Journal of Allergy and Clinical Immunology: Global (Nov 2025)
Type 2 immune responses are associated with less severe COVID-19 in a hospitalized cohort
- Naresh Doni Jayavelu, PhD,
- Jingjing Qi, MSc,
- Carly E. Milliren, MPH,
- Al Ozonoff, PhD,
- Shanshan Liu, MPH,
- Ofer Levy, MD, PhD,
- Lindsey R. Baden, MD,
- Esther Melamed, MD, PhD,
- Grace A. McComsey, MD,
- Charles B. Cairns, MD,
- Joanna Schaenman, MD, PhD,
- Albert C. Shaw, MD, PhD,
- David A. Hafler, MD,
- David B. Corry, MD,
- Farrah Kheradmand, MD,
- Mark A. Atkinson, PhD,
- Scott C. Brakenridge, MD,
- Nelson I. Agudelo Higuita, MD,
- Jordan P. Metcalf, MD,
- Catherine L. Hough, MD,
- William B. Messer, MD, PhD,
- Bali Pulendran, PhD,
- Kari C. Nadeau, MD, PhD,
- Mark M. Davis, PhD,
- Linda N. Geng, MD, PhD,
- Ana Fernandez Sesma, PhD,
- Viviana Simon, MD, PhD,
- Florian Krammer, PhD,
- Chris Bime, MD,
- Carolyn S. Calfee, MD,
- Steven E. Bosinger, PhD,
- Walter Eckalbar, PhD,
- Hanno Steen, PhD,
- Holden T. Maecker, PhD,
- Alison D. Augustine, PhD,
- Joann Diray-Arce, PhD,
- Elias K. Haddad, PhD,
- Rafick-Pierre Sekaly, PhD,
- Monica Kraft, MD,
- Prescott G. Woodruff, MD,
- David J. Erle, MD,
- Lauren I.R. Ehrlich, PhD,
- Ruth R. Montgomery, PhD,
- Patrice M. Becker, MD,
- Matthew C. Altman, MD,
- Slim Fourati, PhD,
- Patrice M. Becker,
- Alison D. Augustine,
- Steven M. Holland,
- Lindsey B. Rosen,
- Serena Lee,
- Tatyana Vaysman,
- Al Ozonoff,
- Joann Diray-Arce,
- Jing Chen,
- Alvin Kho,
- Carly E. Milliren,
- Annmarie Hoch,
- Ana C. Chang,
- Kerry McEnaney,
- Brenda Barton,
- Claudia Lentucci,
- Maimouna D. Murphy,
- Mehmet Saluvan,
- Tanzia Shaheen,
- Shanshan Liu,
- Caitlin Syphurs,
- Marisa Albert,
- Arash Nemati Hayati,
- Robert Bryant,
- James Abraham,
- Sanya Thomas,
- Mitchell Cooney,
- Meagan Karoly,
- Matthew C. Altman,
- Naresh Doni Jayavelu,
- Scott Presnell,
- Bernard Kohr,
- Tomasz Jancsyk,
- Azlann Arnett,
- Bjoern Peters,
- James A. Overton,
- Randi Vita,
- Kerstin Westendorf,
- James A. Overton,
- Ofer Levy,
- Hanno Steen,
- Patrick van Zalm,
- Benoit Fatou,
- Kinga K. Smolen,
- Arthur Viode,
- Simon van Haren,
- Meenakshi Jha,
- David Stevenson,
- Oludare Odumade,
- Lindsey R. Baden,
- Kevin Mendez,
- Jessica Lasky-Su,
- Alexandra Tong,
- Rebecca Rooks,
- Michael Desjardins,
- Amy C. Sherman,
- Stephen R. Walsh,
- Xhoi Mitre,
- Jessica Cauley,
- Xiofang Li,
- Bethany Evans,
- Christina Montesano,
- Jose Humberto Licona,
- Jonathan Krauss,
- Nicholas C. Issa,
- Jun Bai Park Chang,
- Natalie Izaguirre,
- Scott R. Hutton,
- Greg Michelotti,
- Kari Wong,
- Scott J. Tebbutt,
- Casey P. Shannon,
- Rafick-Pierre Sekaly,
- Slim Fourati,
- Grace A. McComsey,
- Paul Harris,
- Scott Sieg,
- Susan Pereira Ribeiro,
- Charles B. Cairns,
- Elias K. Haddad,
- Michele A. Kutzler,
- Mariana Bernui,
- Gina Cusimano,
- Jennifer Connors,
- Kyra Woloszczuk,
- David Joyner,
- Carolyn Edwards,
- Edward Lee,
- Edward Lin,
- Nataliya Melnyk,
- Debra L. Powell,
- James N. Kim,
- I. Michael Goonewardene,
- Brent Simmons,
- Cecilia M. Smith,
- Mark Martens,
- Brett Croen,
- Nicholas C. Semenza,
- Mathew R. Bell,
- Sara Furukawa,
- Renee McLin,
- George P. Tegos,
- Brandon Rogowski,
- Nathan Mege,
- Kristen Ulring,
- Pam Schearer,
- Judie Sheidy,
- Crystal Nagle,
- Vicki Seyfert-Margolis,
- Nadine Rouphael,
- Steven E. Bosinger,
- Arun K. Boddapati,
- Greg K. Tharp,
- Kathryn L. Pellegrini,
- Brandi Johnson,
- Bernadine Panganiban,
- Christopher Huerta,
- Evan J. Anderson,
- Hady Samaha,
- Jonathan E. Sevransky,
- Laurel Bristow,
- Elizabeth Beagle,
- David Cowan,
- Sydney Hamilton,
- Thomas Hodder,
- Amer Bechnak,
- Andrew Cheng,
- Aneesh Mehta,
- Caroline R. Ciric,
- Christine Spainhour,
- Erin Carter,
- Erin M. Scherer,
- Jacob Usher,
- Kieffer Hellmeister,
- Laila Hussaini,
- Lauren Hewitt,
- Nina Mcnair,
- Susan Pereira Ribeiro,
- Sonia Wimalasena,
- Ana Fernandez-Sesma,
- Viviana Simon,
- Florian Krammer,
- Harm Van Bakel,
- Seunghee Kim-Schulze,
- Ana Silvia Gonzalez Reiche,
- Jingjing Qi,
- Brian Lee,
- Juan Manuel Carreño,
- Gagandeep Singh,
- Ariel Raskin,
- Johnstone Tcheou,
- Zain Khalil,
- Adriana van de Guchte,
- Keith Farrugia,
- Zenab Khan,
- Geoffrey Kelly,
- Komal Srivastava,
- Lily Q. Eaker,
- Maria C. Bermúdez-González,
- Lubbertus C.F. Mulder,
- Katherine F. Beach,
- Miti Saksena,
- Deena Altman,
- Erna Kojic,
- Levy A. Sominsky,
- Arman Azad,
- Dominika Bielak,
- Hisaaki Kawabata,
- Temima Yellin,
- Miriam Fried,
- Leeba Sullivan,
- Sara Morris,
- Giulio Kleiner,
- Daniel Stadlbauer,
- Jayeeta Dutta,
- Hui Xie,
- Manishkumar Patel,
- Kai Nie,
- Adeeb Rahman,
- William B. Messer,
- Catherine L. Hough,
- Sarah A.R. Siegel,
- Peter E. Sullivan,
- Zhengchun Lu,
- Amanda E. Brunton,
- Matthew Strand,
- Zoe L. Lyski,
- Felicity J. Coulter,
- Courtney Micheleti,
- Holden Maecker,
- Bali Pulendran,
- Kari C. Nadeau,
- Yael Rosenberg-Hasson,
- Michael Leipold,
- Natalia Sigal,
- Angela Rogers,
- Andrea Fernandes,
- Monali Manohar,
- Evan Do,
- Iris Chang,
- Alexandra S. Lee,
- Catherine Blish,
- Henna Naz Din,
- Jonasel Roque,
- Linda N. Geng,
- Maja Artandi,
- Mark M. Davis,
- Neera Ahuja,
- Samuel S. Yang,
- Sharon Chinthrajah,
- Thomas Hagan,
- Elaine F. Reed,
- Joanna Schaenman,
- Ramin Salehi-Rad,
- Adreanne M. Rivera,
- Harry C. Pickering,
- Subha Sen,
- David Elashoff,
- Dawn C. Ward,
- Jenny Brook,
- Estefania Ramires Sanchez,
- Megan Llamas,
- Claudia Perdomo,
- Clara E. Magyar,
- Jennifer Fulcher,
- David J. Erle,
- Carolyn S. Calfee,
- Carolyn M. Hendrickson,
- Kirsten N. Kangelaris,
- Viet Nguyen,
- Deanna Lee,
- Suzanna Chak,
- Rajani Ghale,
- Ana Gonzalez,
- Alejandra Jauregui,
- Carolyn Leroux,
- Luz Torres Altamirano,
- Ahmad Sadeed Rashid,
- Andrew Willmore,
- Prescott G. Woodruff,
- Matthew F. Krummel,
- Sidney Carrillo,
- Alyssa Ward,
- Charles R. Langelier,
- Ravi Patel,
- Michael Wilson,
- Ravi Dandekar,
- Bonny Alvarenga,
- Jayant Rajan,
- Walter Eckalbar,
- Andrew W. Schroeder,
- Gabriela K. Fragiadakis,
- Alexandra Tsitsiklis,
- Eran Mick,
- Yanedth Sanchez Guerrero,
- Christina Love,
- Lenka Maliskova,
- Michael Adkisson,
- Aleksandra Leligdowicz,
- Alexander Beagle,
- Arjun Rao,
- Austin Sigman,
- Bushra Samad,
- Cindy Curiel,
- Cole Shaw,
- Gayelan Tietje-Ulrich,
- Jeff Milush,
- Jonathan Singer,
- Joshua J. Vasquez,
- Kevin Tang,
- Legna Betancourt,
- Lekshmi Santhosh,
- Logan Pierce,
- Maria Tecero Paz,
- Michael Matthay,
- Neeta Thakur,
- Nicklaus Rodriguez,
- Nicole Sutter,
- Norman Jones,
- Pratik Sinha,
- Priya Prasad,
- Raphael Lota,
- Sadeed Rashid,
- Saurabh Asthana,
- Sharvari Bhide,
- Tasha Lea,
- Yumiko Abe-Jones,
- David A. Hafler,
- Ruth R. Montgomery,
- Albert C. Shaw,
- Steven H. Kleinstein,
- Jeremy P. Gygi,
- Shrikant Pawar,
- Anna Konstorum,
- Ernie Chen,
- Chris Cotsapas,
- Xiaomei Wang,
- Leqi Xu,
- Charles Dela Cruz,
- Akiko Iwasaki,
- Subhasis Mohanty,
- Allison Nelson,
- Yujiao Zhao,
- Shelli Farhadian,
- Hiromitsu Asashima,
- Omkar Chaudhary,
- Andreas Coppi,
- John Fournier,
- M. Catherine Muenker,
- Allison Nelson,
- Khadir Raddassi,
- Michael Rainone,
- William Ruff,
- Syim Salahuddin,
- Wade L. Shulz,
- Pavithra Vijayakumar,
- Haowei Wang,
- Esio Wunder, Jr.,
- H. Patrick Young,
- Albert I. Ko,
- Xiomei Wang,
- Dylan Duchen,
- Denise Esserman,
- Leying Guan,
- Anderson Brito,
- Jessica Rothman,
- Nathan D. Grubaugh,
- David B. Corry,
- Farrah Kheradmand,
- Li-Zhen Song,
- Ebony Nelson,
- Jordan P. Metcalf,
- Nelson I. Agudelo Higuita,
- Lauren A. Sinko,
- J. Leland Booth,
- Douglas A. Drevets,
- Brent R. Brown,
- Monica Kraft,
- Chris Bime,
- Jarrod Mosier,
- Heidi Erickson,
- Ron Schunk,
- Hiroki Kimura,
- Michelle Conway,
- Dave Francisco,
- Allyson Molzahn,
- Connie Cathleen Wilson,
- Ron Schunk,
- Trina Hughes,
- Bianca Sierra,
- Mark A. Atkinson,
- Scott C. Brakenridge,
- Ricardo F. Ungaro,
- Brittany Roth Manning,
- Lyle Moldawer,
- Jordan Oberhaus,
- Faheem W. Guirgis,
- Brittney Borresen,
- Matthew L. Anderson,
- Lauren I.R. Ehrlich,
- Esther Melamed,
- Cole Maguire,
- Dennis Wylie,
- Justin F. Rousseau,
- Kerin C. Hurley,
- Janelle N. Geltman,
- Nadia Siles,
- Jacob E. Rogers
Affiliations
- Naresh Doni Jayavelu, PhD
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Jingjing Qi, MSc
- Icahn School of Medicine at Mount Sinai, New York, NY
- Carly E. Milliren, MPH
- Clinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Al Ozonoff, PhD
- Clinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Shanshan Liu, MPH
- Clinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Ofer Levy, MD, PhD
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Lindsey R. Baden, MD
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Esther Melamed, MD, PhD
- University of Texas, Austin, Ga
- Grace A. McComsey, MD
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Charles B. Cairns, MD
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Joanna Schaenman, MD, PhD
- David Geffen School of Medicine at the University of California, Los Angeles, Palo
- Albert C. Shaw, MD, PhD
- Yale School of Medicine, New Haven, Conn
- David A. Hafler, MD
- Yale School of Medicine, New Haven, Conn
- David B. Corry, MD
- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Tex
- Farrah Kheradmand, MD
- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Tex
- Mark A. Atkinson, PhD
- University of Florida, Gainesville, Fla
- Scott C. Brakenridge, MD
- University of Florida, Gainesville, Fla
- Nelson I. Agudelo Higuita, MD
- Oklahoma University Health Sciences Center, Oklahoma City, Okla
- Jordan P. Metcalf, MD
- Oklahoma University Health Sciences Center, Oklahoma City, Okla
- Catherine L. Hough, MD
- Oregon Health Sciences University, Portland, Ore
- William B. Messer, MD, PhD
- Oregon Health Sciences University, Portland, Ore
- Bali Pulendran, PhD
- Stanford University School of Medicine, Palo Alto, Calif
- Kari C. Nadeau, MD, PhD
- Stanford University School of Medicine, Palo Alto, Calif
- Mark M. Davis, PhD
- Stanford University School of Medicine, Palo Alto, Calif
- Linda N. Geng, MD, PhD
- Stanford University School of Medicine, Palo Alto, Calif
- Ana Fernandez Sesma, PhD
- Icahn School of Medicine at Mount Sinai, New York, NY
- Viviana Simon, MD, PhD
- Icahn School of Medicine at Mount Sinai, New York, NY
- Florian Krammer, PhD
- Icahn School of Medicine at Mount Sinai, New York, NY
- Chris Bime, MD
- University of Arizona, Tucson, Ariz
- Carolyn S. Calfee, MD
- University of California San Francisco, San Francisco, Calif
- Steven E. Bosinger, PhD
- Emory School of Medicine, Atlanta, Ga
- Walter Eckalbar, PhD
- University of California San Francisco, San Francisco, Calif
- Hanno Steen, PhD
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Holden T. Maecker, PhD
- Stanford University School of Medicine, Palo Alto, Calif
- Alison D. Augustine, PhD
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Joann Diray-Arce, PhD
- Clinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Elias K. Haddad, PhD
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Rafick-Pierre Sekaly, PhD
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Monica Kraft, MD
- University of Arizona, Tucson, Ariz
- Prescott G. Woodruff, MD
- University of California San Francisco, San Francisco, Calif
- David J. Erle, MD
- University of California San Francisco, San Francisco, Calif
- Lauren I.R. Ehrlich, PhD
- University of Texas, Austin, Ga
- Ruth R. Montgomery, PhD
- Yale School of Medicine, New Haven, Conn
- Patrice M. Becker, MD
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Matthew C. Altman, MD
- Benaroya Research Institute, University of Washington, Seattle, Wash; Corresponding author: Matthew C. Altman, MD, Center for Systems Immunology, Benaroya Research Institute, 1201 Ninth Ave, Seattle, WA 98101.
- Slim Fourati, PhD
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Patrice M. Becker
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Alison D. Augustine
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Steven M. Holland
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Lindsey B. Rosen
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Serena Lee
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Tatyana Vaysman
- National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
- Al Ozonoff
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Joann Diray-Arce
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Jing Chen
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Alvin Kho
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Carly E. Milliren
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Annmarie Hoch
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Ana C. Chang
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Kerry McEnaney
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Brenda Barton
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Claudia Lentucci
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Maimouna D. Murphy
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Mehmet Saluvan
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Tanzia Shaheen
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Shanshan Liu
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Caitlin Syphurs
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Marisa Albert
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Arash Nemati Hayati
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Robert Bryant
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- James Abraham
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Sanya Thomas
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Mitchell Cooney
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Meagan Karoly
- Clinical and Data Coordinating Center (CDCC) Precision Vaccines Program, Boston Children’s Hospital, Boston, Mass
- Matthew C. Altman
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Naresh Doni Jayavelu
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Scott Presnell
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Bernard Kohr
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Tomasz Jancsyk
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Azlann Arnett
- Benaroya Research Institute, University of Washington, Seattle, Wash
- Bjoern Peters
- La Jolla Institute for Immunology, La Jolla, Calif
- James A. Overton
- La Jolla Institute for Immunology, La Jolla, Calif
- Randi Vita
- La Jolla Institute for Immunology, La Jolla, Calif
- Kerstin Westendorf
- La Jolla Institute for Immunology, La Jolla, Calif
- James A. Overton
- Knocean Inc, Toronto, Ontario, Canada
- Ofer Levy
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Hanno Steen
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Patrick van Zalm
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Benoit Fatou
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Kinga K. Smolen
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Arthur Viode
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Simon van Haren
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Meenakshi Jha
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- David Stevenson
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Oludare Odumade
- Precision Vaccines Program, Boston Children’s Hospital, Harvard Medical School, Boston, Mass
- Lindsey R. Baden
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Kevin Mendez
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Jessica Lasky-Su
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Alexandra Tong
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Rebecca Rooks
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Michael Desjardins
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Amy C. Sherman
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Stephen R. Walsh
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Xhoi Mitre
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Jessica Cauley
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Xiofang Li
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Bethany Evans
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Christina Montesano
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Jose Humberto Licona
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Jonathan Krauss
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Nicholas C. Issa
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Jun Bai Park Chang
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Natalie Izaguirre
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass
- Scott R. Hutton
- Metabolon Inc, Morrisville, NC
- Greg Michelotti
- Metabolon Inc, Morrisville, NC
- Kari Wong
- Metabolon Inc, Morrisville, NC
- Scott J. Tebbutt
- Prevention of Organ Failure (PROOF) Centre of Excellence, University of British Columbia, Vancouver, British Columbia, Canada
- Casey P. Shannon
- Prevention of Organ Failure (PROOF) Centre of Excellence, University of British Columbia, Vancouver, British Columbia, Canada
- Rafick-Pierre Sekaly
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Slim Fourati
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Grace A. McComsey
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Paul Harris
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Scott Sieg
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Susan Pereira Ribeiro
- Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio
- Charles B. Cairns
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Elias K. Haddad
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Michele A. Kutzler
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Mariana Bernui
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Gina Cusimano
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Jennifer Connors
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Kyra Woloszczuk
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- David Joyner
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Carolyn Edwards
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Edward Lee
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Edward Lin
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Nataliya Melnyk
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Debra L. Powell
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- James N. Kim
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- I. Michael Goonewardene
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Brent Simmons
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Cecilia M. Smith
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Mark Martens
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Brett Croen
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Nicholas C. Semenza
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Mathew R. Bell
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Sara Furukawa
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Renee McLin
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- George P. Tegos
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Brandon Rogowski
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Nathan Mege
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Kristen Ulring
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Pam Schearer
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Judie Sheidy
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Crystal Nagle
- Drexel University, Tower Health Hospital, Philadelphia, Pa
- Vicki Seyfert-Margolis
- MyOwnMed Inc, Bethesda, Md
- Nadine Rouphael
- Emory School of Medicine, Atlanta, Ga
- Steven E. Bosinger
- Emory School of Medicine, Atlanta, Ga
- Arun K. Boddapati
- Emory School of Medicine, Atlanta, Ga
- Greg K. Tharp
- Emory School of Medicine, Atlanta, Ga
- Kathryn L. Pellegrini
- Emory School of Medicine, Atlanta, Ga
- Brandi Johnson
- Emory School of Medicine, Atlanta, Ga
- Bernadine Panganiban
- Emory School of Medicine, Atlanta, Ga
- Christopher Huerta
- Emory School of Medicine, Atlanta, Ga
- Evan J. Anderson
- Emory School of Medicine, Atlanta, Ga
- Hady Samaha
- Emory School of Medicine, Atlanta, Ga
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
- Erna Kojic
- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
- Arman Azad
- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Daniel Stadlbauer
- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
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- Icahn School of Medicine at Mount Sinai, New York, NY
- Manishkumar Patel
- Icahn School of Medicine at Mount Sinai, New York, NY
- Kai Nie
- Icahn School of Medicine at Mount Sinai, New York, NY
- Adeeb Rahman
- Immunai Inc, New York, NY
- William B. Messer
- Oregon Health Sciences University, Portland, Ore
- Catherine L. Hough
- Oregon Health Sciences University, Portland, Ore
- Sarah A.R. Siegel
- Oregon Health Sciences University, Portland, Ore
- Peter E. Sullivan
- Oregon Health Sciences University, Portland, Ore
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- Oregon Health Sciences University, Portland, Ore
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- Oregon Health Sciences University, Portland, Ore
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- Oregon Health Sciences University, Portland, Ore
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- Oregon Health Sciences University, Portland, Ore
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- Oregon Health Sciences University, Portland, Ore
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- Oregon Health Sciences University, Portland, Ore
- Holden Maecker
- Stanford University School of Medicine, Palo Alto, Calif
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- Stanford University School of Medicine, Palo Alto, Calif
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- David Geffen School of Medicine at the University of California, Los Angeles, Calif
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- David Geffen School of Medicine at the University of California, Los Angeles, Calif
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- Yale School of Public Health, New Haven, Conn
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- Yale School of Public Health, New Haven, Conn
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- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Tex
- Farrah Kheradmand
- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Tex
- Li-Zhen Song
- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Tex
- Ebony Nelson
- Baylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Tex
- Jordan P. Metcalf
- Oklahoma University Health Sciences Center, Oklahoma City, Okla
- Nelson I. Agudelo Higuita
- Oklahoma University Health Sciences Center, Oklahoma City, Okla
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- J. Leland Booth
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- University of Arizona, Tucson, Ariz
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- Ron Schunk
- University of Arizona, Tucson, Ariz
- Hiroki Kimura
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- Michelle Conway
- University of Arizona, Tucson, Ariz
- Dave Francisco
- University of Arizona, Tucson, Ariz
- Allyson Molzahn
- University of Arizona, Tucson, Ariz
- Connie Cathleen Wilson
- University of Arizona, Tucson, Ariz
- Ron Schunk
- University of Arizona, Tucson, Ariz
- Trina Hughes
- University of Arizona, Tucson, Ariz
- Bianca Sierra
- University of Arizona, Tucson, Ariz
- Mark A. Atkinson
- University of Florida, Gainesville, Fla
- Scott C. Brakenridge
- University of Florida, Gainesville, Fla
- Ricardo F. Ungaro
- University of Florida, Gainesville, Fla
- Brittany Roth Manning
- University of Florida, Gainesville, Fla
- Lyle Moldawer
- University of Florida, Gainesville, Fla
- Jordan Oberhaus
- University of Florida, Jacksonville, Fla
- Faheem W. Guirgis
- University of Florida, Jacksonville, Fla
- Brittney Borresen
- University of South Florida, Tampa, Fla
- Matthew L. Anderson
- University of South Florida, Tampa, Fla
- Lauren I.R. Ehrlich
- University of Texas, Austin, Tex
- Esther Melamed
- University of Texas, Austin, Tex
- Cole Maguire
- University of Texas, Austin, Tex
- Dennis Wylie
- University of Texas, Austin, Tex
- Justin F. Rousseau
- University of Texas, Austin, Tex
- Kerin C. Hurley
- University of Texas, Austin, Tex
- Janelle N. Geltman
- University of Texas, Austin, Tex
- Nadia Siles
- University of Texas, Austin, Tex
- Jacob E. Rogers
- University of Texas, Austin, Tex
- DOI
- https://doi.org/10.1016/j.jacig.2025.100515
- Journal volume & issue
-
Vol. 4,
no. 4
p. 100515
Abstract
Background: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly after its identification in December 2019 to cause a global pandemic. The respiratory tract is the primary site of infection, and there is a large range in the severity of respiratory illnesses caused by the virus. Defining molecular and cellular factors for protection from severe disease and death has been a goal to better understand and to predict and mitigate the effects of SARS-CoV-2 and future coronaviruses. Objective: Despite well-known susceptibilities to respiratory viral infections, respiratory allergy and allergic asthma have not been identified as risk factors for severe coronavirus disease 2019 (COVID-19) in most epidemiologic studies and may be protective. We sought to investigate associations between markers of type 2 (T2) immune responses with SARS-CoV-2 clinical outcomes and virus loads in a cohort of 1164 individuals hospitalized for COVID-19 from May 2020 to March 2021 as part of the IMPACC study. Methods: We characterized the clinical outcomes, as defined by severity trajectory groups reflecting the degree of respiratory support required, virus loads, and antibody titers of COVID-19 infections in IMPACC participants in relation to molecular and cellular markers of T2 immune responses through multiple assays, including, (1) IL-4, IL-5, and IL-13 levels in serum Olink data, (2) T2 cellular signatures in blood cytometry by time of flight data, (3) relative quantification of T2 signaling gene pathways in airway RNA sequencing data, and/or (4) T2 pathways in peripheral blood mononuclear cell RNA sequencing data. We also investigated the outcomes of individuals with self-reported asthma and evidence of T2 immune responses. Results: The diagnosis of asthma (odd ratio = 1.27), elevated serum T2 cytokine levels (median fold change = 1.06), and a higher frequency of TH2 cells (difference = +2%) were associated with less severe clinical disease during hospitalization. Distinct T2-related transcriptomic changes in nasal and blood samples were associated with reduced virus loads. This included the expression of T2-regulated genes implicated in T-/B-cell activation and apoptosis in nasal samples and the expression of T2-regulated genes implicated in myeloid differentiation and reactive oxygen species signaling in blood. Among these, several canonical T2-regulated genes that were increased in less severe disease were identified to have antiviral properties in large high-throughput screens. Conclusion: T2 immune responses were associated with lower virus loads and more favorable clinical outcomes, suggesting that T2 inflammation related to asthma and allergic diseases may have a direct protective effect against SARS-CoV-2.
Keywords
