Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Al Ozonoff, Naresh Doni Jayavelu, Shanshan Liu, Esther Melamed, Carly E. Milliren, Jingjing Qi, Linda N. Geng, Grace A. McComsey, Charles B. Cairns, Lindsey R. Baden, Joanna Schaenman, Albert C. Shaw, Hady Samaha, Vicki Seyfert-Margolis, Florian Krammer, Lindsey B. Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P. Shannon, Rafick P. Sekaly, Lauren I. R. Ehrlich, David B. Corry, Farrah Kheradmand, Mark A. Atkinson, Scott C. Brakenridge, Nelson I. Agudelo Higuita, Jordan P. Metcalf, Catherine L. Hough, William B. Messer, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Ana Fernandez Sesma, Viviana Simon, Harm van Bakel, Seunghee Kim-Schulze, David A. Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K. Haddad, Carolyn S. Calfee, David J. Erle, Charles R. Langelier, Walter Eckalbar, Steven E. Bosinger, Bjoern Peters, Steven H. Kleinstein, Elaine F. Reed, Alison D. Augustine, Joann Diray-Arce, Holden T. Maecker, Matthew C. Altman, Ruth R. Montgomery, Patrice M. Becker and Nadine Rouphael ()
Additional contact information
Al Ozonoff: Boston Children’s Hospital
Naresh Doni Jayavelu: Benaroya Research Institute
Shanshan Liu: Boston Children’s Hospital
Esther Melamed: The University of Texas at Austin
Carly E. Milliren: Boston Children’s Hospital
Jingjing Qi: Icahn School of Medicine at Mount Sinai
Linda N. Geng: Stanford University
Grace A. McComsey: Case Western Reserve University and University Hospitals of Cleveland
Charles B. Cairns: Drexel University/Tower Health Hospital
Lindsey R. Baden: Boston Children’s Hospital, Brigham and Women’s Hospital, and Harvard Medical School
Joanna Schaenman: David Geffen School of Medicine at the University of California Los Angeles
Albert C. Shaw: Yale School of Medicine, and Yale School of Public Health
Hady Samaha: Emory University
Vicki Seyfert-Margolis: MyOwnMed, Inc
Florian Krammer: Icahn School of Medicine at Mount Sinai
Lindsey B. Rosen: National Institute of Allergy and Infectious Diseases/National Institutes of Health
Hanno Steen: Boston Children’s Hospital, Brigham and Women’s Hospital, and Harvard Medical School
Caitlin Syphurs: Boston Children’s Hospital
Ravi Dandekar: University of California San Francisco School of Medicine
Casey P. Shannon: St. Paul’s Hospital, and the PROOF Centre of Excellence
Rafick P. Sekaly: Case Western Reserve University and University Hospitals of Cleveland
Lauren I. R. Ehrlich: The University of Texas at Austin
David B. Corry: Baylor College of Medicine, and the Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center
Farrah Kheradmand: Baylor College of Medicine, and the Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center
Mark A. Atkinson: University of Florida/University of South Florida
Scott C. Brakenridge: University of Florida/University of South Florida
Nelson I. Agudelo Higuita: Oklahoma University Health Sciences Center
Jordan P. Metcalf: Oklahoma University Health Sciences Center
Catherine L. Hough: Oregon Health & Science University
William B. Messer: Oregon Health & Science University
Bali Pulendran: Stanford University
Kari C. Nadeau: Stanford University
Mark M. Davis: Stanford University
Ana Fernandez Sesma: Icahn School of Medicine at Mount Sinai
Viviana Simon: Icahn School of Medicine at Mount Sinai
Harm van Bakel: Icahn School of Medicine at Mount Sinai
Seunghee Kim-Schulze: Icahn School of Medicine at Mount Sinai
David A. Hafler: Yale School of Medicine, and Yale School of Public Health
Ofer Levy: Boston Children’s Hospital, Brigham and Women’s Hospital, and Harvard Medical School
Monica Kraft: University of Arizona
Chris Bime: University of Arizona
Elias K. Haddad: Drexel University/Tower Health Hospital
Carolyn S. Calfee: University of California San Francisco School of Medicine
David J. Erle: University of California San Francisco School of Medicine
Charles R. Langelier: University of California San Francisco School of Medicine
Walter Eckalbar: University of California San Francisco School of Medicine
Steven E. Bosinger: Emory University
Bjoern Peters: La Jolla Institute for Immunology
Steven H. Kleinstein: Yale School of Medicine, and Yale School of Public Health
Elaine F. Reed: David Geffen School of Medicine at the University of California Los Angeles
Alison D. Augustine: National Institute of Allergy and Infectious Diseases/National Institutes of Health
Joann Diray-Arce: Boston Children’s Hospital
Holden T. Maecker: Stanford University
Matthew C. Altman: Benaroya Research Institute
Ruth R. Montgomery: Yale School of Medicine, and Yale School of Public Health
Patrice M. Becker: National Institute of Allergy and Infectious Diseases/National Institutes of Health
Nadine Rouphael: Emory University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Date: 2024
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DOI: 10.1038/s41467-023-44090-5

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