Making Sense of Medical Science (MSMS)

A medical scientist explains medical news for lay people

recent posts

about

Steve Clark, PhD is a retired university professor with a PhD in immunology and a past Special Fellow of the Leukemia Society of America. Clark has published dozens of papers based on his research and holds two drug patents. He taught medical and graduate students about cancer biology and genetics, and about research ethics. He also directed an NIH-funded PhD Graduate Program and chaired several executive-level faculty committees. Clark served on the University Chancellor’s Speaker’s Bureau. While retired, Clark has been blogging on the COVID pandemic, which is the subject of his next book.

  • Independent Analyses Suggest COVID-19 Can Cause Diabetes

    We know that having co-morbid conditions such as asthma, heart disease, diabetes, and others are risk factors for significant COVID-19 disease and death. Now, independent reports out of the US and the UK strongly suggest that having COVID-19 can also lead to the swift onset of diabetes, even in people with mild infections. This includes children. These observations add to the list of long-term health problems for the millions of COVID-19 survivors living with chronic conditions following infection called "long-haulers."

    Some 10-30% of COVID-19 survivors develop persistent and sometimes debilitating symptoms after apparent recovery from the disease. It has been known for a few months that in a subset of these long-haulers, lingering metabolic complications require high doses of insulin suggesting that they are developing diabetes. This possible link between COVID-19 and new-onset diabetes was noticed as early as last summer and was reported in Scientific American last February. Two more recent analyses of patient data strengthen the COVID-diabetes link.

    • In the US, researchers at the Veterans Affairs St Louis Health Care System’s clinical epidemiology center recently published their findings in the journal, Nature. They used data from VA national health-care databases and found that COVID-19 survivors were about 39% more likely to have a new diabetes diagnosis six months after infection compared to non-infected users of the VA health system. This means that there about 6.5 extra diabetes cases per 1000 COVID-19 patients who are not hospitalized. For hospitalized patients, the risk jumped 5-fold to 37 per 1000, and it is even higher for patients who required intensive care.
    • In the UK, a study of 50,000 hospitalized COVID patients was published about three weeks earlier than the US study. The UK study reported that the patients were 50% more likely to develop diabetes 20 weeks after discharge than matched control patients.

    How does the virus do this? CoV-2 primarily is a respiratory disease, but we have known since the early days of the pandemic that it also can ravage other organs including the kidneys, brain, and others. The leading theory of how COVID-19 can cause diabetes is that the pancreas, where insulin is produced, also can be damaged by the virus, or by the immune inflammatory response that follows infection. Other possible mechanisms are also being considered.

     Bottom line: As of this month, 153 million people around the world have been infected with the virus. That means that the pandemic has caused a LOT of new cases of diabetes, a chronic disease, for the world to absorb. To monitor global COVID-related diabetes, a world-wide registry has been set up by King’s College London and Monash University in Melbourne. Almost 500 doctors around the world so far have agreed to share data via the registry.

    Maybe this information will convince people who down play the disease by only focusing on the low mortality rate of COVID-19 that they also need to consider the accompanying long-term health consequences of the disease.

  • Why It Is Necessary To Vaccinate Kids

    Vaccine makers are applying to the FDA for approval to give the COVID-19 vaccines to children. Some people have questioned the need for this since kids seldom get sick, let alone die from COVID-19. But, there is a very good reason to vaccinate them, which is to protect them, as well as the rest of us from the emerging new viral variants that are more infectious and more potent and that I discussed earlier.

    Vaccines do two things; 1) they protect the vaccinated from the disease, and 2) they prevent the further spread of the pathogen and disease. A good example of the latter point is Japan and flu vaccines. A number of years ago, Japan mandated that all school kids be vaccinated against the flu. A major result was a sharp drop in flu deaths in the elderly. Kids are walking incubators for respiratory viruses and carry them home for their families to enjoy. Thus, Japan's flu vaccination program meant that fewer kids were catching the flu and carrying it home to infect their parents and grandparents. Hence, flu mortality dropped.

    That is why we need to vaccinate kids against CoV-2 even though they seldom get seriously ill from it. Related to that point is the fact that the more CoV-2 spreads, the greater the chance that the virus will mutate into variants that are increasingly infectious, more deadly, and that can evade the immune response to the current vaccines. If that happened, we would be starting all over again. Hundreds of thousands, if not millions around the world would die, countless more would suffer long term consequences from COVID-19, and the disease could very well become more serious in young people. We already are seeing increases in infections and hospitalizations in younger, healthier people from the viral variants that already have arisen in the UK, South Africa, Brazil, and India.

    We need to vaccinate kids in order to slow as much as possible transmission of this virus in order to minimize the development of potentially more deadly variants.

  • What Caused India’s Devastating Second Wave?

    Understanding what contributed to a second, more intense COVID-19 surge in India can inform the rest of the world on how to avoid a similar surge for this and future pathogens. This outbreak threatens to extend the pandemic itself and drive world-wide infections to new highs, creating an enormous a breeding ground for new and potentially more dangerous viral variants. If variants emerge that are not touched by the current vaccines, the world will be at square one with the pandemic. What a depressing thought.

    It appears that the second wave arose due to a combination of three things: 1) India’s relaxing quarantine measures back in January, 2) the emergence of more rapidly spreading viral variants, including one that first appeared in India, and 3) a very poor rollout of vaccines to protect India’s population from spread of the virus. These are further discussed below.

    1. Relaxed safety measures. India’s second surge came after loosening restrictions, which let public complacency set in, which, in turn, was exacerbated by government officials like Prime Minister Modi and Health Minister Harsh Vardhan declaring that the pandemic was defeated. Life returned to normal. Masks went away, as did social-distancing. Weddings and parties resumed, which usually are large events in India. A new season of state-level elections ushered in big political rallies and street parades. A massive religious festival known as the Kumbh Mela took place, bringing an estimated 5 million Hindu pilgrims to the banks of the river Ganges in April. By mid-March, cases started gradually climbing again—then suddenly accelerated, becoming a vertical line rather than an upward sloping curve. The government was slow to respond. It was not until late April that Modi finally acknowledged the urgency of the situation. Local containment measures are beginning to be enacted, including shutting down the capitol of Dehli, and a few Indian states. However, Modi remains reluctant to enact country-wide restrictions like he did during the first wave. Without a more aggressive vaccine campaign, that could be a bad decision.

    The more the virus spreads throughout India, and even into its neighboring countries of Nepal, Pakistan, and Bangladesh, the greater the risk that it will generate more infectious and dangerous viral variants that will not be affected by the current vaccines. If that happens, well vaccinated countries will have to start over. That is not a pleasant prospect, and is further discussed below.

    1. More infectious viral variants. India’s more deadly second wave of the CoV-2 virus can also be attributed to more infectious and more persistent viral variants. In this second wave, India, like many other countries, has been inundated with viral variants first identified in the UK and South Africa that were recently discussed in these pages. The UK variant has a mutation in its spike protein that makes it more infectious than its parent virus. The South African variant has a different mutation in its spike protein that makes the virus more resistant to some vaccines.

    India’s second surge also has introduced the world to a unique viral variant dubbed the "double mutant," which was first identified in October. It is now the dominant strain in the state of Maharashtra, home to India’s financial center, Mumbai.

    “Double mutant” is actually a misnomer for this variant since it has 13 mutations throughout its genome. However, it acquired that sobriquet because it has joined the UK and South African spike protein mutations in the same virus. It is a double whammy.

    While scientists are still learning about the double mutant variant, India is seeing people who were previously infected become re-infected with this new variant. Also, younger and healthier people are being hospitalized in greater numbers. These observations are concerning. Similar observations of re-infection have also been seen in Brazil with yet another viral variant that was first identified there (more about Brazil in a future post). The ability of viral variants to re-infect people can be an important driver of future pandemic waves even in countries where the population is well vaccinated, but where isolation measures have been lifted or ignored.

    For the country overall, the double mutant virus made up 70.4% of the samples collected during the week ending March 25, and that is compared with 16.1% just three weeks earlier, according to Covid CG, a tracking tool from the Broad Institute of MIT and Harvard. The tool mines data from the GISAID Initiative, a global database for coronavirus genomes. These data also show that the double mutant virus has already hopped to at least 21 countries including the US. In Australia viral genome sequencing showed that the double mutant made up 40% of the samples collected over the week ending April 15, compared with 16.7% a month earlier. It accounted for 66.7% of samples from New Zealand for the week that ended April 8, up from 20% a month ago. It also has been detected in California, according to Dr. Benjamin Pinsky, director of the Clinical Virology Laboratory at Stanford University. Clearly, where the double mutant virus appears, it quickly achieves dominance.

    1. Poor vaccine distribution. As of 4/30, India had only administered 15 million vaccinations, a tiny proportion of its population of 1.4 billion people. The country is the primary producer of the AstraZeneca vaccine that has run into supply chain problems causing delays in vaccine delivery. In February, Biden signed the Defense Production Act to boost U.S. COVID-19 vaccine production but that decision cut off US exports of raw materials that India needs in order to maintain its vaccine production capabilities. Thus, vaccine makers around the world, including the Serum Institute of India (SII), the largest vaccine manufacturer in the world, face a shortage of materials to make COVID-19 vaccines. The ban has garnered much criticism as resource hoarding that threatens global vaccine production. On April 16, SII appealed directly to Biden to lift the embargo of raw material exports so that vaccine production could continue. Several days later, the White House announced it would partially lift the ban for materials the Indian company needed to manufacture the AstraZeneca vaccine, specifically.

    The US also inexplicably has a large stockpile of millions of doses of the AstraZeneca vaccine, that were made here, even though it is not approved for use in the US. If we are not using it, why not release the stores to the world? The Biden administration also has faced criticism for hoarding these doses that could help India and other countries around the world that also are experiencing a new surge in infections. On Friday, April 30th, the U.S. Chamber of Commerce called on Biden release the AstraZeneca vaccines to India and other hard-hit countries.

    There is some irony in all of this since India is a huge manufacturer of vaccines and pharmaceuticals for the world, and likes to bill itself as the “pharmacy of the world.” India produces 60 percent of the world’s vaccines, but cannot supply its own country, partly because of reduced production due to the supply chain problems, but also because it failed to order sufficient vaccine doses. India almost completely halted vaccine exports last month in order to divert supplies to its domestic population, which is affecting supply in the rest of the world. Rather than rely on its own manufacturers for vaccines, India approved Russia’s Sputnik vaccine, and has fast-tracked the approval process for other vaccines manufactured in foreign countries. That means that while the industrialized world was being vaccinated with vaccines produced in India, the country was still looking at approving foreign-made vaccines for use in its country.

    Bottom line. The combination of relaxed safety protocols, the appearance of deadlier viral variants, and poor distribution of vaccines to its people has left the country as the world’s epicenter for the pandemic. As the virus races through its huge population, all of this provides an enormous breeding ground for new variants to arise, which is worrisome even for countries that have had successful vaccine rollouts and have begun to see reduced viral spread. Let us hope this is not a perfect storm for restarting the pandemic with vaccine-resistant variants.

    And India is not the only problem. In Africa, vaccination is also off to a slow start. Just 6m doses have been administered in sub-Saharan Africa, fewer than in New Jersey. Just 1% of African adults have received a first jab, versus a global average of 13%. Prepare for Africa to become the next hot-spot and breeding ground for troublesome variants, if Brazil and South America do not beat them to the punch.

    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.

  • What Is Going On In India?

    The situation. India is in the throes of a second major Covid-19 surge that has hit faster and harder than the first wave did. That is often how viral pandemics behave. This catastrophic second wave came after a strict lockdown of the country in early 2020 following the first wave. In January 2021 India’s Prime Minister Modi declared that the lockdown had succeeded and that they had defeated the virus, and he re-opened the country. Until March, India was recording barely 13,000 new COVID-19 cases a day, fewer than Germany or France, and a drop in the bucket for a nation of 1.4 billion people. A few weeks after Modi’s victory declaration, however, daily cases began slowly climbing, then in late March they exploded, becoming a vertical line rather than an upward sloping curve. By mid-April India reported 315,000 new cases in one day, setting a world record. Yesterday (May 5) India set yet another record with 3700 daily deaths, according to the Johns Hopkins University tracker. The case and death rates are still climbing. Today, almost 50% of the world’s new cases come from India, according to the WHO.

    India has reported 2,000-4,000 COVID-19 deaths a day for several weeks now. Since the country’s health infrastructure is poor, this likely represents a significant undercount of the mortality. As of April 30, the official total death count was around 200,000. However, the official tallies do not reflect the thousands in poor and rural areas who cannot get medical care and die at home and are not counted. For example, in just one day at one crematorium in Bhopal, workers cremated 110 COVID-19 victims, but the official total death toll for the city was just 10. Experts suspect that the total death toll in India is 1-2 million.

    The second wave of the pandemic also has overwhelmed hospitals across India. Securing a hospital bed, even for the critically ill, is nearly impossible. Hospitals put up signs declaring they have no beds, and families in large cities have to search for days to find beds, often hundreds of miles away. Sick people die on the roads outside hospitals and in traffic jams created by ambulances ferrying critically ill patients in search of a bed. There are images of patients gasping for oxygen while waiting to see a doctor.

    Because getting admitted to a hospital is so difficult now, patients who are admitted are much sicker than in India’s first wave. The average temperature readings of second wave patients are 2 to 3 degrees higher than they were during the first wave when temperatures averaged 100-101 degrees Fahrenheit. Blood oxygen levels of recently admitted patients run lower than they did last year meaning the patients are more critical and in greater need of oxygen. The patients are also younger this time around, between the ages of 35 and 45, and often without other pre-existing conditions.

    Critical healthcare necessities are in short supply in India, from intensive care beds, medicine, oxygen, and ventilators. Delhi hospitals have tweeted messages appealing for oxygen. At one Delhi hospital, 20 critically ill patients died after the hospital’s oxygen delivery was delayed seven hours. Families are often told that they have to provide their own oxygen for hospitalized family members or take them home. In a video post, the director of a hospital said they had 60 patients in need of oxygen with only two hours of supply left.

    Help for India has been offered by several countries, including the US, UK, Germany and even from India’s archrival Pakistan, which offered ventilators, oxygen supply kits, digital X-ray machines, PPE, and related items.

    Bottom line. This is a snapshot of what things look like in India now, almost a year and a half after the virus first introduced itself to the world. In January, India believed that its strict lockdown measures had defeated the virus. They did not. How the more deadly second wave of the virus and disease appeared, almost overnight, will be the topic of the next blog post. It should concern all of us, because it could also happen 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.

  • COVID-19 mRNA Vaccines Safe For Pregnant Women

    I have received a few questions about the safety of the coronavirus vaccines for pregnant and lactating women. I discussed toward the end of one blog post about how maternal immunity can benefit the baby by passing the mother’s antibodies across the placenta and given in mother’s milk, thereby protecting neonates whose immune systems are still developing.

    Now, an analysis of the CDC’s Vaccine Adverse Event Reporting System, and the “v-safe after vaccination health checker," and its associated v-safe pregnancy registry, shows that the Pfizer and Moderna mRNA vaccines appear to be safe for mothers and babies. The analysis examined almost 36,000 pregnant women who received one of the mRNA vaccines, and was reported in the New England Journal of Medicine.

    Compared to non-pregnant women, pregnant women who were vaccinated reported more injection-site pain, but fewer incidents of headaches, myalgia (muscle pain), chills, and fever. About 14% of vaccinated pregnant women suffered pregnancy loss while about 9% of neonates born to vaccinated women suffered adverse events, and 3% of them were undersized. No neonatal deaths were reported. The important thing is that the incidence of these outcomes was similar to the incidence observed in pregnant women before the pandemic arose. Most of the pregnant women who were evaluated were vaccinated in the third trimester.

    The study concluded that the data revealed no obvious warning signals for pregnant women who receive the mRNA vaccines. But, it also advised that followup with women vaccinated earlier in pregnancy is warranted.

    Stay tuned.

  • The Coronavirus Condiment Conundrum

    The vexing thing about a novel pathogen and its attendant disease is that we expect it to behave like earlier pathogens and maladies we have experienced. But, sometimes historic diseases poorly predict the new problems that novel pathogens can raise. One such unexpected fallout from the current coronavirus pandemic was that farmed fish were getting too big for restaurant plates as discussed earlier in these pages. Now, the current pandemic has us facing another unpredicted conundrum, a critical shortage of ketchup packets!

    CNN recently reported that restaurants have descended into a mad search for ketchup packets. One Denver tavern owner admitted to purloining ketchup packets from nearby McDonald’s and Wendy’s fast food franchises in order to meet his customers’ needs. Adding to his emergency, the tavern is across from Coors Field, to which the baseball All Star Game has been moved, thanks to Georgia’s new voter reform laws. As a 30+ year Wisconsinite (or “Sconnie” for short) and, thereby somewhat expert in brats, and hot dogs, I offer a suggestion to reduce this ketchup shortage–never, ever put ketchup on brats or hot dogs. Mustard is the proper condiment for these tubes of tasty processed meat. Admittedly, if everyone took this advice it could cause a deficit of that tangy yellow or brown topping and add to our COVID misery. There is nothing sadder than a bare brat, unless it is one slathered with ketchup. Folks in Chicago likely agree. Have you ever seen a Chicago dog with ketchup? It will have a luminescent green relish, but never ketchup.

    This shortage of ketchup packets began last summer when the CDC began discouraging dine-in service at sit-down restaurants and encouraging delivery and takeout instead. Sit-down restaurants coast-to-coast began packing food for people who expected condiment packages with their meals. Suddenly, this packet packing by formerly traditional restaurants competed with fast food places for ketchup packets. As a result, demand went up, prices increased, and supply went down for those little 1/3 ounce packets. That is called economics.

    In response, Heinz, the biggest ketchup producer in the country, just days ago announced it was increasing production of ketchup packets to 12 billion a year. A condiment Warp Speed?

    This ketchup shortage also has fueled an underground market for the old packets you might have hoarded in a kitchen or desk drawer, or baked in your car’s glove box or under the seats. Entrepreneurial diners with a cache of ketchup packets are selling their treasures on eBay and Facebook Marketplace. One Indianapolis entrepreneur sold 20 Heinz ketchup packets for $8 shortly after the Wall Street Journal reported on the ketchup shortage. This too is called economics.

    While all this reflects entrepreneurial principles, it is not exactly an efficient market. The prices in dozens of ketchup-packet listings posted online ranged from a quarter to $5 per packet. The latter was offered in a lot of 20 packets for $100. On eBay a week ago, an acupuncturist from NY posted “Assorted Ketchup packets for Apocalypse Survival,” with a starting bid of 99 cents for three packets. They soon were up to $11.50. Who knew ketchup was essential during an apocalypse?

    What is next–a shortage of relish, mayo, and mustard packets? Maybe sugar and fake-sugar packages? It might not be too late to begin stocking up on condiments in case of an apocalypse. Make sure to store your bounty in a secure place, maybe along with your toilet paper and hand sanitizer.

    Amazingly, people fret about vaccine safety during this ketchup shortage. Who ever heard of a vaccine protecting anyone from an apocalypse?

    Is it time for lunch?

  • 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.

  • Paying The Piper

    In the face of a pandemic caused by a new and deadly virus, states and local governments enact social-distancing measures, bans on crowds, closure orders, and mask mandates in an effort to flatten the curve and prevent health care systems from being overwhelmed with critically infected people. Initially, people are fairly compliant with the order, but, as the days of restriction turn into weeks, then months, compliance wanes. Theater owners complain about financial losses. Clergy bemoan church closures. People argue whether children are safer in classrooms or at home, and many rebel at having to wear face masks in public, complaining that the government has no right to infringe on their civil liberties. Sound familiar?

    But this is not about the 2020-21 coronavirus pandemic; these are descriptions of the US response to the deadly Spanish flu pandemic between 1918 and 1920. In many ways our current pandemic mirrors the one that occurred a century ago, and that is presciently described in the book, The Great Influenza, by John M. Barry. Like CoV-2, the H1N1 “Spanish” flu killed less than 1% of the people it infected, but during a third wave of infection with a more virulent strain, that flu killed more people around the world in just 24 weeks than were killed in the 10 years of WWI and WWII combined! In remote areas with little access to health care, the flu wiped out entire villages.

    Like COVID-19, the Spanish flu pandemic hit hard and fast, going from a handful of reported cases in a few cities to a nationwide outbreak within a few weeks, then with increased mobility due to WWI, it quickly spread around the world, from America to Europe and back. Many communities, responding to the ebbs and flows of the epidemic waves, issued several rounds of closure in an attempt to keep the disease in check. These social-distancing orders worked to reduce cases and deaths. However, just as today, they often proved difficult to maintain. By the late autumn of 1918, just weeks after wide-spread social-distancing orders went into effect, the pandemic seemed to be coming to an end as the number of new infections declined. People clamored to return to their normal lives. Businesses pressed officials to be allowed to reopen. Believing the pandemic was waning, some state and local authorities began rescinding public health edicts. Sound familiar?

    Americans hurried to return to their pre-pandemic routines. In some cities, they packed into movie theaters and dance halls, crowded into stores and shops, and gathered with friends and family for holidays and celebrations. Meanwhile, officials warned the nation that cases and deaths likely would continue for months to come, but the warnings fell on increasingly deaf ears, as people enjoyed a return to normalcy. The nation carried on, inured to the toll the pandemic was taking. But as health officials warned, the pandemic wore on, stretching into a third deadly wave that lasted through the spring of 1919, with a fourth wave hitting in the winter of 1920. Some blamed those world-wide resurgences on careless Americans.

    The different responses and experiences of two large American cities are noteworthy here. In Denver, local business interests lobbied heavily to get rid of the quarantine measures that had shut down schools, churches, libraries, pool halls, businesses, and theaters. The city capitulated. The city opened up and was hammered by the deadly third wave of the flu. On Armistice Day, November 11, 1918, residents poured out of their homes to celebrate the end of World War I. A few days later, many were dead, victims of the pandemic flu. Two weeks later, a headline in the Denver Post captured the devastation: “All Flu Records Smashed in Denver in Last 24 Hours.”  An editorial in the Denver Monthly Magazine said, “For some reason, even the most enlightened citizens will not take the influenza epidemic seriously. They know that it is the most widespread epidemic that has ever visited America. They know the disease is a deadly menace and snuffs out life almost before the victim realizes he is ill. Yet when health officers try to impress upon people the necessity of following essential rules and regulations, the average citizen simply refuses to heed these admonitions.”

    In contrast to Denver, St. Louis enacted and maintained strong social distancing measures, including in-home quarantines for infected people. They experienced a fraction of the deaths that Denver saw. The quarantine measures worked there.

    The similarities in our responses to the 1919-20 flu and 2020-? coronavirus pandemics are noteworthy. But, there is one big, hopefully defining difference between the two pandemics that might make the outcomes quite different. Vaccines. There were no flu vaccines to rescue the world from the ravages of the Spanish flu. In fact, the influenza virus would not even be discovered for another 15 years, and a vaccine was not available until 1945. For the first 12 or so months of the current coronavirus pandemic, we were in the same boat—we faced a novel virus with no vaccine or effective medicine. When there is no available medical response to a pathogen, we must rely on protective public health measures to provide a buffer against the pathogen while we learn how to respond to it.

    Today, we have significant advantages with a much better understanding of virology and epidemiology then we did in 1918. We know that both social distancing and masking work to help save lives. Most critically, we now have multiple safe and effective anti-CoV-2 vaccines that are being deployed, with the pace of vaccinations increasingly weekly.

    Still, the deadly third wave of influenza shows what can happen when people prematurely relax their guard against viruses that can mutate and become more deadly. That is why we must remain vigilant while the coronavirus vaccines roll out. We are still learning about this virus and are only beginning to learn about the variants spawned by the virus. We still need a public health buffer from the virus to keep us safe until we better understand its full capabilities and can vaccinate more people.

    Be smart. Stay safe. Get the vaccine.

  • Vaccine Disinformation

    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.

    There is a lot of misinformation and downright disinformation out there regarding face masks, hydroxychloroquine, ivermectin, the seriousness of COVID-19, etc. Many of these I already addressed in prior posts (see here and here). In this post, I focus solely on vaccine misinformation and disinformation in hopes my unvarnished explanation of the science might help vaccine skeptics make decisions based on facts rather than on disinformation spread by people with an anti-vaccine agenda, or who want to sell you something.

    Several anti-vaccine disinformation themes have been circulating over the past weeks and a friend recently sent me a video by an MD that was full of disinformation and dishonesty. The video was thinly disguised marketing propaganda by Houston-based Dr. Steve Hotze. He is an MD, who does not seem to practice much medicine anymore, but has built an alternative medicine empire that pushes many vitamin and mineral supplement nostrums that he claims is all you need to fight the virus and other diseases. In other words, he advises people to avoid the vaccines and, instead, buy his concoctions. In December 2020, the FDA and FTC sent him a cease-and-desist letter to stop claiming that his supplements can treat diseases, especially COVID-19. The FDA found the products and marketing to be misleading. The FTC found him in violation of interstate transportation laws. I address his several points below, many of which have been echoed by other anti-vaxers.

    • The vaccines do not confer immunity to the virus and COVID-19. There is very much evidence that the vaccines do provide immunity against CoV-2 and strongly protect against COVID-19. That evidence is found in the many reports of antibody production, of T cell anti-viral responses, of cytokine responses to the vaccines, and in recently published reports out of Israel that the vaccines retard virus transmission. Then there are the several studies showing that the vaccines strongly prevent COVID-19 disease. Hotze and others provide zero evidence to back their allegations and ignore data that contradict their points.
    • These are not vaccines, but experimental gene therapies. The mRNA shots from Pfizer and Moderna, and the modified adenovirus vaccines from Johnson & Johnson and AstraZeneca are indeed vaccines. Researchers whittled down the virus genome to the essential viral spike genetic sequence needed to confer immunity. This means that the minimally effective part of the virus genome, rather than the whole viral genome, is used to provide protection from future infection. Old fashioned vaccines grew batches of viruses and then crippled them so that upon injection, they would infect cells, use their genetic information to express all their viral molecules on the cells, but not spread. The current vaccines simply use the genetic sequence for the spike protein, eliminating all other viral genetic sequences. That single genetic sequence is translated into the spike protein that is expressed on your cell surfaces much like what would have happened with an inactivated, whole virus vaccine. Therefore, the current vaccines are no more “gene therapy” than the whole virus vaccine. Both require expression of viral genes in order to alert the immune system.

    Also, the term “gene therapy” conjures images of "Frankenscience." This is wrong. First, vaccines are not “therapy,” which is something that treats a disease after you catch it. Rather vaccines are prophylaxis, which prevents you from catching the disease in the first place. Gene therapy is a still developing field that works to replace, correct, or “knock-out” aberrant genes that cause non-viral health problems.

    Furthermore, as I posted earlier, these vaccines are not experimental or hastily developed. They are based on vaccine platforms that have been over a decade in development, and, in some cases, have been used to develop human vaccines to rabies and Ebola. The only novel thing about them is using the CoV-2 spike protein to drive a protective immune response to subsequent infection with the virus. These spike-protein vaccines have been tested in tens of thousands of volunteers in phase 3 trials, and now have been injected into tens of millions vaccine recipients around the world. The vaccines have been wildly successful at preventing COVID-19, and have been proven to be very safe (see below). These are not experimental vaccines, but well developed, and well tested vaccines.

    • The vaccines alter your DNA. They absolutely do not. It is biologically impossible for them to do that. I discussed this fallacy in a prior post.
    • There is no off switch for the viral gene expression caused by the vaccines. This too is not at all true. No vaccine in history has had its viral genes expressed long term. In fact, your cells continually produce their own mRNA to direct production of cellular proteins that drive cell function. Cells are also full of enzymes called RNases that digest mRNA once it has done its job. Thus, your own mRNA is very short lived in your cells. The same is true for the viral mRNA inserted into cells from an inactivated viral vaccine, from an adenovirus-based vaccine, or from an mRNA vaccine. The mRNA will only last a day or two in your cells before it is digested and permanently disappears. This is the off switch.
    • We do not know about the long-term or delayed responses to the vaccines. Yes we do. First, I challenge people who purport to be worried about long-term effects to name one vaccine that has ever had a long-term adverse effect. As I described above, vaccines are short-lived; their only long-lasting legacy are memory T and B cells that protect you from future exposure to the pathogen.

    On the other hand, delayed adverse effects were a potential concern when the vaccine was being developed as I described earlier, but that has proven to be of no concern. There is a rare adverse response to prior exposure to a pathogen, whether naturally or via vaccine. This is called Antibody Dependent Enhancement (ADE) of the infection. This was seen with the vaccine against the Dengue virus where the antibody response actually enhanced viral infection in new cells. Because of this, all new vaccines to novel viruses are carefully tested for potential ADE effects.

    During the early stages of anti-CoV-2 vaccine development, caution prevailed, and the vaccines were assessed for potential ADE, as reported earlier in these pages. The clinical trials showed absolutely no evidence for ADE. Since then, millions of people around the world have been vaccinated and not a single case of ADE has been found.

    Therefore, concern over ADE was theoretical and never became a practical matter. Anti-vaxers who keep bringing this up as a concern, such as Dr. Hotze, and America’s Frontline Doctors choose to ignore demonstrable facts in favor of continued fear mongering and appealing to emotions. A few countries around the world have begun arresting people for spreading such disinformation that disuades people from being vaccinated, which can lead to deaths caused by the disease.

    • Many people have died from the vaccines. That is flat wrong, and in fact, the opposite is true. In the US, ~550,000 people have died from recognizable COVID-19 while only nine (out of several million vaccinated people) might have died due to vaccine complications (discussed below). The CDC has a Vaccine Adverse Event Reporting System (VAERS) that lists all reported adverse events and deaths that occur shortly after vaccination, whether or not they are caused by the vaccine. Seeing as how tens of millions od people in the US have been vaccinated, unrelated health problems and deaths are expected to occur by chance. If you blew kisses at 50 million people, several of them would die in the next day or two just by chance. The air kisses did not kill them. The trick is to distinguish chance deaths vs possible vaccine-related deaths.

    In order to determine whether a new vax causes adverse health effects, CDC doctors look for recurring patterns. If they see a pattern of similar types of death in certain people they pay closer attention to that group and even back off vaccinating them. With one extremely rare exception with one of the current vaccines as discussed below, these kinds of patterns have not been seen with the current vaccines.

    • The COVID vaccines will not eradicate the virus any more than flu vax eradicates flu. This statement by Hotze and others is either dishonest or they are ignorant of basic virology. It ignores the fact that flu rapidly changes every season, making it very hard to eradicate. The statement also ignores the facts that small pox has been fully eradicated by vaccines, and that in the US measles and polio have been eradicated—the only cases we see here come from overseas. Whether or not the COVID vaccines can eradicate CoV-2 depends on how well they work against the viral variants, how quickly the variants arise, and how many people are vaccinated in the next few months.
    • Herd immunity caused by natural infection is better than the vaccine. This statement too betrays ignorance of the disease and of vaccinology. Natural immunity to CoV-2 comes with the cost of many deaths and with many more people suffering long-term health problems caused by COVID-19. Again, the vaccines have not been linked to deaths or to lasting health problems. Vaccines are used to confer herd immunity without running the risk of the deadly consequences of the disease. By all measures, the vaccines confer significant protection against the disease and are more reliable than natural immunity where you cannot ensure a uniform level of infection and immunity for everyone.
    • Companies are reaping great profits off their lies. Pfizer and Moderna and other vaccine producers are providing the vaccines at cost during the pandemic. They are not profiting from them. Also, Moderna has announced it will not enforce its patents on its vaccine platform, but will share its technology with other companies and researchers during the current pandemic. In contrast, Dr. Hotze and others clearly are using the pandemic for their profit.
    • Companies are withholding raw data on their vaccines. Raw data for the approved vaccines was shared with two CDC committees consisting of scientists, vaccinologists, pathologists, epidemiologists and statisticians. That raw data was the basis for the emergency authorization of the vaccines (see below). Generally, raw data are only released to CDC and FDA and not to the public. What is released to the public are data summaries in the form of peer-reviewed journal publications and these are coming out and will continue to come out over the next few years.

    The above are points Hotze has made and that are often repeated by other anti-vaxers. Below, I address other criticisms and questions about the vaccines that I have heard others, but not Hotze raise.

    • The vaccines are not FDA approved. Well, I wonder then who gave the vaccines Emergency Use Authorization (EUA)! True, EUA is not full FDA approval, but EUA approval still comes from 30 FDA experts after a rigorous evaluation of all existing data for efficacy and safety. That is well above the 2-3 experts that typically review science papers for peer reviewed publications. The EUA approval for each vaccine was based on data from about 40,000 subjects enrolled in the late stage clinical trials. Since then, millions more people have been vaccinated and their data continues to be collected and reviewed. Recent reports of this "real world" data continue to support the great safety and efficacy of the vaccines.
    • Some vaccines are better than others. The Pfizer and Moderna mRNA vaccines, which were the first tested and approved, showed ~95% efficacy, while the Adenovirus-based Johnson & Johnson vaccine, which was later tested and approved, only showed around 70% efficacy. So, shouldn’t we favor the Pfizer and Moderna vaccines? No. All the currently approved vaccines, including the J&J one, are very effective. And it is impossible to compare the relative efficacy of different vaccines from data obtained in separate trials. In order to gain an accurate comparison of different vaccines, they need to be tested in head-to-head, controlled trials in order to assure that similar patient populations are being tested against the same viral variant. For example, the Pfizer and Moderna vaccines were tested before we noticed viral variants that seem to be more infectious than the original virus. And neither company tested their vaccines in South Africa where one of the more infectious variants is rampant. In contrast, J&J began testing their vaccine after the variants began spreading around the world, and they also tested their vaccine in South Africa. This means that the Pfizer/Moderna vaccines were tested against different strains of the virus than the J&J vaccine, which confounds comparing their relative efficacy.
    • Bill Gates is promoting vaccines so he can inject us with microchips to track us. [big sigh]…Yeah, and one of the America’s Frontline Doctors, a group that claims hydroxychloroquine can cure COVID-19, said there is alien DNA in some of our medicines. I don’t waste my time with tinfoil-hat comments.
    • The vaccines cause infertility. This is based on bunk-science that began circulating last December. That rumor was solidly debunked by several sources, but the meme has been repackaged into new messages about de-population strategies. I give this the same attention I give to the silly notion that Bill Gates is trying to use the vaccines to microchip us. The vaccines do not cause infertility.

    But, what about nursing mothers? Will the vaccines affect their babies? The answer is yes, but in a good way. Since babies are born with a very immature immune system, their first line of defense against pathogens comes from their mother’s antibodies that cross the placenta and that are found in mother’s milk. This “passive immunity” is an important first line of immune defense for newborns. Lactating women who have been vaccinated do show anti-CoV-2 antibodies in their milk, which provides the newborns with a temporary defense against the virus. That is a good thing.

    • The AstraZeneca vaccine causes blood clots. Over the past few weeks, 25 patients in Europe, almost all women under the age of 55, who received the AstraZeneca vaccine developed rare blood clots and nine died. The European Medicines Academy (EMA) met to review the data and found that overall clotting in vaccine recipients was less than in the general unvaccinated population. However, there are different clinical types of blood clotting problems, and for two very, very rare types, it was expected that ~2 clotting cases would arise by chance out of the ~20 million vaccinated people. But, 17 cases were reported. This is the kind of adverse event pattern that public health officials look for, as I described above. Again, exercising an abundance of caution, more than 20 European countries paused using the vaccine. However, within a week, the WHO and the EMA had reviewed the data and found that the extremely rare risk of vaccine-associated blood clots was significantly less than the risk of serious health problems from COVID-19 disease and advised that the vaccine be continued.

    Final words. The disinformation about the anti-CoV-2 vaccines is disheartening, but seems to have been spawned by the roundly discredited claims by Dr. Andrew Wakefield a few years ago that the MMR vaccine was responsible for autism in kids. For that fraudulent reporting, Dr. Wakefield's paper was retracted and his medical license was taken away. Sadly, the damage was already done and continues today against all vaccines. Vaccines are one of the greatest health protection tools in the healthcare tool box and the naysayers are indeed killing people with their illogical and emotional appeals that are bereft of facts. How to counter such disinformation was a topic in a very recent article in Scientific American. What they recommend is beyond the scope of this post, but I hope that my presentation of the facts and reasoned criticism of anti-vax rhetoric is a step in that direction.

  • 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.