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So the President received 8 grams of Regeneron monoclonal antibodies as a therapy & while that seems like a huge dose, we& #39;ve been here before...Ebola patients evacuated from W. Africa got big experimental doses of ZMapp in 2014. Hard to say if it will do anything. https://twitter.com/PeterHotez/status/1312355823889330178">https://twitter.com/PeterHote...
ZMapp was also a monoclonal antibody cocktail with 3 antibodies targeting Ebola virus gp, which is analogous to the Spike protein on SARS-CoV-2. It& #39;s the protein on the surface of the virus particle that binds the receptor and allows the virus to infect a host cell.
They gave ZMapp to Dr. Kent Brantly and Nancy Writebol, two medical workers and missionaries who were infected while treating Ebola patients in Liberia. They both recovered. Dr. Brantly claimed that he felt better immediately after receiving the infusion.
https://www.cnn.com/2014/08/04/health/experimental-ebola-serum/">https://www.cnn.com/2014/08/0...
https://www.cnn.com/2014/08/04/health/experimental-ebola-serum/">https://www.cnn.com/2014/08/0...
ZMapp also showed promising results in non-human primates. It protected rhesus macaques from lethal Ebola virus disease (EVD) up to five days post-infection, in animals who were already showing signs of severe disease. https://www.nature.com/articles/nature13777?proof=t">https://www.nature.com/articles/...
ZMapp was eventually in such high demand that the global supply of the drug was exhausted while treating (mostly European and American) Ebola patients. There was insufficient amounts of the drug to do randomized clinical trials in West Africa. https://www.independent.co.uk/life-style/health-and-families/health-news/ebola-virus-outbreak-norwegian-patient-get-last-available-dose-zmapp-world-9781740.html">https://www.independent.co.uk/life-styl...
There were a lot of questions about the ethics of distributing ZMapp like this, since West Africans were not getting access to it and there wasn& #39;t enough drug available to perform a trial. https://www.washingtonpost.com/news/monkey-cage/wp/2014/08/06/ebola-research-ethics-and-the-zmapp-serum/">https://www.washingtonpost.com/news/monk...
By 2015, more ZMapp had been manufactured, and a (small) randomized controlled trial was initiated in Guinea. This trial was disappointing, as ZMapp plus the standard of care showed only a modest benefit. https://www.nejm.org/doi/10.1056/NEJMoa1604330?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov">https://www.nejm.org/doi/10.10...
Unfortunately, there was another Ebola epidemic in the Democratic Republic of Congo in 2018. The PALM trial was set up to test efficacy of 4 drugs, including ZMapp. The PALM trial also tested remdesivir, as well as a single antibody and a 3-antibody cocktail made by Regeneron.
Despite the promising observational and preclinical data, the ZMapp arm of the trial was stopped early. So was remdesivir. Neither therapy showed a significant mortality benefit. https://www.nejm.org/doi/full/10.1056/NEJMoa1910993">https://www.nejm.org/doi/full/...
However, even the Regeneron cocktail (REGN-EB3) and the single antibody therapy (MAb114) had modest benefits for survival.
28 days post-treatment mortality:
MAb114: 35.1%
REGN-EB3: 33.5%
ZMapp: 49.7%
Remdesivir: 53.1%
28 days post-treatment mortality:
MAb114: 35.1%
REGN-EB3: 33.5%
ZMapp: 49.7%
Remdesivir: 53.1%
So even for monoclonal antibodies that worked relative to standard of care or ZMapp or remdesivir, mortality rate was still high. For Ebola, these drugs save some patients but they are by no means a sure-fire cure.
Part of this is probably due to timing: Ebola patients don& #39;t present for treatment until they are already sick and symptomatic. It& #39;s likely that all antiviral drugs (such as monoclonal antibodies or remdesivir) will work better if treatment can be started as early as possible.
Also clearly the antibodies themselves matter. The difference between REGN-EB3 and MAb114 and ZMapp are the targets of the antibodies. They are all directed at Ebola GP, but different parts (epitopes) of the protein.
It& #39;s hard to say if the Regeneron monoclonal antibody cocktail Trump was treated with is targeting the optimal epitopes of SARS-CoV-2 Spike. There& #39;s just not enough data showing efficacy in people to assess this & as with ZMapp, preclinical monkey studies aren& #39;t perfect.
With President Trump, it will likely come down to whether he was he treated early enough in the course of infection. This is hard to say since it& #39;s pretty unclear when he was even diagnosed or became symptomatic, or how clinically ill he is now.
Whatever his outcome, we won& #39;t be able to tell if treatment did anything at all. Even if the treatments work, it may not lead to a rapid or complete recovery. And while an 8 gram dose is a metric shit-ton of antibody to give, it& #39;s hard to say if it will be clinically meaningful.
So we should just wish President Trump well and focus on clarifying the important information that hasn& #39;t been fully disclosed (ie: exposure risk to others around him) & not waste time overthinking the therapeutic efficacy of the experimental drug(s) he has or will receive.
