A new international project aims to enroll 500 COVID-19 patients to search for genetic mutations that make some people more vulnerable to severe infection.
HHMI scientists are joining many of their colleagues worldwide in working to combat the new coronavirus.Theyre developing diagnostic testing, understanding the viruss basic biology, modeling the epidemiology, and developing potential therapies or vaccines. Over the next several weeks, we will be sharing stories of some of this work.
Hundreds of clinicians worldwide are banding together in an effort to study some types ofseverecases of the new coronavirus disease.
The project, led by Howard Hughes Medical Institute (HHMI) Investigator Jean-Laurent Casanova at The Rockefeller University, seeks to identify genetic errors that make some younger patients especially vulnerable to the virus that causes COVID-19, the infectious respiratory illness also known as coronavirus disease 2019.
Casanova aims to enroll 500 patients internationally who meet three broad criteria: theyre less than 50 years old, have been diagnosed with COVID-19 and admitted to an intensive care unit, and have no serious underlying illnesses, such as diabetes, heart disease, or lung disease.
By studying these patients' DNA, scientists may pinpoint genetic mutations that make some people more susceptible to infection. Such information could one day help doctors identify people who are most at risk of developing severe coronavirus disease, says Casanova, a pediatrician at Rockefeller. It could also offer clues for scientists searching for new therapeutics. For example, if patients cells arent making enough of a particular molecule, doctors may be able to offer a supplement as treatment.
Were going to try to find the genetic basis of severe coronavirus infection in young people.
Jean-Laurent Casanova, HHMI Investigator at The Rockefeller University
That day may still be years away. This is not a short-term effort, Casanova says. Some scientists have hypothesized that COVID-19 might be a seasonal illness, with infections ebbing in the spring and summer, and then returning in the fall. But Casanovas team is optimistic. They have already begun enrolling patients and have started sequencing their exomes spelling out all of the DNA letters in every gene in a persons genome. Were going to try to find the genetic basis of severe coronavirus infection in young people.
Late last year, when the first coronavirus infections began cropping up in China, Casanova started reaching out to his colleagues there. Though the most severe cases seemed to concentrate among older adults and those with other conditions, Casanova was interested in the outliers kids and young adults hit hard by the illness who didnt have any of the usual risk factors, such as age or underlying illness.
His team kicked off a new project to study these mysterious cases, and in January just weeks after the Wuhan outbreak began enrolling patients. Clinicians mailed patient blood and DNA to his lab, and researchers there and elsewhere began processing samples the first steps needed for scientists to peer into patients genomes. Now, the project is global, and Casanova is collaborating with scientists and healthcare workers from Europe to Africa, Asia, and Oceania.
We will recruit children and adults <50 yo without risk factor admitted to ICU for idiopathic #COVID19. We will test the hypothesis that they carry inborn errors of immunity to this virus. Please refer patients to @casanova_lab and please RT. pic.twitter.com/DXPoFKieEy
Hunting for the genetic underpinnings of severe infectious diseases is nothing new for Casanovas team. What were doing with coronavirus is what my lab has been doing for 25 years with other infections, he says.
They look for weak spots in peoples immune systems small genetic changes that make people more vulnerable to disease. His group has previously searched the genomes of patients infected with viruses, bacteria, fungi, and even parasites. The infection closest to COVID-19 his team has studied is severe influenza pneumonitis, for which theyve discovered three genetic links. Theyve also identified specific genetic errors that can predispose patients with herpes to viral encephalitis. And theyve found that children with mutations in an immunity gene called IFN-gamma are vulnerable to the bacteria that cause tuberculosis. These children make low levels of the IFN-gamma protein, which is critical for fighting off bacterial infections.
Casanovas team has put these findings to use clinically. For example, the researchers have shown that tuberculosis patients with these genetic errors can benefit from treatment with IFN-gamma. Hes hoping to identify problematic genes in patients with severe coronavirus infection that can bring similar clinical gains. These genes could tell scientists which cellular defenses are crucial for warding off COVID-19 and pave the way for understanding whether such defenses are derailed in older adults or patients with an underlying medical condition.
In the US and around the world, severe coronavirus disease seems to hit older patients hardest, though scientists have reported some country-to-country variation. As of March 24, more than 44,000 confirmed and presumptive positive cases have been reported in the US. Fatality has been highest in people over 85 years old, according to a recent report from the Centers for Disease Control and Prevention (CDC). Though young people may be more susceptible than scientists once suspected,the older you are, the higher the likelihood you have a severe form of the disease, Casanova says.
Last week, Rockefeller closed all labs except those working on the coronavirus, and Casanova whittled his team to a skeleton crew of about eight people down from 35 who rotate so there is only one person per room at a time. He and his lab members are following CDC recommendations, and taking protective measures to keep themselves and others safe, including social distancing, washing hands, and disinfecting surfaces. Theyve also taken to Twitter to get the word out about their work. A tweet posted from Casanovas lab last week about recruiting new patients to their study has since been retweeted more than 400 times.
Soon, theyll be testing their genetic theory on a pandemic thats occurring in real time. Im grateful weve been able to start this new project so quickly, he says. God willing, it will be of clinical usein two or three years.
Follow the Casanova lab on Twitter (@casanova_lab) to learn the latest about their work. Doctors interested in enrolling patients in the study can contact Jean-Laurent Casanova at jean-laurent.casanova@rockefeller.edu.
###
See more here:
- IOM not webcast today. Why Not? - November 8th, 2009 [November 8th, 2009]
- National Academies skeptical at Best. - November 8th, 2009 [November 8th, 2009]
- Some Confusion Exists - November 8th, 2009 [November 8th, 2009]
- Why DTC Genomics IS Medicine. - November 8th, 2009 [November 8th, 2009]
- First Mari, Now Linda. Who's next? - November 8th, 2009 [November 8th, 2009]
- Is it true? - November 8th, 2009 [November 8th, 2009]
- Re-Reviewing the National Academies - November 8th, 2009 [November 8th, 2009]
- The problem with nonclinicians....... - November 8th, 2009 [November 8th, 2009]
- Crazy Night of Emails to Government - November 8th, 2009 [November 8th, 2009]
- Adrienne Carlson's Personalized Medicine. - November 8th, 2009 [November 8th, 2009]
- Tell Me, How do you feel now? Sherpa's RX - November 8th, 2009 [November 8th, 2009]
- This Just In. 23andMe to go to GPs. I love my readers!! - November 8th, 2009 [November 8th, 2009]
- Sorry so long away - November 8th, 2009 [November 8th, 2009]
- 2D6 Rears its ugly head..... - November 8th, 2009 [November 8th, 2009]
- Ok, Fine, Back to Plavix - November 8th, 2009 [November 8th, 2009]
- Kaiser a protoype for Collins' Aim - November 8th, 2009 [November 8th, 2009]
- A few months late to the party.... - November 8th, 2009 [November 8th, 2009]
- Stated Another Way....... - November 8th, 2009 [November 8th, 2009]
- Excuse Me? Harvard and Navigenics? WTF? - November 8th, 2009 [November 8th, 2009]
- Follow up to Yesterday's WTF? Harvard, Navi? and Pfizer??? - November 8th, 2009 [November 8th, 2009]
- Did you get your kit? Thanks Dr. Rob from MedCo - November 8th, 2009 [November 8th, 2009]
- Gluco...Wha? Parkinson's Disease and Glucocerebrosidase mutations. - November 8th, 2009 [November 8th, 2009]
- Away and now back, What did I miss???? 23andme layoffs? Selling Genomes for cheap up next! - November 8th, 2009 [November 8th, 2009]
- Change IS Needed. I agree with William, sometimes. - November 8th, 2009 [November 8th, 2009]
- Good Enough Science? Apparently so at 23andme - November 8th, 2009 [November 8th, 2009]
- Long QT Syndrome, location matters - December 13th, 2009 [December 13th, 2009]
- Congratulations Generation Health. Nice pick up! - December 13th, 2009 [December 13th, 2009]
- An argument 23andSerge can't win...23andme but not medicine - December 13th, 2009 [December 13th, 2009]
- Stop. Breathe. Repeat. An analysis of the direction of DTC Genomics Field. - December 13th, 2009 [December 13th, 2009]
- Hey DTC genomics, Stay Private, Stay Alive, Go Public and Die - December 13th, 2009 [December 13th, 2009]
- You can't have it both way. Either scared your genome is sold off or not. - December 13th, 2009 [December 13th, 2009]
- 15 Days Away Gives Time for Perspective. - December 13th, 2009 [December 13th, 2009]
- What about the SACGHS registry? Another missed opportunity? - December 13th, 2009 [December 13th, 2009]
- AJHG is in and my Favorite Muin is in it! But He Is NOT the Father! - December 13th, 2009 [December 13th, 2009]
- Navigenics for 23andMe prices? - December 18th, 2009 [December 18th, 2009]
- Lp(a) Maybe there's something there that wasn't there before? - December 24th, 2009 [December 24th, 2009]
- Another Year, Another Bankruptcy - December 31st, 2009 [December 31st, 2009]
- 5 Technologies going bye bye in this decade? - January 6th, 2010 [January 6th, 2010]
- Hackers, HITECH and HIPAA in DTC Genomics, Oh My! - January 7th, 2010 [January 7th, 2010]
- Personal Genomics Flop.....big Belly Flop! - January 8th, 2010 [January 8th, 2010]
- Gotta Love It. Even the daycare....... - January 11th, 2010 [January 11th, 2010]
- Congratulations Navigenics. You ARE a clinical lab! Uh-Oh... - January 12th, 2010 [January 12th, 2010]
- CETP, Jewish Centenarians and Alzheimers - January 14th, 2010 [January 14th, 2010]
- Enter the "Not" DTC Genomics Rep - January 17th, 2010 [January 17th, 2010]
- Why Dr. Vanier's Navigenics appointment is good for PM - January 22nd, 2010 [January 22nd, 2010]
- Holy Crap! MedCo Follows in CVS footsteps - February 3rd, 2010 [February 3rd, 2010]
- FDA, Warfarin, still not as sexy to me. - February 5th, 2010 [February 5th, 2010]
- Hype, Hype, Hype from a single study. - February 11th, 2010 [February 11th, 2010]
- I love my readers, even Renata M! - February 17th, 2010 [February 17th, 2010]
- How can insurers use DTC genomics to profile? - February 17th, 2010 [February 17th, 2010]
- 9p21.....ahem. Paynter et.al. Smackdown. Again. - February 18th, 2010 [February 18th, 2010]
- Hey! It's Pete Hulick! Are you Going to GET? - February 19th, 2010 [February 19th, 2010]
- I was wrong......AHEM - February 28th, 2010 [February 28th, 2010]
- G2C2, finally a tool for genomic education! - March 2nd, 2010 [March 2nd, 2010]
- Just 4 million? What 23andMe is worth. - March 5th, 2010 [March 5th, 2010]
- What a difference a year makes - March 9th, 2010 [March 9th, 2010]
- ........DTC Genomic Medicine? - March 12th, 2010 [March 12th, 2010]
- The FDA, 2c19 and the ACC - March 13th, 2010 [March 13th, 2010]
- The problem with Comparative Whole Genomics...... - March 13th, 2010 [March 13th, 2010]
- BRCA testing by 23andME is the same as Myriad Genetics. - March 15th, 2010 [March 15th, 2010]
- The Argument Against DTC Genomics Marketing and such - March 16th, 2010 [March 16th, 2010]
- A moment of Clarity. Some DTCG is not bad. - March 18th, 2010 [March 18th, 2010]
- SNPs for breast cancer risk? It Depends. - March 18th, 2010 [March 18th, 2010]
- How can MDVIP use Navigenics Test for Medicine? - March 18th, 2010 [March 18th, 2010]
- Why did P&G invest in Navigenics? - March 23rd, 2010 [March 23rd, 2010]
- PGx in DTCG? Doesn't stand up to Useful testing. - March 25th, 2010 [March 25th, 2010]
- End of Gene Patents? - March 29th, 2010 [March 29th, 2010]
- Sherpa Accepting Chief Medical Officership - April 3rd, 2010 [April 3rd, 2010]
- The Rumors of My Death........ - April 20th, 2010 [April 20th, 2010]
- Happy DNA Day! - April 25th, 2010 [April 25th, 2010]
- 99 USD, DNA day and patient letters - April 25th, 2010 [April 25th, 2010]
- 2C19, Navigenics and Clinical Reality. - May 1st, 2010 [May 1st, 2010]
- Coriell Personalized Medicine Collaborative rising - May 7th, 2010 [May 7th, 2010]
- Personal Genomes in Clinical Care. Quake paper is a waste! - May 11th, 2010 [May 11th, 2010]
- Personal Genomes in Clinical Care. Quake paper Falls Short! - May 13th, 2010 [May 13th, 2010]
- Last post edited by Drew - May 13th, 2010 [May 13th, 2010]
- GateKeeper? FCUK U! - May 13th, 2010 [May 13th, 2010]
- GateKeeper? F! U! - May 15th, 2010 [May 15th, 2010]
- Potential of genomic medicine, LOST - May 19th, 2010 [May 19th, 2010]
- How Bad Can a House Investigation be for DTC Genomics? - May 20th, 2010 [May 20th, 2010]