Archive for the ‘Coronavirus’ Category

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.

 

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.

 

 

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.

 

 

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 – herehere, 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 PaperFace 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.

 

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.

 

Important COVID-19 Workers’ Compensation Questions

Wednesday, May 13th, 2020

Economic chickens are coming home to roost all over America. Except for the one percenters, and I may be wrong about them, everyone is feeling it, the pain. Biomedical devastation is leading us to places we have never imagined, let alone seen. In the quiet little room called workers’ compensation where I have sat for some number of years, there are questions that are going to need answering. Let’s look at a few of them.

But first, a little background. A week ago we wrote about a recent National Council on Workers’ Compensation (NCCI) analysis of workers’ compensation cost projections due to COVID-19. NCCI’s analysis projected a best case scenario, in which loss costs increase $2 billion, and a worst case scenario, in which they increase $81.5 billion, or 250% more than current total loss costs. Willis Towers Watson also released a scenario-based analysis that suggested pretty much the same thing.

On 8 April, the California State Assembly Insurance Committee asked the the California Workers’ Compensation Insurance Rating Bureau (WCIRB) to project loss costs if conclusive (rebuttable) presumptions were provided to front line workers, something Governor Gavin Newsom actually did through Executive Order one month later, so the “if” became a “done.” Later in April, the WCIRB released the requested report and concluded:

…the cost estimates in this Research Brief are presented as a range of potential impacts based on varying assumptions of the number of COVID-19 claims filed. On this basis, the WCIRB estimates that the annual cost of COVID-19 claims on ECI (Essential Critical Infrastructure) workers under a conclusive presumption ranges from $2.2 billion to $33.6 billion with an approximate mid-range estimate of $11.2 billion, or 61% of the annual estimated cost of the total workers’ compensation system prior to the impact of the pandemic.

Note two things. First, for perspective, if California were a country, it would have the fifth largest GDP in the world. Second, regardless, the WCIRB’s best case scenario is $.2 billion more than NCCI’s best case scenario for all 38 states where it provides ratemaking services.

Clearly, whatever scenario happens, workers’ compensation losses are going to be cataclysmic.

So, about those questions:

  1. Who’s going to pay for all of this? In normal times, the answer is obvious: Employers and insurers (when losses exceed an employer’s liability). But if we know one thing for sure, these are not normal times. So, who takes the hit?
  2. What about secondary chronic conditions the virus has been shown to cause in some people? Many survivors of SARS (Severe Acute Respiratory Syndrome) suffered crippling ailments for more than a decade. We’re already seeing COVID-19 survivors come home from hospital with severe, possibly persistent, chronic conditions. Are these conditions covered by the initial claim? I can see the plaintiff’s attorney now. “Your Honor, but for the COVID-19 occupational disease, poor John here would never have immediately lost kidney function requiring dialysis three times per week, and would be the picture of health.”
  3. How will COVID-19 claims impact experience modification, which affects an employer’s premium for three years? It is only logical that if loss costs increase by billions in one year, an employer of essential workers, say a hospital, will see its experience modification factor take off like a SpaceX rocket. That is a recipe for economic doom and disaster beyond what we’re already seeing.
  4. What happens when an essential worker who has contracted COVID-19 and filed a claim infects other family members, or the neighbor next door, for that matter? Would they be covered by the claim, or by health insurance if they happen to have it? Keep in mind, job losses due to COVID-19 are now in excess of 20.6 million. Many have lost not only a job, they have also lost the health insurance the job provided. The Kaiser Family Foundation has said, “26.8M would become uninsured after losing job-based coverage during the coronavirus if they don’t enroll in other coverage.” Consequently, this question is very important, because workers’ compensation health care is totally free, unlike employer-based and nearly all other insurance options that all come with deductibles and co-pays.

Meanwhile, back at the California Workers’ Compensation Insurance Rating Bureau, the organization has submitted a proposed rule to deal with number 2, above. It wants to exclude COVID-19 loss costs from the calculation of experience modification. Specifically, the proposed rule says:

Claims directly arising from a diagnosis of Coronavirus disease 2019 (COVID-19), reported with a catastrophe Number 12 pursuant to the Uniform Statistical Reporting Plan, shall not be reflected in the computation of the experience modification.

The proposed rule would also reclassify workers now working remotely from home as clerical – 8810, which is the lowest premium rate possible.

Let’s suppose for just a moment that the WCIRB’s proposed rule is approved, and California’s employers are off the hook with respect to experience modification. This presents another question: Will other states do the same? All of them? Some of them? None? Whatever happens, it seems to me we need a nationally consistent approach. Wouldn’t you agree?

Finally, this all leads back to the first question: Who’s the guy at the end of the line left holding the bill for COVID-19 claim costs?

How Are States Handling Workers’ Compensation During COVID-19?

Monday, May 11th, 2020

Last week we wrote about Governor Gavin Newsom’s Executive Order implementing a workers’ compensation rebuttable presumption for all essential workers who contract COVID-19 in California.

To review, a rebuttable presumption means an essential worker who contracts COVID-19 does not have to prove work-relatedness. The burden is on the employer to prove the disease was not caused by work.

Writing that other states have also taken action, I noted those actions varied widely across the country. But the monumentality of COVID-19 requires more on this topic. Just what are other states doing? Specifically.

Thirty-nine have either done nothing or have legislation pending. That is, they have taken no action via Executive Order, as Newsom did, or have yet to enact legislation. The District of Columbia is also in this group. Neither, have any of these states declared COVID-19 an occupational disease, although it obviously can be one.

The other 12 states have taken the following actions:

Akaska: On 9 April, Alaska Governor Mike Dunleavy signed legislation declaring a rebuttable presumption for first responders and other health care workers.

Arkansas: On 21 April Governor Asa Hutchinson issued an Executive Order creating a rebuttable presumption for first responders, other health care workers and National Guard personnel assigned to COVID-19 duties.

Florida: The state published a Memorandum saying first responders and health care workers “would be eligible for workers’ compensation benefits under Florida law.” Given the torment COVID-19 is causing throughout society, this is pretty wimpy, don’t you think?

Illinois: On 16 April, Governor J. B. Pritzker issued an Executive Order declaring a rebuttable presumption for first responders and other health care workers. Then, under intense pressure from the business and insurance communities, Pritzker, whose family owns the Hyatt hotel chain, rescinded the order. Obviously, a stand-up guy. So, I guess you could say Illinois now belongs in the camp of the other 38 states that have done nothing.

Kentucky: On 9 April, Governor Andy Beshear issued an Executive Order similar to Newsom’s, creating a rebuttable presumption for all essential workers who contract COVID-19. The business community isn’t happy, but, unlike Pritzker, Beshear has not changed his position.

Michigan: On 30 March, the Workers’ Disability Compensation Agency declared an Emergency Rule creating a rebuttable presumption for all First Response Employees, a term, as Michigan defines it, that includes just about everyone in health care.

Minnesota: On 7 April, Governor Tim Walz signed legislation establishing a rebuttable presumption for first responders, health care workers, correctional officers and child care workers.

Missouri: The Department of Labor and Industrial Relations issued an emergency rule, effective 22 April, declaring a rebuttable presumption for first responders, but, not, perplexingly, for other health care workers exposed to COVID-19. First responders are defined as “a law enforcement officer, firefighter or an emergency medical technician (EMT).”

New Mexico: On 23 April Governor Michelle Lujan Grisham issued an Executive Order creating a rebuttable presumption for state-employed first responders and volunteers to the health care system fighting the disease. Private sector employees are not covered.

North Dakota: On 25 March, Governor Doug Burgum issued an Executive Order creating a rebuttable presumption for all first responders and health care workers. On 16 April, he issued another one to cover funeral directors.

Utah: On 22 April, enacted legislation creating a rebuttable presumption for all first responders.

Washington: On 5 March, Governor Jay Inslee issued an Executive Order  creating a rebuttable presumption for first responders and other health care workers. The order also applies if the workers are merely quarantined.

The majority of states not listed here have some kind of legislation filed awaiting legislative action. But as anyone who has ever wandered the halls of a state capital watching the sausage being made knows, it doesn’t mean a thing until the Governor in the corner office signs it.

Time is wasting.

 

Pandemics: Are We Smart Enough To Learn From Them?

Friday, May 8th, 2020

“As the world becomes more of a global village, infectious disease could by natural transmission become more threatening in the United States. Here monitoring is lax because of a mistaken belief that the threat of infectious disease has been almost wiped out by antibiotics.” American Medical Association conference on infectious disease, 2001, from Norman F. Cantor, In the wake of the plague, 2001, Harper Collins.

Pandemics and the Roman Empire: From glory to gory

History’s first pandemic, the Antonine Plague, struck in AD 165 at the height of the Roman empire, the time Edward Gibbon described as when “the condition of the human race was most happy and prosperous.” Nobody knew, but the Roman Climate Optimum (RCO) was approaching its end. The RCO was an extremely propitious climatological period (BC 400 – AD 250) that allowed the empire to keep all its ~70 million people well fed and relatively healthy, which led to the development of the greatest army the world had ever seen, and would not see again for more than a thousand years. The Antonine Plague, named for the family of Emperor Pius Antoninus, killed at least seven million of the empire’s people, more than 10% of the population.

The greatest physician of the age was Galen (born AD 129). He treated and cured a number of distinguished Romans and extensively documented the spread of the disease in his masterpiece, The Method of Medicine. He said, “Hippocrates showed the path; I made it passable.” Galen didn’t know what caused the Antonine Plague, but he did know that it spread quickly in densely packed pockets of humanity and less quickly when people stayed away from each other.

The Roman Empire survived the Antonine Plague, its imperial fibers frayed, but not broken. The empire recovered its strength. Relative good health returned. Until AD 249, that is, when the Plague of Cyprian ambushed the empire. The Plague, named for the Christian Bishop from Carthage whose writings document the event, was probably smallpox. The Plague of Cyprian lasted 20 years and, at its height, killed about 5,000 people per day in Rome.

Once again, the empire recovered, but now it was weaker with reduced resources. Moreover, the RCO was steadily ending and climate was beginning to turn unfavorable. Egypt, the empire’s breadbasket, began to experience drought, something that had never happened during the RCO. This time, the empire dissolved into anarchy and saw the emergence of the “barracks emperors,” who righted the ship of state once more – for a time. But now, disease was always just over the horizon.

In AD 378, the Roman army suffered its worst defeat ever at Adrianople where 20,000 soldiers were killed, a terrible loss of life, but tiny compared to plague deaths. In 410, the Visigoths sacked the city, the first time an enemy army had ever been inside the the Roman walls. Rome was heading inexorably toward its ruin.

In AD 541, the Justinian Plague landed the knockout punch for the Roman Empire. This greatest of pandemics, until then, anyway, was the pandemic of yersinia pestis, the agent that causes bubonic plague, and it lingered off and on for 200 years. That was when Rome descended into a high-end, Byzantine rump state, its former glory a distant memory. Roman records show the city inhabited by one million people during the time of Marcus Aurelius in AD 165, now housed about 20,000. The world would not see another million person city until London at the end of the 17th century.

Where did all the disease come from? Until the Antonine Plague, Rome had never been struck on such a grand scale. Today, experts believe it hitched a ride with people who travelled more and more in a vast empire. For example, the Justinian Plague is thought to have originated in China, making its way to Rome through trade. Just like today.

The Romans didn’t have the scientifically designed medical therapies to combat infectious disease. But even then mitigation efforts were aimed at running from the disease, creating separation, wherever it manifested. For example, in AD 452 Attila the Hun was plundering all of Italy on his way to Rome, whose soldiers were powerless against him. But then, confounding the Romans, he stopped, decamped and headed for the high ground of the Alps. Why? To get away from the anopheles mosquito. Malaria was suddenly killing his men and his horses. Which proves germs were better at killing than soldiers.

The Black Death of the Middle Ages

In the 14th century, bubonic plague (and probably anthrax, too) struck again causing the greatest pandemic the world has ever seen. The population of England was reduced by ~50% and did not recover until about 1800.

At that time, Edward III, King of England, Wales and one-third of France, was poised to add Spain to his conquests by marrying his 15-year-old daughter, Princess Joan, to Spain’s Prince Pedro. The marriage would change the face of Europe and give Edward control over most of the continent. The year was 1348, and bubonic plague struck as Joan and her large entourage were crossing the channel. They landed at Bordeaux, where the plague was suddenly and viciously cutting down the population leaving bodies stacked in the streets. The stench was terrible. People dealt with it by walking around covering their noses with handkerchiefs drenched in perfume. The 14th century’s version of face masks.

The welcoming committee advised the Princess and her party to get far away from the plague. But the English thought they knew better and settled into Chateau de l’Ombriere, overlooking the Mediterranean and dead smack in the middle of the disease. Within weeks, they were all dead except for one English minister who brought the news back to Edward.

And so the bite of a flea altered the course of history.

The Spanish Flu of 1918/1919

And in the early 20th century we were visited by the Spanish Flu, which carried off 50 million souls worldwide. We told the story of the Spanish Flu here, early in our waltz with COVID-19.

Americans then did what Americans are doing now: they kept apart, stayed home to avoid contact, and wore masks when they moved around in society. At least most of them did, just as most are doing now.

Those Americans had to wait 20 years for a vaccine that only 40% of us now take, and thousands still die every year from the flu.

Conclusion

You may say, “Why is this history, interesting though it may be, even being mentioned? Here in 2020, we’re 2,000 years removed from ancient Rome; 650 years from the death of Princess Joan, and the Spanish Flu was 100 years ago. Why bring this stuff up now?” After all, the combination of more energy, more food, sanitary reform, germ theory, antibiotics and all around jet-propelled science have led to a population boom unlike anything else in the history of the planet. People are living longer and better. So, why look to ancient history in the midst of COVID-19?

Social distancing is nothing new. Throughout history, when societies were confronted with infectious disease on a grand scale, people tried to evacuate the area. Some of them could, most could not. They had no knowledge of the value of hand washing, and hand shaking was as common then as it is now, or at least as it was ten weeks ago, so disease transmittal was rampant.

But beyond all that, although blind luck and more than a little mismanagement contributed to the decline and fall of Rome, infectious disease and climatological degradation were the driving forces. And the Romans were blindsided by both. In the Black Death period, aristocratic hubris and tremendous poverty throughout the population’s underbelly led to death on a massive scale. During the Spanish Flu, many in the U.S. ignored warnings and directives to be “socially distant.” Many chose not to mask in public. Many protested government edicts to contain the spread of the disease. And many died.

Here, during COVID-19, we’ve had:

  • Gross mismanagement from the top, as well as in some of the states;
  • Aristocratic hubris on a massive scale;
  • Profound economic inequality and, consequently, disease in large sections of our urban communities; and,
  • Misguided protesters who endanger themselves and others as they gather together clamoring for the freedom to do just that.

Science and our seeming societal sophistication have led many of us, too many, to believe we actually can plant cut flowers and watch our garden grow.

In the words of that great American philosopher, Pogo, “We have met the enemy, and he is us.”