Tuesday, April 7, 2020

Dr. Reynolds Protocol for Coronavirus

[This guest post is by a new correspondent, Dr. Reynolds. We asked him to share his thoughts about treatments for the coronavirus. -CBS]

I am a neuromuscular neurologist, not a virologist, nor an infectious disease specialist; please keep that in mind as I share my thoughts on COVID19. I have been appalled by the federal government’s lack of preparation and leadership during the pandemic; but I will leave that to others to discuss. I am more interested in medicine than politics.

The development of effective treatment or prophylaxis against COVID19 is of paramount importance. At this point, only anecdotal evidence exists regarding the efficacy of COVID19 treatments. Testing existing treatments against COVID19 is the primary focus at this time, and each therapy mentioned in this letter is under active investigation for COVID19 application . Therapies with proven efficacy against other highly morbid coronavirus such as Severe acute respiratory syndrome-related coronavirus (SARS) or Middle East respiratory syndrome-related coronavirus (MERS) are worth considering first. One such drug is remdesivir, an RNA polymerase inhibitor that was previously tested against ebola. Remdesivir has demonstrated suppression of viral replication in humanized mouse models of SARS in both early treatment and prophylactic dosing regimens.  Remdesivir is dosed IV, which would make prophylaxis against COVID19 impossible, but would allow for treatment of infection. The first COVID19 clinical trials of remdesivir are due to report preliminary results in the coming weeks. Convalescent plasma is another candidate therapy with proven efficacy in SARS, though with limited data in COVID19. This involves transfusing plasma from recovered COVID19 patients into acutely ill patients. There are other promising candidates being tested as well, including hydroxychloroquine.

The tendency of a minority of Covid-19 cases to progress to respiratory and multiple-organ failure often followed by death is now well documented, and is mediated by a runaway immune response known as Cytokine Release Syndrome (CRS) or colloquially as “cytokine storm.” Interleukins (IL) 1, 6, tissue necrosis factor alpha and a host of other cytokines are all inappropriately up regulated resulting in a massive inflammatory response. CRS then becomes more deleterious to the patient than the viral infection itself. There are multiple lab abnormalities that may portend the development of CRS, including changes in IL-6 and ferritin, which could be used to guide treatment. Fortunately, there are multiple existing drugs that can reduce circulating cytokines. Tocilizumab is a monoclonal antibody used for rheumatoid arthritis. It targets IL-6, and has already been approved for certain cases of CRS prior to the COVID19 pandemic. Anakinra blocks IL-1, another culprit implicated in CRS. Clinical trials of anakinra for COVID19 are also ongoing. Many other potential treatments offer some hope in treating CRS, but often have obvious limitations: such as plasma exchange (too labor intensive for widespread use in a pandemic), IVIG (already limited by a pre- COVID19 shortage), and prednisone, and multiple trials are ongoing. Of course, the obvious risk of treating CRS with immunosuppressant therapy is of decreasing viral suppression and worsening infection.

The efficacy of zinc supplementation in treating the common cold, which is generally caused by rhinovirus or coronavirus, has been debated for years. There is some emerging consensus that zinc lozenges may reduce duration of cold symptoms if started at the onset of cold symptoms. It is not clear if zinc lozenges will successfully treat COVID19 or function as a prophylactic against COVID19 infection, and zinc toxicity is rare but possible.

I do not foresee any of the above therapies as a game changer on its own.  I suspect a multi-modal approach will be needed to reduce the mortality of severe cases of COVID19 until either a successful vaccine or "herd immunity" is established. A therapeutic approach including an anti-viral such as remdesivir IV, started on admission to the hospital, followed by immunosuppression in those showing signs of impending CRS may hold the most promise. 

My strategy to minimize my personal risk of COVID19 infection is to practice social distancing, get plenty of sleep, take a zinc lozenge immediately prior to making my rounds in the hospital and again at bedtime, and to wear an N95 mask to the extent possible. I own three N95 masks, and there is little prospect of obtaining more in the near future, and so I use a UV light to clean my masks between uses. Please consult your physician regarding zinc dosing and stay safe!


Dr. Reynolds

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