Why was a marathon runner in his 40s stricken with a case of COVID-19 so severe it landed him in the intensive care unit? Why did a healthy 12-year-old boy lose his life to a disease that mostly harms older people? One of the most terrifying aspects of the pandemic is that the severity of the disease seems so cruelly and arbitrarily variable.
Although the SARS-CoV-2 virus is most often fatal in patients who are elderly or have chronic medical conditions such as diabetes, heart disease or high blood pressure, exceptions that bring down apparently healthy young people are commonplace. Even patients who do not die of the infection show a huge spread in their symptoms: Some never get sick; some need to be hospitalized but recover; some have lingering disabilities that last for months.
So far, scientists have been largely at a loss to explain why COVID-19 hits patients as hard as it does, though reasons surely exist. Its not just bad luck, said Helen Su, an immunologist at the National Institute of Allergy and Infectious Diseases.
One possibility under investigation is that some people harbor genes that put them at greater or lesser risk from COVID-19. The COVID Human Genetic Effort, for example, is enrolling hundreds of patients from around the globe who wound up in intensive care after infection with the SARS-CoV-2 virus. Initially, the project only enrolled patients who were under age 50 and had no underlying health conditions, though it has more recently expanded eligibility.
My hope is to understand the genetic basis of severe COVID in patients of all ages and regardless of comorbidities, said Jean-Laurent Casanova, a researcher in pediatric medicine and immunology at the Rockefeller University who co-founded the project with Su and others. And from that, to understand the mechanism that makes them vulnerable to SARS-CoV-2.
Some genetic clues may already be coming to light. Last week, a team of researchers in the Netherlands published a preliminary communication online in JAMA about four young male patients from two families who all suffered severe COVID-19 respiratory illnesses. The men, who were between the ages of 21 and 32, had no history of chronic medical problems, but DNA sequencing revealed that each of them had a rare form of a gene on his X chromosome that was linked to a deficient immune response. Much more study will be needed to determine whether similar deficiencies, possibly involving other genes, are common among COVID-19s worst cases.But in a study appearing in Nature today, researchers at the Yale University School of Medicine who followed the progression of COVID-19 in 113 hospitalized patients for two months found that greater severity of the disease was associated with maladaptive immune responses. (The causes for those immunological misfires was not determined.)
The significance of these discoveries may not be limited to COVID-19. Casanova is a champion for an idea that has been slowly gaining credence among medical researchers for many years: that genetics is always a factor in infectious diseases. Many if not all people may have very specific genetic vulnerabilities, such as weaknesses in their immune system, that go unnoticed until one particular pathogen crosses their path. That genetic trait is their Achilles heel, and that pathogen is the one thing that can take advantage of it.
The theory has emerged out of both clinical practice and scientists growing appreciation of the interconnection between genes and infectious diseases. Casanova has spent the past 25 years scanning the genomes of young people who were inexplicably debilitated by commonplace pathogens like the herpes simplex and varicella zoster viruses (which cause cold sores and chickenpox, respectively). In these children, who showed no outward symptoms of compromised immunity, he has found defects in genes that make them susceptible to severe infection with a single pathogen. In most cases, there were no clinical signs of a genetic problem until they were infected.
For many of these immune deficiencies where children or adults have very severe infections there is a genetic basis, said Trine Mogensen, a physician at Aarhus University and a member of the COVID Human Genetic Effort steering committee.
If the COVID project succeeds in finding genes relevant to the course of the infection, it could fuel interest in widening that search for other conditions. Further work on the interplay of infections, immunity and genomes could change how future gene-based medicine routinely diagnoses and treats diseases.
Infectious disease has always been one of greatest threats to humanity. Before the invention of antibiotics, infections killed half of all children by age 15. Yet as terrible as their collective toll has been, even the worst infectious diseases kill relatively few of those they infect. Tuberculosis has been a scourge, but fewer than 10% of people infected with it even get sick. Even the terrible Spanish flu pandemic that started in 1918 had a mortality rate often estimated at around 2.5%.
Variability in disease severity is usually chalked up to circumstantial factors: the virulence of different pathogen strains, the amount of pathogen exposure, the nutrition or general health of a patient. Researchers have suspected, however, that something more is lurking in the genes of the hardest-hit patients.
The idea of a genetic component to infection dates back to 1905, when an English scientist named Rowland Biffen discovered a gene responsible for a devastating fungal disease called yellow rust that was killing wheat and diminishing crop yields across England. He found that resistance to the fungus was present in some of the plants as a recessive trait passed down from parent to offspring without affecting other characteristics of the plant. The discovery was celebrated, and his method of breeding for resistant plants is still widely used today.
These types of genes were later found in other plants and animals. But genetic immunodeficiencies in humans didnt start to attract attention until the 1950s, when an immune disorder was identified in an 8-year-old boy being treated at Walter Reed Army Medical Center for recurrent blood infections. The disorder, known as X-linked agammaglobulinemia, inhibits the bodys ability to make the antibodies called gamma globulins, resulting in severe infections even from fairly innocuous pathogens.
The boy had suffered 19 bouts of pneumococcal meningitis, which were repeatedly treated with antibiotics. His condition improved more lastingly only after his physician, Ogden Bruton, discovered that the boy had almost no gamma globulins in his blood. Bruton promptly began treating him with monthly injections of gamma globulins, and the boy survived to adulthood. The discovery, which was described in Pediatrics in 1952, was later recognized as a milestone, highlighting the role of defects of the immune system in inhibiting the fight against infection. These defects were later termed inborn errors of immunity.
- Atsena Therapeutics Raises $55 Million Series A Financing to Advance LCA1 Gene Therapy Clinical Program, Two Preclinical Assets, and Novel Capsid... - December 17th, 2020
- Locanabio Announces $100 Million Series B Financing to Advance Portfolio of Novel RNA-Targeted Gene Therapies for Neurodegenerative, Neuromuscular and... - December 17th, 2020
- NeuBase Therapeutics Announces Positive Preclinical In Vivo Data for PATrOL-enabled Anti-gene for the Treatment of Myotonic Dystrophy Type 1 -... - December 17th, 2020
- Genetic Analysis Services Market: Uptake of Next-generation Sequencing and Multi-gene Tests to Drive Market - BioSpace - December 17th, 2020
- FDA Clears Genetic Modification in Pigs for Biomedicine and Food - The Scientist - December 17th, 2020
- Key Genes Related to Severe COVID-19 Infection Identified - The Scientist - December 17th, 2020
- UNLV Researcher on the Curious Case of COVID-19 Reinfection - UNLV NewsCenter - December 17th, 2020
- Genomics and medicine it's complicated | Health | willistonherald.com - Williston Daily Herald - December 17th, 2020
- Emedgene collaborates with Illumina to scale the interpretation of genomic data for rare diseases - PRNewswire - December 17th, 2020
- Polymerase Chain Reaction Market | Increased Outbreak of Infectious Diseases to Accentuate Demand in the Market - BioSpace - December 17th, 2020
- LogicBio Therapeutics names Daphne Karydas and Jeff Goater to Board of Directors - BioSpace - December 17th, 2020
- rBIO Achieves Crucial Milestone on Mission to Lower the Cost of Insulin by 30% - BioSpace - December 17th, 2020
- Report: More than 1,300 Medicines and Vaccines in Development to Help Fight Cancer - PRNewswire - December 17th, 2020
- San Diego's Locanabio raises $100 million for treatments aimed at degenerative diseases - The San Diego Union-Tribune - December 17th, 2020
- Worldwide SNP Genotyping Industry to 2025 - Pharmacogenomics Led the End-user Segment of the SNP Genotyping Market - ResearchAndMarkets.com - Business... - December 17th, 2020
- Potential Weakness in SARS-CoV-2 Discovered Single Protein Needed for COVID-19 Virus to Reproduce and Spread - SciTechDaily - December 17th, 2020
- Landing of $75M expansion of Texas-based Taysha adds to Triangle's growing gene therapy hub - WRAL Tech Wire - December 17th, 2020
- Track the Vax: What Do We Need to Know About the New Vaccines? - Everyday Health - December 17th, 2020
- Medical history from the year you were born - Quad City Times - December 5th, 2020
- Sarepta Therapeutics to Share Clinical Update for SRP-5051, its Investigational PPMO for the Treatment of Duchenne Muscular Dystrophy - GlobeNewswire - December 5th, 2020
- Biochip Market | Increased Popularity of Personalized Medicine to Boost the Market Growth | Technavio - Business Wire - December 5th, 2020
- December: Baby birth weight research | News and features - University of Bristol - December 5th, 2020
- Global Next Generation Sequencing Market (2020 to 2026) - Growth, Trends, Competitive Landscape, and Forecasts - GlobeNewswire - December 5th, 2020
- NIH researchers link cases of ALS and FTD to a mutation associated with Huntington's disease - National Institute on Aging - December 5th, 2020
- Precision Medicine Market Poised to Grow at 11.5% By 20227 - GlobeNewswire - December 5th, 2020
- Fact check: mRNA vaccines kept at very cold temperatures so that they do not break apart; COVID-19 vaccines will not genetically modify humans -... - December 5th, 2020
- Stoke Therapeutics Announces Presentations Related to the Company's Work to Advance STK-001, the First Potential New Medicine to Target the Underlying... - December 5th, 2020
- King George III's illness debunked as symptom 'caused by medicine prescribed to him' - Express - December 5th, 2020
- Stoke Therapeutics to Present at the Needham Virtual Epilepsy & Pain Specialty CNS Therapeutics Conference - Business Wire - December 5th, 2020
- Following the science: the writers who have made sense of Covid - The Guardian - December 5th, 2020
- Gene experts claim they identified human genes that can protect against Covid-19 - CNBC - November 23rd, 2020
- Genome Medical Reaches 90 Million Covered Lives in US - PRNewswire - November 23rd, 2020
- Sarepta Therapeutics Named One of The Boston Globe's Top Places to Work 2020 - GlobeNewswire - November 23rd, 2020
- New Study Highlights the Importance of Genetic Testing for Pancreatic Cancer Patients - PRNewswire - November 23rd, 2020
- Baylor Genetics Launches Combination Test for COVID-19 and Influenza A and B; Multi-Panel Test Seeks to Address Dilemma of "Overlapping symptoms... - November 23rd, 2020
- CHOP Researchers Reverse Severe Lymphatic Disorder in Patient with Noonan Syndrome by Targeting Genetic Pathway - BioSpace - November 23rd, 2020
- Myriad Genetics Announces Global Expansion of Myriad myChoice Tumor Testing in Europe and China - GlobeNewswire - November 23rd, 2020
- Epigenetics and pulmonary diseases in the horizon of precision medicine: a review - DocWire News - November 23rd, 2020
- Four years after landing in US, graduating ISU senior is on his way to medical school - Iowa State University News Service - November 23rd, 2020
- Lethal brain infections in mice thwarted by decoy molecule - Washington University School of Medicine in St. Louis - November 23rd, 2020
- Reducing barriers to mainstream gene therapy - BioPharma-Reporter.com - September 4th, 2020
- Mapping Genetic Diversity of Lung Tumors Over Time May Lead to More Effective Therapies - UCSF News Services - September 4th, 2020
- Multi-site study to evaluate the role of testing guidelines in ensuring access to genetic information for men with prostate cancer - PRNewswire - September 4th, 2020
- Global Prime Editing Market to Witness Heightened Growth During the Period 2020 2030 - The Daily Chronicle - September 4th, 2020
- Liquid biopsies to disrupt the oncology testing market - Medical Device Network - September 4th, 2020
- Global RNA-interference (RNAi) Market Growth, Trends and Forecasts to 2025: Focus on Key Players Alnylam Pharmaceuticals, Arrowhead, Quark... - September 4th, 2020
- Yale researchers find a cause and possible treatment for Fragile X - Yale News - September 4th, 2020
- 'Coming into their own': FDA approval of liquid biopsy tests puts early, less invasive cancer detection in broader reach - USA TODAY - September 4th, 2020
- Fusion Genes Associated With More Aggressive Papillary Thyroid Cancer in Pediatric Patients - Targeted Oncology - September 4th, 2020
- Existing Class of Drugs May Improve Neurological Function in Patients with Rare, Aggressive Genetic Disorder - Newswise - September 4th, 2020
- Genomic analysis reveals insights on virulent, emerging foodborne pathogen - UB Now: News and views for UB faculty and staff - University at Buffalo... - September 4th, 2020
- Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors - 2 Minute Medicine - September 4th, 2020
- Health history platform launches to trace genetic conditions | Digital Healthcare - Healthcare Global - Healthcare News, Magazine and Website - September 4th, 2020
- New HIV Gene Therapy, CAR-T Treatments Could be on the Horizon for Patients - BioSpace - September 4th, 2020
- Cell Suicide Gene Further Linked to Immunotherapy Response - Technology Networks - September 2nd, 2020
- Genetic mutations may be linked to infertility, early menopause - Washington University School of Medicine in St. Louis - September 2nd, 2020
- How to use precision medicine to personalise COVID-19 treatment according to the patient's genes - Down To Earth Magazine - September 2nd, 2020
- UCT professors research offers hope of treatment for sickle cell anaemia - Daily Maverick - September 2nd, 2020
- Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia - 2... - September 2nd, 2020
- Finding order in the chaos of cancer mutations - Drug Target Review - September 2nd, 2020
- Mustang Bio Announces Orphan Drug Designation for MB-107 for the Treatment of X-linked Severe Combined Immunodeficiency in Newly Diagnosed Infants -... - September 2nd, 2020
- Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine - GlobeNewswire - September 2nd, 2020
- Department of Genetic Medicine | Johns Hopkins Medicine - August 10th, 2020
- Genetic Medicine | Internal Medicine | Michigan Medicine ... - August 10th, 2020
- Genetic Medicine | Department of Medicine - August 10th, 2020
- Genomics and Medicine - Genome.gov - August 10th, 2020
- New Approach to Treating Osteoarthritis Advances | NYU Langone News - NYU Langone Health - August 10th, 2020
- Stoke Therapeutics Reports Second Quarter Financial Results and Provides Business Updates - Business Wire - August 10th, 2020
- Here's Why Shares of Editas Medicine and Beam Therapeutics Are Soaring Today - Motley Fool - August 10th, 2020
- Grant will fund study into COVID outcome disparities in NYC - Cornell Chronicle - August 10th, 2020
- A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate - Science Advances - August 10th, 2020
- Spark Therapeutics Deepens Drug Development Expertise in Hematology and Rare Disease with Appointment of Gallia G. Levy, MD, Ph.D., as Chief Medical... - August 10th, 2020
- Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra - August 10th, 2020
- Jae Jung, Ph.D., Appointed as Chair of Cleveland Clinic Lerner Research Institute's Department of Cancer Biology - Health Essentials from Cleveland... - August 10th, 2020
- The UK and TCELS to jointly support COVID-19 research in Thailand - GOV.UK - August 10th, 2020
- Akouos Announces Expansion of Executive Team and Board of Directors - BioSpace - August 10th, 2020
- Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank. - Physician's Weekly - August 10th, 2020
- Coronavirus vaccine breakthrough: New generation cure that stops virus developed - Express - August 10th, 2020
- Global Cell and Gene Therapy Market, Forecast to 2025 by Product, Disease, End-user and Region - COVID-19 Updated - PRNewswire - August 10th, 2020
- Not Everyone Needs 8 Hours of Sleep, New Research Reveals | Time - TIME - August 10th, 2020