Treatment options for Severe Infection with COVID-19: current and on the horizon
Antiviral Therapy: favipiravir (Aviga) and remdesivir (neither of which are currently available in the US as or today). Favipiravir - approved in Japan for treatment of influenza.
Favipiravir : “Patients who were given the medicine in Shenzhen turned negative for the virus after a median of four days after becoming positive, compared with a median of 11 days for those who were not treated with the drug, public broadcaster NHK said.
In addition, X-rays confirmed improvements in lung condition in about 91% of the patients who were treated with favipiravir, compared to 62% or those without the drug.”
https://www.livescience.com/flu-drug-could-treat-coronavirus.html
remdesivir: general antiviral was being used for Ebola. I see more challenges with this moving forward from a timing standpoint as it was not previously approved by regulatory agencies for treating anythi,g unlike the Favipiravir.
Antivirals that are already approved in the US is Kaletra (lopinavir/ritonavir) which looks like just failed as being better than standard of care despite the Chinese using it the last few months.
https://news.trust.org/item/20200318231107-sqloz
Other therapies:
Hydroxychloroquine and Chloroquine - drugs against malaria and Hydroxychloroquine used commonly in autoimmune disease.
https://doi.org/10.1038/s41421-020-0156-0 (nature.com)
Early study showed Hydroxychloroquine 600mg/day to increase conversion from positive to negative for coronavirus more rapidly. There's currently a phase III clinical trial looking at Hydroxychloroquine for COVID-19. One study combined with IV azithromycin with better outcomes but was limited to 24 patients and was not randomized.
Famotidine/Pepcid: undergoing clinical trials currently
IV Vitamin C + Thiamine
There's been lots of controversy about the original single center trial published in 2017, but I think there's some weight there and since multiple other studies have come out particularly for severe pneumonia. In particular, I think the reason we're seeing the most severe illnesses in Men and older age groups is due to immunosenescence. Augmenting immune system I think is key to reducing severity of illness.
Marik PE et al. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: A retrospective before-after study. Chest 2017 Jun; 151:1229. (http://dx.doi.org/10.1016/j.chest.2016.11.036)
https://doi.org/10.1016/j.jcrc.2018.07.004
China is conducting a clinical trial of 24,000 mg/day of intravenous vitamin C to treat patients with coronavirus and severe respiratory complications.
In this clinical trial, participants will receive IV vitamin C for seven days straight at Zhongnan Hospital of Wuhan University.2
Administering high doses of vitamin C by way of IV therapy delivers this powerful antioxidant directly into the bloodstream and is generally well tolerated by most people. Because intravenous administration of vitamin C has a higher absorption rate than when taken orally through supplementation, resulting in higher concentrations in the blood, IV therapy is considered a more effective method of delivering high doses of vitamin C to the body.
Insufficient vitamin C intake is a global problem that can be addressed with proper nutrition and supplementation. With even modest amounts of supplemental vitamin C, deaths will decrease. In a study, modest amounts of supplemental vitamin C (200 mg of vitamin C per day) resulted in an 80% decrease in deaths among severely ill, hospitalized respiratory disease patients. [Hunt C. The clinical effects of vitamin C supplementation in elderly hospitalized patients with an acute respiratory infection. Int J Vit Nut Res 1994;64:212-19]
NAC/ N-acetylcysteine
IV and PO NAC is being used in majority of patients in China with severe disease. Studies are small but it appears to attenuate severity of viral illnesses like influenza. I think there is little downside to NAC therapy, either via oral or IV route and potential high benefit.
F.S. De, C. Grassi, L. CaratiAttenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment
Eur Respir J, 10 (7) (1997 July), pp. 1535-1541
A. Garozzo, G. Tempera, D. Ungheri, R. Timpanaro, A. CastroN-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection
Int J Immunopathol Pharmacol, 20 (2) (2007 April), pp. 349-354
https://www.reddit.com/r/science/comments/figm1w/nac_as_treatment_for_influenza_and_covid19_found/
Lastly, the Chinese appear to be have significant deficiency in Selenium, particularly those who were severely effected. Not sure yet what this means, but there are some suggesting selenium and zinc infusions for those significantly deficient. Brazil nuts are a great source of selenium, but do not exceed 4-5 per day.
After reviewing the literature as of 3/20/20, I’d consider following treatment for Severe COVID 19 infection with: IV steroids, obtain Favipiravir as soon as possible, consider Hydroxychloroqine and Azithromycin early in course, use IV vitamin C and thiamine pneumonia/sepsis protocol, and give some form of NAC. The literature and knowledge is rapidly evolving, updates to follow. Many other therapies are under investigation as well as a world-wide effort for vaccine development.
Stay safe and contact Dr. Silhan with any questions.
Leann Silhan, MD