Hi I’m Wendy Zukerman and you’re listening to Science Vs from Gimlet. As this Covid-19 pandemic rages on, we at Science Vs been keeping an eye on all the treatments that doctors are trying around the world... About a month ago we told you about some promising research out of China into an antimalarial drug.[1] It was pretty obscure back then. But just this week it felt like this drug had been upgraded to celebrity status[2].

TRUMP PRESSER STARTS W/ SOUND OF CAMERAS[3] Thank you very much

TRUMP 3/23: At my direction the federal government is working to help obtain large quantities of chloroquine.

Chloroquine -- it’s the drug that’s making the headlines..[4] And Trump is a big fan. In one press conference this week he said that he’d heard the story of a man who took it and had a remarkable recovery.

TRUMP 3/23: A gentleman they thought he was not going to make it, he said goodbye to his family. They had given him the drug just a little while before, but he thought it was over, his family thought he was going to die, and a number of hours later he woke up, felt good, then he woke up again and he felt really good, and he’s in good shape.

And Trump said this drug might be able to help lots of people.

TRUMP 3/23: There's a real chance, I mean again, we don’t know, but there’s a real chance that it could have a tremendous impact. It would be a gift from god if that worked, it would be a big game changer.

And people all around the world have really latched onto this idea that this drug could help fight this coronavirus.. Google searches for it soared[5] [6] [7] [8][9] ... some pharmacies are saying that demand for the drug has skyrocketed[10] and one company told that at hospitals, orders were up 3,000%[11] - but when some people went looking for chloroquine… it took a dark turn

They thought a drug could protect them from coronavirus, but he and his wife made a terrible mistake

A couple ended up in this hospital after they each took a teaspoon of an old aquarium product they had - it contained chloroquine

So is this drug a danger or a gift from god?

Today on the show what is going on with chloroquine. We speak to a scientist running a clinical trial into this very drug and coronavirus right now. And we’ll find out does it really have the chance to be a game changer of this pandemic?

When it comes to this coronavirus there is a lot of talk of

A gift from god 

But then there’s science…

AHHHH

Science Vs The Coronavirus Part 6.
 Return of the Jedi. Coming up after the break.

BREAK

Welcome back. So chloroquine is making a lot of headlines right now. What is it? Well... It’s a drug that’s been on the market for decades, it’s often used for malaria[12] , and it’s old - people have been taking it for around 70 years.[13][14][15]. And there's a few different kinds of this drug, like hydroxychloroquine ... that's used for diseases like lupus.[16] So chloroquine has been hanging around for years, doing its thing … But this week. The story of this drug took a bizarre turn. 

 

*Riiiing*

Hello

Hi can I please speak to Daniel

Yeah this is Dan Brooks

Dan[17] is a professor of toxicology and medical director of the Banner Poison and Drug Information Center in Phoenix, Arizona. People call his hotline when they’re worried they’ve been exposed to something toxic ...  

DB So we take calls from people dealing with occupational exposures, rattlesnake...

WZ Wait did you just say Rattlesnakes?

DB Yeah yup

WZ That's the second one you said

DB Yeah we get like 80-85 rattlesnake patients a year

But recently something else was rattling Dan - as the coronavirus started to spread in the US, Dan was getting worried that people would take matters into their own hands and start using homespun treatments and Dr. Google to cure all their coughs and fevers.

DB We’ve seen this happen dozens of times before, you know, we’ve seen this with influenza when we had bad years with influenza. We've seen this over and over again [18].

Yeah, Dan says that for flu, people will try all sorts of stuff..[19] [20] … and in this pandemic[21], he says people were even calling the Poison Centre to see if they should take bleach[22] to avoid getting sick with coronavirus …

DB And so we just knew when as more and more things were being promoted to heal and prevent covid so we just tried to get out and warn people…

Last Friday Dan’s team reached out to some media to get the word out about this.

So we released that and unfortunately within 48 hours we had our first event Y'know our prediction came true.

Dan’s poison center got a call from a couple in their 60s. This pair had heard all the excitement around chloroquine … including what Trump was saying about it[23]. And then …

DB They got concerned about some vague symptoms that they interpreted may have been for coronavirus

WZ Do you mean like a sore throat, cough something like that?

DB Correct. So my understanding only the husband but they became concerned about it, and they decided that they may be able to prevent or treat coronavirus with a home product, that contained chloroquine

The woman involved talked to NBC[24]  about what happened. She said that she saw this stuff in her pantry - that had chloroquine in it - it was something she had used to keep her fish healthy…[25] ..[26]

<<I just saw it sitting in the back shelf and said hey isn't that the stuff they talked about on TV, and yeah it was.>>

They decided to take some. They mixed it with soda. And pretty quickly started to feel sick

<<It happened so fast. It got so bad so fast.>>

Here’s Dan Brooks again…

DB And within 30 minutes of taking this powdered substance, both of them became sick, and the wife had significant vomiting, which may have saved her life, because all this vomiting helped her NOT absorb this potentially deadly drug.

But her husband took a turn for the worst

DB He had abnormal heart rhythm, and the electrical activity in his heart wasn't normal. Paramedics and ER folks did as much as they could - but he apparently had a very very massive ingestion, and he was not resuscitated, he died in the emergency department.

He died from heart failure[27]. As the head of the Poison Center, Dan was told about what happened.

DB Paramedics called us, the poison center, on Sunday

WZ What was going through your mind when you heard about this, given that you tried to get in front of this?

DB I don’t know, I've been doing this for 20 years, so this happens to us almost every week… but you can't blame people for being afraid

<<MUSIC POST>>

MP It’s sad I think they were driven by understandable fear and worry

This is Matthew Pullen, he’s a doctor and an infectious disease specialist[28] at the University of Minnesota

MP And I think fear in this situation is understandable, it’s a very uncertain time, with yknow not a lot of good options in a lot of situations, but yeah as a clinician all I can say is I feel for them, and I hate that it happened to them, and I wish it hadn't.

Matthew is part of a team in the US that's running a clinical trial into whether chloroquine can help people with the coronavirus. And he says we know when people take chloroquine at high doses - which is what this couple took - this chemical can be dangerous[29]. [30] [31] [32]

MP They were taking many many times more than the recommended amount[33]-01

But Matt says that people take chloroquine at lower doses all the time for malaria. And then main side effects are stomach troubles - like nausea [34][35]  and headaches[36][37][38][39]. Some people get itchy all over their body.[40][41][42] But generally at low doses, this drug is thought to be safe.[43] Matt has taken it to prevent malaria, and he’s given it to patients for autoimmune diseases…

MP It’s a drug I've personally prescribed it probably a hundred times, It’s very very safe, I've never had anyone that had adverse effects taking it chronically

The upshot here is that dosage is SUPER important. Chloroquine is not something you want be to self-medicating with. But at the right dose and for short periods - it can be safe -- the big question though is can it actually help people with Coronavirus? And that answer is coming up after the break.

BREAK

Welcome back. We’re talking about chloroquine …And although we’ve been talking about this for 10 minutes… I had to clear something up with … Dr. Matthew Pullen.

WZ Chloroquine or qYne?

MP Depends on which side of the ocean you’re from

Ahh I think it’s aluminum aluminium

WZ It’s like the metric system!!

MP We say Chloroquin

WZ Isn’t that weird why do we do this

So in respect for you I will say chloroquine.

MP Ok

And now that that’s settled, we asked him …  how could chloroquine(KWINE) … chloroquine(KWIN) … work for this coronavirus? Ok - so you first have to know that a virus wants to copy itself. To make more tiny particles so it can spread into more and more and more cells…  And ...to do that, it first has to get into our cells.[44][45][46] So it binds to - what’s called a receptor - and that triggers this process

MP And then the cell ingests it into a little pocket inside the cell. 

This process of getting ingested is called invagination.[47] Which is just a great word. Invagination. But what’s actually important here is that when a virus gets into that pocket in our cells - the cell is like - woopah! YOU?! You gotta go.

MP It tries to digest it a lot like our stomach you know shoots acid into itself to digest food that’s kind of what the cell is doing.

And so to get rid of the nasty virus and so the cell squeezes acid into that pocket. But it turns out, this strategy backfires!  Because. The coronavirus actually wanted the cell to shoot that acid all along. You see, the virus needs acid to reproduce to get more virus particles.

MP Correct yeah yeah. So it's kind of taking advantage of a self defence mechanism that cell has

WZ That's very rude

MP Yeah very rude

Here’s where our old pal chloroquine comes into the mix. We think that it tells the cells - stop that with the acid thing![48] And it steps in to put the brakes on that process. Or as Matt says ...  

 

MP Yeah it alkalises or raise the pH.

In this case you want to be basic. Ok so by slowing down this acid thing … keeping the virus from copying itself... chloroquine could delay the spread of the virus in your body.  Karla Satchell a professor at Northwestern[49] described it to us like this.

KS Anything that slows that cycle of 1 virus makes a 100, 1000 makes, 10,000 makes a million, anything you can do to slow that down, gives your body time to mount this immune response.

Chloroquine is thought to do some other stuff too - like dampen down inflammation[50][51], which is a big part of why this coronavirus makes some people so sick.

Okay, so that's how researchers think chloroquine might stop this virus. But does it actually work? Well, there are a couple studies[52] [53] done in petri dishes, where it looks like putting chloroquine onto cells protects them from getting infected with coronavirus And, we got a hold of some very early, unpublished, data[54] coming from a clinical trial in China, it had around 200 people in it.[55] It found that those who got chloroquine? … Their fevers went away faster than those who didn’t. [56]

But what might have kicked off a lot of this talk[57] of chloroquine was a study out of France.[58] It looked at 36 people with this coronavirus[59] - and gave 20 of them hydroxy - chloroquine.  Some of them got an antibiotic too. And the researchers said the treatment eliminated the infection in some patients.[60] 

MP It did look very promising but the attitude that’s going on around is that it should be viewed with caution-01

The reason that Matt isn’t that excited is because the study was basically a small grab bag of different patients…and not all did well here. 1 died. 3 were sent to the ICU.[61] And just generally it’s a pretty small study. 

MP It's definitely a good step, and it’s definitely meaningful but there’s a question of how meaningful

On top of this, another small study - of 30 patients in China - found that hydroxy - chloroquine didn’t help their symptoms.[62] So what to make of all this? Well we need more data. And there’s actually more than a dozen clinical trials looking into this right now.[63][64] [65]

And one of them is Matt’s. In the last week his team has started recruiting people from all across the country.[66] And he’s trying to see if hydroxy- chloroquine can help people who are sick. But also - in a separate part of the trial - they’re giving it to people who have been exposed - like healthcare workers[67] - to see if it can keep them from getting the virus.[68] They’ve already enrolled around 500 people[69].

MP Quite a few in a short amount of time

WZ Yeah! When do you think you will you get results?

MP We're hoping in 4 to 6 weeks, near the end of April, we will have a preliminary sort of thumbs up thumbs down answer on whether this is working or not

4 to 6 weeks. And while we’re living in self isolation, that might feel like an eternity. In the land of science. It’s the opposite. Many trials like this take years to recruit enough people and then analyse results.

MP Quite honesty, it's an insanely fast turn around, in a clinical trial

So pardon me, it's not coronavirus my cough at least

WZ It’s alright we're social distancing, over the phone

MP We're over the phone at least

WZ Since we are in desperate times, heading into desperate time, for doctors on the front lines now  if they have patients not doing well should they just give them drug? Even with this preliminary data.

MP I think ethically it would be very questionable without any solid human data to give that kind of recommendation unfortunately

WZ But I guess we’ve got the French data, the Chinese data that’s promising, we've tried things with less data in the desperate times

MP We don't know if it will work yet, we're optimistic that it will, but you know as a physician, I don't want to give anyone the impression that this medication has been proven to work

Some academics we reached out to agreed with Matt, others said that for desperate doctors on the front line, who are running out of options for their patients - well chloroquine might be a good option now. But everyone agreed that for us at home? Until there is more data, you should not be taking this stuff for coronavirus. Already, we’re hearing that the demand is creating shortages[70] - and remember, there are people who really need this drug for other stuff - like lupus.

Meanwhile, Dan - over at the Poison Center in Phoenix has some wise words for us… if you’re seeing any exciting stuff online. Or Uncle Bill forwards you some cure-all…he says 

DB There is no such thing as a miracle drug. And that’s an important message for everyone to know, There are no miracle pills, that’s science fiction.

So we don’t know if chloroquine will save the day here. There’s some promising research - but then there’s some not so promising research. That’s all part and parcel of living in a pandemic, and doing science on the fly. At least with this drug though - the way science is moving - it looks like we won’t have to wait too long… until we get better data.

 

Ok… and now… for a little non-coronavirus content. Cos we need it. Today. Bats. And we know bats feels like coronavirus content… but it’s not.  Here goes [71][72]. Scientists[73] …carefully watched about 40 bats in captivity for 15 months… and they noticed that these bats built very cute relationships with friends. First they would groom each other, then they would scratch each other’s backs. And ultimately became BFFS. BAT FFs … they even started sharing food! The researchers said that no one had seen this kind of behavior before - we just didn’t know that bats formed these kinds of friendships. So there you go. Bats. Friends. And not just disease vectors.

That’s Science Vs.

And one more thing -- we’ve set up a voicemail to collect all of your questions about coronavirus. Or if you’re a healthcare worker with a personal story you want to share with us ... please call ‪774-481-1238, this is an American number ‪774-481-1238‬ and leave us a message. Or you can always email us at sciencevs@gimletmedia.com.

(phone ringing)

Hello this is Ben

Hey Ben this is Wendy calling from Science Vs.

Hi there Wendy, how are you doing?

I’m good. You had a gripe with our last episode.

(laughing) I did.

Alright, do you want to school me? How do you do it?

Waukesha is the correct pronunciation.

Waukesha

Waukesha

Waukesha, Wisconsin.  

Correct

Are you from Waukesha Wisconsin?

I’m not from Waukesha, Wisconsin, but I have lived in Wisconsin for about the last 20 years.

All right, so you are pretty well placed to know how to pronounce this city. Congratulations on having the world’s oldest fossilized scorpion in your neck of the woods.

Thank you.

This episode was produced by Meryl Horn, Wendy Zukerman, Rose Rimler, Michelle Dang, Laura Morris, Meg Driscoll and Sinduja Srinivasan. We’re edited by Blythe Terrell and Caitlin Kenney. Fact checking by Eva Dasher. Mix and sound design by Peter Leonard. Music written by Peter Leonard, Emma Munger, and Bobby Lord. Thanks to the NBC News Archives. A big thanks to all the researchers that we got in touch with for this episode, including Professor Thomas Doerner, Dr. Hue, Professor David Boulware, Dr. Anne Melzer. And special thanks to the Zukerman family and Joseph Lavelle Wilson.


[1] “a drug used for malaria... is also showing a lot of promise in China” from March 4th script

[2] https://twitter.com/realDonaldTrump/status/1241367239900778501

[3] Remarks by President Trump, Vice President Pence, and Members of the Coronavirus Task Force in Press Briefing 

[4] From Sunday March 22: The Governor also announced that the state will begin to implement drug trials and has acquired 70,000 doses of Hydroxychloroquine, 10,000 doses of Zithromax and 750,000 doses of Chloroquine. The trials will start Tuesday. March 24 “The president and the FDA accelerated that drug coming to New York so the hospitals will start using that drug today”

[5] https://trends.google.com/trends/explore?q=chloroquine&geo=US

[6] https://trends.google.com/trends/explore?geo=IN&q=chloroquine

[7] https://trends.google.com/trends/explore?geo=FR&q=chloroquine

[8] https://trends.google.com/trends/explore?geo=CL&q=chloroquine

[9] https://trends.google.com/trends/explore?geo=PH&q=chloroquine

[10] As Trump touts an unproven coronavirus treatment, supplies evaporate for patients who need those drugs

[11]Email with Premier, Inc.PLUS  Trump Claim That Malaria Drugs Treat Coronavirus Sparks Warnings, Shortages. This statement “In the U.S., hospital orders for chloroquine were up 3,000% from March 1 to 17 compared with typical demand, according to Premier Inc., one of the largest group-purchasing organizations in the U.S. for drugs and other hospital supplies.”

[12] https://apps.who.int/iris/bitstream/handle/10665/162441/9789241549127_eng.pdf;jsessionid=8535DA4A4784A83D3A63ADD22209593C?sequence=1 

[13] The Allied push to synthesize antimalarial agents during World War II was prompted by Japan's seizure of Java in 1942. At the time, 90% of the world's quinine came from Java. Allied interest in chloroquine followed the capture of German supplies of an analogue called sontoquine in Tunis in 1943. Chloroquine and sontoquine had been patented in the United States in 1941 by the Winthrop Company, which had a cartel agreement with IG Farbenindustrie, their original manufacturer, but drug development had stalled [5]. Chloroquine (which can safely be used by pregnant women and children) rapidly controlled clinical symptoms of susceptible malaria with minimal toxicity and was useful as a once-weekly prophylactic drug. Chloroquine, a 4-aminoquinoline, was approved by the FDA in October 1949 [11].

[14] In July, 1934, Andersag modified atabrine by replacing its acridine ring with a quinoline ring. The resulting compound, which would later be termed chloroquine (Fig. 3c), was found to have high antimalarial activity, and unlike methylene blue or atabrine, did not discolor skin and eyes.

[15]  A large series of 4-amino quinolines were investigated. Of these, chloroquine proved to be the most promising and was released for field trial.2 By the end of World War II, it had replaced quinacrine in the therapy of malaria.

[16] Despite widespread clinical use of antimalarial drugs such as hydroxychloroquine and chloroquine in the treatment of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and other inflammatory rheumatic diseases,

[17] Daniel E. Brooks, MD | The University of Arizona College of Medicine

[18] https://wayback.archive-it.org/7993/20170111194035/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm410086.htm

[19] https://www.fda.gov/news-events/press-announcements/fda-warns-fraudulent-and-unapproved-flu-products This year’s severe flu season raises new concerns about the potential for consumers to be lured into buying unproven flu treatments, and even worse, buying counterfeit antivirals online from websites that appear to be legitimate online pharmacies.

[20] FDA, FTC Issue Joint Warning Letter to Web Site Offering Fraudulent H1N1 Flu Supplements - see warning letter "[D]uring the flu season, I suggest taking a daily antioxidant, multivitamin-mineral supplement, as well as astragalus, a well-known immune-boosting herb that can help ward off colds and flu.

[21] Fraudulent Coronavirus Disease 2019 (COVID-19) Products

[22] Danger: Don’t Drink Miracle Mineral Solution or Similar Products - this is being touted as a coronavirus cure: QAnon YouTubers Are Telling People to Drink Bleach to Ward Off Coronavirus 

[23] https://twitter.com/VaughnHillyard/status/1242258629278875648?s=20 

[24] <<0:00:04 - 0:00:28 Did you see the President's press conf? Where did you hear about? Yeah we saw the President' press conference. It was on a lot actually. And then did you seek out chloroquine? I had in the house because I used to have koi fish.

0:00:49 - 0:01:02 I was in the pantry stacking dog food and I just saw it sitting on the back shelf and said hey isn't that the stuff they are talking about on TV and yeah it was. >>

<<0:01:37 - 0:01:42 It happened so fast. It got so bad so fast. 0:02:02 - 0:02:13 And then how did you start to feel dizzy hot I started vomiting and my husband started developing respiratory problems >>

<<...significant vomiting, might have saved her life, didn't absorb this potentially deadly drug. >>

https://twitter.com/VaughnHillyard/status/1242258629278875648?s=20

[25] Experimentally infested clownfish (Amphiprion ocellaris) were free of A. ocellatum infestation after a 10-day exposure to a single water-borne treatment of 5-10 mg/1 chloroquine diphosphate. Chloroquine has no effect on tomont division, but kills dinospores immediately upon their excystment. This concentration is non-toxic to fish, but is highly toxic to micro- and macroalgae and to various invertebrates (C.E. Bower, Connecticut, personal communication, 1987)

[26] Chloroquine was rarely part of the routine quarantine but was used commonly in teleosts, either as an alternative to copper sulfate therapy or to specifically treat Cryptocaryon, Ichthyophthirius, or Amyloodinium.  Chloroquine was also used as an antiprotozoal treatment, rather than as an antibacterial, and has the benefit of a wider therapeutic index than copper

[27] Press Releases

[28] Dr. Matthew Pullen, MD – Minneapolis, MN | Infectious Disease 

[29] Given chloroquine at doses of 5 g "usually" die https://sci-hub.tw/https://doi.org/10.1159/000109767 

[30]  A number of case reports in the medical literature have suggested an association between seizures and parenteral chloroquine, both at therapeutic concentrations and overdose.

[31] Case report of a woman who overdosed and had a seizure plus heart failure

[32] Revised Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy 

[33] She said in the NBC interview they took 1 teaspoon each (4.2 grams)

https://twitter.com/VaughnHillyard/status/1242258629278875648?s=20

[34] Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Other than its direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases

[35] https://drive.google.com/file/d/1uc3awZ5ZytODFQIiLl9sochTwc4dO9aq/view?usp=sharing  The hydroxychloroquine dose in this study is similar to what is given for malaria treatment. It is a very safe medicine when used for short periods. The most common side effect is upset stomach and is usually mild. Other side effects reverse when stopping. Serious side effects can occur, but generally only when taken for extended periods, generally >1 year of continuous use.

[36] Chloroquine: “Usually well tolerated.” But can cause itchiness; exacerbate psoriasis; can cause cardiovascular problems. It’s rare but there can be seizures, psychosis, and retinal damage (when taken long term, and esp. In older people). Also can cause confusion, convulsions, and coma. Doses of more than 5 g delivered by injection/ IV usually fatal. Overdose can also cause blindness.

[37] Systemic side effects commonly seen with all three drugs include pruritus [itch], sweating, headaches, and insomnia. Anorexia, nausea, vomiting, and diarrhea occur less commonly. The major toxic side effects of these compounds are cutaneous, hématologie, neuromuscular, and ocular

[38] There is a relatively small number of adverse effects related to chloroquine analogues used in standard doses, such as gastrointestinal disturbances, headaches, skin reactions, hypotension, convulsions, extrapyramidal symptoms and visual disturbances. Psychiatric side effects of chloroquine seem to be rare, but may manifest in a wide range of symptoms, such as confusion, disorientation, ideas of persecution, agitation, outbursts of violence, loss of interest, feeling sad, suicidal ideas and impaired insight.

[39] Chloroquine is a relatively well-tolerated medicine. The most common adverse reactions reported are stomach pain, nausea, vomiting, and headache.

[40] A mild degree of itching with or without a rash can follow the use of chloroquine in all races. However, in Africans, a more severe itching reaction occurs (1, 2). The itching has a curious biting or pricking character and affects all parts of the body including the scalp, the palms of the hands, and the soles of the feet….It is usually severe enough to make sleep impossible for as long as it lasts.  

[41] Chloroquine (CQ) is an antimalarial drug that elicits severe pruritus in black Africans with malaria fever. This acute itching (2–7 days duration) exhibits age dependency and a racial and genetic predilection. 

[42] Chloroquine is a relatively well-tolerated medicine. Chloroquine may also cause itching in some people...Overdose of antimalarial drugs, particularly chloroquine, can be fatal.

[43] https://clinicaltrials.gov/ct2/show/NCT04308668   This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide post-exposure prophylaxis / preemptive therapy.

[44] Some viruses enter their target cells by endocytosis. This process targets the virus to the lysosomal compartment where the low pH, along with the action of enzymes, disrupts the viral particle, thus liberating the infectious nucleic acid and, in several cases, enzymes necessary for viral replication

[45] Coronavirus cell entry occurs through the endolysosomal pathway… The mechanism of inhibition likely involved the prevention of endocytosis and/or rapid elevation of the endosomal pH and abrogation of virus–endosome fusion…. The activation step that occurs in endosomes at acidic pH results in fusion of the viral and endosomal membranes leading to the release of the viral SARS-CoV-1 genome into the cytosol

[46] Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell…The well-studied mouse hepatitis virus (MHV) is often used as a safe model to study CoV infections…We confirmed that MHV entry requires clathrin-mediated endocytosis

[47] “Entry of CoVs into the host cells is mainly mediated by the endocytic pathway…”

For general endocytosis “invagination” citations: 1) “One pathway of clathrin-independent endocytosis involves the uptake of molecules in small invaginations of the plasma membrane”, 2) “This allowed a dissection of the endocytic pathway into four stages representing distinct protein modules involved in coat formation, membrane invagination

[48] Both chloroquine and hydroxychloroquine are weak bases that are known to affect acid vesicles… Chloroquine/hydroxychloroquine can impair the replication of several viruses by interacting with the endosome-mediated viral entry…

[49] Karla Fullner Satchell : Faculty Profile: Faculty Profiles 

[50]The anti-viral and anti-inflammatory activities of chloroquine may account for its potent efficacy in treating patients with COVID-19 pneumonia.

[51] Chloroquine can affect virus infection in many ways, and the antiviral effect depends in part on the extent to which the virus utilizes endosomes for entry. Besides having a direct antiviral effect, chloroquine is endowed with an immunomodulatory activity, suppressing the production and release of tumor necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases

[52] Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro “In conclusion, our results show that HCQ can efficiently inhibit SARS-CoV-2 infection in vitro.

[53] Our time-of-addition assay demonstrated that chloroquine functioned at both entry, and at post-entry stages of the 2019-nCoV infection in Vero E6 cells.. Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro.

[54] https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.01047/_pdf Thus far, results from more than 100 patients have demonstrated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion, and shortening the disease course according to the news briefing.

[55] https://drive.google.com/file/d/1xJtLnN4c-2JasBp0Eg4ShscU0gziBOf7/view?usp=sharing 

[56] China: Based on in vitro evidence and still unpublished clinical experience, the panel recommended chloroquine phosphate tablet, at a dose of 500 mg twice per day for 10 days, for patients diagnosed as mild, moderate and severe cases of SARS-CoV-2 pneumonia, provided that there were no contraindications to the drug”  Dutch “The Dutch Center of Disease control (CDC), in a public document on its website, suggested to treat severe infections requiring admission to the hospital and oxygen therapy or admitted to the ICU with chloroquine,” Italians “Another guideline document by the Italian Society of Infectious and Tropical disease (Lombardy section) recommend the use of chlorochine 500 mg × 2/die or hydroxychloroquine 200 mg die for 10 days,”

[57]Paper came out March 17th, Google Trends start to spike https://trends.google.com/trends/explore?date=today%201-m&q=chloroquine,french%20study

[58] Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomized clinical trial Philippe their conclusion “Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.” Caveats: low N, some patients dropped out (“A total of 26 patients received hydroxychloroquine and 16 were control patients.” but 6 didn’t complete the study: 3 were sent to the ICU, one died, one left the hospital, and one stopped because of nausea.) not randomized: Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls.  And they didn’t look at symptoms, only percentages of patients with PCR-positive nasopharyngeal samples

[59] Hospitalized patients with confirmed COVID-19 were included in this study…  The results presented here are therefore those of 36 patients (20 hydroxychloroquine-treated patients and 16 control patients).

[60] Among hydroxychloroquine-treated patients six patients received azithromycin

[61] Six hydroxychloroquine-treated patients were lost in follow-up during the survey because of early cessation of treatment. Reasons are as follows: three patients were transferred to intensive care unit, ... one patient died on day 3 ... one patient decided to leave the hospital ...finally, one patient stopped the treatment on day3 post-inclusion because of nausea… The results presented here are therefore those of 36 patients (20 hydroxychloroquine-treated patients and 16 control patients). None of the control

patients was lost in follow-up.

[62] http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf  did not report any significant differences to control group, only 30 people

[63] WHO report

[64] Advance of Novel Coronavirus Registration Clinical Trial Gao Song1,*, Meng Qun Cheng2,† ,Xian Wen Wei3,† 1Department of Phar In the CMT study, the top three drugs studied by frequency: Chloroquine (n=16, 16.84%), Lopinavir/ritonavir (n=15, 15.79%), and I-IFN (n=11, 11.58%).

[65] https://www.medrxiv.org/content/10.1101/2020.03.18.20038190v1.full.pdf The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5).

[66] Matt’s study is using Drug: Hydroxychloroquine

[67] From clinicaltrials.gov application: “Inclusion Criteria:... Exposure to a COVID19 case within 4 days as either a healthcare worker [MH] or household contact,

[68] Post-exposure Prophylaxis for SARS-Coronavirus-2 - Full Text View “To test if post-exposure prophylaxis with hydroxychloroquine can prevent progression development of symptomatic COVID19 disease after known exposure to the SARS-CoV2 virus.” [Note- Dr. David Boulware (Lead PI) says this site hasn’t been updated to include the arm of the trial which will test whether giving hydroxychloroquine will help people who are already sick -MH]

[69] We are currently at 481 enrolled participants, cruising along nicely in recruitment but always looking for more! Emailed Matt

[70] A run on anti-malaria drugs chloroquine and hydroxychloroquine has wiped out supply of potential coronavirus treatment -... The sudden shortages of the two drugs could come at a serious cost for lupus and rheumatoid arthritis patients who depend on them to alleviate symptoms of inflammation, including preventing organ damage in lupus patients

[71] Situation Summary

[72] Three species of vampire bats (Desmodus rotundus, Diaemus youngi, and Diphylla ecaudata) rely on blood as their only food.

[73] Development of New Food-Sharing Relationships in Vampire Bats