Seen Vax?

    With vaccines and reverse technology in the news so much, it can be difficult to keep up with who and what is leading the pack regarding the fight against this novel coronavirus and the search for a vaccine; and yes, there is a LOT of bad information out there mixed in with the good.  As The Conversation warned: It’s an increasingly important skill to identify between reliable and unreliable sources.  Social media is often superficial and prone to spreading misinformation.  On the other hand, journal articles and clinical trial registries can be hard to interpret for anyone except specialists...Seek out publications with editorial oversight and a track record of reliable scientific and medical reporting.  Reading more than one interpretation can help you get a balanced view.  It’s also important to ask where a journalist found the information they are reporting on.  Referencing results published in peer-reviewed journals is a good sign – it shows some rigorous fact checking has occurred.  Be careful if an article’s main sources seem to be preprints (papers not yet peer reviewed) or other so-called grey literature, such as press releases or company reports.  Likewise, be careful if the main source seems to be interviews or quotes from people with PhDs or impressive sounding job titles.  A quote from a scientist in an interview is not equivalent to a quote from the same scientist in a peer-reviewed academic paper.  

    All that being said, many traditional websites DO have updated and reliable information, not only about the coronavirus itself but on what vaccines are currently leading the pack and the many ways that they vary in their approach to efficacy.  Nonetheless, even after attempting to sort through some of the mess I still had a few questions of my own such as how do the vaccine makers decide who gets what; has the virus mutated; why are we still wearing fur (related to the previous question); what the heck is mRNA (the most common variety of vaccine being explored by Pfizer and Moderna); how many of these vaccines have been tested on children; has Moderna ever had a drug approved by the FDA; how much money is being spent on all of this; and is Medicare or Medicaid required to purchase any or all of the vaccines?  

     Blah, blah, blah...so many questions and yet it would seem that everywhere you look there's an "answer," including those on the posts of Facebook and Parler, so please note the cautionary tale from above.  What follows should be considered as just one of the many mini-guides to this ever-changing labyrinth.  Fasten your seatbelts, proceed with caution, and above all think of this as only a starting point...do your research, especially if you're considering rushing out to get a Covid-19 vaccine.

   1) A good overall summary of recent developments in the vaccine race is from The Conversation article mentioned above.  In part, it helps to explain what's involved in the process in developing a vaccine and said in part: Historically, pharmaceutical companies have been able to suppress negative results, but it’s now legally required for all trials to post their results so that other scientists can review them.  As a consequence the sector is generally far more trusted than it used to be, although we should still be cautious if only interim results are being reported...Trials will also have several secondary research questions, but answering these is not considered a mark of success.  If you test enough different objectives, a few will always be met due to blind chance.  Misrepresenting trial data in this way is a form of research misconduct called p-hacking. You can find out the primary and secondary objectives of any trial by checking a clinical trial registry.  Again, it is important to consider whether these are interim results. Although such results can be promising – as Pfizer and Moderna have shown – they are not guaranteed to be the final result.  

    Scientists are asking for more such data before the FDA issues emergency approval, something that so far has not been provided.*  Said National Geographic of the 94-person initial study (Pfizer has now completed it 60,000-person study while Moderna has completed its 30,000-person study):  Several experts say they’re concerned that the public is getting an incomplete picture about the vaccine’s success that doesn’t reveal critical information, such as which demographic groups it protected and whether it was from a mild or severe form of the virus.  There’s also the real possibility that the 90-percent figure could change as the trial ticks on and investigators collect more results.  Plus, the unpublished results have not been peer-reviewed or even released as a preliminary preprint.  “The lack of data is very concerning,” adds Peter Doshi, associate professor of pharmaceutical health services research at the University of Maryland School of Pharmacy.  “All we have right now is a headline by Pfizer.”  

    2) That being said, the FDA will stop its inspections of the manufacturing facilities of those vaccine makers who are seeking Emergency approval (that would include Pfizer and Moderna).  Said Bloomberg: The U.S. Food and Drug Administration inspects a few thousand drug manufacturing plants every year to ensure their standards are up to par.  Many of those inspections are required before a pharmaceutical company can gain approval of a new drug.  They serve as a check on whether drug makers can produce quality therapies.  But that won’t be the case for Covid-19 vaccine developers that gain emergency authorization of a shot.  FDA regulations don’t require what’s known as a pre-approval inspection for products seeking emergency use, said Jerry Weir, director of the Division of Viral Products in the FDA’s vaccines office.  Weir spoke last week at a meeting of FDA advisers to discuss standards for Covid-19 vaccines.  Before approval, FDA inspections ensure compliance with regulations.  Once a product is being made—as vaccines already are to get them out as quickly as possible—they can uncover quality breaches and assess whether pharmaceutical companies handled them correctly or are possibly downplaying or ignoring serious issues.  Take Eli Lilly, for example.  In less than a year, the FDA twice found questionable conditions in inspections of Lilly’s New Jersey plant that’s producing its experimental antibody treatment for Covid-19.  Pfizer is the frontrunner in the race for a coronavirus vaccine, and Moderna is just behind.  Moderna was founded in 2010, according to its website, and has yet to gain FDA clearance of a product.  An FDA database shows the company has never been inspected by the agency.

    3) And if you're wondering about the differences among the 150 vaccines currently under development, this abbreviated guide from National Geographic helps to break down some of the confusion: ...some vaccines use the whole coronavirus, but in a killed or weakened state.  Others use only part of the virus—whether a protein or a fragment.  Some transfer the coronavirus proteins into a different virus that is unlikely to cause disease or even incapable of it.  Finally, some vaccines under development rely on deploying pieces of the coronavirus’s genetic material, so our cells can temporarily make the coronavirus proteins needed to stimulate our immune systems.  Yes, it's confusing but it should be noted that the latter mRNA method (or messenger RNA) used by both Pfizer and Moderna, has never been used to make a human vaccine, said Bloomberg.  Another quick summary in explaining how vaccines already in use such as polio, rabies, and shingles use different methods came from TIME.

    4)  And how much money are we talking about?  Reported STAT: Major companies are racing to find a Covid-19 vaccine, but their political action committees have cut roughly 4,500 checks this election cycle alone, totaling roughly $11 million for 356 individual Congress members.  One result is the Warp Speed confusion, a White House program that initially sent $10 billion to 6 companies, with an additional estimated $8 billion left to purchase vaccines and Covid-19 treatments.  To take one example, Daniel O'Day, Gilead's CEO who personally visited the White House to discuss his drug (the company has long made remdesivir) said that since their shelved drug reduced a hospital stay by four days that it was worth $48,000 per dose (Trump was treated with the drug).  Said Rolling Stone, the Institute for Clinical and Economic Review noted that when it came to producing remdesivir: ...it costs just $10 of raw materials to make each dose of remdesivir.  Generic-drug producers in Bangladesh and India were already making a version of it, and their price per course of treatment was $600.  Meanwhile, Gilead’s own price for governments around the world  --the price it settled on for everyone except American private insurers-- was $2,340 per treatment...the U.S. pays $3,120 per does, according to Wired.  Trump ordered the U.S. to purchase 500,000 doses of remdesivir.  The World Health Organization has come out against the use of the drug to treat Covid-19, said STAT.  

    Earlier in the month, the White House also purchased $375 million of Eli Lilly's equally controversial** antibody treatment; said Bloomberg: The Trump administration has aggressively corralled doses of coronavirus antivirals and experimental vaccines—even malaria drugs that have since shown to be ineffective against the infection.  But in this case, the U.S. can’t snap up all of Lilly’s supply.  Initially, the deal will allow the U.S. to procure 300,000 vials of the antibody, if it’s authorized.  But Lilly’s keeping additional vials at arm’s length...The broader monoclonal antibody class, which includes Regeneron Pharmaceuticals’ therapy that President Trump received, has been called a  “bridge to a vaccine.” ...The U.S. deal implies a top-end price of about $1,250 per dose. 

    Moderna has said that it would price its vaccine between $32 and $37 per dose (two will likely be needed), while Pfizer has announced a target price of just under $20 per dose...multiply that even 1/3 of the world's population and the potential profits seem obvious.  Warp Speed is awarding much of this funding as "no-bid contracts" which is proving concerning to some in the industry; said STAT: Some announcements have raised questions about the government’s procurement process and its methodology for awarding no-bid contracts.  Before the Covid-19 pandemic, ApiJect had only manufactured its prefillable syringe in prototype form and limited quantities.  And the company’s own executives have acknowledged there’s no precedent for using the technology en masse — especially not during a pandemic.  Prefillable syringes “have to be precisely manufactured under the right conditions,” said Irwin Redlener, the director of the Pandemic Resource and Response Initiative at Columbia University.  “It’s really unconscionable that a small company is being given this kind of responsibility.”

    5) How will taxpayers pay for the cost of the treatments or hospitalizations (the fact that many hospitals may be facing the possibility of bankruptcy is an entirely different story, said Bloomberg), and who will get the vaccine first?  Said the earlier piece in TIME: Even once countries receive their allotted doses, deciding which people should be immunized first raises additional ethical and practical challenges.  In the U.S., the National Academies of Sciences, Engineering and Medicine released a draft of prioritization guidelines in September, proposing four tiers of vaccination groups.  The first wave of vaccinations would be for high-risk populations including health care workers, people with existing health conditions such as obesity, asthma and heart disease, and the elderly in group living conditions.  Next come “critical risk” workers, teachers, older adults, people in group homes, and the incarcerated; then young adults and children; and finally, the rest of the nation (yes, prisoners are scheduled to be vaccinated ahead of the general public).  

   And all of that rests on the basic decision of how many people will decide to even take the vaccine; at this point only about 50% of the country will do so said MarketWatch.  This downward trend could be reflected in the anticipated drop in the number of childhood vaccines being administered overall; said STAT: The number of measles cases in 2019 were the highest in 23 years, according to new estimates from the WHO and CDC.  There were nearly 870,000 cases worldwide last year, and deaths from the disease --roughly 207,500-- were up nearly 50% since 2016. The report's authors attribute these startling totals to children not being vaccinated with both the recommended doses of the measles vaccine. Coverage rates have to be at 95% for both doses in order to prevent outbreaks, but the rate for the first dose has been stagnant at around 85% for the past decade, and despite gains for the second dose, the rate is still only at around 71%.  

    What's concerning about the Covid-19 vaccine is that none of the testing so far has included children; said the American Academy of Pediatrics, 1 in 10 people who test positive for Covid-19 is a child.  As far as the cost of distributing such vaccines, states are only now recognizing the mounting expenditures that will be required; said Bloomberg: Virginia estimates it will need about $2.5 million to buy freezers, thermometers, and equipment to transport the vaccine, among other hardware.  It includes another $71 million to help local health districts set up vaccination clinics, with staff, facility rentals, travel and other costs.  Those numbers are sure to change as new details emerge, such as the federal government paying for 6.6 million ancillary supply kits.  Virginia has received about $5.4 million of federal funds geared toward the planning effort.

Farmed mink.  Photo: The Guardian

    6) What else?  As you've read above, different vaccines will mean there'll be different storage and transportation issues; the mRNA vaccines need sub-zero temps (from -4F to -94F) to stay viable, which means your hospital or clinic has to have freezer units capable of keeping those temperatures, not to mention workers needing heavy freezer gloves to handle the dry ice or the vials.  And questions emerge about how long the vaccines will remain viable, not only in their vials but also in your body?  Some estimates are that "immunity" or resistance in your body may prove little longer than 3 months (almost all vaccines in development will require a person to have 2 doses spaced three weeks to a month apart). 

    As Smithsonian noted: "If a vaccine has a two-year shelf life at refrigerator temperatures, then the manufacturer actually needs to put the vaccine at that refrigerated temperature for two years and see if at the end the product is still effective," says Debra Kristensen to NPR.  And what about side effects, asked Bloomberg.  More importantly, can the virus mutate from other animals as was recently discovered in Denmark and other countries from its mink farms (Denmark has already begun the killing of all 17 million minks on its farms)?  Said Bloomberg's New Economy letter: The next virus to jump from animals to humans could be far deadlier.  Humanity was relatively lucky this time: Covid-19 has a so-called attack rate—the probability of at-risk individuals falling ill—of no more than 3%.  What percentage of the population could the most virulent virus infect?  Up to 100%, said Wang Linfa, director of the Program in Emerging Infectious Diseases at Duke-NUS Medical School in Singapore.  Estimates are that 1.7 million viruses still wait to be identified. 

    As you can gather, it's far bigger a picture than originally imagined.  Limited studies are only now being completed and none of them have any long term results.  What, if anything, will be the effects on your body a year from now?  Will one vaccine be better than another, or will there be specific vaccines targeted just for the young or the elderly (from the CDC: the Fluzone high-dose flu shot for those over 65 contains 4x the normal dosage of antigens, which shouldn't be confused with Fluad's MF59 adjuvanted vaccine that's also given to the elderly...what??)  

    Eighteen percent of our gross domestic product is spent on health care (the most of any country in the world), and yet the U.S. allocates less than three cents of every dollar of that spending to public health.  Will this change, and if so, will the public go along with it?  If we can't even agree on wearing or not wearing masks, will we agree on being vaccinated against Covid-19?  And what if a new virus arrives, or if the Covid-19 virus adapts to our bodies as easily as bacteria does...what then?  Scientists feel that our warming planet is unearthing systemic changes to a world we once felt was so stable.  

    It's a scary time, so no wonder people appear to be flocking back to the world of Rod Serling and his creation, The Twilight Zone.  A review in The New York Review of Books summed up his world (and perhaps our world now) as being a time that: “was a daydream of gleaming chrome, bright white smiles, and bleach-blond hair.”  But behind them were “strange monsters, quivering with fear and anger.  Serling was able to see those monsters walking in broad daylight,” and he invited them into America’s living rooms.

*As of 11/21/2020, Pfizer finally did release it data for outside study; Bloomberg put it this way: The FDA staff will be combing through Pfizer’s raw data, which the public doesn’t have access to, rather than relying on the company’s own results to determine the safety and efficacy of the vaccine.  The agency and Pfizer will each summarize their findings for the advisory panel...And the FDA isn’t the only U.S. agency that needs to consider the vaccines.  Another group of advisers for the Centers for Disease Control and Prevention also must meet on the vaccine and make recommendations as to who should be first in line to get it.  The timing of this meeting is unclear.  

    To be fair to Pfizer, it took no money from the initial Warp Speed government funding (although its partner firm BioNTech took $445 million from the German government): “I wanted to liberate our scientists from any bureaucracy,” Pfizer Chief Executive Officer Albert Bourla said in an interview on CBS’s “Face the Nation” on Sept. 16.  “When you get money from someone, that always comes with strings.  They want to see how we are growing to progress, what types of moves you are going to do.  They want reports.  I didn’t want to have any of that.”  Before you applaud Pfizer (Moderna DID take the funding). Bloomberg added this comment: What the U.S. has done is commit to buying hundreds of millions of vaccines in advance to ensure Americans were among the first in line if the shot clinches an emergency-use authorization or approval from the regulators.  The Trump administration agreed in July to pay almost $2 billion for 100 million doses, with an option to acquire as many as 500 million more, once it is cleared.  Put another way, Warp Speed put down a payment for product, rather than making an investment in research.

**Said STAT on 11/11/2020: The FDA on Monday gave emergency use authorization to Eli Lilly's monoclonal antibody treatment for Covid-19, but the decision has left physicians confused about the best dosage for patients.  The agency gave the green light to a 700-milligram dose of bamlanivimab in patients older than 12 who have serious infection but haven't yet been hospitalized.  But data released in September showed that a 2,800-milligram dose was beneficial, compared to two other doses of 700 and 7,000 milligrams.  Even then, the finding seemed like a fluke because most patients, even those receiving a placebo, cleared the virus after 11 days, anyway.  Experts are now speculating whether the government opted for the 700-milligram dose because the drug is in short supply.  Operation Warp Speed therapeutics head Janet Woodcock said the lower dose also helped reduce hospitalizations.  "You don’t want to give more of a drug than you need...I think you could probably go lower, frankly,” she said.