Nathan writes:

Hello Y’all.

I’m JUST an urgent care PA from San Antonio, TX who plans to specialize in Infectious disease, I love tropical, wilderness and disaster medicine. I started listening to TWIV at the start of the Pandemic while looking for virologic updates. Found and have listened to every TWIV since then. I’m also trying to work my way through TWIP  from the beginning (as parasitology is my favorite ID infection).  

Any ways. My question for Dr. Griffin, what are your thoughts on using indomethacin IN PLACE OF other NSAIDS such as iburpofen/naproxen for antipyresis in outpatients who have no contraidications to NSAIDs?

There have been two studies looking at indomethicin against coronavirus in vitro and in vivo canine models. The first by Amici et. al  is a 2006 study on SARS-CoV-1 using monkey VERO (I know not great) and human lung (A549). They also tested against canine coronavirus (an alphacoronavirus) in vitro in A72 canine cells  and in vivo. I don’t know how different phenotypically apha and betacoronvirus are though. Ribavirin and aspirin were used as controls in virto. They found significant viral inhibition of viral replication in vivo (not mediated by viral binding or cell entry). In the canine (extremely small sample size) model they showed a significant decrease in time ford viral RNA  shed was no longer detectable in feces compared to control.

The second study by  Tianhon et al. follows a similar plan as the first but uses SARS-CoV-2 pseudovirus. They didn’t use the human lung cells only the VERO cells for the in vitro portion. Their canine model’s ( using canine coronoavirus) sample size was slightly larger though and had three cohorts ( about 8-9 dogs each) one cohort had symptomatic treatment and oral indomethacin,  symptomatic treatment + ribavirin, and symptomatic treatment + anti CCoV serum + canine hemoglobin + canine blood immunoglobulin + interferon. In vero (for what it’s worth) indomethacin showed antivral activity compared to aspirin.  In the canine model they found that recovery was quicker in the indomethacin group that in the ribaviron group, but not the serum/interferon group. 

Fully acknowledging significant limitations in these studies (when you read them), and by no means suggesting patients with contraindications take NSAIDs. Acknowledging there’s not data to call this a miracle cure etc.  Is there a down side to prescribing otherwise healthy patients (with COVID) indomethacin as opposed to other NSAIDS when NSAID therapy is merited? My personal belief is that if I am going to take an antipyretic, why not take one that has the potential for secondary benefit?

I’d love to see prospective human double blinded randomized controlled trials. This has the POTENTIAL to be a significant future therapeutic agent. And it’s cheap. 

Respectfully,

 Nathan 

Penny writes:

Hello – We love your podcast and my husband is a true devotee!  This is our dilemma. 

 My husband’s mother passed away in June, and the memorial service will be held next week.  He is not sure about driving this distance and the risks he will encounter.  And, once he reaches his destination will he be able to spend time with his 92 year old father – masks and social distance?  And he is also concerned about any risks to me even though at this time the plan is that he will travel alone –  about a 12 hour drive to the midwest. I think he would get a test upon return and we would distance while in the house together.  We are both in our late 60’s – early 70’s.

Your thoughts and input are greatly appreciated.

Stay safe and healthy.

Take care and thanks very much!

Penny

Philadelphia

Jo writes:

Bugger, even the snapping turtles!

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205209

Charles writes:

From the Washington Post article a suggested quote for today:

https://www.washingtonpost.com/nation/2020/09/11/trump-churchill-covid-calm/?utm_campaign=wp_main&utm_medium=social&utm_source=facebook&fbclid=IwAR3y2LX05610IsubiOFt2jt85UvDHUiZ3qcLcRYjIKeUP-fCcKmbxt_KZo0

From Churchill: “The British people can face any misfortune w/ fortitude & buoyancy as long as they are convinced that those in charge of their affairs are not deceiving them, or are not dwelling in a fool’s paradise.”

Thanks,

Charles

Betsy writes:

Dear TWIV,

I’m a long time listener, big fan, first time writer. Thank you so much for the important work that you do!!

In TWIV 660, you discussed a recent paper from Rafi Ahmed’s group which involves analysis of bone marrow aspirates. Alan Dove mentioned that his wife was a bone marrow donor (good for her!) and discussed the pain involved should she decide to donate. I’m concerned that this was a very misleading discussion that may actually discourage listeners from becoming donors!

I wanted to write to ask you to revisit this important topic to clarify what is involved and encourage your listeners to consider joining the bone marrow registry at https://bethematch.org/support-the-cause/donate-bone-marrow/join-the-marrow-registry/! 

Importantly, many donors donate stems cells harvested from their peripheral blood rather than through a bone marrow aspirate! You can read more about the donation process here: https://bethematch.org/transplant-basics/how-marrow-donation-works/

I know several people who have received bone marrow transplants after receiving a cancer diagnosis. Joining the registry is easy, and it may give you the opportunity to save a life! 

Warm regards,

Betsy

Sam writes:

Dear TWiV Team,

21 C in San Diego tonight with a chance of Labor Day superspreader events.

On Episode 659, a listener’s letter said new infections in China were being blamed on imported food. This is just another in the long list of examples I’ve seen of this bizarre impulse people have where they refuse to believe that there can be local spread in their area. I’ve heard so many people insist–without evidence–that the infections in their state or county were from people outside the community bringing it in, as if it’s a matter of shame to have community spread, as if their people couldn’t possibly be infectious.

I’ve heard this enough to notice the pattern–I don’t know anything about studies on the newer cases in New Zealand, but it seems that’s an example too. When I heard there were new cases there, my first instinct was to think that it had just been circulating at very low levels for awhile and then reached a critical mass. Maybe only a few asymptomatic people were getting infected after the initial clampdown. Because if the new cases in New Zealand are solely due to imported infections, that means the country managed to eradicate the virus completely before–right? That seems unlikely. The null hypothesis, to me, seems to be that they just got their cases low enough to not be a problem, but not low enough to drive the virus extinct on the islands, and now it’s risen back up.

All the best,

Sam

Sam writes:

Hi Twiv Team

I had Guillain-Barré syndrome when I was 11, I’m 38 now. The last time I had a flu vaccine was in 2009 during H1N1, the subsequent year they warned anyone who had Guillain-Barré syndrome not take the vaccine. Has this changed, ‘cause I haven’t had a flu vaccine since?

Thx

A Fan,

Sam

Nicole writes:

Hello TWIV crew,

Our housekeeper hasn’t been over since early in the pandemic. She contracted COVID about 2 weeks ago, and she is thankfully feeling better. She plans to return to work next week. Do you think it’s safe to assume she has immunity for the next 2 or 3 months and have her over while we are all home working and schooling?

Thanks for your insight! 

Nicole in Arkansas 

Ken writes:

There seems to be some debate about whether flu vaccine increases one’s chances of non-influenza respiratory infections. This paper says yes:

https://academic.oup.com/cid/article/54/12/1778/455098

and this one only in children:

https://www.sciencedirect.com/science/article/pii/S0264410X18303153?via%3Dihub

While other papers seem to indicate there is no connection

This debate seems to be discouraging some people from getting a flu vaccine. I’ll get mine but wonder how in principle a vaccine could make one more susceptible to other viruses.

Ben writes:

Just want to reiterate one factor often lost in many discussions around reaching herd immunity from COVID-19 through natural infection.

A few million people more dying would be an unthinkable tragedy, yes.

Also consider the (likely) greater number of people who’d suffer from longer-term effects of infection, such as the documented cardiovascular damage, the long haul post-viral syndrome, or effects we can’t yet anticipate.

These effects would have a material effect on those millions’ quality of life for years or decades to come.

Thanks for everything you and the crew do.

Keep on TWiVering,

Ben (from the SF Bay Area, where it’s a scorching 102°F beneath smoke filled skies)

Kjetil writes:

aloha!

  Listener from Oslo in Norway here!

  After listening to TWiV 658, I went to your homepage for that episode,

  https://www.microbe.tv/twiv/twiv-658/ and quote from the introduction:

      “Daniel Griffin provides a clinical report on COVID-19, […..]

       [….], and reinfection with a distinct SARS-CoV-2 isolate, [….]”.

  The Director general of the World Health Organization, Tedros Adhanom Ghebreyesus,

  has on 11’th of February this year said the following, ref transcript pdf on page 2,

  second last paragraph, from

https://www.who.int/docs/default-source/coronaviruse/transcripts/who-audio-emergencies-coronavirus-full-press-conference-11feb2020-final.pdf

     “Now to coronavirus. First of all we now have a name for the disease and it is

      CoViD-19 and I will spell it; C O V I D – 19. Co – C O – stands for corona,

      as you know; V I stands for virus; D for disease so CoViD.”

  So, in the same way that the new virus named “SARS-CoV-2” has a lower letter “o” in the

  “Co[rona]V[irus]” middle part, I think that the new disease should be written

  “Co[rona]Vi[rus]D[isease]-19”, and without the […] parts, it becomes “CoViD-19”.

  This would then also be in line with the 2 usages in that quoted paragraph above.

  Keep up the good work!

  — Kjetil 

Greg writes:

The issue of screening test sensitivity summarized in a couplet:

High sensitivity makes PCR tests seem the hero
But the accuracy of a test which you can’t get is zero!  

Keep it up, everyone!

–Craig

John writes:

Hi TWIV,

It’s currently sunny and 88 degrees Fahrenheit here in Nashville, TN.

I work as a physician assistant at a neurology clinic with subspecialty expertise in demyelinating disorders, and I wanted to make a few comments about the discussion around transverse myelitis in Episode 661. 

Transverse myelitis is a term that fails to capture the full clinical picture of pathologies that present in the spinal cord in an acute/subacute clinical setting.  A better term is “transverse myelopathy”, given that the differential diagnosis is quite broad, including but not limited to:

-Demyelinating diseases such as idiopathic transverse myelitis, multiple sclerosis and neuromyelitis optica spectrum disorders.

-Infectious etiologies

-Vascular pathologies (i.e. spinal cord infarction)

-Mechanical (spinal stenosis)

Most commonly however, transverse myelopathy IS driven by an inflammatory condition, and can be the first symptom of what eventually becomes multiple sclerosis in many patients.  The incidence of transverse myelopathies goes up significantly when you account for conditions such as multiple sclerosis and neuromyelitis optica spectrum disorders.  

While it’s true that we don’t know the full case history of the patient, and the patient is an “N of 1”,  it’s entirely possible that this patient is a young female (<50 years old) where transverse myelopathies secondary to an inflammatory, i.e. likely autoimmune pathology such as the beginning of what may eventually turn out to be MS.  The age, gender, family history, and co-morbidities will be quite important in this clinical scenario, and to the points already made in the podcast, I have rarely seen a temporal association of inflammatory transverse myelopathies with a temporal association with a recent vaccination.  

Thanks for all that you do and keep up the great work!

Best,

John Kramer, PA-C

Nashville, TN

Agda writes:

I try to keep my grumpy side at bay but after listening to the last TWiV I thought I would write with a different perspective, since so many people were commenting on how to get Christian Drosten to appear on TWiV more or some of his content translated for TWiV listeners.

I would say don’t bother as you guys are doing an excellent job and I don’t think there are many huge insights lurking in his German content. Starting in March I’ve listened to every Das Corona Virus podcast and then switched to scanning the transcripts when they became available, and I have a theory why people here are so fascinated. First, his speech cadence in German is really nice to listen to, relaxed and self-assured at once. The format is very didactic; science communication is badly needed here and the podcast helped fill the gap. Second, due to his standing as a researcher and maybe his personality, Drosten sounds very very sure of what he’s talking about. I would love to know more about how he got to the figures that Sars-CoV2 transmission is 10% fomites, 40% aerosol and 50% droplets or why 1-5% of people could be reinfected, since critics would often latch on some of those statements. I guess many listeners loved to hear him linking different pieces of evidence/research and then coming up with a possible mechanism (who doesn’t like mechanisms). I’m not sure all of those exercises stood the proof of time. Anyway the research he refers to is the same that is being discussed on TWiV, often by the authors themselves! One of Drosten’s more interesting mechanism-hunting episodes was ep. 47 commenting on work from Ralph Baric’s lab among others. I’ve been waiting for Baric to come back to TWiV for a while now!

Thanks,

Agda