Wednesday, April 1, 2020

My old piece titled "In search of the anthrax attacker" which was featured on RedFlagsDaily and my old anthrax vaccine website

In Search Of The Anthrax Attacker - Following Valuable Clues
By Meryl Nass, MD
February 3, 2002
"Senior Bush administration officials have privately said that little progress is being made in the anthrax investigation, which has involved hundreds of investigators, [who] are no closer to finding the culprit, they say." So reported Todd J Gillman and Michelle Mittelstadt of the Dallas Morning News on January 31.
It has been four months since the first case of inhalation anthrax was diagnosed. Last week, the FBI announced that it would be sending flyers to 500,000 residents of the Trenton, New Jersey region, asking for leads. This week, the FBI arranged with the American Society for Microbiology to e-mail its US membership, in another attempt to reach out to scientists that might have insight into the attacks.
Dr. Barbara Hatch Rosenberg, an arms control expert at the State University of New York, Purchase, and chair of a bioweapons panel at the Federation of American Scientists authored an analysis of the attacks that may have prodded the FBI into investigating the US bioterrorism establishment. She thinks the scientific details could be too complicated for investigators to grasp.
But if the FBI has no anthrax expertise, there are plenty of scientists who do, and who would be happy to assist in the investigation.
Last October, both Ken Alibek (the defector who was #2 in the Soviet biowarfare establishment, and who also developed the most virulent Soviet anthrax) and William Patrick (the man who was #1 in the US biowarfare establishment, and developed a powder used for weaponizing anthrax, allegedly the same material used in the attacks) were quoted as saying that no one had sought their help in the investigation. That made me extremely curious, since they were two public figures most knowledgeable about weaponized anthrax, and would know how to analyze the anthrax and identify its origin.
Why had the anthrax been sent in letters, rather than released in ventilation systems, tunnels or subways? The (estimated) two trillion spores per letter could have caused a lot more mischief in another setting.
Something else was odd. The attacker had actually warned the recipients that the letters contained anthrax, and suggested they take penicillin. Then a lightbulb went off: someone was sending these letters to create an effect, not to cause damage. The letters were sealed with tape, presumably to further prevent the escape of spores. The point was to frighten, not to kill. And the targets were chosen with an eye to getting publicity and making an impact on Congress.
The attacker also had familiarity with forensic investigations. He avoided using saliva on the letters, used a form of printing that is most difficult to analyze, and otherwise left a paucity of evidence. Did he have professional help?
(I am referring here to the anthrax attacker in the singular and using the male gender, although I suspect that, for logistical reasons, it is unlikely that one person acted alone, or was even a loner, as the FBI profile has suggested.)
I subsequently learned of William Patrickís 1999 analysis of anthrax sent by mail, written for a defense contractor. Iíve not seen the report, but have been told he did not consider that envelopes contained pores, and was not aware that postal machines squeeze and compress the mail, forcing anthrax spores out of intact envelopes.
The attacker may well have read Patrickís report, or even used it as a model. Who had access to this report?
To commit a crime one must have a motive. Because of the unpredictability of who might become ill, or die after exposure to the letters, I doubt that the attacker had specific victims in mind. A grudge against Tom Brokaw or Senator Daschle has been postulated. Did the attacker really think they opened their own mail?
More likely, the attacker wanted to frighten Congress, which controls spending for bioterrorism. If new appropriations for bioterrorism defense are a measure of the attackerís success, he has certainly triumphed.
Who are the beneficiaries of a bioterrorism scare?
The biowarfare establishment has benefited so far: CDC got $450 million extra for bioterrorism, and the states will get $1.1 billion dollars. More money has been spent on stockpiling antibiotics, and the government has contracted for 209 million doses of smallpox vaccine, at a cost of $850 million. Other biowarfare vaccines in development have probably had new life breathed into them.
The US Army Medical Research Institute of Infectious Diseases (where the Armyís center for biodefense, Fort Detrick, is located) will receive increased funding and stature. Bioport, the anthrax vaccine manufacturer that tried in vain for the past 2 years to get FDA approval, after as major overhaul of its facility, just got it - though Congressman Ben Gilman has asked the GAO to investigate this, and the Defense Department has declined to say whether anthrax inoculations for the military will resume.
Who had the means?
After the attacks it was revealed that the powdered, weaponized anthrax is identical to that made by our own biowarfare establishment; that is, by the same people who are benefiting from the attacks.
One area of wasted investigative effort was the search for the origin of the "Ames" anthrax strain used. It was reported initially that hundreds of labs held Ames anthrax samples. Then it turned out that few actually did.
On October 11, after receiving FBI approval to do so, Iowa State University destroyed their anthrax collection. Did this result in the loss of crucial evidence?
But how would tracing back the Ames strain solve the case? Even if only 20 labs had samples, not all of them had high levels of security. After all, some are university labs. Scientists share strains with hardly a thought. Ames anthrax could have been stolen, shared, or even dug up from Texas soil. Or removed from one of the labs by a scientist with access.
Dr. Paul Keim of Northern Arizona University maintains an extensive anthrax database; he examined the Ames anthrax used in the attacks with a series of genetic probes, and said it was identical to the strain held at several government labs. But to be certain, the entire genome of the attack anthrax and the government anthrax are being deciphered, so that individual differences can be counted and examined, and estimates made as to precisely how close (or how many generations apart) the two strains really are. (Of course, this assumes that the actual government strain, and the actual letter strain were provided to the Institute for Genomic Research in Rockville, Md.)
Reading William Broadís article, "Geographic Gaffe Misguides Anthrax Inquiry," in the January 29 New York Times, one finds confusion over the meaning of the strainís origin. Broad also takes Dr. Rosenberg to task over her earlier statement that the anthrax "may be a remnant of the US biological weapons program."
Broad discovered that the Ames strain came from a cow that died in Texas in 1981, not from a cow that died in Iowa in the 1930ís. He then inferred that the strain did not come from the US biowarfare stockpile, which was officially destroyed by 1975, when the Biological Weapons Convention went into effect.
But a CIA memo signed by Thomas Karamessines, and provided to the Senate, informs us that the CIA (at least) kept 100 grams of anthrax, illegally, after the Convention went into effect. So some of the old stockpile could still be around.
The fact that the Ames strain was isolated from a cow in 1981, and from a goat several hundred miles away in 1997, indicates that there is a lot of Ames in Texas, and it most likely was there well before 1981, and ever since. So it could have comprised part of the old US stockpile. William Patrick and others would know, and there should be records to show what was actually produced.
The more germane issue, however, is whether the isolation of Ames in 1981 exonerates the Defense Department, CIA, or US government contractors from possible involvement in the anthrax attacks. It does not.
No matter whether the government first got its supply of Ames before or after 1970, when it officially ended its offensive biowarfare program, Ames was eventually used to create a government supply of dry, weaponized anthrax, which at this time appears to be identical to that used in the attacks.
Of more importance to the investigation, however, is the origin of:
a) the material added to the anthrax spores that causes them to separate from each other, greatly enhancing virulence, and
b) the method that assured the spores were relatively uniform in size, and were sized for optimal lethality.
Although Ames was shared, this method of production, as well as the additive, would have been closely-guarded secrets. They are what made Ames extremely lethal, and the same could be done with other strains.
Furthermore, the Biological and Toxin Weapons Convention, which the US initiated and signed in 1972, prohibits the possession of biological agents that are not used for defensive purposes. No defensive use for this form of anthrax has ever been publicly disclosed.
In contrast, the Ames anthrax that is used in (defensive) vaccine experiments is dispersed by an aerosolizer from a liquid slurry. No dry anthrax is used. (In liquid form, anthrax is a poor weapon.)
To test our defenses against dry anthrax, you can use a benign Bacillus spore, a cousin of anthrax. The mere possession of dry, weaponized anthrax could be deemed illegal under the terms of the Convention. So the United States kept its existence secret, and would have had little reason to share it. We wouldnít want the material or recipe for making highly dispersible spores to reach potential enemies.
The real question is: who had access to this material, or knew the method for its production? A clue: you will find the attacker among the very small clique of bioweaponeers with this specialized knowledge or access to the weaponized end product.
Now to the question of whether the anthrax was homemade, or snatched from a government inventory. It is much more likely to have been snatched, but either is possible.
Anthrax cannot be produced without leaving evidenceótelltale spores that have escaped into the environment. Companies that use spore-forming organisms to manufacture vaccines (for tetanus and botulinum toxoid, for instance) can never use the facility for making other products, due to persistent contamination with invisible spores. The Hart Senate Office Building clean-up took 3 months and cost $14 million, and may not have rid the building of every anthrax spore.
Therefore, production in a basement lab could lead to spore detection (and proof of guilt) for the foreseeable future, if environmental samples were obtained and cultured. Furthermore, the equipment and materials the attacker purchased to produce the anthrax could be traced.
In addition to increasing the attackerís chances of being detected, spore production is dangerous. Remember, this is someone who knows all about anthrax. He knows what these spores can do, and would not have wanted to expose himself to them.
Anthrax experts know that physical protection (particularly the use of a self-contained breathing apparatus) is your primary protection from inhaled anthrax. It has long been established that large spore counts can overwhelm vaccine-induced immunity and antibiotic protection. In fact, for a long time the Ames strain was called "vaccine resistant" at Fort Detrick. So anyone in-the-know would have worked with the spores in a safe setting. They might well have been vaccinated and used antibiotics, but would not have relied on them exclusively for protection.
Therefore, anthrax was almost certainly manufactured, mixed with the anti-cling powder, and placed into envelopes in a protected environment.
Placing the spores - two trillion at a time - into envelopes would have been particularly dangerous. These spores floated off the glass slides when scientists first tried to look at them. You canít fill an envelope without losing millions or billions of spores in the process.
It is only logical that the filling occurred within an official anthrax "hot suite"- a Biosafety Level 3 or 4 facility, by someone in a "moon suit" using a protected air supply. There are a small number of these facilities. They must have substantial security, possibly video cameras, and there must be logs that indicate who used them.
If the attacker used government-made (or defense contractor-made) anthrax, and filled the envelopes in hot suites already contaminated with Ames anthrax, he will have left no evidence. He could walk out of the hot suite with his filled envelopes in a plastic bag or other secure container, and no one would be the wiser.
Furthermore, the first known letters were postmarked September 18, and contained a fake Islamic message.
Yet another clue: although anthrax degrades extremely slowly, and could have been obtained or produced at any time, the choice of September and an Islamic message suggests the first envelopes, at least, were filled between September 11 and 18. Who used the hot suites then?
This past week a new, important wrinkle was reported. An Egyptian-born scientist, Dr. Ayaad Assaad, had been fingered as a possible bioterrorist in an anonymous letter sent to Quantico Marine Corps Base, before any anthrax letters had even been discovered. It is unclear whether the letter was sent to the military or to the FBI, which maintains a substantial presence on the base.
Assaad had worked at Fort Detrick for years, but was laid off in 1997, and had an age discrimination lawsuit pending against his former employer. Furthermore, while at Detrick he had been the butt of a salacious and demeaning poem circulated by a group of coworkers- all Army scientists- who called themselves the "Camel Club." Unauthorized nighttime research and missing anthrax slides at the lab where the club members worked embellish the story.
Although one might manage to grow anthrax from a spore found on a stolen pathology slide, itís unlikely. Slides are generally heated, and the material may have been treated with formaldehyde, which kills anthrax. There must be easier ways to obtain anthrax, especially if you work at Fort Detrick. Although itís a juicy story, there is a huge divide between anthrax on a pathology slide and the production of weaponized anthrax. They do not equate.
At first glance, the letter about Assaad seemed to have been written by a former Camel Club member, who decided to revive an old antagonism. But it is much more likely that the real attacker knew of the club, and meant to lay guilt on former club members. (The club members were not anthrax scientists, but instead worked on pathogenic viruses.)
Letís look more closely. The first letters to arrive with anthrax took a long time to cause illness. Until then, they were dismissed as hoaxes. The letters to the New York Post and NBC were postmarked September 18; the letter to The Sun, a Florida-based tabloid, has never been found. The first anthrax case was diagnosed in Florida on October 3, probably 15 days after the letter was sent.
It seems logical, therefore, that the Quantico letter (that insinuated Assaad was a bioterrorist) was meant to arrive after the public had become aware of an anthrax attack. Had that happened, the letter would have been perceived as a response to the attacks. But since it arrived first, indicating foreknowledge of the attacks, it could only come from the attacker himself.
Therefore, where the letter came from, when it was sent, and the personal details of Assaadís life that it contained are vitally important. Only a small number of people could be sufficiently familiar with Assaad and the Camel Club shenanigans to have written it.
A very important clue: one of these people is the perpetrator. He may also have some connection to Quantico.
Where does this leave us?
Most likely, the suspect still works in the biodefense field, but might be a former employee. He may have read William Patrickís report on mailed anthrax. Places where the perpetrator likely worked may include Fort Detrick, Dugway Proving Ground (where a large Biosafety level 3 facility for testing biowarfare aerosols exists), Battelle Memorial Institute, CDC, and Bioport, but there are others. All these entities potentially stand to benefit from the new interest in bioterrorism. The person probably worked at Fort Detrick years ago, and knew Assaad and the Camel Club members. Either recently, or in the past, the attacker had access to weaponized anthrax. He used a high containment, Biosafety 3 or 4 facility to prepare his anthrax-laden envelopes between September 11 and 18.
Where do we go from here?
People who fit this profile should be investigated, to include interviews possibly using lie detectors. If warranted, their homes and businesses should be carefully cultured for stray spores. Retired Fort Detrick workers, who are familiar with what was stockpiled, and how anthrax products were made, should be interviewed. Several are on record as saying they have not been approached. All appropriate Biosafety facilities, here and in other nations, should have their logs reviewed. It should be easy to construct lists of those who worked at Detrick and knew Assaad, those who had access to weaponized anthrax or knew the recipe, and those with access to the hot suites. However, if there do exist several attackers, the overlap might be hard to find. This person, or his program, if such is the case, is likely to benefit nicely from the anthrax scare.
The anthrax attacks were a heinous crime in a number of ways. First, they caused the deaths of five innocent civilians, who in military jargon might be considered "collateral damage." Second, they directly attacked the center of our government, and our free press. Third, they appear to have been motivated by the calculation that the country needed to be scared to death, in order to act in a way the attacker wanted. And so we have, allocating billions of taxpayer dollars for responding to and preparing for bioterrorism. That is not how decisions should be made in a democracy. Finally, biological attacks are a clandestine, cowardly method of attack, in which the perpetrator is usually difficult to identify.
If the attacker remains free, the attractiveness of future biological attack only increases.

Tuesday, March 31, 2020

A negative coronavirus test doesn't always mean you are not infected/ WaPo

Various interviewees estimated the that the coronavirus tests they are familiar with are 75%, 85% or 100% accurate:

Demetre Daskalakis, deputy commissioner for the division of disease control of the New York City Department of Health and Mental Hygiene, said he recently told a patient with mild symptoms who sought a test and received a negative result to act like he had it.
“The pretest probability if you have fever or cough in a pandemic — if you have a fever, cough and shortness of breath, it’s covid-19. Even if the test is negative,” Daskalakis said.

How dependent is the U.S. on China for its drugs? The fact is, the FDA doesn’t know/ FiercePharma

Janet Woodcock has spent most of the last 20 years as the head of FDA's Center for Drugs.  Most of that time, while China and India took over the manufacturing of most of the world's drugs, her head has been buried in the sand.  From FiercePharma:

"As the spread of COVID-19 threatens to disrupt pharma supply chains and create drug shortages, the Trump administration is reportedly looking for ways to reduce U.S. dependence on APIs and drugs from China. So, how dependent is the U.S. on China for its drugs? The fact is, the FDA doesn’t know. 
Janet Woodcock, FDA’s director of the Center for Drug Evaluation and Research, in congressional testimony in October said while it is clear drug production, particularly of APIs, has moved out of the U.S., the FDA doesn’t know a lot more than that. FDA info show the number of Chinese facilities licensed to produce APIs for U.S. drugs is smaller than in the U.S., 13% versus 28%, but those statistics don’t mean much. 
“The FDA doesn’t know whether Chinese facilities are actually producing APIs, how much they are producing, or where the APIs they are producing are being distributed worldwide, including in the United States,” Woodcock reported. “… Similarly, we do not have information that would enable us to assess the resilience of the U.S. manufacturing base, should it be tested by China’s withdrawal from supplying the U.S. market.”

CDC considering recommending general public wear face coverings in public/ WaPo

This WaPo piece provides further evidence that the government is well aware this virus transmits via the airborne route.  As a result, indoor air that is shared with those infected (who may be asymptomatic or presymptomatic) carries risk of infection.  You don't need to have someone cough on you.  Breathing infected air is enough to catch coronavirus.

Of 60 members of a choir who came together for a rehearsal, practiced social distancing, used hand sanitizer and did not hug each other, 45 developed COVID and 2 have died.

Dr. David Price, a new pulmonology graduate at Weill Cornell Medical Center, is spreading a terribly dangerous rumor that 99% of infections are spread through touching a contaminated object.  It isn't true.  Airborne spread is a terribly important mode of transmission.  Please don't let your guard down.

Monday, March 30, 2020

Battelle has had an (unused) method to decontaminate N95 masks aka respirators for years!

Unbelievable.  4 years ago, the FDA gave contractor Battelle half a million dollars to study the use of commercial decontamination equipment, using hydrogen peroxide gas, on N95 masks.  Battelle said the method worked in 2016.  But we are only just hearing about it, as thousands of healthcare workers get infected due, in part, to lack of these masks. WTF??!!
Battelle received an emergency go-ahead from the FDA over the weekend to deploy its decontamination system for personal protective equipment (PPE), allowing healthcare workers to clean and reuse scarce N95 respirator masks.
The system is currently operating at Battelle’s Ohio facility—capable of processing up to 80,000 masks per machine, per day, within what looks like a large metal shipping container—and has been working to help stretch supplies for the OhioHealth system based in Columbus.

Using concentrated hydrogen peroxide vapor, the filters are gassed for two and a half hours to destroy bacteria, viruses and other contaminants, including the novel coronavirus SARS-CoV-2. According to the company, the system can clean the same N95 mask up to 20 times without degrading its performance. 
The FDA had first OK’d the use of the system on Saturday but initially limited its use to 10,000 masks per day, according to Republican Ohio Gov. Mike DeWine, who called on the agency to unlock the system’s full decontamination capacity. DeWine also said this would have limited Battelle’s plans to deploy machines to the hard-hit New York metro area as well as Washington state and Washington, D.C.
Within hours, and after President Donald Trump also urged the FDA to approve the equipment on Twitter, FDA Commissioner Stephen Hahn tweeted late Sunday evening that the agency had issued an amended authorization
Donald J. Trump
Thank you Dr. Hahn & the FDA for your fast approval of this respected Ohio company recommended by Governor @MikeDeWine. Great potential! Dr. Stephen M. Hahn
We issued a new authorization this evening to @Battelle for their decontamination system. @US_FDA staff have been working nonstop across gov and with the private sector to deliver solutions to the American public.
45K7:07 AM - Mar 30, 2020Twitter Ads info and privacy
In the near term, Battelle’s facility plans to begin decontaminating respirator masks for three other central Ohio health systems this week.
Battelle previously engaged with the FDA from 2014 to 2016 to study the use of its decontamination machine in the midst of a potential pandemic and PPE shortage. Currently, the company is exploring its use outside of N95 masks to other equipment such as ventilator components.

Why is the World's Richest County Short of Medical Masks?/ NYT

From  the NY Times:

Few in the protective equipment industry are surprised by the shortages, because they’ve been predicted for years. In 2005, the George W. Bush administration called for the coordination of domestic production and stockpiling of protective gear in preparation for pandemic influenza. In 2006, Congress approved funds to add protective gear to a national strategic stockpile — among other things, the stockpile collected 52 million surgical face masks and 104 million N95 respirator masks.
But about 100 million masks in the stockpile were deployed in 2009 in the fight against the H1N1 flu pandemic, and the government never bothered to replace them. This month, Alex Azar, secretary of health and human services, testified that there are only about 40 million masks in the stockpile — around 1 percent of the projected national need.
As the coronavirus began to spread in China early this year, a global shortage of protective equipment began to look inevitable. But by then it was too late for the American government to do much about the problem. Two decades ago, most hospital protective gear was made domestically. But like much of the rest of the apparel and consumer products business, face mask manufacturing has since shifted nearly entirely overseas. “China is a producer of 80 percent of masks worldwide,” Laverdure said.
Hospitals began to run out of masks for the same reason that supermarkets ran out of toilet paper — because their “just-in-time” supply chains, which call for holding as little inventory as possible to meet demand, are built to optimize efficiency, not resiliency.
“You’re talking about a commodity item,” said Michael J. Alkire, president of Premier, a company that purchases medical supplies for hospitals and health systems. In the supply chain, he said, “by definition, there’s not going to be a lot of redundancy, because everyone wants the low cost.”
In January, the brittle supply chain began to crack under pressure. To deal with its own outbreak, China began to restrict exports of protective equipment. Then other countries did as well — Taiwan, Germany, France and India took steps to stop exports of medical equipment. That left American hospitals to seek more and more masks from fewer and fewer producers...

Thursday, March 26, 2020

There are many ways the novel coronavirus may have come about/ Nass

Nature Medicine ran a 3 page article that claimed to explain why the novel coronavirus is not a lab construct.  USA Today wrote a summary piece explaining it:

“If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness,” the report said. “But the scientists found that the SARS-CoV-2 backbone differed substantially from those of already known coronaviruses and mostly resembled related viruses found in bats and pangolins.”—USAT

Yet it turns out to be a specious argument, relying on the fact that the novel coronavirus backbone sequence was not already known in the open virology literature.

1.  While starting from a known RNA sequence is one easy way to create a pathogen, it is certainly not necessary to do so. 
2.  Nor is it likely that biodefense/biowarfare programs share knowledge of all their creations.  They never have before.  
3.  Finally, it is relatively easy to detect the human hand when a chimera of known virulence factors is strung together.
4.  And because plausible deniability is a critical component of a bioweapons attack, I doubt that a chimera using known sequences is the path that would have been followed by a modern biowarrior.

I will briefly mention some of the old techniques for creating bioweapons, none of which require that a known, published RNA backbone would be required to build a novel, virulent coronavirus:

1.  China has unique bats.  So do other countries.  Unique bats likely harbor unique viruses.  Bits of these viruses can be strung together, while no outside parties are aware that these particular RNA threads exist in nature.

2.  You take an already virulent RNA virus, subject it to high rates of mutation via chemical or radiological exposure, and test the viruses that survive for the acquisition of new virulence characteristics.

3.  You simply passage the virus through tens, hundreds or thousands of lab animals or cell cultures and test the results for acquisition of new virulence characteristics.

4.  You mix different viruses together with different virulence characteristics, allow them to grow together, and seek recombinants that have obtained the desired new mix of virulence factors.

All these possibilities result in viruses that are hard to pin on lab production.  I dare the Nature Medicine scientists to dismiss these scenarios.

Still, I doubt that any national program would deliberately release this coronavirus onto the people of the earth, because it is so hard to control. 
Historically, bio-weaponeers have required their creations to be controlled at all costs. In one well-documented example of biowarfare, unleashing african swine fever on an island was associated with no spread beyond the island. In another, anthrax spores were used because they stay put-- their use did not cause anthrax cases beyond the border of Rhodesia.

So why do we have this epidemic now?

An accidental biowarfare laboratory release is the best current hypothesis, in my opinion.  Such accidental releases have been documented for many decades, throughout the world.  But I could certainly be wrong.

Wednesday, March 25, 2020

An important proposal that ameliorates our lack of protective equipment and spares both patients and healthcare workers

There is a huge disconnect between the personal protective equipment (PPE) healthcare workers (HCWs) should be wearing to protect themselves from coronavirus, and what actually exists right now for them to use.  The White House has told the governors to find their own supplies.  The equipment market is in chaos.  CDC is now telling HCWs to make their own equipment.  But Kaiser Permanente threatened to fire nurses for wearing their own N95 respirators.  The WHO says the "shortage of personal protective equipment is endangering health workers worldwide."

What many people don't know is that HCWs change in and out of protective gear, which is almost entirely single use, every time they enter a room to see a patient who may be contagious via the airborne route. One contagious patient may lead to the use of 20 changes of PPE in a single day.

Nurses and doctors deserve congratulations for their bravery and commitment to continue working, even without adequate protective equipment.  Though UK doctors have threatened to quit, and Bulgarian doctors have quit.

Having doctors and nurses work under these conditions is extremely shortsighted.  Given the tremendous propensity of the virus to spread--US deaths are doubling every 3 days, and are believed to lag infection by a month--healthcare workers will be infected disproportionately, as in Wuhan and northern Italy.  But worst of all, HCWs may become viral spreaders, transmitting infection to patients who are in their healthcare facility for other reasons.  Doctors in Italy have warned that 
hospitals might be “the main” source of Covid-19 transmission. 
This situation should not be tolerated by the doctors and nurses, who know better, nor by their non-COVID patients, nor by their healthcare administrators and government.

There is only one solution:  keeping patients with COVID-19 in facilities that treat only COVID-19.  And treating other patients in separate facilities.  This requires government to take control of a very messy situation:  hospitals and clinics are about to become, if they are not already, the locations that put their patients at highest risk of infection. But hospitals will not suddenly create separate COVID facilities by themselves.  Government needs to step in to make this happen.
Creating designated COVID-19 facilities would allow healthcare workers to put on a complete set of protective garments: masks, goggles, face shields and head to toe gowns and shoe covers, at the beginning of their shift.  They would then not change out of the garments between patients, since all the patients are already infected.  It would save tremendous amounts of equipment and time, since HCWs would not have to change up their gowns, gloves, etc. between each patient, and would have enough protective equipment to work in safety.

How do you identify the COVID patients, when PCR tests have again slowed due to lack of reagents and swabs?

In Italy and China, ultrasound exams of the lungs, or CT scans, have been used to differentiate the specific lung pattern caused by this coronavirus (a bilateral ground glass appearance, especially in the lung periphery) from other infections.  This can provide a faster diagnosis than a lab test, with almost as much accuracy, at the point of patient contact. Ultrasound machines may be portable and inexpensive.

Hopefully new rapid laboratory tests will also be available to aid in immediate diagnosis.

Patients would be triaged and separated into those who: 

1.  definitely have COVID-19 based on their history, symptoms and a scan
2.  definitely have a different disorder, or
3.  maybe have COVID-19 

The 'maybe' patients must be situated in separate rooms to avoid cross-contamination, and would require HCWs to change their gowns, masks, etc. between patients. The HCWs caring for non-COVID patients would not require protective gear, except perhaps a mask in case they are asymptomatic spreaders.  Those caring for COVID patients would use only one set of gear for each shift.

By so doing, we keep HCWs and patients safe, and sensibly use the limited personal protective equipment currently available.  We avoid reliance on expensive but untested tech solutions for monitoring patients from a distance.  And it saves patient lives.

By keeping HCWs suited up, they can safely work at the bedside, and, when critical patients need urgent intubation, which is required all too often with COVID-19, our doctors and nurses will avoid the several minute delay of getting dressed in gear before they can take care of the patients' immediate needs.

We need strong leadership to immediately enable healthcare facilities to implement this type of system, the same way we needed strong leadership to impose quarantines to 'flatten the curve.'

Tuesday, March 24, 2020

Desperate for Covid-19 answers, U.S. doctors turn to colleagues in China/ Stat

From STAT, a report of an online meeting between Johns Hopkins infectious disease doctors and doctors from Zhejiang, one of China's top medical schools, who had responded to the COVID-19 epidemic: 

...We want to work together with you to help fight Covid-19, Wang told the Americans as the hourlong meeting began. Their first question: If you were in our position, at the very beginning of the outbreak, what are the most important things to know?

The Zhejiang contingent took over one makeshift ICU in Wuhan on Feb. 14, plus one ward for Covid-19 patients in an existing hospital. They had 72 ICU patients, 55% older than 65, yet only nine of the ICU patients died; 17% required intubation in order to breathe, a procedure that risks making virus particles not only airborne but also aerosolized — meaning they can remain suspended in the air for some time.

The Hopkins doctors were keen to hear how their counterparts cured 35 intensive-care patients completely and brought the status of another 28 to only mild disease. With no surefire Covid-19 therapy and a blizzard of conflicting information on what existing drugs might work, Antar said, “one of our main questions was about their experience with off-label use” — repurposing existing drugs approved for other illnesses to use in the fight against Covid-19.

That experience has involved everything but the kitchen sink, though informed as much as possible by science. Several antivirals, including the HIV drugs lopinavir and ritonavir, did not accelerate recovery or reduce mortality, ICU physician Xiao Lu said. Some immune system regulators — including alpha interferon, anti-IL-6 monoclonal antibodies such as tocilizumab, and immunoglobulin — showed hints of efficacy in some critical cases.

Some patients received the malaria drug chloroquine, which President Trump has touted and which is being tested in a World Health Organization-supported clinical trial, but the Zhejiang team did not have rigorous data on its effects. They tried tocilizumab, too, a drug that has enough potential that on Monday, Genentech announced that it had received U.S. Food and Drug Administration approval for a clinical trial in Covid-19 patients with severe pneumonia; the rheumatoid arthritis drug, which goes by the brand name Actemra, might quell the out-of-control immune reaction that has killed many Covid-19 patients.
“All of us want to practice evidence-based medicine,” Antar said. “But the timeline for this might not allow us to wait for that.”

The right equipment helped. The Zhejiang team brought oxygen supply systems, monitors, ultrasounds, ventilators, and protective equipment from Hangzhou.

Who should be hospitalized, the Hopkins physicians asked? Suspected cases can be isolated and observed in their homes, they were told, as doctors in overwhelmed Italy are also telling U.S. doctors. Mild and moderate cases can be treated in mobile units, away from other patients; coronavirus spread within hospitals has been disastrous in Italy. Severe and critical cases in China get hospitalized, but at a dedicated facility, to reduce spread from Covid-19 patient to hospital worker to non-Covid-19 patient.

How do we know when a patient can be discharged, Antar and her colleagues asked? After a normal body temperature lasting three days, minimal respiratory symptoms, two negative tests for the virus more than 24 hours apart, improvements seen in lung imaging, and no serious underlying conditions, especially for older patients.
The Hopkins teams was impressed with China’s scrupulous measures to minimize viral transmission, “especially among health care workers,” Auwaerter said. “Such measures have successfully slowed the epidemic in China.” In contrast, failing to do so has fueled the disastrous spread of Covid-19 in Italy, physicians at a hospital in the country’s hard-hit north warned over the weekend.

Monday, March 23, 2020

What other drugs might be useful?

FiercePharma on other drugs being considered for Covid-19:
Other than remdesivir and chloroquine, researchers and physicians are also looking at other existing drugs to treat COVID-19. These include AbbVie’s HIV combo therapy Kaletra (Aluvia), which just failed a clinical study in China in critically ill patients. Chinese authorities, which have been dealing with the virus longer, are also recommending an influenza med called Arbidol (umifenovir) that’s not approved in Western countries, old antiviral ribavirin and interferon-alpha. And Fujifilm’s flu drug Avigan (favipiravir) has also shown promise in the clinic, according to Chinese officials.
Roche is testing its arthritis drug Actemra’s ability to rein in the potentially deadly inflammatory response called cytokine storm observed in severe COVID-19 patients, just as Sanofi and Regeneron are running clinical trials of their rival IL-6 inhibitor Kevzara in the same setting.  See more about this drug here.
Update NY Post, March 24:
Seriously sick coronavirus patients in New York state’s largest hospital system are being given massive doses of vitamin C — based on promising reports that it’s helped people in hard-hit China, The Post has learned.
Dr. Andrew G. Weber, a pulmonologist and critical-care specialist affiliated with two Northwell Health facilities on Long Island, said his intensive-care patients with the coronavirus immediately receive 1,500 milligrams of intravenous vitamin C.
Identical amounts of the powerful antioxidant are then readministered three or four times a day, he said.
Update FiercePharma, March 26:

News recently came out that hydroxychloroquine—an anti-malaria drug highlighted by President Donald Trump as a promising coronavirus therapy—disappointed in a China clinical trial on mild COVID-19 patients. But a careful examination of the study reveals a more complicated situation.
According to investigators, adding hydroxychloroquine (HCQ), a more tolerable form of chloroquine, on top of conventional therapy didn’t shorten the time to SARS-CoV-2 clearance in a 30-patient trial. No significant differences were observed across the two arms in terms of the time it took to bring body temperature to normal or the number of patients with disease progression as shown in CT scans.
However, most patients in the study's control group were actually treated with other antiviral therapies at the same time, including AbbVie’s HIV combo med Kaletra and flu drug Arbidol. Most, but not all, patients in the hydroxychloroquine group were also treated with Arbidol. All patients got interferon-alpha.
Those meds had already been added to China National Health Commission’s COVID-19 treatment guidelines after showing some promise against the novel coronavirus. As a FiercePharma reader pointed out, “If that is the case, and even one of them has some effect on the virus, then one cannot tell if hydroxychloroquine worked or not.”
The study, published in the Journal of Zhejiang University (Chinese), found that the median time from hospitalization to conversion to virus-negative status was four days in the HCQ group, “comparable to” the two days observed in the control group. After one week of treatment, 13 patients (86.7%) had turned negative in a throat swab test, while 14 (93.3%) in the control group could say that. Again, no significant difference.
Then the question comes down to, do Kaletra or Arbidol work? At least Kaletra has stumbled in a 199-patient clinical trial in serious Chinese patients. But industry watchers also have expressed different opinions on ruling Kaletra a complete dud in the fight against COVID-19.
In a separate, retrospective study published in the Chinese Journal of Infectious Diseases on 134 patients conducted by several members of the same team, researchers reported that both Kaletra patients and Arbidol patients restored normal temperature after a median of six days, while those who got no antiviral med saw their temperatures drop after four days.
All three groups’ median time to viral clearance was seven days, and the disease progression rate on CT scans at day seven also showed no statistically significant difference.

Separately, in another clinical trial on 44 mild-to-moderate COVID-19 patients, neither Kaletra nor Arbidol demonstrated benefits in viral clearance or symptom relief compared with no antiviral treatment.
Nevertheless, the majority of patients in the new study had restored normal temperature after just one day or turned viral negative after two days, the authors noted. Cross-trial comparison of these two important endpoints revealed that fever clearance as a major difference.
It’s possible that the virus itself has changed, reducing COVID-19 severity, the researchers speculated. The new study enrolled patients from Feb. 6 to 25, while the old one looked at those accepted between Jan. 20 and Feb. 6.

Perhaps more importantly, the viral clearance and temperature-lowering data in the HCQ study's control arm were already quite impressive, reaching a “ceiling effect” that makes finding a better treatment more difficult, they wrote.
Let’s not forget the small sample size of just 30 patients. The new study’s authors argue that to reach a conclusion of whether HCQ works, a study needs to enroll around 900 patients, taking potential drop-out into consideration. That would be a major challenge during an ongoing pandemic, so they suggest testing whether the med can lower mortality rate in serious or critically-ill COVID-19 patients.
The World Health Organization is already planning a large-scale global trial, dubbed Solidarity, to test promising antivirals in thousands of patients around the globe. The treatments to be examined include chloroquine and hydroxychloroquine; Kaletra alone; a cocktail of Kaletra plus interferon-beta; and Gilead Sciences’ remdesivir...

Update March 26:  Science magazine describes a wide variety of planned drug trials