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It’s Been Quite A Week — Here Are Some Things You Might Have Missed

Saturday, October 24th, 2020

From the Department of There’s No Accounting For Stupidity

Since 1980, the population of Idaho has grown from about one million to nearly 1.8 million, considerably outstripping the rate of growth of its neighbors Montana and Wyoming. Over the last 14 days, all three states have seen large spikes in Covid-19 cases, according to the New York Times’s Covid Map and Case Count. And they’re not alone. All the Midwest and Pacific region states are seeing similar surges. Their governors are faced with balancing increased restrictions with the personal freedom inherent in pioneering individualism.

Nowhere did this daunting task become more evident than Thursday in Idaho, a state that has seen a 55% rise in cases in the last two weeks and where, minutes after hearing local hospitals were approaching full capacity necessitating moving patients to Seattle, of all places, the regional health board voted to repeal the local mask mandate.

The regional board, composed of seven appointed members with no requirement to have any medical experience, voted 4-3 to end the mandate. Health District epidemiologist Jeff Lee had just finished describing how the state’s hospitals were becoming “overwhelmed” by the surge in cases. For example, even after doubling up patients in rooms and buying more hospital beds, the hospital in Coeur d’Alene had reached 99% capacity. But, not to worry, it’s just an eight hour, 493 mile ambulance ride from Boise to Seattle.

“We’re facing staff shortages, and we have a lot of physician fatigue. This has been going on for seven months — we’re tired,” Lee said.

He introduced several doctors who testified about the struggle COVID-19 patients face, the burden on hospitals and how masks reduce the spread of the virus. But that didn’t matter to the Board’s majority who just did not see the sense in masks, no matter what the experts said.

To put a period on the “Health” Board’s meeting, member Allen Banks got to the heart of the matter by denying the existence of Covid-19. Lecturing the medical professionals who testified, he said, “Something’s making these people sick, and I’m pretty sure that it’s not coronavirus, so the question that you should be asking is, ‘What’s making them sick?”

That penetrating question came from a gentleman with a Ph.D. in chemistry from the University of Colorado, who for 30 years has worked in medical research in biotechnology and pharmaceutical development.

Dr. Banks would make a wonderful addition to the White House Coronavirus Task Force.

How cold is cold enough?

Have you stopped to consider the logistics of delivering upwards of 200 million doses of a future Covid-19 vaccine? That’s a lot of syringes. If you laid them end to end they would stretch from the North Pole to the South Pole, about 13,000 miles.

And the vaccine would have to be kept cold, very cold. Just how cold you ask? Try minus 103 Fahrenheit. That’s nearly four times colder than your home freezer, colder even than Antarctica in the dead of winter.

This is a complex challenge. For months, manufacturers, federal and state governments, and large health care systems have been quietly planning how to navigate this ultra “cold chain” that stretches from vaccine manufacturers to hospitals, nursing homes, doctors’ offices, and many far-flung clinics. Now that Pfizer has announced it plans to apply for emergency-use authorization designation in late November for its vaccine currently in Phase 3 trials, solving the cold problem becomes more urgent.

The nation’s governors wrote the Trump Administration last Sunday expressing concerns about the supply of ultracold freezers and dry ice — already experiencing shortages. Pfizer says it has developed specially designed, temperature-controlled shipping packages, using dry ice, to keep its vials at roughly minus 103 below Fahrenheit for up to 10 days. But what happens if the doses are not used in ten days? This is what is confounding the governors.

This issue is even more difficult than it appears, because the vaccines of both Pfizer and Moderna, another leading vaccine developer in Phase 3 trials, require two shots within 21 and 28 days, respectively. The situation is eased somewhat, because Moderna’s vaccine, at around minus 4 Fahrenheit, does not require the same ultra-cold storage temperature as Pfizer’s.

Might be a good time to buy stock in a maker of dry ice.

High Deductibles: Another nail in the rural hospital coffin

Since 2010, more than 130 rural hospitals have closed, 15 thus far in 2020. One mostly overlooked reason is the health insurance deductible. Depending on the plan (employer-sponsored, ACA Marketplace, etc.) a family deductible can range from $0 (but the out-of-pockets are huge) to well over $8,000.

Families in rural communities often face deductibles in the $2,000 to $4,000 range. And when family members require hospitalization, it often happens they cannot pay the deductible. Rural hospitals are forced to eat this less than tasty bill, send it to a collections company, or set up a payment plan with the patient. They prefer the payment plan route, but this significantly delays getting the money, and the bill is often reduced because of the patient’s economic circumstances. So, the hospital goes further in the red and its patients go further in debt. The pandemic has only exacerbated this problem.

Just another example of our nation’s dysfunctional health care “system.”

How to get rid of an irritating federal employee

Despite a great swath of the public thinking otherwise, federal employees can be fired, although it is true that this happens rarely. Of the 2.1 million federal employees about 10,000 are terminated annually, according to the Merit Systems Protection Board (MSPB).

Firing a federal worker is similar to what would occur in the private sector, with one twist. In both settings, best practice recommends, and the federal system requires, the three step verbal warning, written warning, termination process. The twist comes after that. Federal employees can appeal to the MSPB, and the appeals can take a long time to adjudicate.

This past week, the Trump administration threw an interesting log on the fire when the President issued an Executive Order stripping long-held civil service protections from employees whose work involves policymaking. This will affect tens of thousands of workers, and will reduce them to being, for all practical purposes, “at will” employees, meaning they can be fired for cause or not for cause at a moment’s notice.

Under this order, federal scientists, attorneys, regulators, public health experts and many others in senior roles would lose rights to due process and in some cases, union representation, at agencies across the government.

These are not politically appointed employees who require confirmation to their positions, whom the president can terminate or have terminated by whim. Rather, they are professionals who serve as a cadre of subject-matter experts for every administration. I will let you consider the possible ramifications of this Executive Order, which to me seem profound. The Order, while not affecting a majority of the government, could upend the foundation of the career workforce by imposing political loyalty tests.

It is possible, with less than two weeks before election day, this may be more symbolic than real, because the Order requires agencies to indicate employees who would be affected by 19 January 2021, a day before the next inauguration. If Joe Biden wins the election he would be unlikely to follow through on the president’s order. But if Donald Trump is re-elected, this tectonic Order will monumentally reshape the federal service.

Think about that. Please.

 

 

 

 

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COVID-19 Analysis from Jennifer Christian, M.D., M.P.H.

Monday, September 21st, 2020

I have written before of my great admiration for Dr. Jennifer Christian and for her Work Fitness and Disability Roundtable (WFDRoundtable@groups.io). The Roundtable is a mainstay for clinicians and other health care professionals.

I thought this morning’s Roundtable post by Jennifer to be particularly thoughtful and thought-provoking, so I asked her if she would allow us to republish the post in its entirety here at the Insider. She very kindly gave permission.

I think Jennifer is one of those brilliant three or four folks I’m lucky enough to know who think around corners. Her mind makes intuitive leaps where others (like mine) plod along.

Here is Jennifer’s post:

How many people have some pre-existing immunity to COVID-19

There is growing uncertainty about what this fall and winter is going to look like with regard to the COVID-19 pandemic.  Are we going to have a second, and possibly even bigger wave of worldwide infections — or is the biggest part of this pandemic over and done with once each geographic area has had its first wave?

A new review from the British Medical Journal says researchers may have been paying too much attention to antibodies and too little attention to a second part of the human immune system that protects against and reacts to infections:  T cells.   More on this in a moment…..

But first, a reminder.  We are in the middle of the first large-scale pandemic with a new and highly contagious respiratory pathogen since the field of immunology was born!   Immunology is still quite young compared to other specialty areas in biological science and medicine.  It was only in the mid-20th century that advances in cell biology started making it possible to study the detailed processes that make up the immune response in detail.  That has led to much deeper understanding of the mechanisms by which vaccines work, to the development of the first cancer chemotherapy agents that selectively killed rapidly-proliferating immune cells, and to the development of immune-modulating drugs, which enable the transplantation of organs by muting the body’s natural rejection of foreign tissues.

The appearance of HIV/AIDS in the 1980’s again precipitated huge leaps in funding for research to increase our understanding of the immune system, which in turn highlighted the function of T cells and other previously unrecognized aspects of it.   However, in comparison to other bodily systems and organs, our knowledge of the human immune system is still primitive — it’s obvious there is much left to learn — and some of what we don’t know may seem very basic!

If you’re an immunologist, virologist, epidemiologist — or a public health officer trying to figure out how to protect and guide your local population — this is the overwhelming challenge of a lifetime.  Personally, I hope that the media and the general public will remember that this pandemic has attacked our society at the very edge of what is known.  All of those professionals are working at a feverish pace to observe carefully, assemble enough data to be confident they have enough to detect a real pattern if it’s actually there, make sense of what they are seeing, and then figure out the implications for action.  Let’s agree to be forgiving of the fact that “the facts” have not all been revealed to us yet, and “the scientists” simply don’t yet know everything we wish they did.

Back to the T cell story.   Researchers have shown that people with the most severe cases of COVID-19 (the ones in ICU and who are most likely to die) often have low T cell levels.  But some other puzzling data has appeared. For example:

  • some countries — and especially some areas within those countries that had bad initial outbreaks — have not seen widespread new infections despite having relaxed protective restrictions; and,
  • blood tests in a noticeable fraction of people with no record of exposure to SARS-CoV-2 virus show some of the T cells reacting weakly to it anyway — indicating a potentially partial immune response.

This has led scientists to start wondering whether we really know enough about the human immune system’s ability to develop partial T cell “cross-reactivity” to families of closely-related viruses and whether that might predictably and reliably reduce the severity of illness or even reduce the likelihood of getting ill at all when a new-but-related virus appears.   And, that, of course, raises some possibilities that need to be investigated:

  1. Does cross-reactivity explain why some geographic areas that had first pandemic peaks are not seeing second ones — because the people who got sick had no immunity and were more susceptible, and most of the remaining ones have some limited immunity which is protecting them?
  2. Does cross-reactivity explain some of the disparity between people who get deathly sick from COVID-19 and people who are exposed to the virus but never get infected, or, if they do, remain asymptomatic or have only mild illness?  Note that there are two  possibilities:  Cross-reactivity could be making the illness worse or it might be making it less severe — we don’t know yet.
  3. How could cross-reactivity be protective if it develops after prior exposure to coronaviruses, because children are the least likely to get a severe case of the disease and adults are the most susceptible to severe COVID-19 illness and death?  (Children have not had a lifetime of colds, and thus less opportunity to be exposed to coronavirus and develop partial-immunity to SARS-CoV-2)

In short, my best advice as of 21 September 2020 is:

  1. Stay tuned for further developments in the factual realm – both changes in case counts and new research results;
  2. Hope for the best but prepare for the worst as autumn approaches and we all retreat indoors.

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Sisyphus Must Have Felt Like This

Wednesday, September 16th, 2020

The COVID-19 boulder, full of facts, lies, information, misinformation, disinformation, and just plain delusional thinking keeps rolling back down the mountain. Try as we might, it’s certainly difficult to make sense of COVID-19. But we keep trying, anyway. As in:

Unions during COVID-19

I have written previously about the perplexing case of union participation in America. In 1960, about a third of hourly workers belonged to unions. In January of this year, the BLS reported that number had dropped to 10.3%. Yet, in the same press release, the BLS reports:

Nonunion workers had median weekly earnings that were 81 percent of earnings for workers who were union members ($892 versus $1,095).

Right now we won’t get into why this puzzling paradox exists, except to say we now have another log to throw on the pyre.

A new study authored by researchers at George Washington University, the University of Pennsylvania Perelman School of Medicine and the Boston University School of Medicine, published in Health Affairs, found that having a unionized workforce at a nursing home greatly reduces the likelihood that residents or staff will die from COVID-19. From the study’s Abstract:

Health care worker unions were associated with a 1.29 percentage point mortality reduction, which represents a 30% relative decrease in the COVID-19 mortality rate compared to facilities without health care worker unions.

The study analyzed data from more than 300 nursing homes in New York from March 1 through May 31. The authors conclude the unionized health care workers in the nursing homes were able to negotiate for more PPE, higher pay, and better working conditions.

During the pandemic, New York has suffered nearly 7,000 nursing home deaths, more than any other state except New Jersey.

My take on this? If you have loved ones who may be headed for a nursing home, it might be a good idea to ask if the staff is unionized.

Avoiding medical care during COVID-19

Since early in COVID-19, we’ve known that many people, fearful of the disease, have put off getting routine, or, in some cases, emergency medical care. What we have not known is what demographic groups are doing that and to what degree. Now, the CDC has put a full stop period to that issue.

In its 11 September weekly Morbidity and Mortality Report, the CDC published a comprehensive analysis concluding 40.9% of U.S. adults delayed or avoided medical care as of June 30. This includes urgent or emergency care (12%) and routine care (32%). Regarding what population segments are doing this, the study had this to say:

The estimated prevalence of urgent or emergency care avoidance was significantly higher among the following groups: unpaid caregivers for adults versus non-caregivers (adjusted prevalence ratio [aPR] = 2.9); persons with two or more selected underlying medical conditions† versus those without those conditions (aPR = 1.9); persons with health insurance versus those without health insurance (aPR = 1.8); non-Hispanic Black (Black) adults (aPR = 1.6) and Hispanic or Latino (Hispanic) adults (aPR = 1.5) versus non-Hispanic White (White) adults; young adults aged 18–24 years versus adults aged 25–44 years (aPR = 1.5); and persons with disabilities§ versus those without disabilities (aPR = 1.3).*

So, Mary, taking care of her aged mother at home, foregoes either emergency or routine care at nearly three times the rate of Sarah, her next door neighbor who is not burdened with an aged relative, because she doesn’t want to bring COVID-19 home to Mom. Even more troubling is that people with two or more co-morbidities forego care at nearly two times the rate of people without such underlying conditions.

The CDC’s paper advises that, “… urgent efforts are warranted to ensure delivery of services that, if deferred, could result in patient harm.”

Enough said.

*By way of example for the statistically challenged, an adjusted prevalence ratio of 2 means that the prevalence of cases among a study group is 2 times higher than among the control subjects. It’s calculated through a series of regression analyses. There. Now you know.

U. S. life expectancy

COVID-19 has sucked all the air out of any national attempt at healthcare reform, while revealing in sharp detail the foundational flaws in the current system. Eventually, however, America is going to have to confront this issue in a meaningful manner. Healthcare cost in America is still twice the average of all 37 member countries of the Organization for Economic Cooperation and Development (OECD), and Americans still have poorer health and lower life expectancy than the average of the member countries (78.7 versus 79.5)

In its latest Health At A Glance publication, the OECD updated its life expectancy data, as shown here:

There are many cracks in our healthcare house that Jack built. Ignoring them is not a strategically viable plan for improvement, improvement that all citizens deserve.

To quote the venerable A. E. Housman, “Terrence, this is stupid stuff.” Another example of our woebegone healthcare system.

Trump’s Nevada rally

Last night, during an ABC-TV Town Hall Meeting President Trump once again pilloried cities and states run by Democrats and blamed their leaders for any problems with the response to COVID-19.

A little contextual background is required here. On 14 April, Trump asserted “absolute authority” to control the nation’s response to the pandemic, saying, “When somebody is president of the United States, your authority is total.” He made it clear he would be in charge and the states would have to fall in line.

Two days later, he reversed himself on a call with all the governors, telling them, “I’ve gotten to know almost all of you, most of you I’ve known and some very well. You are all very capable people, I think in all cases, very capable people. And you’re going to be calling your shots.”

Since then, he has repeatedly repeated the “You’re on your own” line. The result, of course, has been that we have seen 51 different plans and approaches  with varying degrees of success.

Nevada, one of the “you’re on your own” states, is still in the midst of a tough fight against the disease with a Daily Positivity Rate of 7.1% and a Cumulative Positivity Rate of 10.2% as of 10 September.

On 24 June, Nevada Governor Steve Sisolak imposed certain restrictions, among them the requirements that all Nevada residents wear masks when in public and that no more than 50 people, socially distanced, congregate in one place.

Enter Donald Trump and his the-sky-is-the-limit indoor rally of last Sunday evening at Xtreme Manufacturing in Henderson, Nevada. Fire officials estimated the size of the crowd was 5,600 people, nearly all of whom were maskless (except for the people right behind Trump who were constantly on full TV view).

Just as we saw in Tulsa after his previous rally, we’ll probably see a spike in cases in Nevada in two to three weeks.

Beyond the nonchalant and willful endangerment to peoples’ lives, what bothers me most of all about this event is Donald Trump’s cavalier and metaphorical raising high of his two middle fingers to Nevada’s scientifically-based efforts to keep its citizens alive. After repeatedly telling the nation’s governors they should do what they think they need to do to combat COVID-19, this “law and order” president, without compunction of any kind, imperiously violates the law while telling his large crowd Nevada’s Governor Sisolak is “a hack” and “weak.”

Allow me to close with Joseph Welsh’s question to Senator Joe McCarthy on 9 June 1954: “Have you no decency, sir?”

 

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Why Dr. Fauci Is “Cautiously Optimistic”

Monday, August 3rd, 2020

As I’ve previously written, until now, vaccines have taken years to develop. The fastest until now? The Mumps vaccine, developed and approved in four years (1963 – 1967) by Maurice Hilleman.

In recent times we have the Ebola vaccine, approved in the U.S. in 2019. Scientists from around the world had tried to develop a vaccine for this deadly disease since the mid-1990s, but funding and, let’s face it, lack of interest in an African disease, continually stalled the work. But a large outbreak in the Democratic Republic of Congo in 2014 reignited Pharma’s interest, and last December the FDA approved Merck’s Ervebo vaccine. It took five years.

Now we have COVID-19, the disease caused by  SARS-CoV-2 (the scientific name of the new coronavirus), and immunologist Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases since 1984, is “cautiously optimistic” we’ll have a vaccine by the end of the year. This means we could have needles going into arms in less than a year since the first case was reported. How is that so?

Although Donald Trump would probably swallow his smart phone rather than acknowledge this, we owe a debt of gratitude to the Chinese for the quick start. In early January, before the disease even had a name, a team of Chinese scientists uploaded its genetic sequence to a public site. This kicked off the gold rush-like vaccine hunt. Here are some facts that contribute to the light-speed development:

  • The disease is a coronavirus. Scientists have been trying to develop vaccines for this family of diseases for decades. Coronaviruses are diseases that can leap from animals to humans, and much work had already been done. Vaccine projects currently underway were simply redirected to SARS-CoV-2.
  • Many of the vaccine teams now attacking SARS-CoV-2 had worked on the SARS virus, which in 2003 killed 800 people, and the MERS virus, which has killed 2,500 people since 2012. They were deep into coronaviruses.
  • The earlier projects had identified a part of coronaviruses called the spike protein as a potential target for a vaccine. In particular, the work on SARS had suggested strongly that the spike protein was the key. Moreover, that work had already identified the difficulties inherent in attacking the spike protein.
  • Most people recover from COVID-19. That indicates a conquering immune response that a vaccine can be targeted to induce in people.
  • The spike protein, which gives SARS-CoV-2 the crown-like appearance that’s characteristic of coronaviruses, attaches to receptors on people’s cells, allowing the virus to enter and replicate. By blocking spike proteins, then, vaccines may prevent infection.
  • Money is no object. Because COVID-19 is the biggest health crisis the world has faced in more than 100 years, governments are shoveling unheard of amounts of cash into vaccine development. If vaccine developers don’t have to worry about funding their work, they can try anything and everything without worry. And, most important, the traditional steps taken in vaccine development can be shortened and compressed, which is exactly what’s happening.
  • Government regulators learned a lot from Ebola. During the development of Ervebo, they adopted a new dexterity in streamlining decisions and a nimbleness in communication. That has continued over to COVID-19. Case in point: the FDA has let developers know that vaccines need to prevent infections or reduce the severity of Covid-19 in 50% of recipients to be approved.

Here is where we are now in vaccine development according to the New York Times Coronavirus Vaccine Tracker:

If you’re wondering about that one “Approval” on the far right, that is a vaccine developed by the Chinese company CanSino Biologics. Hong Kong-listed CanSino Biologics said in a filing to the stock exchange that data from clinical trials showed the Chinese military vaccine had a “good safety profile” and potential to prevent disease caused by the novel coronavirus. Consequently, on 25 June, China’s Central Military Commission approved the use of the vaccine for one year. The rest of the world has no idea of whether this vaccine works. One wonders what the soldiers in the Chinese Armed Forces who are being injected with it think of it.

If history is any predictor of the future, most of the vaccines currently under development will fail. However, the sheer size of the effort, as well as the mountains of work already done on SARS and MERS, suggest that Dr. Fauci’s cautious optimism may, indeed, be well founded.

 

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AstraZeneca And Oxford Surge To The Lead

Monday, July 20th, 2020

Lord knows, good news is hard to come by these days, but, H’Alleluia, we got some this morning.

Researchers from pharmaceutical giant AstraZeneca* and Oxford University’s Edward Jenner Institute for Vaccine Research announced promising results from a Phase 1/2 study of their COVID-19 vaccine candidate, known as AZD1222.

Researchers gave AZD1222 to about 500 volunteers and compared the results to those from around the same number getting a meningococcal vaccine.

For the AZD1222 vaccine, antibodies against the SARS-CoV-2 spike protein peaked by day 28 and remained elevated to day 56, the end of the study, indicating an immune response against the virus. Much has recently also been made of T cells, a type of white blood cell: Here, the vaccine levels of T cells peaked 14 days after vaccination and were still present two months later.

Ages in the study group ran from 18 to 55; the median was 35. This is much younger than the median age of the group that will need it the most: the elderly. Also, nobody in the study group had co-morbidities associated with heightened risk of bad outcomes.

There were side effects, but they were relatively minor: fevers, aches, headaches and fatigue, but acetaminophen, the active ingredient in Tylenol, alleviated these.

Phase 3 trials are now underway in the U.K., Brazil and South Africa and are due to start in the U.S.

The UK has already ordered 100 million doses of the unproven vaccine, which scientists from Oxford’s Jenner Institute have said could be ready for approval in September.

A word or two about the light speed of this vaccine’s development, as well as the roughly 100 others being developed around the world.

First, Oxford has been working toward developing a novel coronavirus vaccine for two or three years. After the 2014 Ebola epidemic, the British government invested  £120 million (about $149 million at the time) to create vaccines aimed at protecting against the 10 or 11 health threats deemed to be the most likely to threaten the country. Coronaviruses were on that list, and the government gave the Jenner Institute some of the money.

Once that happened, Oxford doctors Sarah Gilbert and Adrian Hill pioneered a way to put a bit of a novel coronavirus in a vaccine, but without the part that makes it replicate in humans. At that point it would be safe to inject in people. What Gilbert and Hill created was a platform that theoretically should work for many viruses and has been proven to be safe in vaccines for other diseases. And that methodology, called recombinant adenovirus vector, is what AstraZeneca and Oxford are making the foundation of their COVID-19 vaccine candidate.

So, because of the work of Gilbert, Hill and their Oxford team, Oxford and AstraZeneca had a head start on the COVID-19 vaccine derby. But still, AZD1222 entered its Phase 1 clinical trial the last week in March, 2020. If they succeed and have a vaccine ready for humanity by September, that will be six months from start to finish. This is way beyond unheard of!

Don’t believe me? Typically, and this is anything but, clinical trials go through four phases according to the FDA:

Phase 1: 

Study Participants: 20 to 100 healthy volunteers

Length of Study: Several months (For this example, let’s say 4)

Purpose: Safety and dosage

Result: Approximately 70% of drugs move to the next phase

Phase 2: (AZD1222’s Phase 1 and 2 were done in two months)

Study Participants: Up to several hundred people

Length of Study: Several months to 2 years (Let’s say 4 months to two years)

Purpose: Efficacy and side effects

Result: Approximately 33% of drugs move to the next phase

Phase 3: (This is what AZD1222 is beginning now)

Study Participants: 300 to 3,000 volunteers

Length of Study: 1 to 4 years

Purpose: Efficacy and monitoring of adverse reactions

Result: Approximately 25-30% of drugs move to the next phase

There is a Phase 4 with several thousand volunteers, but it appears the government may be combining Phase 3 and 4 as it did Phase 1 and 2.

If there is one thing Donald Trump and I can agree about it is that this is being done at Warp speed. If you do the math from above, you’ll see the fastest a drug typically makes it through the first three trials is 20 months, not six. Also, by rapid calculus, you’ll note that if we start with 100 drugs going into trials, five make it through Phase 3. We’re dealing with long odds here.

A couple of other things to think about.

First, drug discovery and development involves pre-clinical work that begins with mice, moves on to rats, guinea pigs, rabbits, pigs and non-human primates. Yes, monkeys. After all that, scientists apply for what’s called an Investigational New Drug Award, an NDI. If the FDA approves that, one can move into a Phase 1 trial. None of that has happened here, at least it hasn’t been reported as happening.

Second, even if good results happen from AZD1222’s Phase 3 trial, or one of the other vaccines under development, with such little longitudinal study how certain will we be that long-term immunity will result?

Finally, there are the old folks. One presumes they represent a cohort in the Phase 3 study. What happens if the vaccine succeeds beautifully in young people, but fails miserably in the elderly?

John Milton famously wrote, “Hope springs eternal.” But, frankly, I prefer the advice of my old commanding general in the mountains of Vietnam: “Hope for the best; prepare for the worst.”

 

* AstraZeneca is a British/Swedish company formed from the merger of Astra Pharmaceuticals, a British firm, and Zeneca, a Swedish one, in 1999. It’s headquarters are in Cambridge, England.

 

 

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The “K” Factor and EU and USA Cases

Friday, June 26th, 2020

The K Factor

Ever heard of the “K” factor? Neither had I. But in yesterday’s Work Fitness and Disability Roundtable, Dr. Jennifer Christian’s long-running and valuable daily roundup of workers’ compensation medical news and musings, we were introduced.

Turns out the “K” factor could be tremendously important in helping leaders figure out how reopening the economy should proceed.

I thought Jennifer’s Roundtable post was so important I asked her if we could reprint it in the Insider. She gave permission, for which I’m grateful. So, here it is:

Hey, nothing like a fact-based “aha” to sharpen the mind and help point the way forward. A thought provoking article in New York Magazine (https://nymag.com/intelligencer/2020/06/coronavirus-meatpacking-plants-america-labor.html?utm_source=fb&utm_campaign=nym&utm_medium=s1&fbclid=IwAR0jnJXCeUx_zYVQuayha1XSMpMtjT-TSXIv7-RfIFNCDtlrz1hn558Da2w) on the reason for major differences between the COVID-19 experience in meatpacking industries in the USA and Europe brought up the “k” factor in the COVID-19 pandemic.  Ever heard of “k”?

Until yesterday, I hadn’t noticed (or paid attention to) any discussion about the implications for action of SARS-CoV-2’s  “k” factor. The “k” factor is an infecting organism’s observed dispersion behavior. Now is the time to start paying attention to the “k” factor because it points us straight to the main cause of the majority of COVID-19 cases: superspreading events in crowded indoor settings. We’ve all known that a lot of the cases have occurred due to spread on board ships, in prisons, hospitals, nursing homes, nightclubs and meatpacking plants – but to be truthful, I’m not sure we’d gotten the take-home message: SARS-CoV-2 is heavily dependent on crowded indoor spaces for its spread.

So, I did a bit more Googling and found a good Science Magazine article (https://www.sciencemag.org/news/2020/05/why-do-some-covid-19-patients-infect-many-others-whereas-most-don-t-spread-virus-all) that lays it all out quite clearly.  In addition to the R value (the mean number of subsequent new infections resulting from each infected individual), epidemiologists calculate how much a disease clusters. The lower k is, the more transmission is coming from a small number of people. The k value for the 1918 influenza pandemic was estimated at 1.0 – clusters weren’t too important. But during the 2003 SARS and 2012 MERS epidemics the vast majority of cases occurred in clusters, and their calculated k values were therefore low: 0.16 and 0.25 respectively.

In COVID-19, most infected people are not creating any additional cases. Adam Kurcharski from the London School of Hygiene & Tropical Medicine has conducted an analysis of COVID-19 dispersion and says, “Probably about 10% of cases lead to 80% of the spread.” A pre-print of his paper (https://wellcomeopenresearch.org/articles/5-67) has a calculated k value of COVID-19 at 0.1. Previous studies have pegged it just a tad higher than SARS or MERS.

There’s no point in trying to figure out which people are shedding the most viruses – though some of us clearly do disperse more bugs than others.  We professionals need to focus most of our attention on the places and types of events that SARS-CoV-2 needs in order to spread efficiently: loud and crowded indoor spaces, where people are cheek by jowl and raising their voices or breathing deeply: talking, singing, or shouting or aerobically exerting themselves. Ventilation and air flow in these settings also plays an important role.

Almost none of the clusters have resulted from outdoor crowded events.  Chinese studies of the early spread of COVID-19 outside Hubei province identified only one cluster among a total of 318 that originated outdoors. A Japanese study found that the risk of infection indoors is almost 19 times higher than outdoors. And here in the USA people who participated in (largely outdoor) Black Lives Matter protests have not been getting sick. (I also saw some data earlier saying that the virus is almost immediately disabled by sunlight.)

As the Science Magazine article says, the low k factor is …..”an encouraging finding, scientists say, because it suggests that restricting gatherings where superspreading is likely to occur will have a major impact on transmission, and that other restrictions—on outdoor activity, for example—might be eased.” So duh, let’s make the hierarchy of risk much more explicit. We need to make it crystal clear to the public (and patients and workers and employers) that the worst thing a person can do is participate in events in loud, crowded, and  indoor settings without rapid air turnover.

HOWEVER:  Many people are stuck. They live in crowded housing or congregate housing. The places where they live and work (ships, factories, office buildings, and medical facilities) already exist. People need to work, and winter is coming when we have to be inside.

I see this call to action: Are you, personally, confident that you are collaborating with all of the professionals whose input, cooperation, and contributions will be required? Think outside your silo. All of the various types of professionals who do event planning & commercial building design & engineering, industrial hygiene, HVAC, public health, and occupational health & safety need to join up and get deeply and rapidly involved in adapting / redesigning / re-configuring / re-engineering existing places and events to reduce the potential for superspreading.

A look at European Union and U.S. case statistics: Stunning

The following chart from the Johns Hopkins Tracker Project, printed in yesterday’s Statista Daily Alert needs no introduction or even analysis. It puts the period to Dr. Christian’s words.

 

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Today’s Class: Impeccable Timing 101

Monday, June 15th, 2020

No one will ever accuse the Republican Party of being overburdened with sensitivity. In two stick-in-the-eye moves just oozing with impeccable timing, the Grand Old Party is telling the world just what it can do with its Black Lives Matter folderol.

First, the GOP’s unquestioned leader, President Donald Trump, like a too long cooped up horse, has decided to resume his rallies, which for him seem to be better than crack cocaine. This week in Tulsa Oklahoma he and as many of his followers as campaign officials can cram into the 19,000-seat BOK Center will gather for a couple of hours of The Best Of Trump as if the COVID-19 pandemic had never happened, neither masks nor social distancing required. Reminds me of Ebenezer Scrooge discussing innovative methods to “decrease the surplus population.”

In the first of his two impeccable timing decisions, Mr. Trump announced he would hold his Tulsa rally on 19 June, known as Juneteenth, the date on which in 1865, the last of the South’s slaves were notified of their freedom under the Emancipation Proclamation. It would take until the following December and the 13th Amendment to officially abolish slavery in America.

Juneteenth is recognized as a state holiday or ceremonial holiday in 47 states and the District of Columbia (what are you waiting for Hawaii, North Dakota, and South Dakota?) and is the oldest celebration marking the end of slavery, dating from 1866.

According to the Associated Press, Trump was unaware of Juneteenth, let alone the significance of it to the Black community, when he announced his rally’s date. Consequently, he did not anticipate the blowback he would get. But get it he did. Even from his own supporters.  In a rare instance of backing down, he moved the rally to the next day, the 20th, still in Tulsa at the BOK Center.

But in America’s Black consciousness, Tulsa is known for a lot more than Juneteenth, as significant as that is. On another day in June, the 1st June day of 1921, Tulsa was the site of the worst race massacre in American history.

The day before, police had arrested a young black man by the name of Dick Rowland for allegedly attacking a white woman in a Tulsa elevator. Soon after Rowland’s arrest, rumors began to spread about a group of whites planning a lynching party. To protect Rowland, African American World War 1 veterans surrounded the jail holding him. There was a standoff with a mob of whites. Somebody fired a shot, and a firefight ensued. The much larger white mob pushed the black vets all the way to Greenwood, Tulsa’s black section.

Greenwood was the wealthiest black neighborhood in the country. Oil had made it rich. Racism was about to destroy it. Over the course of the day, 6,000 homes and businesses and 36 square city blocks were turned to ash. Pilots of two airplanes dropped turpentine bombs on buildings, instantly igniting them. Three hundred African Americans were slaughtered, most thrown into mass graves. Not a soul was ever prosecuted for anything. Then Tulsa, population 100,000, swept it all under the rug. Two generations later nobody knew a thing about it. It was never taught in schools, no books were written, no oral history passed down. It was as if it never happened.

Tulsa’s current mayor, G. T. Bynum, wants to take the rug up to see what’s hiding under it. He’s committed to investigating what happened and determining accountability. He thinks he’s found a couple of the mass graves and is having them excavated. The goal is to at least identify as many victims as possible through DNA analysis.

For the people of Tulsa, especially the black people of Tulsa, this is a deep, open, festering wound, and next Saturday Donald Trump will come riding into town on his big, very white horse to preach the gospel of Trump to 19,000 of his followers. It’ll be an interesting day.

There is one more incident of impeccable timing.

The Republican National Covention had been scheduled for North Carolina, but because North Carolina’s Democratic Governor Roy Cooper, concerned about the spread of COVID-19, would not guarantee a full house for the late August event, the Republican party has moved most of the convention to Jacksonville, Florida. The Coronation of Mr. Trump is set for the night of 27 August.

And, you guessed it, there is a black history story about 27 August and Jacksonville. It is known as Ax Handle Saturday.

The year is 1960 and the Jacksonville Youth Council of the National Association for the Advancement of Colored People (NAACP) is holding peaceful lunch counter sit-ins. Peaceful demonstrations. A group of outraged whites taking exception to this level of daring, begin spitting on the demonstrators and calling them names no one should ever be called. Then ax handles, mercifully without ax heads, suddenly appear along with baseball bats, and the demonstrators begin to get hit. Things go downhill from there. When it is all over dozens of young African Americans would be wounded in various ways. On a brighter note, nobody died, but that was probably blind luck.

To give you an idea of racial relations in Jacksonville at the time, a year earlier, in 1959, the year before Ax Handle Saturday, Nathan Bedford Forrest High School opened in Jacksonville, celebrating the memory of a Confederate General and the first Grand Dragon of the Ku Klux Klan.

The 60th anniversary of Ax Handle Saturday will be celebrated on 27 August in a park about a mile away from the convention at about the same time the balloons come down. Impeccable timing.

 

 

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More About The Moderna Vaccine Results

Friday, May 22nd, 2020

Scientists and Wall Street analysts are now beginning to peal the onion of Moderna’s announcement about its Phase One Trial results in which it reported its vaccine candidate had produced antibodies in eight of the study’s 45 participants. Following the announcement, Moderna’s shares rose nearly 30%. A profitable day, indeed.

On Tuesday, I wrote it was way too early to get excited based on this teeny tiny study. Since then, it’s nice to see that Evercore ISI’s Umer Raffat, an analyist Institutional Investor called a Rising Star of Wall Street Research, has added context and perspective. Early Tuesday, Raffat sent a 78-page slide deck to his clients explaining why, while possibly encouraging, Moderna’s announcement  and Monday conference call should not give anyone a serious sense of hope until a lot more work is done and a lot more is known about this particular Phase One Trial.

Getting into the science weeds, Raffat focused his analysis on antibodies and T-Cells.

First, the antibodies. Raffat thinks the most impressive thing about Moderna’s data release concerns “binding” antibodies. These are antibodies that attach to SARS-CoV-2, the virus that causes COVID-19. The concern with Moderna’s announcement is that what’s really important for an effective vaccine is its ability to generate “neutralizing” antibodies that actually prevent the virus from infecting healthy cells, and Moderna provided no information about neutralizing antibodies except to say its neutralizing antibodies “were at or above convalescent serum” collected from people who recovered from COVID-19. Studies have shown that people who have recovered from COVID-19 can generate a wide range of neutralizing-antibodies in their convalescent serum. So, it is unclear just how comparable Moderna’s convalescent serum samples were to samples taken from the trial participants.

The FDA will have to determine what level of neutralizing antibodies are required for an approved vaccine. The Agency has already said that when convalescent serum is used to treat COVID-19 patients the neutralizing antibodies should be high, whatever that means.

Another issue with Moderna’s mRNA-1273 vaccine rests with T-Cells. The level of T-Cell generation is an indicator of the degree to which the immune system is attacking COVID-19. Moderna’s announcement and subsequent call did not address this. Some researchers have shown that a high level of T-Cell generation, even without high levels of neutralizing antibodies, have been found in people who have recovered from COVID-19, leading to speculation that T-Cell generation may be very important for any successful vaccine. However, when asked about this during the conference call, Moderna’s Chief Medical Officer, Tal Zaks, M.D., Ph.D., said  “You would expect that based on the fundamental scientific principles of how an mRNA vaccine works because it teaches the body’s own cells to make the protein from within the cell.”

One last point – The study participants numbered 45. Eight produced binding antibodies. Only four were sampled for neutralizing antibodies. Four.

As I wrote earlier this week, Moderna has made it to the one yard line. Ninety-nine to go.

 

 

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The Continuing Saga Of COVID-19 In Long Term Care Facilities And New Research

Thursday, May 21st, 2020

We have written about the ongoing death spiral in LTCFs four times – here, here, here, and here.

We’ve done this, because for three months authorities have known that LTCF’s were lethal hot spots, the most lethal in the country, actually. And to this day the federal government has devoted nothing more than lip service to it. Don’t believe me? Read on.

Last Thursday, OSHA issued COVID-19 Guidelines, not Requirements, for nursing homes. The Guidelines recommend screening residents and staff for symptoms, keeping everyone six feet apart and creating alternatives to group activities. I challenge anyone to read the Guidelines and find the word, “must.” OSHA has become the quintessential paper tiger. Remember, it only took three months to produce these groundbreaking recommendations.

And it is now exactly one month since CMS Administrator Seema Verma, to much ballyhoo, announced new COVID-19 reporting requirements for nursing homes. Specifically, CMS was requiring:

…nursing homes to inform residents, their families and representatives of COVID-19 cases in their facilities. In addition, as part of President Trump’s Opening Up America, CMS will now require nursing homes to report cases of COVID-19 directly to the Centers for Disease Control and Prevention (CDC).  This information must be reported in accordance with existing privacy regulations and statute. This measure augments longstanding requirements for reporting infectious disease to State and local health departments. Finally, CMS will also require nursing homes to fully cooperate with CDC surveillance efforts around COVID-19 spread.

So, how has that worked out? Keep in mind that, as reported by the New York Times, “While just 11 percent of the country’s cases have occurred in long-term care facilities, deaths related to Covid-19 in these facilities account for more than a third of the country’s pandemic fatalities.” As of 9 May, the Times reported the death toll in Long Term Care Facilitites (LTCF) was 28,100. Those are the ones we know of.

Unfortunately, that number is probably low, because we are still waiting for the CMS reporting requirement to produce anything. And now, it appears CMS’s plan has changed. On 14 May, one week ago, Administrator Verma said data from LTCFs would not be posted on the CDC website. Rather, it will be reported by the end of this month somewhere on Medicare’s website Nursing Home Compare.

Nursing Home Compare is exactly what the name suggests. It is a site where, by inputting a zip code, one can compare what Medicare calls Health Deficiencies in specific nursing homes within the relative geography chosen. It includes a humongously large database containing a number of datasets devoted to health deficiencies. This may be the place one would search for nursing home data regarding COVID-19. But we won’t know that until “the end of this month.” Maybe.

We shall see.

By the way, Verma’s announcement of one month ago began with this:

Today, under the leadership of President Trump, the Centers for Medicare & Medicaid Services (CMS) announced new regulatory requirements that will require nursing homes to inform residents, their families and representatives of COVID-19 cases in their facilities.

“Leadership.” Really?

Research on what is most effective to stop COVID-19 transmission

Two new research papers look into the effectiveness of the measures governments have either required or recommended for slowing the spread of the virus.

The first, Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate, published in Health Affairs on 14 May, investigated the efficacy of four social distancing policies taken by most state and local governments: Shelter-in-place orders (SIPOs), public school closures, bans on large social gatherings, and closures of entertainment-related businesses. Specifically, the researchers were trying to estimate the relationship between social distancing policies and the exponential growth rate of confirmed COVID-19 cases using an event-study regression with multiple treatments.

There were surprising results.

First, from the Paper:

Adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4 percentage points after 1–5 days, 6.8 after 6–10 days, 8.2 after 11–15 days, and 9.1 after 16–20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions,…

Second, only two of the policies produced statistically significant impacts on the growth rate at the 95% confidence level: SIPOs and the closures of entertainment-related businesses.

In contrast, the researchers found no evidence that bans on large social gatherings or school closures influenced the growth rate. That is not to say there was no influence on the growth rate due to these measures, just that whatever influence was there, it was not statistically significant.

The school closure finding is important as school boards and college trustees ponder whether to reopen in the fall. Yesterday, Boston College, where I spent some of my youth, announced that the campus would be open for classes for the fall semester.

The second Paper, Face Masks Against COVID-19: An Evidence Review, “synthesized the relevant literature to inform multiple areas: 1) transmission characteristics of COVID-19, 2) filtering characteristics and efficacy of masks, 3) estimated population impacts of widespread community mask use, and 4) sociological considerations for policies concerning mask-wearing.”

The verdict of the researchers: “The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at stopping spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low.” In otherwords, masks work.

This paper carried the following supplemental tidbit:

While the focus of this article is on preventing the spread of COVID-19 disease through public mask wearing, many countries face concurrent epidemics of contagious respiratory diseases like tuberculosis and influenza. Tuberculosis kills 1.5 million people globally per year, and in 2018, 10 million people fell ill. Face covering has been shown to also reduce the transmission of tuberculosis. Similarly, influenza transmission in the community declined by 44% in Hong Kong after the implementation of changes in population behaviors, including social distancing and increased mask wearing, enforced in most stores, during the COVID-19 outbreak.
This could be important when one considers that an effective vaccine for tuberculosis exists: the Bacillus Calmette-Guérin vaccine. It isn’t usually given to infants in the U.S., because the disease isn’t a widespread problem here. However, when we eventually have a vaccine for COVID-19, we’re going to have to face the fact that getting it to people around the world is not going to be easy.
And, God help us, we’ll also have to deal with the anti-vax cult living among us here at home.

 

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COVID-19: Two Updates

Tuesday, May 19th, 2020

Who pays?

The last question asked in our question-filled Post of 13 May was the same as the first question asked, namely: Who’s the guy at the end of the line left holding the bill for COVID-19 workers’ compensation claim costs?

Right now, as we have written here, each state is addressing this in its own way; fifty different plans for one national crisis.Thus far, workers’ compensation is the pot out of which, in one way or another, claims are addressed. Employers do not like this.

Employers of essential workers haven’t wanted to scream too loudly about being the last in line guy, what with so many of their  workers falling ill, even dying, every day. That kind of crass insensitivity would be bad for business. But inwardly, they have to be nervous about getting stuck with the check, the cost of which, as we have documented here, could be enormous.

Employers have already taken a high hard one to the side of the head with the complete and utter devastation COVID-19 has done to their economic well being, and the requirement to pay the workers’ compensation claims which are going to avalanche over the top of them is something with which they strongly disagree. For what it’s worth, I think they have a point.

Back at the state capitals, I would venture, governors don’t really care where the money comes from, just as long as it’s not coming out of their state treasuries.

And throughout history, insurers have resisted paying for occupational disease claims. Witness the 20-year fight to avoid paying the costs of pneumoconiosis, which resulted in the Federal Coal Mine Health and Safety Act of 1969, amended four years later by the Black Lung benefits Act, which created the Black Lung Disability Trust Fund.

So, if the states don’t pay and if insurers don’t pay and if employers don’t pay, who is left?

Brothers and sisters, the federal government is left, which is another way of saying we are left. We will all share the risk and share the costs. If you cannot bring yourself to believe that, you haven’t been paying attention.

In fact, a model exists: The September 11th Victim Compensation Fund, which:

…provides compensation to individuals (or a personal representative of a deceased individual) who were present at the World Trade Center or the surrounding New York City exposure zone; the Pentagon crash site; and the Shanksville, Pennsylvania crash site, at some point between September 11, 2001, and May 30, 2002, and who have since been diagnosed with a 9/11-related illness.  The VCF is not limited to first responders.  Compensation is also available to those who worked or volunteered in construction, clean-up, and debris removal; as well as people who lived, worked, or went to school in the exposure zone.

The wheels are already in motion. Last week, a bipartisan group in the House unveiled the Pandemic Heroes Compensation Act, a plan to compensate essential workers who fall sick or die from COVID-19. The Act is modeled on the September 11th Victim Compensation Act.

Senate democrats are also proposing legislation. Like everything else in D.C. these days, the road from here to eventual victim compensation will be tortuous, but I cannot see any other way of paying for this national catastrophe other than with a national program. Can you?

The Moderna results

For a number of years, I chaired the Board of a BIOTECH pre-clinical Contract Research Organization (CRO). We took compounds, whose makers hoped would become the next blockbuster drugs, and tested them in mice, rats, guinea pigs, rabbits, pigs and non-human primates (that’s right, monkeys). In the biotech business, everyone knows everyone else, and we certainly knew a lot of scientists trying to develop vaccines.

Yesterday, the Boston pharmaceutical company Moderna reported a vaccine it was developing for COVID-19 produced antibodies in humans. In vaccine development, this is the beginning of a Phase One trial, and its purpose is to confirm the vaccine is not toxic. Moderna’s Phase One trial is composed of 45 participants, eight of whom  Moderna says produced the antibodies. We know nothing of the other 37.

While encouraging, you won’t find respected scientists getting too excited yet. They know what Moderna has done is to take the ball out of the end zone and reach the one yard line. Nintey-nine to go.

Two things are exciting, however. First, Moderna was able to get to this point at light speed. What Moderna did in about 70 days usually takes three to four years. That is over the moon fast, but the other ninety-nine yards are going to be increasingly more arduous. Second, there are more than 100 other groups around the world, both pharmaceutical and academic, who are also going hell bent for leather to develop the vaccine that will eradicate COVID-19. Although I have every confidence one of these groups, maybe Moderna,  will cross the goal line at the other end of the field, it will take a miracle on the order of the Raising of Lazarus for this to happen before mid to late 2021.

Until then: Constant vigilance. Complacency will kill you. Really. Please keep this in mind as all the beaches and parks open this coming Memorial Day weekend. It will be highly tempting to revert to former form.

 

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