Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Cassandra E Burnett; Trine Line Hauge Okholm; Iliana Tenvooren; Diana M Marquez; Stanley Tamaki; Priscila Munoz Sandoval; Andrew Willmore; UCSF COMET Consortium; Carolyn M Hendrickson; Kirsten N Kangelaris; Charles R Langelier; Matthew F Krummel; Prescott G Woodruff; Carolyn S Calfee; David J Erle; K Mark Ansel; Matthew H Spitzer

doi:10.1016/j.immuni.2022.06.004

Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Immunity. 2022 Jul 12;55(7):1284-1298.e3. doi: 10.1016/j.immuni.2022.06.004. Epub 2022 Jun 7.

Authors

Cassandra E Burnett¹, Trine Line Hauge Okholm¹, Iliana Tenvooren¹, Diana M Marquez¹, Stanley Tamaki², Priscila Munoz Sandoval³, Andrew Willmore⁴; UCSF COMET Consortium; Carolyn M Hendrickson⁵, Kirsten N Kangelaris⁶, Charles R Langelier⁷, Matthew F Krummel⁸, Prescott G Woodruff⁵, Carolyn S Calfee⁴, David J Erle⁹, K Mark Ansel¹⁰, Matthew H Spitzer¹¹

Collaborators

UCSF COMET Consortium:
Ravi Patel, Yumiko Abe-Jones, Saurabh Asthana, Alexander Beagle, Sharvari Bhide, Cathy Cai, Maria Calvo, Sidney A Carrillo, Suzanna Chak, Zachary Collins, Spyros Darmanis, Gabriela K Fragiadakis, Rajani Ghale, Jeremy Giberson, Pat Glenn, Ana Gonzalez, Kamir Hiam-Galvez, Alejandra Jauregui, Serena Ke, Tasha Lea, Deanna Lee, Raphael Lota, Leonard Lupin-Jimenez, Viet Nguyen, Nishita Nigam, Logan Pierce, Priya Prasad, Arjun Rao, Sadeed Rashid, Nicklaus Rodriguez, Bushra Samad, Cole Shaw, Austin Sigman, Pratik Sinha, Kevin Tang, Luz Torres Altamirano, Erden Tumurbaatar, Vaibhav Upadhyay, Alyssa Ward, Kristine Wong, Chun Jimmie Ye, Kimberly Yee, Mingyue Zhou

Affiliations

¹ Department of Otolaryngology-Head and Neck Cancer, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Immunology & Immunology and Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
² UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
³ Department of Immunology & Immunology and Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158, USA.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA.
⁶ Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
⁷ Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA 94143, USA.
⁸ UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
⁹ UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁰ Department of Immunology & Immunology and Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
¹¹ Department of Otolaryngology-Head and Neck Cancer, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Immunology & Immunology and Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address: matthew.spitzer@ucsf.edu.

Abstract

While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.

Keywords: COVID-19; disease resolution; immune cell signaling; immune response; recovery.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

COVID-19*
Disease Progression
Humans
Pneumonia*
SARS-CoV-2

Abstract

Publication types

MeSH terms

Grants and funding