Lower Respiratory Tract Myeloid Cells Harbor SARS-Cov-2 and Display an Inflammatory Phenotype

Creators: Bain, William G.; Peñaloza, Hernán F.; Ladinsky, Mark S.; van der Geest, Rick; Sullivan, Mara; Ross, Mark; Kitsios, Georgios D.; Methé, Barbara A.; McVerry, Bryan J.; Morris, Alison; Watson, Alan M.; Watkins, Simon C.; St. Croix, Claudette M.; Stolz, Donna B.; Bjorkman, Pamela J.; Lee, Janet S.

Abstract

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pneumonia may induce an aberrant immune response with brisk recruitment of myeloid cells into the airspaces. Although the clinical implications are unclear, others have suggested that infiltrating myeloid cells may contribute to morbidity and mortality rates during SARS-CoV-2 infection. However, few reports have characterized myeloid cells from the lower respiratory tract, which appears to be the primary site of viral-induced disease, during severe SARS-CoV-2 pneumonia.

Additional Information

© 2020 Published by Elsevier Inc. under license from the American College of Chest Physicians. Under an Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Received 19 September 2020, Revised 26 October 2020, Accepted 28 October 2020, Available online 18 November 2020. This work was supported by Career Development Award Number IK2 BX004886 from the United States Department of Veterans Affairs Biomedical Laboratory R&D (BLRD) Service (W. Bain); the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers K23 HL129987 (G. Kitsios); P01HL114453 (J. Lee, B. McVerry); and R01 HL136143, R01 HL142084, K24 HL143285 (J. Lee) and R21 HL143091 (B. A. Methé); and the UPMC Immune Therapy and Transplant Center (A. Morris). Electron and confocal microscopy at the University of Pittsburgh Center for Biologic Imaging was supported by National Institutes of Health Office of the Director awards S10OD010625 and S10OD019973 (S. Watkins). Electron tomography at the California Institute of Technology was supported by a George Mason University Fast Grant (P. Bjorkman), National Institute of Allergy and Infectious Diseases (NIAID) Grant 2 P50 AI150464 (P. Bjorkman). Electron microscopy was performed with a TF-30 electron microscope that is maintained by the California Institute of Technology Kavli Nanoscience Institute. Author contributions: W. Bain takes responsibility for the content of this manuscript. W. Bain enrolled patients, collected samples, performed the experiments, designed, analyzed, and interpreted the data, and wrote the manuscript. H. Peñaloza and M. Ladinsky performed the experiments and designed and interpreted the data. R. van der Geest, M. Sullivan, and M. Ross performed the experiments and revised the work for important intellectual content. G. Kitsios enrolled patients, collected samples, provided critical input to the design of the experiments, and revised the work for important intellectual content. B. A. Methé, B. McVerry, and A. Morris provided critical input to design of the experiments and revised the work for important intellectual content. A. Watson and S. Watkins provided critical input to the design of the experiments, expert imaging input, and revised the work for important intellectual content. C. St Croix and D. Stolz performed the experiments, designed and interpreted the data, and revised the work for important intellectual content. P. Bjorkman conceived, designed, interpreted the data, and revised the work for important intellectual content. J. Lee conceived, designed, analyzed, interpreted the data, and wrote the manuscript. Role of sponsors: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, Department of Veterans Affairs, or any other sponsoring agency. Other contributions: The authors thank the patients and patient families who have enrolled in the University of Pittsburgh Acute Lung Injury Registry; the physicians, nurses, respiratory therapists, and other staff at the University of Pittsburgh Medical Center Presbyterian and Shadyside Hospital ICUs for assistance with coordination and collection of endotracheal aspirate samples; Nicole Bensen, BS, and Caitlin Schaefer, MPH, at the University of Pittsburgh for assistance with identifying and consenting patients and their families and for assistance with collection of endotracheal aspirate samples; and Heather Michael, BS, and Lauren Furguiele, BS, at the University of Pittsburgh for assistance with processing endotracheal aspirate samples.

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