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15 Jan, 8 tweets, 3 min read
UPDATE: Coronavirus is the only respiratory virus I have ever encountered that causes inflammation of blood vessels (vasculitis). One of the great challenges in #COVID medicine is understanding why so many of these patients also get blood clots. 1/
In some cases, these clots are fatal. During the first wave of the pandemic, my team and many others focused our attention on factors in the blood to explain this phenomenon (d-dimer, fibrinogen, INR, etc.). Tests didn't solve the mystery.
Subsequent studies and observations have advanced a different idea about clots: It's not the blood, it's the blood *vessels*. A new theory suggests that #coronavirus pathology is similar to Behçet's syndrome, a vasculitis that causes eye and genital problems.
Behçet's patients get clots, too, but they're attributed to lung and blood vessel inflammation, not abnormal factors in the blood. This has important implications for treatment that may be relevant for COVID.
thelancet.com/journals/lanrh…
We avoid blood thinners with Behçet's, focusing instead on immunosuppression, including steroids and tumor necrosis factor blockade. To treat clots, we drive down inflammation. Blood thinners can actually make things worse.
ncbi.nlm.nih.gov/pmc/articles/P…
As COVID medicine evolves, we may similarly turn to drugs that decrease vessel inflammation (immunomodulators) instead of blood thinners to treat clots. This year, we will test all sorts of immunomodulators on #COVID patients, including lenzilumab, risankizumab, and anakinra.
This week, I randomized someone to the cenicriviroc arm of a #COVID19 immunomodulator study. It's a drug I had never heard of until recently. But the trial might help explain why blood vessels become inflamed and clots form. It could turn conventional thinking on its head.
Takeaway: We're using blood thinners to treat COVID clots, but that may change. Immunomodulators could be a better option.
Soon we will solve one of the enduring mysteries of the pandemic: Why do some #COVID patients develop life-threatening blood clots and how can we save them?

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Matt McCarthy Profile picture
4 Jan
UPDATE: COVID medicine has changed substantially over the past few months. The questions we're grappling with today are very different than the ones we were dealing with just a few months ago.
Here are some of the #COVID19 questions recently posed to me by frontline doctors: 1/
1. Why isn't anyone using baricitinib? The drug just received emergency authorization but we never hear about it.
2. How does cenicriviroc work & why is the NIH studying it?3. Does dexamethasone cause secondary bacterial infections?
My thoughts:
1. Baricitinib is an arthritis drug. In November, it was authorized in combination with remdesivir for adults hospitalized with #COVID19 who need help breathing. The combo was better than remdesivir alone in reducing reducing recovery times. That's great!
nejm.org/doi/full/10.10…
Read 13 tweets
Matt McCarthy Profile picture
30 Dec 20
UPDATE: Operation Warp Speed won't hit its goal of 20 million Americans vaccinated against #coronavirus by the end of 2020. To improve the rollout, we should: 1) Look back, 2) Look ahead, and 3) Look in the mirror. My thoughts:
1. Look back: This isn't the first mass vaccination in the midst of an outbreak. In 1947, New York City inoculated millions against smallpox in a matter of days. How did they do it? Vaccination was available at more than 250 hospitals, clinics, police stations, and schools.
Vaccination was voluntary and free of charge. There was also a massive citywide doorbell-ringing campaign. As we become more comfortable with the safety of covid vaccines, we must increase outreach. Most don't know how or where they'll get vaccinated.
vanityfair.com/culture/2013/1…
Read 5 tweets
Matt McCarthy Profile picture
29 Dec 20
UPDATE: A #coronavirus patient is considered contagious as long as they carry "replication-competent" virus. Based on limited CDC data, patients with severe immune impairment are thought to be contagious for up to 20 days after onset of COVID19 symptoms. This may soon be revised:
We've known that patients with weakened immune systems can remain contagious for up to twice as long as those without immune impairment (20 days vs. 10 days) and these findings have informed transmission-based precautions around the country.
But 20 days may be insufficient.
A new study of immunocompromised #COVID patients found that some remain potentially contagious far longer than previously thought: 15% had replication-competent virus after 20 days. 
Key finding: 1 patient grew virus in culture 61 days after symptom onset. nejm.org/doi/full/10.10…
Read 6 tweets
Matt McCarthy Profile picture
29 Dec 20
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…
Read 5 tweets
Matt McCarthy Profile picture
27 Dec 20
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/
Read 5 tweets
Matt McCarthy Profile picture
27 Dec 20
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/
Read 10 tweets

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