COVID-19 Therapeutics and Advanced Supportive Care

Therapeutic drugs and other therapies are being aggressively debated, tested, used under compassionate-use expanded access and the like. Below are articles that may be of interest. Really Correct has no strong opinion other than compassionate-use doctor options are good when risks and contraindications are well known or life saving choices are limited. Perhaps obviously, the more severe the case, the less there is to lose when a doctor is trying to save a life with a compassionate-use medical gamble. Also see Severe Treatment and Staying Healthy.

Monoclonal Antibodies

Immunosuppressants, Steroids, Tocilizumab, Cyclosporine A, Etc.

Anticoagulants

https://www.umc.edu/CoronaVirus/Mississippi-Health-Care-Professionals/Clinical-Resources/Patient%20Treatment%20Guidelines/Anticoagulation%20Dosing%20Recommendations.html

Hydroxycloroquine / Cloroquine (+ Antibiotics)

Notably, the May 22 2020 release study (below) appeared to be in context of high dose HCQ on the order of 600 to 780 mg per day whereas malaria dosages are 200 to 400 mg per week. Lupus and arthritis doses 200 to 400 mg per day. Maybe less is more? More research on control group characteristics desirable. Patient disease severity stage not yet reviewed. Generally known from other sources that HCQ is not effective late stage and claims of effectiveness from other sources were during early stage. Review incomplete, but results of this study looks like high dosages are likely harmful, possibly even to patients with healthy hearts. HCQ well known to be contra-indicated when patient on beta blockers or other heart health issues – prescription only even for malaria and lupus use. Is there a study of low dose use such that heart health is less impacted? While there is still some potential that HCQ is helpful in low doses in early infection stages, the comic relief we may want to consider is in the following video segment. Again, there may be some place for HCQ in COVID-19 treatment (prophylaxis?) but enjoy the needed humor relief indicating it does not appear to be as promising as once thought.

It has been interesting seeing all the debate. With daily dosages in the studies on the order of 600mg and larger initial loading doses and observed that HCQ half-life is ~ 40 days, and compared that with malaria dosage, even lupus dosage, it is understandable that very sick people were getting sicker in many of the studies. Toxic / excess usage of anything is problematic. “clinical series suggest that 4g of hydroxychloroquine is potentially fatal in adults”
Here’s a sad story:
https://www.medintensiva.org/en-hydroxychloroquine-potentially-lethal-drug-articulo-S2173572717300577

And the debate continues. Two studies below were published and then retracted by The Lancet and other respected publishers.

And the debate continues.

At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms
compared with 30% (59 of 194) receiving placebo (P = 0.21).
Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine
versus 22% (46 of 211) receiving placebo (P < 0.001).
With placebo, 10 hospitalizations occurred (2 non–COVID-19–related), including 1 hospitalized death.
With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).”
Interesting that the hospitalizations of hydroxy were reduced to <50% of placebo. .
Would still like to see data from a lower dose study. This one is 800mg initial + 600mg in 7hrs + (600mg/day 4 days) appears to have a total dosage of 3800 mg which far exceeds the 2000mg FDA maximum for active malaria treatment. Would adverse effects be minimized with substantially lower dose? Seems like there may be some benefit in this study – don’t understand why conclusion says none. HCQ half-life is on the order of 40 days. Malaria prophylaxis FDA recommendation is 400 mg (310 mg base) once weekly.

HCQ continues to be hotly debated. While the safety and efficacy of HCQ is debated, it is clear that some studies appeared to have used near toxic doses with negative impact. The “Surgisphrere Scandal” that is related to Lancet and NEJM publication retractions further add to the controversy. The retracted papers related to the scandal indicated HCQ had no benefit and added potential harm. Some doctors vehemently argue for HCQ as helpful in early stages to avoid severe late stage disease. Other doctors vehemently argue against it, though less-so after the publication retractions. Most agree it is not helpful in late stage disease. While the debate should have science at the center, it often travels along political lines. Really Correct continues to follow the debate and attempts to provide multi-representational perspectives of the available information.


Remdesivir

Sorrento’s COVID-SHIELD (COVID-GUARD or whatever they end up calling it)

“Sorrento’s COVID-SHIELD is meant to address this through a potent mix of different antibodies that provide protection against different strains of the virus, but the company says it also will be pursuing development of the STI-1499 antibody on its own as a dedicated, standalone therapy. The company is already in discussion with regulators about how to expedite development of that potential treatment, and is ramping its production capacity as well with the goal of producing as many as one million doses at the same time it pursues FDA approval for its use.”

“The company plans to test whether STI-1499 prevents infection in monkeys and possibly ferrets — two species that are susceptible to the virus. If all goes well, Sorrento Therapeutics could begin testing the antibody in clinical trials of severe COVID-19 patients by mid-July, Ji says.”

Mesenchymal

ECMO

Cytokine Adsorption

HIV Meds

“But then lopinavir/ritonavir failed against COVID-19 in a decently sized study in China. While there are still other trials planned to investigate this medication, many lost hope in its promise after news of this study broke.”

An article discussed HIV meds being a possible therapy because some studies of HIV patients with SARS or COVID led a researcher to believe they helped. A hypothesis exists such that better outcomes were not the HIV meds, but the fact that the patients were HIV+ and had lower cytokine production due to lower CD4 T-helper cell counts (or something like that). Is it possible that HIV+ have lower risk of cytokine storm related COVID-19 morbidity? Does this point to some potential therapy areas and/or the genesis of SARS-CoV-2 virus RNA changes? Also see Hypotheses


Thrombotics


Miscellaneous

Also see: COVID-19, SARS-CoV-2, and Severe-Case Treatment