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Here are 3 #COVID19 questions we're trying to answer:
1. Why do monoclonal antibodies fail hospitalized patients? Cocktails made by Eli Lilly & Regeneron may be useful for high-risk outpatients, but they don't help hospitalized patients. Why does the treatment setting matter? 1/
1. Why do monoclonal antibodies fail hospitalized patients? Cocktails made by Eli Lilly & Regeneron may be useful for high-risk outpatients, but they don't help hospitalized patients. Why does the treatment setting matter? 1/
Part of this is timing. By the time someone shows up in the ER with symptoms, they may have been infected for a while (incubation is ~6 days). Most COVID treatments fail if they're given late in the course of disease and antibodies are no exception. They should be given early. 2/
But there are other theories to explain the failure: Antibodies may fail to efficiently penetrate the infected tissue of hospitalized patients. Or coronavirus may mutate to evade the monoclonal antibodies (these are called escape mutations). 3/ https://pubmed.ncbi.nlm.nih.gov/32540904/
There's also a concern that infusing antibodies into an infected patient could worsen inflammation through a process called antibody-dependent enhancement. Simply put, hospitalized patients may already have too much inflammation to derive a benefit. 4/ https://www.nejm.org/doi/full/10.1056/NEJMoa2033130?query=featured_home
Antibodies can potentially enhance the entry and replication of virus in human cells. These various concerns and disappointing trial results have dramatically limited our use of monoclonal antibody therapies. They're sitting on shelves for a reason. 5/ https://pubmed.ncbi.nlm.nih.gov/12725690/
Question 2: Why is the new variant of #coronavirus more contagious? Is it something at the molecular level, like better binding of spike protein to the ACE2 receptor? Or is due to higher viral loads in the upper respiratory tract? Or better evasion of neutralizing antibodies? 6/
Perhaps kids are more susceptible, providing a new avenue for transmission? Or, it's a combination of factors. For now, we mostly have modeling data to explain the spread of B.1.1.7; soon we'll have experimental data.
It is certainly in the U.S.; we just haven't found it yet. 7/
It is certainly in the U.S.; we just haven't found it yet. 7/
Question 3: How can we modify the human immune system to save lives? At most hospitals, patients with #coronavirus who need supplemental oxygen receive remdesivir (an antiviral) and dexamethasone (a steroid). We're trying to add more drugs to the cocktail. 8/
A large, NIH-sponspored trial called ACTIV-1 is testing immunomodulators that are normally used to treat other conditions, including: abatacept, infliximab, and cenicriviroc. Volunteers receive one of these drugs as well as remdesivir & dexamethasone as part of a new cocktail. 9/
A year from now, one of these 3 drugs may emerge as part of a new standard of care to treat patients hospitalized with coronavirus.
Vaccines are on the way, but coronavirus research will continue for a very long time.
Vaccines are on the way, but coronavirus research will continue for a very long time.
