What is it?

An investigation to find the immune “signatures” that distinguish different severity levels of COVID-19 illness.

What problem does it aim to solve?

“The immunological mechanisms that differentiate patients with mild, moderate, and severe COVID-19 are poorly understood. Unraveling the underlying immune pathogenesis across the spectrum of COVID-19 presentations is important to both understand the drivers of disease severity as well as to identify clinically relevant biological signatures that could inform therapeutic interventions.”

How does it work?

Samples from 97 people who had tested positive for COVID-19 (but hadn’t yet received treatment at the time blood was drawn) were compared to each other and to samples drawn before the pandemic from 40 healthy people. “In this cross-sectional study, we combined the mass cytometry analysis of immune cell signaling responses with the high-content proteomic analysis of plasma analytes in blood samples from patients identified with mild, moderate, and severe COVID-19 to establish biological signatures that demarcate COVID-19 clinical manifestations.”

What are the real-world implications?

“Two major biological signatures associated with the progression from mild to moderate and severe disease emerged from our integrated analysis: (1) the dampening of NF-κB, MAPK/mTOR, and JAK/STAT intracellular signaling responses in multiple innate and adaptive immune cell subsets, and (2) the mobilization of a proteomic network enriched for elements of the RAS, lung homeostasis, and hemostasis pathways, alongside canonical elements of the cytokine storm signature of severe COVID-19.”

What are the next steps?

“The observations identified by this model contribute clinically relevant insights into the status of patient’s immune responses during SARS-CoV-2 infection and provide promising severity-specific biological signatures for future validation that may inform decision-making on potential therapeutic targets for the prevention of disease progression.”

Source

“Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19”, Cell Reports Medicine, Volume 3, Issue 7, 19 July 2022, 100680 https://is.gd/ikipud

Authors

Feyaerts, Dorien
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Hédou, Julien
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Gillard, Joshua
Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
Center for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, Netherlands

Chen, Han
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States

Tsai, Eileen S.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Peterson, Laura S.
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States

Ando, Kazuo
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Manohar, Monali
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Do, Evan
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Dhondalay, Gopal K.R.
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Fitzpatrick, Jessica
 Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Artandi, Maja
Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, United States

Chang, Iris
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Snow, Theo T.
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Chinthrajah, R. Sharon
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University, Stanford, CA, United States
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States

Warren, Christopher M.
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States

Wittman, Richard
Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, United States

Meyerowitz, Justin G.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Ganio, Edward A.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Stelzer, Ina A.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Han, Xiaoyuan
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States
Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, United States

Verdonk, Franck
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Gaudillière, Dyani K
Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States

Mukherjee, Nilanjan
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States

Tsai, Amy S.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Rumer, Kristen K.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Jacobsen, Danielle R.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Bjornson-Hooper, Zachary B.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States

Jiang, Sizun
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States

Saavedra, Sergio Fragoso
Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Plan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

Valdés Ferrer, Sergio Iván
 Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Kelly, J. Daniel
Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, United States
Institute for Global Health Sciences, UCSF, San Francisco, CA, United States
F.I. Proctor Foundation, UCSF, San Francisco, CA, United States

Furman, David
Buck Artificial Intelligence Platform, Buck Institute for Research on Aging, Novato, CA, United States
Stanford 1000 Immunomes Project, Stanford University School of Medicine, Stanford, CA, United States
Austral Institute for Applied Artificial Intelligence, Institute for Research in Translational Medicine (IIMT), Universidad Austral, CONICET, Pilar, Buenos Aires, Argentina

Aghaeepour, Nima
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States
Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States

Angst, Martin S.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States

Boyd, Scott D.
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States

Pinsky, Benjamin A.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States

Nolan, Garry P.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States

Nadeau, Kari C.
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, United States
Department of Medicine, Stanford University, Stanford, CA, United States
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University, Stanford, CA, United States
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, United States

Gaudillière, Brice
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States
Department of Pediatrics, Stanford University, Stanford, CA, United States

McIlwain, David R.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States