Author Archive

COVID-19 Update

Friday, September 18th, 2020

To close out your week we offer a few items that may have flown nap-of-the-earth under your radar.

The AstraZenica/Oxford vaccine bump in the road

On 8 September AstraZenica (AZ) halted its Phase 3 study, because one of its study participants came down with Transverse Myelitis, a neurological condition affecting the spine and caused by infection, immune system disorders or other disorders that can damage or destroy myelin, the fatty tissue that protects nerve cell fibers.

The UK has allowed AZ to restart its study there (AZ is a UK-based company), but as of this writing, the U.S. has not. In fact, in an interview with Kaiser Health News, the National Institute for Neurological Disorders and Stroke’s Avindra Nath said “the highest levels of NIH are very concerned.” According to Nath, the NIH has yet to access tissue or blood samples from the patient, who was part of the U.K. portion of AZ’s Phase 3 study. NIH believes AZ is being far too coy with its data. Nath called for the company “to be more forthcoming,” adding that “we would like to see how we can help, but the lack of information makes it difficult to do so.”

Given this halt in the U.S. study, it is not inconceivable that, if the AZ vaccine, known as AZD1222, proves efficacious and safe in the UK, regulators there could approve it for general use well before the U.S. does. This would not make our Commandeer in Chief happy.

The Mask versus Vaccine dust up

Speaking of the Commander in Chief, he recently took CDC Director Dr. Robert Redfield for a quick walk to the woodshed for suggesting during testimony to a Senate subcommittee, “Masks are more guaranteed to protect me against COVID-19 than a vaccine.”

President Trump, who is not a doctor, but repeatedly plays one on TV, took exception to this. He publicly chastised Redfield for his comments and said a vaccine could be available in weeks and go “immediately” to the general public. Diminishing the usefulness of masks, despite a wealth of scientific evidence to the contrary, he said his CDC chief was “confused.”

Well, no, he wasn’t. Redfield told subcommittee members that if everyone in the U.S. would wear masks in public the pandemic could be under control within 12 weeks. His issue with a vaccine lies in its degree of immunogenicity, which he suggested would be in the area of 70%, meaning if 100 vaccinated people are exposed to the virus, 30 of them will have insufficient protection to ward it off. Those 30 will probably be comprised of groups who are most susceptible to the vaccine now, like the elderly.

People, masks will be with us for a long time.

Health insurance losses

Before the pandemic, 49% of Americans got health insurance through employer sponsored insurance (ESI). COVID-19 has reduced that percentage, because 6.2 million of our neighbors have lost their jobs and, consequently, their health insurance. When you factor in spouses and children, the number of people who have been shoved out the door into the COVID cold becomes 12 million.

Researchers at the Economic Policy Institute (EPI) have recently documented the losses in a new study. Researchers Josh Bivens and Ben Zipperer write:

  • Extreme churn after February 2020 has led to very large losses in ESI coverage. In March and April, for example, new hiring led to 2.4 million workers gaining ESI coverage each month, but historically large layoffs led to 5.6 million workers losing coverage each month. This rate of lost coverage—over 3 million workers—dwarfs a similar calculation for the number of workers losing coverage each month during the biggest job-losing period of the Great Recession (September 2008–March 2009). Our analysis using the monthly, high-quality measure of the total number of jobs in the economy from the Current Employment Statistics (CES) program of the Bureau of Labor Statistics (BLS) is consistent with 9 million workers having lost access to ESI in March and April 2020 but 2.9 million workers having gained coverage between April and July 2020.

Bivens and Zipperer say about 85% of those who lost ESI coverage were able to gain at least some coverage either through a spouse’s plan, the Affordable Care Act or state Medicaid programs, but that still leaves about a million laid off workers and their familes with nothing. Bivens, Zipperer and others argue the job losses have only worsened the public health crisis created by COVID-19.

Of course, recognizing that millions of people losing employer sponsored health insurance is a public health crisis is not the same as fixing the system to prevent it from happening again. However, as I have written before, having exposed gross inadequacies in the nation’s health care system, COVID-19 also provides opportunities for improvement. What is needed now is the determined motivation and will to make that happen. That is a Herculean task about which I wish I were more optimistic.

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?”

 

The Pledge, AstraZenica’s Hiccup, An Important WCRI Study, And An Homage To Bourbon!

Wednesday, September 9th, 2020

Having put The Insider on pause for a few weeks to have some fun researching pandemics in earlier times (they were awful) and to improving my tennis game (it’s pretty good), we now dive back into the blogging fray. Today, we get a running start.

The Pledge

At a press conference on 24 August, President Trump and FDA Commissioner Stephen Hahn trumpeted (pun very much intended) the FDA’s Emergency Use Authorization (EUA) of blood plasma to treat COVID-19 patients.  The Trump/Hahn announcement came less than a week after officials at the National Institutes of Health (NIH) had put a hold on releasing the EUA, saying randomized trials were needed before such an action could occur. The President disagreed, saying, “There are people in the FDA and actually in your larger department [HHS] that can see things being held up and wouldn’t mind so much — its my opinion, a very strong opinion — and that’s for political reasons. We are being very strong and we are being very forthright, and we have some incredible answers, and we’re not going to be held up.”

In yet another example of Olympian Hyperbole, a disease to which Mr. Trump seems to be terminally infected, he also called the EUA a “truly historic announcement,” which puts it alongside something like the Emancipation Proclamation.

Like most of Trump’s hyperbolic pronouncements, the blood plasma EUA created quite the controversy, especially when the FDA released the comments of one of its own scientists tasked with reviewing the appropriateness of the same blood plasma EUA. That scientist— displaying far less enthusiasm than Trump and Hahn, and whose name was redacted from a memo released by the agency — wrote that the data:

 “…support the conclusion that [convalescent plasma] to treat hospitalized patients with COVID-19 meets the ‘may be effective’ criteria for issuance of an EUA. Adequate and well-controlled randomized trials remain nonetheless necessary for a definitive demonstration of … efficacy and to determine the optimal product attributes and the appropriate patient populations for its use.”

After the 24 August press conference, it took about 1.5 nanoseconds for Joe Biden and many media pundits to accuse Trump and Hahn of politicizing the EUA to influence the coming election.

Which brings us to The Pledge.

On 8 September, wanting to get out of firing range, the CEOs of all the leading Western developers of COVID-19 vaccines vowed to only file for FDA approval after demonstrating safety and efficacy in their Phase 3 trials. Their Pledge and descriptions of all nine trials can be found here.

The Pledge also promises all the developers will share some, but not all, of their data to propel their vaccines to the finish line. However, although every CEO wants their vaccine to be the first approved, not one of them wants to get there only for the world  to discover they’ve cut corners and now endanger humanity. These are people who want to go down in history for the right reason.

Mr. Trump will push, prod and kick these vaccine developers to get one of their efforts approved before 3 November. But I have a 95% confidence level none of them will buckle under that pressure. I sure hope I’m right.

AstraZenica’s Hiccup

In an example of the caution just described, yesterday AstraZenica announced  it was putting its Phase 3 vaccine trial on hold, due to a suspected serious adverse reaction in a participant in the United Kingdom.

This is not an uncommon happening in vaccine development, but it does show how fraught with uncertainties these trials can be. It proves that AZ’s data and safety monitoring group is doing its job, and that’s what is supposed to happen. I previously wrote about all the leading COVID-19 vaccine candidates, as well as ChAdOx1, the one being tested by AstraZenica in partnership with the University of Oxford’s Jenner Institute.

It is entirely possible we will experience more bumps in the road before one of the developers wins FDA approval.

An Important, New WCRI Study Is Released

Low back pain (LBP) is something that has afflicted humanity since Homo Sapiens decided to stand straight and walk upright. And it’s been the bane of claims adjusters since Otto von Bismarck, Germany’s Iron Chancellor, created the first workers’ compensation program in the 1880s.

Back injuries are the leading cause of all musculoskeletal claims, which are the leading cause of all workers’ compensation claims, and have been since it seems forever. If you’ve ever looked at a workers’ compensation loss run for any hospital in America, you’ll know what I mean.

One of the myriad treatment modalities for these claims is physical therapy (PT). However, it’s always been a bit of a crap shoot as to when to prescribe PT for a patient beset by a work injury resulting in low back pain.

Now, the Workers’ Compensation Research Institute (WCRI) has produced a study that convincingly puts the matter to rest. The study’s conclusion: the earlier PT is begun, the better.

The study, The Timing of Physical Therapy for Low Back Pain: Does It Matter in Workers’ Compensation?, is based on a review of  nearly 26,000 LBP-only claims with more than seven days of lost time from 27 states, with injuries from 1 October 2015, through 31 March 2017, and detailed medical transactions up through 31 March 2018.

One of the many reasons this study is important is that PT can sometimes be the last resort, not the first, in many cases being recommended only after opioids and other invasive procedures have been tried.

The WCRI study found:

  • Later timing of PT initiation is associated with longer temporary disability (TD) duration. On average, the number of TD weeks per claim was 58 percent longer for those with PT initiated more than 30 days post-injury and 24 percent longer for those with PT starting 15 to 30 days post-injury, compared with claims with PT within 3 days post-injury.
  • Workers whose PT treatment started more than 30 days post-injury were 46 and 47 percent more likely to receive opioid prescriptions and MRI, respectively, compared with those who had PT treatment initiated within 3 days of injury. The differences between PT after 30 days post-injury and PT within 3 days post-injury were 29 percent for pain management injections and 89 percent for low back surgeries.
  • The average payment for all medical services received during the first year of treatment was lower for workers with early PT compared with those with late PT. For example, the average medical cost per claim for workers who had PT more than 30 days post-injury was 24 percent higher than for those who had PT within 3 days post-injury.
  • Among claims with PT treatment starting more than 30 days post-injury, the percentage with attorney involvement was considerably higher (27 percent compared with 13–15 percent among those in the early PT groups) and workers received initial medical care much later (on average 18 days compared with 2–3 days in the early PT groups).

If you’re a claims adjuster wary of incurring the cost of sending injured workers with resultant low back pain to PT, this study should make you press the “Reset” button in your mind.

And, finally, an homage to bourbon (which is also good for low back pain)

In the constant sea of terrible, divisive, set-your-hair-on-fire news, we now row to a bipartisan safe harbor: Bourbon.

In the halls of Congress, bipartisanship seems to have gone the way of the Woolly Mammoth. But, reader, that is not the case in the case of Bourbon! That’s because on 2 August 2007, Congress ratified a bill designating September as National Bourbon Heritage Month. More notable, however, is that it passed unanimously. Thus, history shows that amid the countless issues and places and opinions that divide us, nothing unites Americans like bourbon.

And that aint all. A 1964 act declared bourbon “America’s Native Spirit,” making it the only spirit distinctive to the United States, if you don’t count the “spirits” the QAnon folks are worried about.

So, although I can’t stand the stuff, on this first day after 2020’s Labor Day as we all get sucked along the giant tube of political rigarmarole, you might want to consider the nationally endorsed benefits of America’s Native Spirit. Things will still be dire, the President will continue his hyperbolic rants, many of your fellow Americans will continue to “choose liberty” over masks, but you? You’ll hardly notice any of it.

 

 

COVID-19 Update And Promising Vaccine Reports

Monday, August 10th, 2020

An alarming and disquieting milestone

Yesterday, we passed the five million mark. Five million confirmed cases of COVID-19 in America since January. To put this in a better perspective consider this: If you took every one of those five-million people and stood them shoulder to shoulder, the line would extend from Canada to the Mexican border. About 2,200 miles.

As for deaths, we have reached 163,000, and still rising with no end in sight. That number is more than three times the number of American soldiers who died in World War 1. More than three times the number of American soldiers killed during the 16-year Vietnam War.

This continuing death spiral is happening as Congress and the Administration are, as legendary Boston sportscaster Johnny Most used to say, “fiddling and diddling.” And all this fiddling and diddling is going on while millions of our fellow citizens watch their livelihoods and their dreams of a better life for them and their children dissolve into thin air.

We deserve better than this. Fiddling and diddling with a human tragedy of this magnitude is an obscene abomination.

Vaccine update

In the pre-clinical biotech world, we call them non-human primates. To everyone else, they’re monkeys, usually rhesus monkeys.

We have reported, and I’m sure you’re aware, that a number of companies have entered Phase 3 clinical trials testing their vaccines on thousands of people. Until COVID-19, that always followed years of pre-clinical work that usually began with mice. But because regulators have compressed and redesigned the vaccine development process, companies and institutions are running their pre-clinical and clinical trials simultaneously, in parallel.

Now, four groups have reported promising results with non-human primates, those rhesus monkeys. All of the approaches are different, but they settle into two methodologies:

  • Attacking SARS-CoV-2, the virus that causes COVID-19, through Messenger RNA.
  • Using a replication-deficient chimpanzee adenovirus to deliver a SARS-CoV-2 protein to induce a protective immune response.

You don’t really need to understand the science. What is important to know is all four groups reported that their vaccines have shown promising results in monkeys. The critical thing here is this: Three or four weeks after vaccinating the monkeys, each of the groups put SARS-CoV-2 into the monkeys’ noses. Each of the vaccines offered protection for the monkeys. Three of the four groups gave the vaccine in two shots, a prime followed weeks later by a booster.

The team of Oxford University and AstraZenica injected with one shot. Their results presented some concerns. While their vaccine prevented the monkeys from developing pneumonia, it did not clear the virus, indicating the vaccinated monkeys remained infected and able to spread the disease. It should be noted that the scientists infected the monkeys with ten times the viral load that a person would experience. Still, the group said protection might have been significantly enhanced had they given two shots.

These monkey trials are tremendously important, because scientists can give the monkeys their vaccine and then infect them with SARS-Cov-2, something they cannot do with their human volunteers in their Phase 3 trials.

The four groups are:

  • Moderna, working with the Swiss company Lonza, New Jersey-based Catalent and the National Institutes of Health. Its vaccine, mRNA-1273, contains snippets of viral mRNA, a molecule with instructions for making proteins. Moderna packs the mRNA inside a slippery pod made of lipids, so it can slide easily into the cells.
  • Oxford University’s Jenner Institute, working with AstraZenica. Its vaccine, ChAdOx1, uses a replication-deficient chimpanzee adenovirus to deliver a SARS-CoV-2 protein to induce a protective immune response. Their approach has been successful before as the first Ebola vaccine.
  • Pfizer, working with BioNTech, a German biotechnology company. Their vaccine, BNT162b2, also takes the mRNA route encoding an optimized version of the whole spike protein, which we wrote about here.
  • Johnson & Johnson, working with Beth Israel Deaconess Medical Center in Boston. Its vaccine candidate, Ad26.COV2.S, delivers the SARS-CoV-2 spike protein into cells using an inactivated common cold virus as the delivery vehicle. J & J gave a single shot of Ad26.COV2.S, and that provided significant immunity to COVID-19. But previous J & J studies showed giving a second booster shot raised the antibody response by tenfold in both animals and people.

All of this is promising, indeed. It is evidence we should be optimistic that we’ll have one or more effective vaccines by early 2021. However, it is worth noting that the road to a successful vaccine is littered with the decaying carcasses of failures.

 

 

When This Is Over, We Must Do Better!

Thursday, August 6th, 2020

For decades, we have swept our health care problems under the rug for posterity to trip over.    And right now, posterity is flat on its face.

Let me ask you this: Whether you believe high quality health care is a basic human right or just a privilege to be earned (I argued the former here), what do you think about 5.4 million Americans losing health insurance in the middle of the worst health care crisis in more than 100 years, because they lost their jobs?

One of the many terrible things COVID-19 has done is to expose our health care foundational flaws for all the world to see. For example, if there is ever a time not to lose health insurance it is during a pandemic. Another deep and open wound suddenly exposed to bright light is the abominable, even obscene, way in which COVID-19 has been allowed to impact the African American, Native American and LatinX communities. Health care is neither universal nor applied equally throughout the country.

As far back as 2008, I, along with others, documented the many ways our health care system, if you can call it that, lags behind the rest of the developed world*, in some case far behind. This, despite costing twice as much as the average of the other 36 member countries in the Organization for Economic Cooperation and Development (OECD), 25 of whom are members of the European Union. Since then, except for the passage of the Affordable Care Act (ACA), things have only gotten worse, and the ACA has been flayed, gutted and nearly beaten to death more than once. It should not, but it does to many, come as any surprise that the EU countries are performing significantly better in the battle against COVID-19 than we are, despite having a total population that is 27% greater than America’s. These two charts prove the point:

First, Population – From the World Bank:

Second, COVID-19 cases – from Johns Hopkins University and Statista as of 30 July, seven days ago:

What more does one need to see to conclude America’s response to COVID-19 has been tragically woeful?

Yesterday, I was speaking with a friend, a pulmonologist who has been on COVID-19’s front lines in Massachusetts since March. He and his patients, a number of whom are no longer with us, have been through a lot. His biggest complaint? The lack of “consistent, cohesive and comprehensive leadership from the federal government.” He said, “I’m a God-fearing man, but right now my God is science.”

The rug under which we swept our problems has been pulled up, and bad things have crept out into the light of day. But COVID-19, for all its horror and misery, has presented us with an opportunity. When this is over, and someday it will be, we will have an opportunity, nay, an imperative, to build a better American health care program, less fragmented, less costly, less complicated, and universally provided to every person within the confines of our nation’s borders. If the leaders we elect have even a modicum of courage, if they have entered public service to actually serve the public – all of it – we and they may be able to take the iniquity of this virus and leverage it to the point where health care in this nation, rather than having to be earned as a privilege, available only to people who can afford it, becomes a basic human right for all of us.

* The link is to the conclusion of a 5-part series. For the first four parts, enter “The best health care in the world” in the search box on the right sidebar

 

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.

 

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.

 

 

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.

 

It Bears Repeating: We Have Been Here Before

Friday, June 19th, 2020

In the summer of 1918, during the first wave of the Spanish Flu pandemic, American troops were at war in Europe’s killing fields. That was when Philadelphia officials decided they would hold a massive parade for the ages to promote Liberty Loans – government bonds issued to pay for the war. The City Of Brotherly Love organized an extraordinary spectacle: marching bands, women’s auxiliaries, Boy Scouts, soldiers and floats showcasing the latest innovation in warfare – floating biplanes built in Philadelphia’s Navy Yard.

That Philadelphia’s medical community thought this a very bad idea didn’t matter. That the nation was awash with flu had to be put aside in order to support the war effort. The flu could wait.

When two miles of parade marchers took their first steps on the morning of 28 September, some 200,000 people jammed Broad Street, cheering wildly.

The Spanish Flu had been circulating in America for six months at the time of the parade, and the flu, like COVID-19, loved a crowd. The flu couldn’t, and wouldn’t, wait.

Within 72 hours of the parade, every bed in Philadelphia’s 31 hospitals was filled. In the week ending 5 October, nearly 2,600 people in Philadelphia had died from the flu or its complications. A week later, that number rose to more than 4,500, with 200,000 more sick. With many of the city’s health professionals pressed into military service, Philadelphia was unprepared for this deluge of death.

City leaders closed Philadelphia, locked it down. But it was too late. Morgues and undertakers could not keep pace. Grieving families had to bury their own dead. Casket prices skyrocketed. And a rumor started to spread – The Germans did it.

History continually repeats itself. Tomorrow night we have a potential case in point when 19,000 followers of the Cult of Donald Trump will gather in the BOK Center in Tulsa Oklahoma. That the city’s medical officials have unanimously declared this a very bad idea doesn’t seem to matter. That the nation is awash with COVID-19 has to be put aside in order to support the election effort. COVID-19 can wait.

Campaign officials say they’ll take peoples’ temperatures as they enter and pass out face masks and hand sanitizer. But they won’t insist any be used and they won’t enforce social distancing. Can you, in your most far out imagination, visualize the camera shot of Donald  Trump at his podium with his amped-up ardent followers behind him, each six feet apart and all wearing masks?

Since 17 June, two days ago, Tulsa’s COVID-19 cases have risen 42%, going from 259 to 450. At one time, New York City had 450 cases.

As we have seen, this is not the first time in the midst of a pandemic people have been irresponsible and downright wacky.

Both President Trump and Vice President Pence have lately taken to declaring victory over the virus. You’d be hard pressed to find a single medical expert who agrees. We can only hope that somehow Trump’s medical experiment tomorrow night will not turn a very bad idea into a tragic one.

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.