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Physician-Scientists Continue to Tackle COVID-19

Physician-Scientists Continue to Tackle COVID-19

By Larry Katzenstein
Since our coverage of the COVID-19 crisis in the Summer/Fall 2020 issue of Einstein magazine, physician-scientists at Einstein and Montefiore have made further progress in understanding the disease and developing strategies for preventing and treating it. Here are some recent highlights.

Vaccine Unit

In November, Einstein and Montefiore opened a new COVID-19 vaccine unit, enrolling people in a phase 3 clinical trial to test the efficacy of the AstraZeneca-University of Oxford vaccine. The unit is led by Barry Zingman, M.D., professor of medicine at Einstein and clinical director of infectious diseases at the Moses division of Montefiore.

In recruiting people for the vaccine trial, Dr. Zingman and his team required that more than half the participants were adults most affected by COVID-19, with a focus on people of color and people older than 65.

The randomized, placebo-controlled, double-blind trial vaccinated two people with the vaccine for each person who received a placebo injection. Two injections were given to each participant over 29 days. “To the healthcare providers and investigators who enthusiastically joined the effort and to the people who come in to participate in these critically important trials, we thank you for your role in helping the world end this pandemic,” Dr. Zingman says.

Monoclonal Antibodies and Blood Thinners

Einstein and Montefiore have become a testing site for trials funded by the National Institutes of Health (NIH) known as ACTIV-3 and ACTIV-4. The ACTIV-3 trial is evaluating the safety and effectiveness of Eli Lilly’s monoclonal antibody (bamlanivimab) in patients hospitalized with COVID-19.

ACTIV-4 is assessing several blood-thinner drugs for treating people with COVID-19, particularly patients with life-threatening blood clots. The principal investigator for both trials is Michelle Ng Gong, M.D., M.S., chief of the divisions of critical care and of pulmonary medicine at Montefiore and Einstein and professor of medicine and of epidemiology & population health at Einstein.

Combination Therapies

Montefiore is also the testing site for the NIH-funded ACTT-4 clinical trial assessing combination therapies for COVID-19. Those enrolled are people hospitalized with moderate to severe COVID-19 who are on oxygen but are not intubated.

All participants receive the antiviral drug remdesivir, and are randomized to receive one of two anti-inflammatory drugs: baricitinib and dexamethasone. ACTT-4 seeks to compare the safety and effectiveness of the anti-inflammatory drugs, both of which have shown promise in treating COVID-19. Each of the patients receiving combination therapy is matched with a patient receiving remdesivir alone. The principal investigator is Robert M. Grossberg, M.D., associate professor of medicine (infectious diseases) at Einstein and medical director of the Montefiore Center for Positive Living/Infectious Diseases Clinic.

COVID-19 and Children

In the first-ever study comparing the immune responses of adults and children with COVID-19, researchers at Einstein and Montefiore and at Yale University detected key differences that may explain why children usually have a milder course of disease. The findings, which were published in September 2020 in Science Translational Medicine, suggest that children’s stronger innate immunity protects them against SARS-CoV-2, the novel coronavirus that causes COVID-19. Betsy Herold, M.D., chief of pediatric infectious diseases and vice chair for research in the department of pediatrics at Einstein and Children’s Hospital at Montefiore, was one of the senior authors of the study.

Neurological Symptoms

People hospitalized with COVID-19 who have neurological problems have a higher risk of dying than other COVID-19 patients, according to a study that Einstein and Montefiore researchers published in December 2020 in Neurology.

The research is the first to show that the presence of neurological symptoms, particularly stroke and confused or altered thinking, can predict a more serious course of illness even when problems with breathing aren’t severe. The study looked at data from 4,711 people admitted to Montefiore with COVID-19 between March 1 and April 16, 2020.

The findings could potentially help medical workers identify and focus their treatment efforts on individuals most at risk, and could decrease COVID-19 deaths. The study’s co-authors were David Altschul, M.D., chief of the division of cerebrovascular neurosurgery at Einstein and Montefiore, and Emad Eskandar, M.D., M.B.A., the Jeffrey P. Bergstein Chair in Neurological Surgery in the Leo M. Davidoff Department of Neurological Surgery at Einstein and the David B. Keidan Chair of Neurological Surgery at Montefiore and Einstein.

Convalescent Plasma

A study published in January 2021 in JCI Insight found that plasma donated by people who’ve recovered from COVID-19 is effective in treating younger patients hospitalized for the disease.

Einstein and Montefiore researchers administered convalescent plasma to 103 severely ill patients with COVID-19 who were admitted to Montefiore between April 13 and May 4, 2020. Seventy-three of those patients were matched with 73 COVID-19 patients admitted during the same period who did not receive plasma. The authors found no difference in mortality between the people who received convalescent plasma and those who had not at 28 days following admission.

However, when patients were stratified by age, those plasma recipients under age 65 had a fourfold lower mortality after 28 days compared with similarly aged control patients. Liise-anne Pirofski, M.D., was the study’s senior author. She is the chief of infectious diseases at Einstein and Montefiore and holds the Selma and Dr. Jacques Mitrani Chair in Biomedical Research at Einstein.

Psychiatric Problems

In a letter published in the Journal of Psychiatric Research in August 2020, members of Einstein and Montefiore’s department of psychiatry and behavioral sciences added to evidence indicating that COVID-19 may cause psychiatric problems.

The authors described two adults with COVID-19 admitted to the emergency department with severe psychosis and mania. Neither patient had a prior psychiatric history or significant medical or pulmonary symptoms; both were discharged following treatment with antipsychotic drugs. The authors speculated that the patients’ psychiatric problems may have resulted from immune-system activation and its effect on the central nervous system. Vilma Gabbay, M.D., was the corresponding author. She is an associate professor of psychiatry and behavioral sciences and in the Dominick P. Purpura Department of Neuroscience and a co-director of the Psychiatry Research Institute at Einstein, and a clinical psychiatrist at Montefiore.

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