An “Off-Label” Drug Combination to Block Progression of COVID-19 Disease to Critical Illness: CYCLOSPORINE + Medrol Dosepak

An off-label combination of CYCLOSPORINE and Medrol Dosepak to block progression of COVID-19 disease to critical illness in pre-Hospital outpatients and pre-ICU inpatients.

It’s becoming abundantly clear that COVID-19 disease causes severe disease and mortality because of an overactive immune response to the SARS-CoV-2 virus. In the more advanced cases this over-reaction is called a “cytokine storm”.

So it’s actually not the virus itself causing harm to the patient, but rather an out of control immune response that makes the patient sick — or lands them in ICU on death’s door.

So, when a patient has had symptoms of COVID-19 disease for over a week and is not improving or is deteriorating, it’s time to put the brakes on the immune response and cool things down a bit.

The main cells of the immune system involved in causing the hyperimmune reaction and cytokine storm are cells known as T-cells and macrophages. Fortunately, we have a very safe and effective drug that specifically cools down activation of these immune cells — and, importantly, can be used in the outpatient setting. This drug is called CYCLOSPORINE.

I’ve written about CYCLOSPORINE and its mechanism of action before — Please review these HERE, HERE, HERE, HERE, HERE and HERE.

CBS Los Angeles news clip on the potential role of CYCLOSPORINE in blocking progression of COVID-19 disease.

The bottom line is that the hyperimmune response and cytokine storm that SARS-CoV-2 causes is driven by T-cells and Macrophages — and CYCLOSPORINE puts the damper on both these cells’ activation process.

So the proposition of this public message is that patients with SARS-CoV-2, whose symptoms are not improving or are getting worse after a week, ought be treated with CYCLOSPORINE.

It is a fact that millions of people around the world who are not hospitalized, take this drug every day for treatment of a variety of hyperimmune disease flares — anything from Rheumatoid arthritis to Ulcerative Colitis to Psoriasis. The drug is well-tolerated, safe and effective in controlling hyperimmune diseases in outpatients, as well as cytokine storm syndromes in hospital inpatients and ICU patients.

Today, given that there is no current standard of care treatment for COVID-19 outpatients and pre-ICU hospital inpatients, I propose the following “off-label” regimen for COVID-19 patients with unremitting or deteriorating COVID-19 symptoms for greater than one week. I suggest that this treatment regimen in the pre-ICU phase of COVID-19 disease will block progression to critical illness or death in a substantial number of COVID-19 patients:

1. Loading oral dose of Modified CYCLOSPORINE at 5–10mg/kg/day in two divided doses on Day 0.
2. maintenance oral dose of Modified CYCLOSPORINE at 2.5mg/kg/day in two divided doses of another 9 days.
3. End treatment regimen with a Medrol Dosepak (6 day dose oral steroid pack).

During the 8–10 day treatment period with CYCLOSPORINE, the patient should not take their STATIN cholesterol lowering medications. Additionally, because SARS-CoV-2 causes blood clots and because CYCLOSPORINE may stimulate platelets to become activated as (an experimental side effect described in dogs), it will be important to add 80–160mg of Aspirin (i.e., one or two baby Aspirins) daily to the outpatient treatment regimen.

With this public letter, I urge all physician colleagues involved with the care of COVID-19 patients to consider immediate use of this generic off-label therapy — in order to possibly block progression of COVID-19 hyperimmune disease to hospitalization or critical illness.

A final note to consider is that CYCLOSPORINE, though marketed as an “immunosuppressant” drug, is a highly mechanistically specific, safe and effective dampener of T-cell and macrophage hyperimmune responses. It does NOT block production of anti-viral antibodies — particularly when initiated after 7–10 days of symptomatic disease when the antibody response has already ramped up within the patients’ lymphoid organs.

I am happy to discuss the immunological and legal rationale for use of this drug combination with any interested colleagues or COVID-19 patients. Please write me at noorchashm@gmail.com.

Please note that since mid-March 2020, myself and group of academic clinicians have been formally attempting to bring this drug, CYCLOSPORINE, to the attention of Federal Regulators at FDA and CDC, academic medical leaders and prominent members of the press. Unfortunately, currently testing and deployment of this drug in the clinical setting has been hampered by administrative and political wrangling at multiple levels. Therefore, I am now compelled to make this public proposal that all practicing physicians involved with the care of COVID-19 patients in the community or outpatient setting, consider use of this off-label treatment regimen — specifically, in COVID-19 patients with unremitting or deteriorating disease for over one week. NOTE: CYCLOSPORINE treatment is NOT to be used prophylactically to prevent COVID-19 disease. It is only scientifically and mechanistically sound therapy in patients with over one week of unremitting or deteriorating symptoms in whom the anti-SARS-CoV-2 antibody response is expected to be underway.