Defective Severe Acute Respiratory Syndrome Coronavirus 2 Immune Responses in an Immunocompromised Individual With Prolonged Viral Replication

Claire L Gordon; Olivia C Smibert; Natasha E Holmes; Kyra Y L Chua; Morgan Rose; George Drewett; Fiona James; Effie Mouhtouris; Thi H O Nguyen; Wuji Zhang; Lukasz Kedzierski; Louise C Rowntree; Brendon Y Chua; Leon Caly; Mike G Catton; Julian Druce; Michelle Sait; Torsten Seemann; Norelle L Sherry; Benjamin P Howden; Katherine Kedzierska; Jason C Kwong; Jason A Trubiano

doi:10.1093/ofid/ofab359

Defective Severe Acute Respiratory Syndrome Coronavirus 2 Immune Responses in an Immunocompromised Individual With Prolonged Viral Replication

Open Forum Infect Dis. 2021 Aug 2;8(9):ofab359. doi: 10.1093/ofid/ofab359. eCollection 2021 Sep.

Authors

Claire L Gordon^{1

2}, Olivia C Smibert^{1

3

4}, Natasha E Holmes^{1

5}, Kyra Y L Chua¹, Morgan Rose¹, George Drewett¹, Fiona James¹, Effie Mouhtouris¹, Thi H O Nguyen², Wuji Zhang², Lukasz Kedzierski^{2

6}, Louise C Rowntree², Brendon Y Chua², Leon Caly⁷, Mike G Catton⁷, Julian Druce⁷, Michelle Sait⁸, Torsten Seemann⁸, Norelle L Sherry^{1

8}, Benjamin P Howden^{1

8}, Katherine Kedzierska², Jason C Kwong^{1

2}, Jason A Trubiano^{1

3

4

9

10}

Affiliations

¹ Department of Infectious Diseases, Austin Hospital, Heidelberg, Victoria, Australia.
² Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
³ Department of Infectious Diseases, Peter McCallum Cancer Centre, Melbourne, Victoria, Australia.
⁴ National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, Victoria, Australia.
⁵ Data Analytics Research and Evaluation Centre, Austin Health and University of Melbourne, Heidelberg, Victoria, Australia.
⁶ Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁷ Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁸ Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁹ Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
¹⁰ Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.

Abstract

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in a patient with lymphoma and recent programmed death 1 (PD-1) inhibitor therapy with late onset of severe coronavirus disease 2019 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR⁺/CD38⁺ activation, interleukin 6, and interleukin 18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2-specific antibody responses were absent and SARS-CoV-2-specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

Keywords: COVID-19; SARS-CoV-2; cellular immunity; humoral immunity; immunocompromise; lymphoma.