Just a brief post collating some of the high-level evidence on therapies approved or under investigation for COVID-19. I’d written this up for another audience, and it could be obsolete as soon as I post – and hopefully mooted in just a few months!
Hydroxychloroquine:
No. What a farce.
https://www.nejm.org/doi/full/10.1056/NEJMoa2022926
https://www.nejm.org/doi/full/10.1056/NEJMoa2021801
https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
https://www.nejm.org/doi/full/10.1056/nejmoa2019014
Remdesivir:
A controversial repurposing of an antiviral previously trialled against ebola. Consistent benefits have been difficult to replicate. ACTT-1 in the U.S. showed a small length-of-stay and mortality benefit, but SOLIDARITY by the WHO found none.
https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1
Dexamethasone:
The best reliable evidence for benefit so far, with face validity in treating inflammation-mediated lung disfunction. For “moderate to severe” COVID-19, which is effectively anyone with hypoxia requiring supplemental oxygen.
https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
Convalescent plasma:
Over 250,000 people in the U.S. have been treated with plasma donated by persons recovered from COVID-19. However, minimal evidence of efficacy exists. It certainly does not work in the very ill, but is still being explored in those early in the disease process.
https://www.nejm.org/doi/full/10.1056/NEJMoa2031304
Bamlanivimab:
This is the Eli Lilly neutralizing antibody, approved for emergency use in the U.S. This is a monoclonal antibody to the SARS-CoV-2 spike protein. Interestingly, this product failed in ACTIV-3, hospitalized inpatients. The interim results leading to FDA approval are from BLAZE-1, preventing deterioration of mild disease at high-risk for progression.
https://www.fda.gov/media/143603/download
Casirivimab plus imdevimab:
This is the Regeneron “antibody cocktail” given to President Trump. These are both monoclonal antibodies to different, non-overlapping domains of the SARS-CoV-2 spike protein. These are also similarly targeted at high-risk outpatients with mild disease with the goal of preventing progression.
https://www.fda.gov/media/143892/download
JAK (Janus kinase) inhibitor:
Baricitinib is approved as second-line therapy for moderate-to-severe rheumatoid arthritis. Per FDA EUA data, this conferred mortality benefit when given in tandem with remdesivir in ACTT-2. However, few patients in this trial received steroids, limiting generalizability.
https://www.fda.gov/media/143823/download
Tocilizumab:
This is an IL-6 inhibitor currently approved for moderate-to-severe rheumatoid arthritis. Mixed results have been observed with tocilizumab, and current use is primarily as a salvage in the mechanically ventilated. However, there is not much face validity for its effectiveness when added to dexamethasone.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772187
https://www.nejm.org/doi/full/10.1056/NEJMoa2028836
Ivermectin:
Antiparasitic agent theorized to reduce severity of COVID-19 through inhibition of viral protein transport. Widely used in the developing world due to its availability and low cost; virtually no useful data available.
https://journal.chestnet.org/article/S0012-3692(20)34898-4/fulltext
https://www.researchsquare.com/article/rs-109670/v1
Lopinavir and rotonavir:
Antiviral combination therapy typically used for HIV-1. No clinical benefit detected in the RECOVERY trial, and adverse effects led to discontinuation in other trials.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32013-4/fulltext
https://www.nejm.org/doi/full/10.1056/NEJMoa2001282
The NIH also features fairly good tables of agents under ongoing evaluation, if you’re interested in seeing more extensive summaries of evidence for each:
https://www.covid19treatmentguidelines.nih.gov/tables/table-2/
https://www.covid19treatmentguidelines.nih.gov/tables/table-3a/