After saving his own life with a repurposed drug, a Professor David Fajgenbaum reviews every drug being tried against Covid-19

By Ryan Prior

Every morning, Dr. David Fajgenbaum takes three life-saving pills. He wakes up his 21-month-old daughter Amelia to help feed her. He usually grabs some Greek yogurt to eat quickly before sitting down in his home office.

Then he spends most of the next 14 hours leading dozens of fellow researchers and volunteers in a systematic review of all the drugs that physicians and researchers have used so far to treat Covid-19. His team has already pored over more than 8,000 papers on how to treat coronavirus patients.

The 35-year-old associate professor at the University of Pennsylvania Perelman School of Medicine leads the school’s Center for Cytokine Storm Treatment & Laboratory. For the last few years, he has dedicated his life to studying Castleman disease, a rare condition that nearly claimed his life.

Against epic odds, he found a drug that saved his own life six years ago, by creating a collaborative method for organizing medical research that could be applicable to thousands of human diseases.

But after seeing how the same types of flares of immune-signaling cells, called cytokine storms, kill both Castleman and Covid-19 patients alike, his lab has devoted nearly all of its resources to aiding doctors fighting the pandemic.

During a cytokine storm, the body’s overactive immune response begins to attack its own cells rather than just the virus. When that inflammatory response occurs in Covid-19 patients, cytokines are often the culprit for the severe lung damage, organ failure, blood clots or pneumonia that kills them.

Having personal experience tamping down his own cytokine responses gives him a unique insight.
“I’m alive because of a repurposed drug,” he said.

Now, repurposing old drugs to fight similar symptoms caused by a novel virus has become a global imperative.


Researchers from Fajgenbaum’s lab gather in a video call to discuss Covid-19 treatment data.

A global repository for Covid-19 treatment data

Researchers working with his lab have reviewed published data on more than 150 drugs doctors around the world have to treat nearly 50,000 patients diagnosed with Covid-19. They’ve made their analysis public in a database called the Covid-19 Registry of Off-label & New Agents (or CORONA for short).

It’s a central repository of all available data in scientific journals on all the therapies used so far to curb the pandemic. This information can help doctors treat patients and tell researchers how to build clinical trials.

The team’s process resembles that of the coordination Fajgenbaum used as a medical student to discover that he could repurpose Sirolimus, an immunosuppressant drug approved for kidney transplant patients, to prevent his body from producing deadly flares of immune-signaling cells called cytokines.

The 13 members of Fajgenbaum’s lab recruited dozens of other scientific colleagues to join their coronavirus effort. And what this group is finding has ramifications for scientists globally.

Based on their database, the team published the first systematic review of Covid-19 treatments in the journal Infectious Diseases and Therapy in May.

In that first analysis of the data, the team reviewed 2,706 journal articles published on the topic between December 1, 2019, and March 27, 2020. Just 155 studies met the team’s criteria for being included in the meta-review based on standards such as the size of the cohort, the nature of the study and the end points researchers chose for concluding their inquiries.

“It’s frustrating because we all want a drug that works for everyone,” he said. But that isn’t happening because the coronavirus affects people in ways that are much more complex.

They’re sorting through oceans of data

The first key thing to consider, Fajgenbaum said, was the huge variety of Covid-19 patient experiences. It’s hard to zero in on one particular therapy because there can be such significant differences in the timing of when the drug is administered, how severely Covid-19 strikes a given individual and the stage at which the disease has progressed.

Any change in one of those variables can render an otherwise effective drug impotent. But with massive amounts of patients, the clinical data was bearing out a few noticeable themes, he said.

First, the Covid-19 patients with more severe cytokine storms were more likely to need drugs targeted toward suppressing the immune system. Those with less severe cytokine storms were likely to benefit from an immune-boosting drug.

Outside of drugs designed to boost or suppress the immune system, another major category is antiviral therapies. Various antivirals hit the “viral cascade,” Fajgenbaum said. Some work by stopping the virus from infecting cells, others by halting replication within cells. Other antivirals act in between cells and the virus.

Keeping the database is a huge undertaking, given how stunning the pace of global scientific progress and collaboration has been in the face of the disease’s human toll.

“We set the really ambitious goal of just getting this started,” Fajgenbaum said.

In the three months since the cutoff date for their first paper, the team has reviewed more than 5,000 additional papers published by scientists around the world.

One of their biggest challenges has been fitting the puzzle pieces of the different studies. With each study designed differently, one data set can’t necessarily be grafted neatly onto another. That’s especially tricky when most people diagnosed with Covid-19 eventually get better anyway. It’s hard to parse out if a particular drug was effective and saved lives.

The goal of the CORONA database isn’t to find a wonder drug per se, but to help design better clinical trials that can establish a real cause-and-effect relationship between a drug agent and an individual’s survival.

In the war against the coronavirus, Fajgenbaum hopes CORONA aims to help light the way so the heavy artillery on the front lines can better know what to shoot at Covid-19.

“It’s hard to fight a war if you’re not keeping track of what weapons are being used against the enemy,” he said.


Shown here is one of the researchers’ computer screens as they review Covid-19 treatment data while on a video call. The left side shows a spreadsheet where they tabulate data from the studies. The right side shows the study they’re currently analyzing.

They’re collaborating with FDA analysts

Fajgenbaum’s CORONA database dovetails with ongoing work at the US Food and Drug Administration. For years, the agency has been developing an app called CURE ID, a platform designed to help health care providers capture novel uses of already approved drugs.

The app launched in December with two goals in mind: The first was to help advise physicians searching for new treatment ideas, prescription guidelines and emergency use advisories for drugs across hundreds of diseases. The agency’s second aim was to build a structure by which health providers in the trenches could quickly input anonymized information about their patients so that other doctors around the world could quickly see whether they had been successful using an off-label drug.

The app was ready just in time for the pandemic, and Fajgenbaum gave the keynote speech at its launch.

“It’s really been a terrific collaboration,” said a health policy analyst with the FDA. “His life follows very much the model we hope to use.”

Now that he and his team are working on the coronavirus, the urgency of their partnership has strengthened.

“Nobody wants to go to a database with no data in it,” the analyst said. “Rather than reinventing the wheel, he was kind enough to provide all his data.”

And while the CORONA database project is primarily intended to aid researchers, it’s tapping into major currents in health economics that explain weak points in the way the public and private sector develop therapies together.

“Covid-19 illustrates a market failure in how we build vaccines,” said Amitabh Chandra, a health economist with joint appointments as a professor at the Harvard Kennedy School and Harvard Business School. “We haven’t given firms the correct incentives to make vaccines before a pandemic. Vaccines are very hard to test before the pandemic hits.”

There aren’t old vaccines sitting on a shelf waiting to be dusted off to save the world from the coronavirus. But there are hundreds of FDA-approved drugs at your local pharmacy that can save lives immediately.

When teaching classes, Chandra uses a 2017 New York Times story profiling Fajgenbaum to illustrate the value of drug repurposing and motivate his students to think boldly about how to create economic incentives to cure diseases, particularly when a “invisible medicine” might be right under your nose.

“There’s no substitute for a good story to get people motivated,” he said.
Many drugs are beginning to stand out.

The combination of antivirals lopinavir and ritonavir is the Covid-19 treatment protocol with the most number of studies published so far. As of mid-June, the team had looked at papers on that drug pairing involving more than 4,500 patients.

Next, corticosteroids have shown particular promise, making appearances in studies with another 4,000 patients. At the cellular level, antivirals work for a variety of reasons, each with its own specialty in attacking the virus at different points in its life cycle. Corticosteroids are different, however.

“Steroids tend to act the same, with replicating cortisol,” Fajgenbaum said.

He feels particularly elated about a recent United Kingdom-based study on the steroid dexamethasone. The study garnered headlines for its result showing that a low-dose 10-day regimen of the drug could reduce the risk of death by a third among hospitalized patients requiring ventilation.

In their spreadsheets, the numbers around dexamethasone were like a beacon.
“We built CORONA to help uncover something like dexamethasone,” he said. “It’s a cheap repurposed drug that’s been around for 60 years. This is what it’s all about.”

Studies need rigor

Because Covid-19 is so new, many of the studies are observational or anecdotal. These types of studies obviously matter as scientists are building a foundation of knowledge.

But the best insights come from running double-blind placebo-controlled studies. One shortfall is that many of the published studies just don’t have the level of rigor to inform larger-scale scientific decision-making.

“There are a lot of biases in these observational studies,” Fajgenbaum said.
One drug, the anti-malarial drug hydroxychloroquine, has famously received a lot of boosterism from US President Donald Trump. But in the published studies available for Fajgenbaum’s team to review, the drug hasn’t outperformed others.

Two French studies on hydroxychloroquine drew red flags for the University of Pennsylvania-based team because of the clinical end point the researchers chose: the time when the coronavirus cleared the body. It can be problematic to base an argument for a drug’s success only on that particular metric, because it leaves out crucial details from a person’s longer-term experience following infection.

“‘Virally cured’ is a challenging term,” Fajgenbaum said. “We don’t know if they’re discharged how they fared after leaving the hospital.”

On top of that, the reviewers were skeptical because the virus took a long time to leave the patients’ bodies, which they refer to as “a high time to viral clearance.”

That indicator that could suggest the drug was slow to take effect, or that other factors, including the patient’s own immune system, played a larger role in expelling the pathogen.

Know how to sort through the data

With dozens of people working full time to sort through thousands of studies, it’s obviously impossible for a single frontline health provider to keep abreast of all there is to know about Covid-19 while also treating patients at the same time.

It’s even harder for the average person following the story in the news, especially if you’re not equipped with a graduate degree in statistical analysis.

“Covid threw the world in flux,” said Sheila Pierson, associate director for clinical research at the CSTL. A biostatistician originally hired to study Castleman disease, she’s accepted the new mission along with her colleagues.

“There’s a lot of great science being done,” she explained. With that pace of innovation, it’s incredibly difficult for the average person to stay up to date, so the CORONA database helps everyone with a little extra scientific literacy amid headlines about new treatments that induce a form of intellectual whiplash.

“You should rely on multiple news sources,” Pierson said, in order to sort through what may appear to be conflated messages about whether a certain drug works or not for a certain group of people.

“It’s difficult when you’re only looking at one person’s view of a drug,” she said. “Look for a different write-up and a different view.”

He’s repeating the same methods that saved his life

As of June 27, Fajgenbaum has lived free of Castleman’s cytokine storms for 77.72 months. His last Castleman relapse ended on January 5, 2014. He’s a living experiment, and in his personal accounting he won’t round up to the next full month. Each new day is a precious moment with a daughter he feared he’d never meet.

The doctor and researcher remains immune compromised and won’t take risks with the coronavirus.
He hasn’t set foot in a building other than his home since March 13. And his life still relies on siltuximab and chemotherapy infusions administered monthly through a chest port.

“I’m reminded every time I touch the port in my chest of the cytokine storms I had,” he said. “I want so badly to solve (Covid-19) the way I did with Castleman. I have the same sense of urgency.”

Castleman disease nearly killed Fajgenbaum five times in his 20s while he was working his way through University of Pennsylvania’s Perelman School of Medicine and then earning an MBA at the University of Pennsylvania’s Wharton School.

Each time, the deadly disease triggered cytokine storms that led to multiple organ failure.

But the young man created a global organization to rally doctors, scientists and patients toward finding a cure. With intense study and brilliant partners, he zeroed in on an already available immunosupressant that could be repurposed to save his life.

Last year he published his memoir, “Chasing My Cure,” detailing a journey in which at one point a priest was brought to his hospital room to give his last rites.

Fajgenbaum’s story reads likes the teaser for a hit Netflix series. But if it were a show, all of that is really just season one. Because, spoiler alert — then a global pandemic hit.

A year ago you might have thought what the writers threw at him in a second season might be a bit unrealistic. But this project is the obvious next step.

“I see myself bringing our experiences with Castleman now over to the global fight against corona,” he said.

https://www.cnn.com/2020/06/27/health/coronavirus-treatment-fajgenbaum-drug-review-scn-wellness/index.html

Only 40% of Americans have made plans to avoid crowds in the coronavirus crisis

Photos of crowded beaches, packed bars and large crowds at amusement parks like Walt Disney World last weekend shocked many Americans who had decided to heed warnings to hunker down amid the coronavirus pandemic.

Public polling published this week gives a clue into the public mindset before those gatherings, when the scope of the pandemic was becoming clearer: As of last week, only 2 in 5 Americans canceled plans to attend large gatherings, according to a Kaiser Family Foundation poll. That leaves a majority of people in Kaiser’s polling who say they haven’t canceled plans for large gatherings.

The polls did not ask whether the respondents had plans to be in large gatherings, and some of those respondents may not have had plans to be in large gatherings.

Kaiser’s polling, while still relevant, is almost a week old — an eternity in the time of coronavirus, which has proven to be a fast moving pandemic. By Thursday evening, more than 13,000 Americans tested positive for coronavirus and at least 195 people were dead.

As those social media images of packed restaurants and bars circulated, the Centers for Disease Control and Prevention issued guidance on Sunday recommending all in-person events of 50 people or more be canceled. The White House then issued recommendations on Monday that people should not gather in groups of more than 10 to help limit the virus’ spread. That’s led to many restaurants and bars being shut down by state or city entities and required to do take out or delivery service only.

The CDC’s guidelines on coronavirus are to take steps to isolate yourself and observe social distancing measures, as well as washing your hands often, keeping a clean home and staying six feet away from others. Many offices have implemented work from home procedures, with millions of Americans secluded in their houses.

That’s led many Americans to take some precautions against getting sick.

Almost 9 in 10 Americans are washing their hands more frequently as a result of the coronavirus pandemic, according to a new AP-NORC poll. Almost a third of Americans are extremely or very worried about being infected with the virus, the same poll showed.

The pandemic has also wreaked havoc on planned travel.

Four in 10 people were planning domestic travel in the next three months. Of that group, 51% are planning to keep their plans, while 27% are considering going and 22% have canceled.
Of those who had international travel planned in the next three months (around 12% of those polled), 25% still plan to go, 33% are considering what to do and 41% have canceled their trips.

Other polling within the last week finds similar results. Around 4 in 10 Americans have decided to change travel plans because of the recent outbreak, and 40% have canceled plans to attend large gatherings, the Kaiser Foundation poll found.

The AP-NORC poll found two-thirds of Americans are staying away from large groups, and significantly fewer are keeping children out of school.

Polling shows many Americans are split over how the government is handling the crisis.
An Ipsos/Reuters poll finds half of Americans support the federal government shutting down gatherings of over 100 people. Almost half (46%) support shutting down all overseas flights and 44% support closing public schools.

Fewer people support shutting down nonessential government offices (29%), shutting down public transportation (21%) and enforcing a curfew (19%), the poll showed.

In an NPR/PBS/Marist poll from last week, 46% say the federal government is doing enough to prevent the spread of coronavirus, down from 61% who said so in February.

The AP-NORC poll was conducted March 12 through 16 online among 1,003 adults with a margin of error of plus or minus 4.3 percentage points. The Kaiser Family Foundation poll was conducted March 11 through 15 over the phone among 1,216 adults with a margin of error of plus or minus 3.0 percentage points. The Ipsos/Reuters poll was conducted March 16 through 17 online among 1,115 adults with a margin of error of plus or minus 3.3 percentage points. The NPR/PBS/Marist poll was conducted March 13 through 14 among over the phone 835 adults with a margin of error of plus or minus 4.8 percentage points.

https://www.cnn.com/2020/03/20/politics/coronavirus-canceling-plans-polling/index.html

French Peer-Reviewed Study: Our Treatment Cured 100% Of Coronavirus Patients

On Wednesday, Gregory Rigano, an advisor to the Stanford University School of Medicine, claimed that a world-renowned French researcher had tested a promising cure for coronavirus.

He tweeted: “Full peer-reviewed study has been released by Didier Raoult MD, PhD. After 6 days 100% of patients treated with HCQ + Azithromycin were virologically cured.”

Appearing on Fox News Wednesday night, Rigano followed up by stating:

And I’m here to report that as of this morning, about 5:00 this morning, a well-controlled peer-reviewed study carried out by the most eminent infectious disease specialist in the world—Didier Raoult, MD, PhD—out of the south of France, in which he enrolled 40 patients, again, a well-controlled peer review study, that showed a 100 percent cure rate against coronavirus. The study was released this morning on my Twitter account, @Riganoesq as well as our most recent website, @covidtrial.io. The study was recently accepted to the International Journal of Antimicrobial Agents by Elsevier.

Rigano continued, “In fact to be able to cure a virus was said to be mathematically impossible, and the first company that did it was a small biotech called Pharmacet that was acquired by Gilead Sciences in a cure for hepatitis C. What we’re here to announce is a second cure to a virus of all time.”

On Monday, The Daily Wire reported that an Australian team had announced they might have found a cure for coronavirus, and it was in a similar vein:

According to infectious disease experts at the University of Queensland in Brisbane, Australia, they may have found a treatment that could possibly eliminate the coronavirus. “University of Queensland Centre for Clinical Research director Professor David Paterson told news.com.au today they have seen two drugs used to treat other conditions wipe out the virus in test tubes,” News.com.aureported Monday.

The two medications Paterson referred to are Chloroquine, an anti-malarial drug, and HIV-suppressing combination lopinavir/ritonavir. Paterson told the outlet that it seemed reasonable to call the drugs “a treatment or a cure … It’s a potentially effective treatment. Patients would end up with no viable coronavirus in their system at all after the end of therapy.”

According to covidtrial.io, here are the backgrounds for Didier Raoult and another doctor involved in the study:

Didier Raoult created the Rickettsia Unit at Aix-Marseille University. Since 2008, Dr. Raoult has served as the director of URMITE (Research Unit in Infectious and Tropical Emergent Diseases), collaborating with CNRS (National Center for the Scientific Research), IRD (Research for the Development Institute), INSERM (National Institute of Health and Medical Research) and Aix Marseille University. His laboratory employs more than 200 people, including nearly 100 active researchers who publish between 250 and 350 papers per year and have produced over 50 patents.

Dr. Chandra Duggirala has a bio that states:

He founded Novobionics, a medical device company to treat diabetes and obesity non-invasively and invented it’s double sleeve technology. He lead the company through preclinical trials and several US and international patents. He is also the Principal Investigator of the Reset-Youth trial, one of the largest clinical trials for investigating the reversibility of epigenetic markers of aging. He also founded a software company at the intersection of nutritional biology and A.I.

https://itsinterestingdotcom.wordpress.com/wp-admin/post-new.php

How one small Italian town cut coronavirus cases to zero in just a few weeks

By Rachael Rettner

A small Italian town appears to have drastically reduced coronavirus infections — reaching zero cases last week — after implementing an aggressive tactic to curb spread, according to news reports.

The town, Vo Euganeo, in northern Italy, saw a cluster of cases of the new coronavirus disease (COVID-19) in the third week of February and was home to the country’s first death from COVID-19, on Feb. 21, according to The Straits Times.

Following this death, the town was put on lockdown, and all 3,300 residents were tested for coronavirus, according to Sky News.

This mass testing revealed that about 3% of residents were infected with the virus, and of these, about half did not show any symptoms, according to ProMarket, the blog of the Stigler Center at the University of Chicago Booth School of Business. After two weeks of a strict lockdown and quarantine of cases, only 0.25% of residents were infected. The town isolated these last few cases and has since reopened.

Vo Euganeo has not reported any new cases since Friday (March 13), according to Sky News.

“The lesson we learned is that isolating all positive cases, whether they were sick or not, we were able to reduce transmission by 90 percent,” Andrea Cristani, a professor of microbiology at the University of Padua in Italy who helped carry out the testing, told RFI.

This message echoes a recent statement from the World Health Organization (WHO). “We have a simple message to all countries — test, test, test,” Tedros Adhanom Ghebreyesus, director-general of WHO, said at a news briefing Monday (March 16). “All countries should be able to test all suspected cases. They cannot fight this pandemic blindfolded.”

COVID-19 cases in the rest of Italy have soared in recent weeks. The country has reported more than 35,700 cases and nearly 3,000 deaths as of Wednesday (March 18).

https://www.livescience.com/small-italian-town-cuts-coronavirus-cases-testing.html?utm_source=Selligent&utm_medium=email&utm_campaign=15489&utm_content=20200319_Coronavirus_Infographic+&utm_term=3675605&m_i=OguKUMtlVZ2XR0FtmKzVwy23qhJljQ_ECDHOF9yeeiliWl1lAhbCDeG8red8tr52pB6GdMdlKqG0SWmT4cwSI4C0qaXToh

Coronavirus update: Virus could live up to 24 hours on cardboard, 3 days on plastic and steel, study says

Coronavirus could live up to three days on a plastic or stainless steel doorknob, researchers found.

A preliminary study released last week also showed that the virus could be aerosolized, meaning it could potentially live in the air. It could live up to three days on some surfaces.

Though it’s widely acknowledged that coronavirus could be spread via respiratory droplet — the result of coughing or sneezing — there’s not much information yet on how the virus lives on surfaces or in the air.

The new research could inform cleaning recommendations and other measures taken to reduce community spread.

The U.S. Centers for Disease Control and Prevention recommend routine cleaning of high-touch surfaces, like door handles, high-backed chairs, light switches and remote controls.

The study, released last week, is not yet peer-reviewed. That means that other experts have not had the chance to check the quality of the research, and its not advised that doctors use it in a clinical setting. But as people try to cope with the disease, it’s being widely read.

Here’s how long the study indicated the virus could live on various surfaces:

The air: Researchers found the virus could be detected in aerosols up to 4 hours after it was sprayed.

Copper: Up to 4 hours

Cardboard: Up to 24 hours

Plastic: 2-3 days

Stainless steel: 2-3 days

https://www.cleveland.com/news/2020/03/coronavirus-update-virus-could-live-up-to-24-hours-on-cardboard-3-days-on-plastic-and-steel-study-says.html?utm_source=Newsletter&utm_medium=Newsletter%20-%20Wake%20Up&utm_campaign=Newsletter:%20The%20Wake%20Up

Italian man wears isolation donut

A man in Italy has been spotted wearing what has been described as a social-distancing “doughnut” in order to ensure he stays a safe distance from others during the country’s outbreak of COVID-19.

In the footage, which was shared online last week, the man is seen wearing a large yellow saucer, which has been suspended around his waist with two arm straps.

“And this would be a safe distance?” another man can be heard asking him in Italian, to which the doughnut-wearing citizen confirms.

“For coronavirus,” the man responds.

The video was reportedly captured in Rome’s Mercato Testaccio, a popular food market located in the Testaccio neighborhood south of the city’s center, according to a tag placed on the video.

Nowhere in the footage does the man refer to the apparatus as a “doughnut,” although that name had been applied by social media viewers, as well as Popular Mechanics.

Twitter users soon declared the man “un genio” (a genius) and praised him for his ingenuity, while another asked why the World Health Organization hadn’t thought of this idea first.

Despite the jokes, the practice of “social distancing” amid the ongoing coronavirus pandemic has been recommended by health agencies to stem the spread of COVID-19.

“Social distancing for COVID-19 means avoiding places or gatherings where you are likely to be exposed to respiratory droplets from others – directly or on surfaces,” Dr. Jill Grimes, an urgent care physician at The University of Texas, had previously told Fox News. “We know this virus is spread primarily by these droplets, up to a distance of roughly six feet (from a cough or a sneeze) and so avoiding areas where people are physically closer than six feet is key.”