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Association of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (COVID-19)

Educational Objective
To understand the association of Interleukin 7 Immunotherapy with Lymphocyte counts among patients with severe COVID-19
1 Credit CME

Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19). Although there is an initial hyper-inflammatory phase, mounting evidence suggests that virus-induced defective host immunity may be the real cause of death in many patients.1,2

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Article Information

Accepted for Publication: June 30, 2020.

Published: July 22, 2020. doi:10.1001/jamanetworkopen.2020.16485

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Laterre PF et al. JAMA Network Open.

Corresponding Author: Pierre Francois Laterre, MD, Department of Critical Care Medicine, Saint Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium (pierre-francois.laterre@uclouvain.be).

Author Contributions: Drs Laterre and Hotchkiss had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Laterre, François, Remy, Hotchkiss.

Acquisition, analysis, or interpretation of data: Collienne, Hantson, Jeannet, Remy, Hotchkiss.

Drafting of the manuscript: Hantson, Remy, Hotchkiss.

Critical revision of the manuscript for important intellectual content: Laterre, François, Collienne, Jeannet, Remy, Hotchkiss.

Statistical analysis: Remy.

Administrative, technical, or material support: Collienne, Jeannet, Remy, Hotchkiss.

Supervision: Laterre, Hantson, Remy.

Conflict of Interest Disclosures: Dr Hotchkiss reported being an investigator on a sepsis study evaluating interleukin 7 and receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

Funding/Support: Dr Hotchkiss was supported by grant GM126928 from the National Institute of General Medicine Sciences. RevImmune provided recombinant human interleukin 7 to the investigators.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Michael Morre, DVM (RevImmune), provided the original inspiration for the use of interleukin 7 in the management of coronavirus disease 2019 to treat the lymphopenia, a hallmark of the disorder, and was an invaluable resource for important questions on interleukin 7. Teresa Blood, AB (Department of Anesthesiology, Washington University School of Medicine), helped perform data analysis. Lyle Moldawer, PhD (Department of Surgery, University of Florida Gainesville), assisted with review of the manuscript. Manu Shankar-Hari PhD, MD (School of Immunology and Microbial Sciences, Kings College), assisted with data analysis and manuscript review. They were not compensated for their time.

References
1.
Vardhana  SA , Wolchok  JD .  The many faces of the anti-COVID immune response.   J Exp Med. 2020;217(6):217. doi:10.1084/jem.20200678PubMedGoogle ScholarCrossref
2.
Menter  T , Haslbauer  JD , Nienhold  R ,  et al.  Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction.   Histopathology. Published May 4, 2020. doi:10.1111/his.14134PubMedGoogle Scholar
3.
Wang  D , Hu  B , Hu  C ,  et al.  Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.   JAMA. 2020;323(11):1061-1069. doi:10.1001/jama.2020.1585PubMedGoogle ScholarCrossref
4.
Mackall  CL , Fry  TJ , Gress  RE .  Harnessing the biology of IL-7 for therapeutic application.   Nat Rev Immunol. 2011;11(5):330-342. doi:10.1038/nri2970PubMedGoogle ScholarCrossref
5.
Barata  JT , Durum  SK , Seddon  B .  Flip the coin: IL-7 and IL-7R in health and disease.   Nat Immunol. 2019;20(12):1584-1593. doi:10.1038/s41590-019-0479-xPubMedGoogle ScholarCrossref
6.
Francois  B , Jeannet  R , Daix  T ,  et al.  Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial.   JCI Insight. 2018;3(5):3. doi:10.1172/jci.insight.98960PubMedGoogle ScholarCrossref
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