A new study by HSS Research Institute scientists identifies a mechanism by which SARS-CoV-2 induces the inflammatory response in COVID-19 patient lungs, so-called “cytokine storm”, that can lead to lasting tissue damage and poor patient outcomes. The Lead Investigator Dr. Franck J. Barrat and Dr. Lionel B. Ivashkiv at Hospital for Special Surgery worked in collaboration with Drs. Olivier Elemento and Robert E. Schwartz at Weill Cornell Medicine (WCM) on this study, looking at lung tissue samples and bronchoalveolar lavage from COVID-19 patients.
In a study published September 9 in Science Immunology, the investigators outline what controls the cytokine storm by lung-infiltrating macrophages, as these cells are not efficiently infected by SARS-CoV-2.
Researchers found that an immune cell type, called plasmacytoid dendritic cells (pDCs), are infected by SARS-CoV-2 and produce interferons that can provoke epigenetic changes in the nearby macrophages in the lungs of patients. Hence, this priming of macrophages by interferons leads to their exacerbated response to environmental stimuli, inducing the cytokine storm in the lungs of COVID-19 patients.
This is surprising as interferons and pDCs have been demonstrated to protect patients infected by SARS-CoV-2 – but this new research uncovers that they can also provoke damaging cytokine storms.
“There is still a lot we don’t know about the pathogenesis of COVID-19, and why macrophages can produce these cytokine storms that can have such dramatic consequences for patients. We hope that this research will bring us closer to that understanding and will lead to better treatment options for patients with severe COVID-19,” said Dr. Barrat (Michael R. Bloomberg Chair, Hospital for Special Surgery; Professor of Microbiology and Immunology, Weill Cornell Medicine).
This work was supported by a grant from the HSS Research Institute to study the role of pDCs in SARS-CoV-2 pathogenesis as well as grants from the National Institute of Health, the Scleroderma Research Foundation, the Scleroderma Foundation, the Starr Cancer Consortium, the Irma Hirschl Trust Research Award and The Tow Foundation.
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 13th consecutive year), No. 3 in rheumatology by U.S. News & World Report (2022-2023), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2022-2023). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a second consecutive year (2022). Founded in 1863, the Hospital has the lowest complication and readmission rates in the nation for orthopedics, and among the lowest infection rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 145 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.
Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19
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