Opinion | Is our one cylinder pandemic approach about to change?

Opinion | Is our one cylinder pandemic approach about to change?

Don't get me wrong, the success of the new COVID-19 vaccines is a wonderful thing, a scientific triumph.  Unlike with HIV / AIDS it looks like it will be vaccines, not therapeutics, that will allow us to bring SARS-CoV-2 under control.  But even with a successful vaccine roll-out there will likely be fifty million more SARS-CoV-2 / COVID-19 infections in the United States before 2021 is through, most in the coming months.  Assuming only thirty million of those people ever get a positive COVID test, that's still thirty million people we're telling to isolate at home with no treatment, just dread of hospitalization and a pulse oxymeter for company.  The alternative is to find a better way to implement early monoclonal antibody infusions and to find other methods of treating COVID-19 in the first and/or second week (depending on which medication we’re talking about).  Success will save lives.  Failure will cost.

Senator Ron Johnson, Republican of Wisconsin, is a problematic figure in many ways.  The hearings on COVID-19 therapeutics he held (though his committee is not the one that actually oversees Health and Human Services) generated tremendous controversy and division.  While serious doctors presented serious evidence, the headlines were stolen by an anti-vaxer and hydroxychloroquine advocates, leading Democrats and some Republicans to boycott.  Yet on the broader point, that we desperately need to treat people in the early phase of COVID-19 disease on an outpatient basis (while we still have a chance to interrupt viral replication), Johnson is right; none other than Dr. Anthony Fauci is co-signatory of a letter that says so.

We have early outpatient treatments, of course, the monoclonal antibodies Bamlanivimab and REGN-COV2.  These have been the subject of the Parkchester Times articles Vaccination Hubs are not Enough, We Need Full Service COVID Outpatient One Stop Centers, and We Have an Answer and it’s not Let It Be, Bam-Bam and REGN-COV2 are Here!  Further studies of other monoclonal antibodies including a cocktail of Bamlanivimab+Etesevimab, the injectable form of REGN-COV2, and nanoantibodies similar to what llamas produce will be published soon.  Difficult implementation is a problem, though, and while there’s currently more of the two that have already received EUAs than is being dispensed, there’s not enough for everyone who tests positive for COVID-19.  What we need is a low-cost pill.  Wishful thinking doesn’t make it happen, but there is enthusiasm emerging for at least two already FDA approved prescription medications.

Colchicine is one; we are fortunate that a large-scale outpatient study, perhaps the only one of its kind, was launched early in the pandemic.  I interviewed leaders of the study in May.  While many have been frustrated that preliminary data disclosures were not available before now, they are about to be.  The COLCORONA team has pulled off something quite remarkable by starting early, going big, and sticking to the plan.  Their results are undergoing peer review.
 
COLCORONA colchicine clinical trial manuscript:
 
 
GRECCO-19 colchicine clinical trial report:

 

Ivermectin is the other.  In its case the nature of the evidence is controvercial, strong in the eyes of some doctors, weak according to others.  Like hydroxychloroquine, ivermectin is an anti-parasitic, and it's mechanism of action against the SARS-CoV-2 virus is poorly understood; yet epidemiological evidence and observational studies from outside the U.S. indicate efficacy.  So there is a philosophical question: do we look at scientific knowledge probabalistically, or in terms of proof certain?  What if the studies are valid, but they don't mean what one might assume?  In some parts of the world, parasitic co-infection might factor into COVID-19 symptoms and mortality, and ivermectin might simply be doing what we know it does well, killing parasites.  Does that mean we should be giving it routinely for COVID-19 everywhere?  Hard to say.  Doctors are alert for the possibility of secondary bacterial infections, and increasingly for secondary fungal infections, but have pathologists doing autopsys been looking for parasites?

Yet there is evidence ivermectin has at least some anitviral activity in vitro, and some anti-inflammatory properties.  One way or another, a signal of efficacy is there.  Clinical trials are ongoing, including trials that are of better design than those that have reported out thus far, a point made by Dr. Salim Rezaie both on his RebelEM webcast and as a guest on EMRAP.

Concerning COVID-19 therapeutics development generally, these stories have recently appeared on NPR and in the New York Times:

And this video, in which colchicine is discussed, has been issued by the EMRAP Webcast:

Because there are still unkowns many physicians and most reserchers view what we have learned not as actionable information, but as 'hypothesis generating'.  Yet the need is now, and even if we succeed in getting the SARS-CoV-2 virus under control in this country, it's doubtful that's achievable around the world within 2021.  What to do?  Here are suggestions:

  • A more systematic apporoach to co-implementation of testing, monoclonal antibodies, and vaccines, the subject of a previous editorial at https://parkchestertimes.com/opinion-vaccination-hubs-are-not-enough-we-need-full-service-covid-outpatient-one-stop-centers.
  • Clinical trials that are national in scope, and randomized, but are comparative, one treatment vs. another, and outpatient (like the COLCORONA colchicine study), with participation offered to everyone, immediately, upon receipt of a positive COVID-19 test result BY THE PERSON DELIVERING THAT NEWS.  This was the subject of a previous editorial at https://parkchestertimes.com/opinion-taking-the-fight-to-the-virus-part-2-do-you-want-treatment.
  • There's the matter of which FDA approved drugs should be available over-the-counter, and which by precription only.  COVID-19 changes the harm / benefit lanscape, yet our health authorities have been slow to respond with appropriate adjustments.  According to one epidemiological survey, PPI type stomach-acid reducers increase COVID susceptability dramatically, yet they are available over-the-counter.  Ivermectin, on the other hand, appears to benefit COVID-19 sufferers, yet is available by prescription only (unless you're a dog).  Swithching those up so that PPI's are behind the pharmacist's counter while ivermectin is out on the shelves, where people can decide for themselves whether to use it, is a balanced, evidence based approach we could implement tomorrow without a large government expenditure.  It might really help.

In the U.S. Senate it is the Committee on Health, Education, Labor, and Pensions that oversees HHS, the department that includes NIH, NIAID, CDC, FDA, and the Office of the Surgeon General.  Senator Patty Murray now chairs that committee.  I would urge her, and all of our congressional Democrats, not to reflexively oppose calls for expanded early outpatient studies and treatments, nor close themselves to forms of evidence that don't  conform to fixed notions of what contitutes "proof".  Carl Zimmer of the New York Times has said about Dr. Janet Woodcock, formerly Operation Warp Speed's head of therapeutics development and now acting FDA Commissioner

She hopes to tame the chaos with a new effort from the Biden administration. In the next couple of months, she said, the government plans to start large and well-organized trials for existing drugs that could be repurposed to fight Covid-19. “We are actively working on that,” Dr. Woodcock said.

I hope Senator Murray will fully support that effort as well as the intrim steps suggested above.