Cost to launch each human passenger:
  • Shuttle--$170 million
  • SpaceX--$60-70 million
• Cost per kilogram of cargo:
  • Shuttle--$54,500
  • SpaceX--$2,720
• Development cost:
  • Shuttle--$27.4 billion
  • SpaceX--$1.7 billion

Bringing it all together: The science around the CoV-2 virus and SpaceX represent the new science world that contrasts to the old science world of hepatitis C and NASA, respectively. Make no mistake; the old science was very successful; it led to the Nobel Prize for discovering HCV, and to putting men on the moon and the Hubble space telescope. Those old science accomplishments took decades to achieve and cost billions of dollars. The second point above, comparing SpaceX to NASA, points out how far technology has come in a few years regarding space flight. Just a few weeks ago, many of us saw a SpaceX rocket launch astronauts to the space station. Rather than just letting the rocket that propelled the astronauts’ craft to burn up, it was designed to reenter the atmosphere and land upright in the middle of a bulls-eye, on a small barge just off the coast of Ireland. The great increase in technical capability, along with the great decrease in cost of developing SpaceX is a great testimony to our modern science and technology.

Similarly, new bioscience technology that has led to the rapid identification and treatment of the virus that causes COVID-19 represents our modern “BioX” vs the old standard of molecular biology. The “old biology” (it greatly pains me to describe it that way) was highly successful. It illuminated great things about our microscopic world that have been critical in learning how to deal with our macroscopic world. But the old molecular biology is the “biological NASA” that is being usurped by “BioX.”

Consider the great and significant accomplishments of the three scientists who just won the Nobel Prize for discovering HCV. Decades ago, we knew that two types of viruses caused hepatitis in people exposed to bodily fluids of infected people. The viruses were designated hepatitis viruses A and B. Yet, when blood products destined for patients were screened for both of these viruses, people still contracted hepatitis. It was then well accepted that there was yet another blood-borne pathogen that caused non-A, non-B type hepatitis. And the search for the bug was on.

It took a couple of decades to identify the suspected pathogen as a virus. That happened at the end of 1989. Because of the virus’s peculiarities, we still have not been able to develop a vaccine for it, but a drug cure was approved in 2014. That cure took fifteen years to develop and that was on top of the 20 or so years it took to identify the virus; almost four decades in total.

Compare how long it took to identify the pathogen and develop a treatment for HCV to today’s situation with the novel CoV-2 virus. According to a timeline I posted earlier, in Dec/Jan an unusual flu was discovered in China’s 10^th largest city, Wuhan. In just a couple of weeks the virus was isolated and just a few weeks later, we knew its genome sequence. In February, the Chinese began developing the first vaccines. According to the Milken Institute tracker, today 315 treatments for COVID-19 are in development around the world. 199 vaccines also are being developed, 11 of which are in late stage trials and we should have more than one vaccine available in the next 2-5 months. All of this has happened in about a year after the virus was first suspected to exist! That is bioscience working at the speed-of-light, and that is only possible because of what we learned in the “dark ages” of molecular biology.

The age of BioX has turned your humble blogger into a dinosaur.

Note: In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want.

Trump’s Treatment

Being, male, elderly (74 years old), and borderline clinically obese, Mr. Trump meets three high-risk criteria for severe COVID-19 disease. Despite reporting negligible symptoms at this point, his doctors at Walter Reed have him on aggressive precautionary therapeutic measures.

He has been given the anti-viral drug, Remdesivir that shows moderate effects against the CoV-2 virus and has become a standard-of-care treatment for hospitalized COVID-19 patients. He also has received an intravenous dose of Regeneron Pharmaceutical’s cocktail of two experimental anti-CoV-2 monoclonal antibodies. These are antibodies produced in the lab that are designed to mimic the naturally occurring antibodies the immune system produces in response to CoV-2 infection. They provide a boost to the natural immune system, especially during the early stages of infection when one’s natural immunity is still ramping up. While the monoclonal antibody therapy is experimental, early evidence suggests that it provides a significant protective effect. It was approved for Mr. Trump under a “compassionate use” clause for experimental therapies.

He reportedly also has been taking daily aspirin, which has anti-coagulant properties, as well as over-the-counter vitamin D and minerals needed for a healthy immune response. A paper published last month in the journal PLOS ONE found a higher rate of coronavirus cases in people who were deficient in vitamin D than in people who had normal levels of vitamin D. But this is just a correlation and more research is needed to confirm that there is a biological cause-and-effect relationship between vitamin D levels and COVID-19.

It is interesting that it appears Mr. Trump has not been taking hydroxychloroquine, which he earlier pushed, and which more recently has been pushed by some physicians and touted by many lay people to be a COVIID-19 cure despite growing scientific evidence showing that it is not effective, even when given to early stage COVID-19 patients.

Update (Sunday 10/4): It was reported today that Trump has displayed transient low oxygen levels that seemed to be taken care with supplemental oxygen. He also has been given dexamethasone, a steroid, in order to prevent inflammation of his lungs. His doctor expects him to be released from Walter Reed tomorrow (Monday).

Note: In order to have blog updates delivered to your email, see the simple Subscription instructions here. Remember, you can easily unsubscribe when you want.

Disinfectant Treatment Redux

Remember when, at a press conference, Trump turned to some doctors and asked the inelegant question of whether they could use “disinfectants” to treat COVID-19? “Disinfectant” was a poor word choice made by a non-medical expert, and the press did what it does best and over-interpreted that malapropism to claim that he was asking whether Clorox or Lysol could be injected to treat the disease. That was a rhetorical overreach on their part.

What if, instead of “disinfectant,” he used the word “antiseptic?” Antiseptics are biocidal chemicals that stop or slow the growth of microorganisms and are frequently used in hospitals and clinics to sterilize skin and mucous membranes to reduce the risk of infection during medical procedures. Disinfectants also are biocidal chemicals that kill and slow microorganism growth and also are often used in hospitals and clinics to sterilize surfaces and instruments to prevent the spread of pathogens. Many people use the terms interchangeably. For example, antiseptics used to sterilize skin before surgery and are sometimes called skin disinfectants.

But for the hairsplitters, medical professionals admit to a bit of difference between antiseptics and disinfectants. Generally, antiseptics are applied to the body, while disinfectants usually are applied to surfaces, such as countertops and handrails. However, a surface disinfectant, such as alcohol, is also often used as an antiseptic to sterilize skin. Your arm often is swabbed with alcohol before an injection, and alcohol is a common antiseptic ingredient in hand cleanser. Chlorhexidine is a disinfectant used to sterilize surgical instruments, but it also is used as an oral antiseptic. Hydrogen peroxide is another chemical that is used both as a disinfectant and antiseptic. Clearly, there is much similarity and overlap in the use of and terminology between antiseptic and disinfectant agents, which can collectively be called biocides.

Even if Trump had used the word “antiseptic” instead of his unpolished choice, “disinfectant,” one suspects that the press still would have chided him for suggesting that we inject Mercurochrome to treat COVID-19. However, he also might have been vindicated since an antiseptic and a surgical instrument disinfectant are now being tested at the University of Wisconsin-Madison for their ability to prevent CoV-2 virus infection.

The new study will test a common antiseptic, Povidone-iodine, for swabbing the nose, and the common instrument disinfectant, Chlorhexidine, for rinsing the mouth. The idea is that the agents will coat the nose and mouth and kill any virus that comes in contact with the biocidal agents, preventing the virus from gaining entry into mucosal cells from where they grow and spread throughout the body. The trial is now enrolling up to 500 participants. For a six week period, participants will swab their nose twice a day and rinse four times a day, after which they will be tested for CoV-2 infection and compared to a control group that did not “disinfect.”  If effective, this regimen could be useful for protecting healthcare workers, teachers, nursing homes, and other people routinely in high contact with others. Researchers hope to announce their findings by early to mid-fall.

Words are important, but sometimes flubbed; that is excusable, especially when it is a non-expert who did the flubbing. What is less tolerable is jumping to unwarranted and extreme rhetorical conclusions about why a flubbed word was said. If one is honest, one must admit that Trump never suggested “injecting Clorox” to treat COVID-19. Now, it seems that Trump’s poor choice of the word “disinfectant” was not so crazy after all. One day, we all might be gargling with a surgical instrument disinfectant.

Bottom line: When setting up this blog last April, I said it would not be political, and it hasn’t been. What I wrote above is not about politics, it is about science and facts, both of which can transcend politics. Sometimes when a scientist makes statements based on facts and evidence that conflict with certain political positions, people assume that the scientist is being political. That is not necessarily true.

It is not true here.

Note: In order to have blog updates delivered to your email, see the simple Subscription instructions here. Remember, you can easily unsubscribe when you want.

Science vs Nonscience In Understanding Hydroxychloroquine

A recently much shared video of America’s Frontline Doctors Summit shows several clinicians claiming that hydroxychloroquine (HCQ) is a "cure" for COVID-19. Their evidence for this claim is their personal experiences treating these patients with HCQ along with a cocktail of other drugs. The video was shared 14 million times before Facebook and other hosting services took it down, ostensibly for spreading inaccurate information. While the debate whether such censorship is reasonable, it is also reasonable to point out that the doctors were, in fact, sharing information that is not known to be accurate and that has a high chance to be inaccurate; in other words, scientifically unproven. They grossly overstated their conclusions from their non-scientific observations. It is irresponsible for a doctor to claim that her anecdotal experience “proves” the efficacy of any unproven therapy. If the docs had been honest, they should have said that their observations warranted further controlled clinical trials in order to prove or disprove their claims. 

One of these doctors said that she had treated 350 patients with the drug cocktail and that none died; therefore, she irresponsibly declared that she had a “cure” for the disease. While that sounds impressive, she did not do a controlled clinical trial, which means that we have no way of knowing whether the 350 also would have survived without the drug. She also claimed that her success was because the patients she treated with the cocktail were at the early stage of disease. Unfortunately, we don’t know what that means since she didn't report their clinical details as she would have been required to do in a gold standard clinical trial. This doctor also had a web page where she talked about how gynecological problems are caused by engaging in sex with demons, and that alien DNA was being used in modern medicines; all the more reason to suspect her credibility.

In other venues, I have pointed out these problems with the America’s Frontline Doctors Summit and received a lot of push-back from non-scientists. For some reason, some people bring a strong need to believe in HCQ without considering the science. So, they readily jump on ANY report that confirms their bias as proving that the drug is a cure. Several of these “experts” quickly pointed me to a recent report from the Henry Ford Health System that claimed that hydroxychloroquine saved lives. It was published earlier this month in the International Journal of Infectious Diseases. 

However, the Henry Ford report was not a clinical trial, but a much weaker retrospective chart review of more than a thousand COVID-19 patients seen in the system’s nine hospitals. In other words, the patients were not randomized, the “study” was not blinded, and patients were not treated according to a controlled, standardized study protocol. Hence, it was only marginally better than the undocumented anecdotes of America’s Frontline Doctors. At least, because the Henry Ford docs published a report on their personal observations, interested clinicians and researchers could look at the aggregate patient data. That was not the case regarding the claims by the America’s Frontline Doctors.

On Wednesday, in response to the Henry Ford report, the same journal published several scathing critiques claiming the report had serious errors. The major problem was that the patients given the HCQ cocktail regimen were healthier than the patients that were not given it. The patients not given the cocktail had more advanced disease and more frequent comorbidities that put them in a higher risk group compared to those who received the treatment. Furthermore, the HCQ treatment group was more aggressively treated and more than twice as likely to receive steroid therapy, which has been shown to help certain COVID-19 patients.

In other words, in this chart review of patient experiences, the two groups that were compared were very different and it is highly possible that the death rate difference between them would have been the same even if the HCQ protocol was not used. An important goal of randomized, blinded, controlled clinical trials is to make sure that the treatment and non-treatment comparison groups are as similar as possible in order to eliminate such bias that can skew the study’s results. This is why scientific clinical trials and not chart review reports are the gold standard for determining the best health care.

Unfortunately, people who take these anecdotal testimonies, and poorly controlled chart review reports as proof that HCQ is the panacea for COVID-19, also selectively ignore other recently reported gold standard clinical trials that show that HCQ is ineffective. This week, a randomized clinical trial in Brazil showed that hydroxychloroquine doesn't work to treat patients with Covid-19. Another randomized trial last month at the University of Minnesota showed it also doesn't help prevent infection. Other clinical trials -- one in the US, and one in the UK were halted early because interim data analysis showed the drug wasn’t working.

Like America’s Frontline Doctors emphasized, the authors of the Henry Ford report pointed out that HCQ worked for their patients because it was prescribed very early in their hospitalization. But, University of Albany researchers earlier reported that the HCQ cocktail approach was ineffective in a randomized, blinded trial employing subjects at the same point of disease as the patients in the Henry Ford report.

As reported earlier in these pages, because of similar negative clinical trials, the FDA recently pulled its approval for HCQ to treat COVID-19.

There is a very good reason why we rely on carefully designed and controlled clinical trials rather than anecdotal information or retrospective chart reviews in determining the best way to treat disease. The best the latter should contribute is to generate interest in testing the observations in controlled clinical trials to see if they are accurate.

While your humble blogger initially was enthused about the potential of HCQ to treat COVID-19, I increasingly sour on it as science continues to show it doesn’t work. So far, the reports claiming that HCQ is effective against COVID-19 are mostly based on unsubstantiated doctor’s anecdotes, or on uncontrolled retrospective chart reviews. In contrast, the reports that indicate that HCQ is ineffective are based on stronger randomized and controlled clinical trials.

Who are you going to believe?