Findings

Insights Into Ravages of COVID-19

Individuals with compromised immunity and persistent COVID-19 infections can harbor drug-resistant variants of the SARS-CoV-2 virus, which have the potential to spread to the general population, according to a study by Weill Cornell Medicine, the College of Veterinary Medicine at Cornell University and the National Institute of Allergy and Infectious Diseases.

In the study, published in Nature Communications, researchers isolated drug-resistant strains of SARS-CoV-2 from people who had not cleared the virus after two to three months of infection and treatments with antiviral drugs. One variant showed resistance to the antivirals Paxlovid and remdesivir while another strain had mutations associated with a decreased sensitivity to remdesivir and a third antiviral drug, the monoclonal antibody sotrovimab.

“The risk in emerging mutations is the possibility of transmitting these new resistant variants to the general population with fewer viable treatment options available,” says the study’s co-senior author, Dr. Mirella Salvatore, an infectious disease physician who recently retired from Weill Cornell Medicine. “We have to come up with better treatments for immunocompromised patients and consider investigating combinations of therapies.”

In other COVID-19 research, researchers from Weill Cornell Medicine have used a cutting-edge model system to uncover the mechanism by which SARS-CoV-2 induces new cases of diabetes and worsens complications in people who already have it. The team found that viral exposure activates immune cells that in turn destroy beta (β) cells, the pancreatic cells that produce insulin. The study was published in Cell Stem Cell.

“When someone has severe COVID-19, of course the first priority is to treat the life-threatening symptoms,” says co-corresponding author Dr. Robert Schwartz, an associate professor of medicine. “But moving forward, there may be a way to develop clinical therapeutics that help avoid later injury to organs like the pancreas.”

Improving Efficiency of IVF

A new artificial intelligence-based system can accurately assess the chromosomal status of in vitro-fertilized (IVF) embryos using only time-lapse video images of the embryos and maternal age, according to a study from investigators at Weill Cornell Medicine.

The new system, called “BELA,” and described in a paper published in Nature Communications, is the team’s latest AI-based platform for assessing whether an embryo has a normal (euploid) or abnormal (aneuploid) number of chromosomes — a key determinant of IVF success. Unlike prior AI-based approaches, BELA does not need to consider embryologists’ subjective assessments of embryos. It thus offers an objective, generalizable measure and, if its utility is confirmed in clinical trials, could someday be used widely in embryology clinics to improve the efficiency of the IVF process.

“This is a fully automated and more objective approach compared to prior approaches, and the larger amount of image data it uses can generate greater predictive power,” says study senior author Dr. Iman Hajirasouliha, associate professor of physiology and biophysics and a member of the Englander Institute for Precision Medicine at Weill Cornell Medicine.

47%

This was the percentage of 453 individuals seeking asylum in the United States who reported symptoms associated with cardiovascular disease — including heart palpitations, feeling like fainting, stroke and chest pain — in a study by Weill Cornell Medicine researchers, which analyzed medical evaluations of the asylum seekers.

In addition, 31 percent of those who experienced these cardiovascular disease symptoms also reported feeling symptoms of psychological stress and physical pain. Having both stress and pain symptoms strongly predicted cardiovascular disease symptoms, the researchers note.

The median age for the asylum seekers was 30. “We would not have expected the rates of these illnesses or conditions to be this high in such a young, otherwise healthy population,” says Dr. Gunisha Kaur (M.D. ’10), associate professor of anesthesiology and senior author of the study, which appeared in Nature Mental Health.

“Now that we know these diseases are unexpectedly prevalent, we should be addressing this upfront,” says Dr. Kaur. “Increased rehabilitation and decreased health-care costs benefit not only these individuals, but the communities in which they reside.”

Dr. Ching-Hwa Sung, who published a study in Nature Communications showing that a new preclinical model offers a unique platform for studying the Parkinson’s disease process and suggests a relatively easy method for detecting the disease in people.

In the study, the researchers showed that knocking out a key component involved in protein transportation in the light-sensing rod cells of mice leads to the retinal accumulation of the aggregates of a protein called alpha-synuclein found in patients with Parkinson’s disease.

The results suggest that the new model could be very useful for studying disease mechanisms and testing potential therapies, notes Dr. Sung, the Betty Neuwirth Lee and Chilly Professor in Stem Cell Research and a professor of cell biology in ophthalmology, who leads the lab in which the study took place.

The model’s advantages include a rapidly developing disease process, and the absence of any artificial modification to the mice’s alpha-synuclein — unlike existing models that drive pathology using excess, mutant or non-mouse forms of the protein, notes Dr. Sung.

Boosting Response to Cancer Therapy

Stimulating a key metabolic pathway in T cells can make them work more effectively against tumors when combined with immune checkpoint inhibitor therapy, according to a preclinical study led by researchers at Weill Cornell Medicine. The findings suggest a potential strategy for enhancing the potency of anticancer immunotherapies.

In the study, which appeared in Nature Immunology, the researchers discovered that activating a metabolic pathway called the pentose phosphate pathway makes antitumor CD8 T cells more likely to stay in an immature, stem-like, “precursor” state. They showed that combining this metabolic reprogramming of T cells with a standard anticancer immune checkpoint inhibitor treatment leads to big improvements in tumor control in animal models and in tumor “organoids” grown from human tumor samples.

“Our hope is that we can use this new metabolic reprogramming strategy to significantly boost patients’ response rates to immune checkpoint inhibitor therapies,” says study senior author Dr. Vivek Mittal, the Ford-Isom Research Professor of Cardiothoracic Surgery and a professor of cell and developmental biology in cardiothoracic surgery.

Illustrations: Marysia Machulska