A study of some of the sickest COVID-19 patients, such as those placed on ventilators, has identified gene variants that put people at greater risk of severe disease.
By Jocelyn KaiserOct. 13, 2020 , 1:25 PM
Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
Its one of the pandemics puzzles: Most people infected by SARS-CoV-2 never feel sick, whereas others develop serious symptoms or even end up in an intensive care unit clinging to life. Age and preexisting conditions, such as obesity, account for much of the disparity. But geneticists have raced to see whether a persons DNA also explains why some get hit hard by the coronavirus, and they have uncovered tantalizing leads.
Now, a U.K. group studying more than 2200 COVID-19 patients has pinned down common gene variants that are linked to the most severe cases of the disease, and that point to existing drugs that could be repurposed to help. Its really exciting. Each one provides a potential target for treatment, says genetic epidemiologist Priya Duggal of Johns Hopkins University.
In a standard approach to finding genes that influence a condition, geneticists scan the DNA of large numbers of people for millions of marker sequences, looking for associations between specific markers and cases of the disease. In June, one such genomewide association study in The New England Journal of Medicine (NEJM) found two hits linked to respiratory failure in 1600 Italian and Spanish COVID-19 patients: a marker within the ABO gene, which determines a persons blood type, and a stretch of chromosome 3 that holds a half-dozen genes. Those two links have also emerged in other groups data, including some from the DNA testing company 23andMe.
The new study confirmed the chromosome 3 regions involvement. And because 74% of its patients were so sick that they needed invasive ventilation, it had the statistical strength to reveal other markers, elsewhere in the genome, linked to severe COVID-19. One find is a gene called IFNAR2 that codes for a cell receptor for interferon, a powerful molecular messenger that rallies the immune defenses when a virus invades a cell. A variant of IFNAR2 found in one in four Europeans raised the risk of severe COVID-19 by 30%. Baillie says the IFNAR2 hit is entirely complementary to a finding reported in Science last month: very rare mutations that disable IFNAR2 and seven other interferon genes may explain about 4% of severeCOVID-19 cases. Both studies raise hopes for ongoing trials of interferons as a COVID-19 treatment.
A more surprising hit from the U.K. study points to OAS genes, which code for proteins that activate an enzyme that breaks down viral RNA. A change in one of those genes might impair this activation, allowing the virus to flourish. The U.K. data suggest there is a variant as common and influential on COVID-19 as the interferon genetic risk factor.
Other genes identified by Baillies team could ramp up the inflammatory responses to lung damage triggered by SARS-CoV-2, reactions that can be lethal to some patients. One, DPP9, codes for an enzyme known to be involved in lung disease; another, TYK2, encodes a signaling protein involved in inflammation. Drugs that target those two genes proteins are already in useinhibitors of DPP9s enzyme for diabetes and baricitinib, which blocks TYK2s product, for arthritis. Baricitinib is in early clinical testing for COVID-19, and the new data could push it up the priority list, Baillie says.
The chromosome 3 region still stands out as the most powerful genetic actor: A single copy of the disease-associated variant more than doubles an infected persons odds of developing severe COVID-19. Evolutionary biologists reported last month in Nature that this suspicious region actually came from Neanderthals, through interbreeding with our species tens of thousands of years ago. It is now found in about 16% of Europeans and 50% of South Asians.
But the specific chromosome 3 gene or genes at play remain elusive. By analyzing gene activity data from normal lung tissue of people with and without the variant, the U.K. team homed in on CCR2, a gene that encodes a receptor for cytokine proteins that play a role in inflammation. But other data discussed at last weeks meeting point to SLC6Z20, which codes for a protein that interacts with the main cell receptor used by SARS-CoV-2 to enter cells. I dont think anyone at this point has a clear understanding of what are the underlying genes for the chromosome 3 link, says Andrea Ganna of the University of Helsinki, who co-leads the COVID-19 Host Genetics Initiative.
The U.K. genetics study did not confirm that the ABO variants affect the odds of severe disease. Some studies looking directly at blood type, not genetic markers, have reported that type O blood protects against COVID-19, whereas A blood makes a person more vulnerable. It may be that blood type influences whether a person gets infected, but not how sick they get, says Stanford University geneticist Manuel Rivas. In any case, O blood offers at best modest protection. There are a lot of people with O blood that have died of the disease. It doesnt really help you, says geneticist Andre Franke of the Christian-Albrecht University of Kiel, a coleader of the NEJM study.
Researchers expect to pin down more COVID-19 risk genesalready, after folding in the U.K. data plumbed by Baillies team, the COVID-19 Host Genetics Initiative has found another hit, a gene called FOXP4 implicated in lung cancer. And in a new medRxiv preprint posted last week, the company Ancestry.com reports that a gene previously connected to the effects of the flu may also boost COVID-19 susceptibility only in men, who are more likely to die of the disease than women.
Geneticists have had little luck so far identifying gene variants that explain why COVID-19 has hit Black people in the United States and United Kingdom particularly hard. The chromosome 3 variant is absent in most people of African ancestry. Researchers suspect that socioeconomic factors and preexisting conditions may better explain the increased risks. But several projects, including Baillies, are recruiting more people of non-European backgrounds to bolster their power to find COVID-19 gene links. And in an abstract for an online talk later this month at the American Society of Human Genetics annual meeting, the company Regeneron reports it has found a genome region that may raise the risk of severe disease mainly in people of African ancestry.
Even as more genetic risk factors are identified, their overall effect on infected people will be modest compared with other COVID-19 factors, Duggal says. But studies like the U.K. teams could help reveal the underlying biology of the disease and inspire better treatments. I dont think genetics will lead us out of this. I think genetics may give us new opportunities, Duggal says.
Continued here:
Found: genes that sway the course of the coronavirus - Science Magazine
- F.D.A. Says Millions Got Unapproved Drugs, Should the new bioequivalence and bioanalytical guidelines for 2010, be made more stringent [Last Updated On: April 15th, 2010] [Originally Added On: April 15th, 2010]
- F.D.A. Says Millions Got Unapproved Drugs, Should the new bioequivalence and bioanalytical guidelines for 2010, be made more stringent [Last Updated On: April 15th, 2010] [Originally Added On: April 15th, 2010]
- GSK, MedTrust launch iPhone/iPad app for cancer trials [Last Updated On: June 11th, 2010] [Originally Added On: June 11th, 2010]
- GSK, MedTrust launch iPhone/iPad app for cancer trials [Last Updated On: June 11th, 2010] [Originally Added On: June 11th, 2010]
- 22 Million Australian Cloud computing initiative to benefit life science researchers [Last Updated On: June 19th, 2010] [Originally Added On: June 19th, 2010]
- GE Healthcare announces SaaS Electronic Medical Records Management [Last Updated On: June 19th, 2010] [Originally Added On: June 19th, 2010]
- 22 Million Australian Cloud computing initiative to benefit life science researchers [Last Updated On: June 19th, 2010] [Originally Added On: June 19th, 2010]
- GE Healthcare announces SaaS Electronic Medical Records Management [Last Updated On: June 19th, 2010] [Originally Added On: June 19th, 2010]
- How useful would be the Single-patient clinical trials for improving the hopes of Personalized medicine [Last Updated On: August 12th, 2010] [Originally Added On: August 12th, 2010]
- How useful would be the Single-patient clinical trials for improving the hopes of Personalized medicine [Last Updated On: August 12th, 2010] [Originally Added On: August 12th, 2010]
- Life Sciences at Oracle Open World 2010 [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- ChIP Enrichment Analysis can speed up drug discovery [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- GE’s healthymagination initiative lead Smart Patient Room to improve patient safety goes live at Bassett Medical Center [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- The SaaS impact on solution selling for ISVs (via Inner Lining) [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- Oracle starts the Oracle Health Sciences Institute (OHSI), in partnership with Sun Labs [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 70% of Pharmaceutical organisations outsource at least one PV activity. This level is expected to increase to 80% by 2012 [Last Updated On: October 26th, 2010] [Originally Added On: October 26th, 2010]
- Insurance coverage for healthcare IT software, to protect healthcare IT companies from damages inflicted by their software [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- India announce Heart Surgery for $1000 USD [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- Indian Healthcare IT market & Oracle’s presence in Indian Healthcare [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- Insurance coverage for healthcare IT software, to protect healthcare IT companies from damages inflicted by their software [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- India announce Heart Surgery for $1000 USD [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- Indian Healthcare IT market & Oracle’s presence in Indian Healthcare [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- Harvard Medical Schools new automated safety surveillance system provides faster early warnings in the postmarket evaluation of medical device safety [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- SalesForce.com partner introduces CRM for clinical trial management on Force Platform [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- Widespread fraud in the Clinical Trial of Drugs is pervasive event in United States [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- Scott Stern Kellogg School of Management speaks about “New Drug Development: From Laboratory to Blockbuster to Generic,” [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- MNC Pharma tries to capture the $1.9 billion Indian OTC market by selling Drugs through India’s 170000 post offices [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- collaborative clinical trials management software for Central Laboratories [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- Clinical Trial and Pharmacovigilance process automation [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- Microsoft in Clinical Trials Management System (CTMS) and Electronic Data Capture (EDC) [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- Oracle Business Intelligence Enteprise Edition (OBIEE) for Clinical Trial Management System (CTMS) [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- trends in the life sciences and pharma research and development outsourcing (RDO) [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- Sanofi-Aventis ties up with Oxford Univ for oncology research in India [Last Updated On: December 20th, 2010] [Originally Added On: December 20th, 2010]
- PharmaNet unveils touch screen capable data capture platform for Phase I Clinical Trials [Last Updated On: December 20th, 2010] [Originally Added On: December 20th, 2010]
- Adverse Events in Hospitals- United States Department of Health Report slams current measures in US hospitals [Last Updated On: December 21st, 2010] [Originally Added On: December 21st, 2010]
- IBM Files Application to Patent The Patent [Last Updated On: January 4th, 2011] [Originally Added On: January 4th, 2011]
- How to improve R&D productivity: the pharmaceutical industry’s grand challenge [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- AstraZeneca Announce Real-World Evidence Data Collaboration [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- How to improve R&D productivity: the pharmaceutical industry’s grand challenge [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- AstraZeneca Announce Real-World Evidence Data Collaboration [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- Medication adherence improves, When Patients Share Their Stories [Last Updated On: March 13th, 2011] [Originally Added On: March 13th, 2011]
- Questions for the CRO [Last Updated On: March 13th, 2011] [Originally Added On: March 13th, 2011]
- Clinical Research Sites Struggle With Increasing Trial Complexity yet most depend on, Google (or other search sites) as the primary information tool [Last Updated On: March 13th, 2011] [Originally Added On: March 13th, 2011]
- Medication adherence improves, When Patients Share Their Stories [Last Updated On: March 13th, 2011] [Originally Added On: March 13th, 2011]
- Questions for the CRO [Last Updated On: March 13th, 2011] [Originally Added On: March 13th, 2011]
- Clinical Research Sites Struggle With Increasing Trial Complexity yet most depend on, Google (or other search sites) as the primary information tool [Last Updated On: March 13th, 2011] [Originally Added On: March 13th, 2011]
- Law of the land can help or destroy the Pharmacovigilance system [Last Updated On: March 27th, 2011] [Originally Added On: March 27th, 2011]
- Law of the land can help or destroy the Pharmacovigilance system [Last Updated On: March 27th, 2011] [Originally Added On: March 27th, 2011]
- Coast To Coast AM - 15.11.2011 - 1/4 - Regenerative Medicine/Dulce Base - Video [Last Updated On: November 29th, 2011] [Originally Added On: November 29th, 2011]
- Coast To Coast AM - 15.11.2011 - 4/4 - Regenerative Medicine/Dulce Base - Video [Last Updated On: November 29th, 2011] [Originally Added On: November 29th, 2011]
- HIV Resistant Genes...Rhesus Negative, Excess PK [Last Updated On: November 30th, 2011] [Originally Added On: November 30th, 2011]
- Indian Government’s new dose of strong medicine to bring cheers to Foreign Pharma CEOs who cut their teeth by struggling to convince Indian pharma to change sales practices [Last Updated On: December 18th, 2011] [Originally Added On: December 18th, 2011]
- Indian Government’s new dose of strong medicine to bring cheers to Foreign Pharma CEOs who cut their teeth by struggling to convince Indian pharma to change sales practices [Last Updated On: December 18th, 2011] [Originally Added On: December 18th, 2011]
- Drug Reps Soften Their Sales Pitches, as pharma learns from Disney [Last Updated On: January 15th, 2012] [Originally Added On: January 15th, 2012]
- Drug Reps Soften Their Sales Pitches, as pharma learns from Disney [Last Updated On: January 15th, 2012] [Originally Added On: January 15th, 2012]
- Oracle Unveils Oracle® Health Sciences Omics Data Bank as Part of Oracle Health Sciences Translational Research Center [Last Updated On: January 29th, 2012] [Originally Added On: January 29th, 2012]
- Oracle Unveils Oracle® Health Sciences Omics Data Bank as Part of Oracle Health Sciences Translational Research Center [Last Updated On: January 29th, 2012] [Originally Added On: January 29th, 2012]
- One Way to Teach Your Boss About Social Media [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- “The Banks Can Do It, Why Can’t Hospitals?” [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- Internet on any Display Device, or internet on TV at low cost can it transform Healthcare or Clinical Research [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- Is Life Sciences the New Frontier for Analytics? [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- Internet on any Display Device, or internet on TV at low cost can it transform Healthcare or Clinical Research [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- Is Life Sciences the New Frontier for Analytics? [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- Regenerative Medicine: Current Concepts and Changing Trends - Video [Last Updated On: February 12th, 2012] [Originally Added On: February 12th, 2012]
- bluebird bio Appoints David Davidson, M.D., as Chief Medical Officer [Last Updated On: February 16th, 2012] [Originally Added On: February 16th, 2012]
- privacy controlled social networking to connect patients with caregivers [Last Updated On: February 19th, 2012] [Originally Added On: February 19th, 2012]
- SOCIAL CRM and its Impact on Pharmaceutical Industry [Last Updated On: February 19th, 2012] [Originally Added On: February 19th, 2012]
- SOCIAL CRM and its Impact on Pharmaceutical Industry [Last Updated On: February 19th, 2012] [Originally Added On: February 19th, 2012]
- privacy controlled social networking to connect patients with caregivers [Last Updated On: February 19th, 2012] [Originally Added On: February 19th, 2012]
- British Government launches Government Cloud Store with 257 Cloud Computing Suppliers [Last Updated On: February 26th, 2012] [Originally Added On: February 26th, 2012]
- Patient Adherence Investments by Pharma Companies Current Scenario [Last Updated On: February 26th, 2012] [Originally Added On: February 26th, 2012]
- Pharma looks to mobile strategies to effectively reach prescribers | mHIMSS [Last Updated On: February 26th, 2012] [Originally Added On: February 26th, 2012]
- British Government launches Government Cloud Store with 257 Cloud Computing Suppliers [Last Updated On: February 26th, 2012] [Originally Added On: February 26th, 2012]
- Pharma looks to mobile strategies to effectively reach prescribers | mHIMSS [Last Updated On: February 26th, 2012] [Originally Added On: February 26th, 2012]
- Patient Adherence Investments by Pharma Companies Current Scenario [Last Updated On: February 26th, 2012] [Originally Added On: February 26th, 2012]
- Predictive Analytics for Patient Adherence [Last Updated On: March 4th, 2012] [Originally Added On: March 4th, 2012]
- Predictive Analytics for Patient Adherence [Last Updated On: March 4th, 2012] [Originally Added On: March 4th, 2012]
- Genetic manipulation boosts growth of brain cells linked to learning, enhances effects of antidepressants [Last Updated On: March 10th, 2012] [Originally Added On: March 10th, 2012]
- Can “Clinical Data Integration on the Cloud” be a reality? [Last Updated On: March 11th, 2012] [Originally Added On: March 11th, 2012]
- Can “Clinical Data Integration on the Cloud” be a reality? [Last Updated On: March 11th, 2012] [Originally Added On: March 11th, 2012]