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      Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: a case series

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          Abstract

          Background

          Prolonged SARS-CoV-2 shedding has been described in immunocompromised COVID-19 patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable.

          Methods

          Five critically ill COVID-19 patients with severe defects in cellular immune responses, high SARS-CoV-2 viral RNA loads, and no respiratory improvement were treated with interferon gamma, 100 μg subcutaneously, thrice weekly. Bronchial secretion was collected every 48 hours for routine diagnostic SARS-CoV-2 RT-PCR and viral culture.

          Findings

          Interferon gamma administration was followed by a rapid decline in SARS-CoV-2 load and a positive to negative viral culture conversion. Four patients recovered and no signs of hyperinflammation were observed.

          Conclusions

          Interferon gamma may be considered as adjuvant immunotherapy in a subset of immunocompromised COVID-19 patients.

          Funding

          AvL and RvC are supported by National Institute of Health [R01AI145781]. GJO and RPvR are supported by a VICI grant [016.VICI.170.090] from the Dutch Research Council (NWO). WFA is supported by Clinical Fellowship grant [#9071561]) of Netherlands Organization for Health Research and Development. MGN is supported by an ERC Advanced Grant [#833247] and a Spinoza Grant of the Netherlands Organization for Scientific Research.

          Graphical Abstract

          Abstract

          Van Laarhoven and Kurver et al. report five COVID-19 patients with impaired cellular immunity and persistently high SARS-CoV-2 loads, treated with last-resort interferon gamma immunotherapy, which was followed by viral clearance in five and clinical recovery in four patients. No signs of hyperinflammation were observed.

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          Author and article information

          Journal
          Med (N Y)
          Med (N Y)
          Med (New York, N.y.)
          Elsevier Inc.
          2666-6359
          2666-6340
          21 September 2021
          21 September 2021
          Affiliations
          [1 ]Department of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
          [2 ]Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
          [3 ]Department of Intensive Care Medicine, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands
          [4 ]Department of Nephrology, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands
          [5 ]Department of Medical Microbiology, Radboud Centre for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands
          [6 ]Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, 53115, Bonn, Germany
          Author notes
          []Corresponding author
          [7]

          Lead contact

          [#]

          These authors contributed equally

          [$]

          These authors contributed equally

          Article
          S2666-6340(21)00318-4
          10.1016/j.medj.2021.09.003
          8452508
          34568856
          0d464d51-a40f-4567-aae2-750bd0a77f6f
          © 2021 Elsevier Inc.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 28 June 2021
          : 6 August 2021
          : 15 September 2021
          Categories
          Case Report

          covid-19,sars-cov-2,immunocompromised,interferon gamma,immunotherapy

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