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Friday, May 8, 2020
The Testing Mess
I have not written much about testing since the early days of this crisis, because there is almost no reliable information. The Infectious Diseases Society of America issued recommendations about testing two days ago, and the authors admit that their advice is almost evidence-free.
So, this is all I can say reliably at this time.
1. A fabulous review article describing everything about SARS-1, written by scientists from Hong Kong discusses the significant difficulties in developing various tests for coronaviruses. I highly recommend reading it, because it is extremely relevant to SARS-2, and no compilation like this exists yet for the new coronavirus.
2. CDC decided in January it would develop a nasal swab PCR COVID test and that no one else could market COVID tests in the US. It failed to create a usable test, so on Feb 29 FDA said others could apply to FDA for an emergency use authorization (EUA) for their tests. But their EUA process was very cumbersome, so few applied. Until March 16, only 4 EUAs had been issued, including the EUA for CDC's failed test.
Still lacking testing, FDA on March 16 said that anyone could offer COVID tests in the US, and apply later for FDA approval. Between then and now, over 100 companies poured into the testing market, and FDA issued 65 emergency use approvals for both PCR and antibody tests. These were approved on an emergency basis, and do not reflect a guarantee by FDA of test validity.
Beginning March 31, FDA also approved tests that had been developed by 24 university and commercial labs, but only if they were performed on-site at the lab that developed them.
On May 4, FDA issued new guidelines which will attempt to bring some order into this chaos.
3. Antibody tests measure antibodies but do not necessarily identify immunity. As in Lyme disease: you may have antibodies but are still susceptible to another infection. Or, you may have Lyme disease but are not making enough antibody to detect with existing tests, even after weeks or months.
It is a lot more important to determine if you are immune, than to determine if you just have antibodies. I will wait to spend my money on tests of immunity, if and when they become available.
4. PCR (aka "molecular") tests look for a small portion of the virus, generally in your nasopharynx. This is not a culture test for the virus, and does not absolutely guarantee that you have active infection and are contagious--but it is the closest we can come to diagnosing active infection in the lab. We don't know how sensitive nor specific each of the many available tests are, but in China the rule was to perform multiple tests before releasing people from quarantine. We should expect false negatives, which can also result from sampling errors. Here is what the FDA says about negative results, indicating they are quite concerned about false negatives:
What does it mean if the specimen tests negative for the virus that causes COVID-19?
A negative test result for this test means that SARS CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions. A negative result does not exclude the possibility of COVID-19. When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19. The possibility of a false negative result should especially be considered if the patient’s recent exposures or clinical presentation indicate that COVID19 is likely, and diagnostic tests for other causes of illness (e.g., other respiratory illness) are negative. If COVID-19 is still suspected based on exposure history together with other clinical findings, re-testing should be considered by healthcare providers in consultation with public health authorities.
Risks to a patient of a false negative include: delayed or lack of supportive treatment, lack of monitoring of infected individuals and their household or other close contacts for symptoms resulting in increased risk of spread of COVID-19 within the community, or other unintended adverse events.
5. What concerns me as much as unreliable tests, however, is an unreliable supply of testing machines and supplies. I want to know that FDA is identifying the best tests, and that the government is adequately stockpiling the materials needed to perform them, in the event of a massive "second wave" of illness. Since we still lack sufficient supplies to test everyone suspected of COVID now, what plans are being put in place for a potentially much worse situation ahead? The media should report on this.
Posted by Meryl Nass, M.D. at 6:20 PM 0 comments
Americans in need of N95 masks go without so money could be spent on $2.8 billion sweetheart deal for anthrax vaccine manufacturer/ WaPo
A spectacular Washington Post article of May 4 connected the lack of protective respirators (aka N95 masks) with Emergent BioSolutions (the anthrax vaccine manufacturer). Emergent received incredible insider contracts from the current Assistant DHHS Secretary of Preparedness and Response (ASPR), Robert Kadlec, who early in life attended the Air Force Academy and DOD medical school, but has forgotten his air force and physician oaths. He is better described as a voracious Beltway Bandit with little concern for the health of those in his trust.
He is also a former partner and contractor for the majority owner of Emergent BioSolutions, Fuad El-hibri, which he omitted disclosing to Congress, as required, when approved for the job of Assistant Secretary.
Until 2018 the Strategic National Stockpile of drugs, vaccines, devices and personal protective equipment (PPE) was controlled by CDC. CDC failed to resupply needed PPE after the 2009 swine flu and 2014 Ebola epidemics. But at least, under the Obama administration, a contract had been initiated to design and build a machine that would produce 1.5 million N95 masks per day. These are the only masks that protect well against the inhalation of pathogens, including SARS-2. They cost about $1.00 apiece, retail, before this pandemic. They are lifesaving. And they used to be discarded after each use.
The design for the N95 machine was completed, but the current Assistant Secretary, Robert Kadlec, cancelled the $35 million contract to build it. He instead spent that money on contracts for more smallpox vaccine, even though there was enough in the stockpile for all Americans, giving Emergent BioSolutions a deal worth $2.8 billion, 8 times as much as the previous contract, immediately after they purchased the smallpox vaccine maker.
From the April 3 Washington Post:
In September 2018, the Trump administration received detailed plans for a new machine designed to churn out millions of protective respirator masks at high speed during a pandemic.
The plans, submitted to the Department of Health and Human Services (HHS) by medical manufacturer O&M Halyard, were the culmination of a venture unveiled almost three years earlier by the Obama administration.
But HHS did not proceed with making the machine.
The project was one of two N95 mask ventures — totaling $9.8 million — that the federal government embarked on over the past five years to better prepare for pandemics.
The other involves the development of reusable masks to replace the single-use variety currently so scarce that medical professionals are using theirs over and over. Expert panels have advised the government for at least 14 years that reusable masks were vital.
That effort, like the quick mask machine, has not led to a single new mask for the government’s response...
And in the May 4 Washington Post:
In the two years before the coronavirus pandemic, Kadlec aggressively pursued efforts to fulfill his vision for national preparedness, the Post examination found. He assumed greater control over acquisitions for the Strategic National Stockpile, which in 2018 was moved from the Centers for Disease Control and Prevention and placed under his authority, the examination found.
Executives at Emergent BioSolutions specifically identified transferring the stockpile from the CDC to ASPR as part of its annual corporate strategy for 2017, according to people familiar with it. Like many large contractors, the company has long cultivated relationships in Washington, and it has spent almost $45 million on lobbying since 2005, records show.
Kadlec scaled back a long-standing interagency process for spending billions of dollars on stockpile purchases, diminishing the role of government experts and restricting decision-making to himself and a small circle of advisers...
Kadlec committed additional spending to biodefense countermeasures such as smallpox and anthrax vaccines while cutting planned spending on emerging infectious diseases, despite warnings from scientists that a natural contagion could also be devastating. Citing limited resources, his office halted an Obama-era initiative to spend $35 million to build a machine that could produce 1.5 million N95 masks per day, as The Post previously reported...
By the time Kadlec’s office finalized the deal, records and interviews show, it had been extended from five years to 10 and the number of doses per year had doubled, to 18 million. An Emergent executive said the price per dose is $9.44 in the first year, more than twice what the government paid its previous supplier.
Kadlec has largely replaced the old system for making final buying decisions with more-exclusive gatherings in a sensitive compartmented information facility, or SCIF. Invitees often include his deputy and his counterpart for chemical and biological defense at the Pentagon, the official said.
Last year, a simulation organized by Kadlec’s office dubbed “Crimson Contagion” revealed how unprepared the government was for a pandemic. An internal report on the exercise found officials would face “cascading” funding and supply-chain shortages, including “scarce medical countermeasures such as personal protective equipment, diagnostics, and antivirals.”
Facing intense criticism for the stockpile’s inadequate supplies of protective gear and other medical equipment, Kadlec’s office has recently announced new contracts worth billions of dollars for respirator masks, ventilators and other medical supplies...
Chris Meekins, a former congressional staffer who was then an applicant for a senior position in ASPR... and later became Kadlec’s chief of staff at ASPR, wrote that he had told HHS secretary Price in 2017 that putting the stockpile under the control of the assistant secretary would improve the nation’s response in a crisis.
In February 2018, the administration signaled in its proposed budget for the following year that it intended to transfer the stockpile, with contents worth $7 billion, to Kadlec’s office.
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Update: Recent emergency relief efforts are also failing Americans who need the N95 masks. Project Airbridge, Trump's project to pay for flights bringing in medical equipment from overseas, has distributed just 768,000 N95 masks, — far fewer than the 85 million N95 masks procured through conventional federal relief efforts, according to the latest FEMA records. In 122 flights so far.
Posted by Meryl Nass, M.D. at 2:02 PM 0 comments