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/
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/ 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/ nejm.org/doi/full/10.10…
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/ 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/
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.
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Hospitalized patients and research subjects often ask me about antibody treatments. They touch on a recurring theme: Many believe these treatments go unused because a) Doctors don't think to order them or b) We don't have the connections to acquire them. Here are key points: 1/
Monoclonal antibodies made by Regeneron and Eli Lilly are not authorized for patients who are hospitalized due to #COVID19. Trials have been stopped because antibodies don't help these patients. Nevertheless, many are distressed they're not being used. 2/ nytimes.com/2020/10/27/wor…
We've recognized the futility of giving antibodies to hospitalized patients for months, but only recently have we understood why: The timing of the antibody response is more important than the amount of antibody.
Early antibody response is crucial. 3/ medrxiv.org/content/10.110…
UPDATE: Vaccinologists like to say they breathe a sigh of relief after 3 million inoculations of a new vaccine. That's when we get a real handle on side effects. We'll soon reach that milestone with mRNA vaccines (Pfizer, Moderna). There's another phenomenon we should follow: 1/
It's important to determine if people are contracting #coronavirus after vaccination. The phase 3 trials that were the basis for emergency authorization looked at prevention of symptomatic disease; they did not assess prevention of transmission. 2/
This means people could, in theory, contract #coronavirus and transmit it to others after vaccination. But is this happening? Thus far, I've only heard of one case of a person contracting the virus after vaccination. (Are there more?) It happened in Texas. 3/
COVID question doctors are wrestling with: Should patients with profoundly impaired immune systems receive monoclonal antibody therapies after contracting #coronavirus? 1/
These patients are often prioritized for antibody treatments (made by Regeneron and Eli Lilly). And this makes sense: Their immune systems are weak, and antibodies can potentially help fight infections. But there's an issue. 2/
A new hypothesis argues that patients with weak immune systems could serve as an incubator for viral mutations, leading to new strains like B.1.1. 7 that might be more transmissible. 3/
UPDATE: Coronavirus has mutated into a new variant, B.1.1.7, that has the world's attention because it may be more contagious.
Some thoughts on where this came from and how it impacts patient care: 1/
The novel #coronavirus typically acquires a mutation every few weeks. The new variant is interesting because it seemingly developed a bunch mutations all at once: 17 mutations in viral proteins, including 8 changes in spike protein, the target for all of our vaccines. 2/
Why would a flurry of mutations suddenly emerge? The focus now is less on unique properties of #coronavirus and more on unique human hosts: patients with impaired immune systems who are chronically infected and unable to clear the virus. 3/ sciencemag.org/news/2020/12/u…
Here's one of the points I made in this #COVID19 lecture: When I see a politician taking drastic action that is not supported by data, I ask myself, "How did this person respond to warnings in March?"
An example: 1/
While most of the world was focused on mitigation in mid-March, the United Kingdom implemented “delay.” As many experts noted at the time, this was a mistake. The UK inadvertently served as the placebo-controlled arm of a global study aimed at limiting death and disease. 2/
Delay has been widely criticized. Coronavirus moved unchecked throughout England until the prime minister was forced to reverse course and implement harsh restrictions. We're still feeling the repercussions today. 3/ bloomberg.com/news/features/…
UPDATE: Countries are scrambling to contain a new variant of #coronavirus that's reportedly more contagious. Some key points: 1/
Mutations are expected. This variant was detected months ago and there's no evidence it's more deadly or resistant to recently-authorized our vaccines. Viruses are constantly drifting into new shapes and the vaccinated immune system has a variety of ways to contain it. 2/
To justify lockdowns and travel bans, some are citing a figure that the new variant is 70% more contagious. How did we arrive at that number? It's based on mathematical modeling, not experimental evidence. Founder effects confound our interpretation of this noisy data. 3/