Impaired immune responses in the airways are associated with poor outcome in critically ill COVID-19 patients

Clea R Barnett; Kelsey Krolikowski; Radu Postelnicu; Vikramjit Mukherjee; Imran Sulaiman; Matthew Chung; Luis Angel; Jun-Chieh J Tsay; Benjamin G Wu; Stephen T Yeung; Ralf Duerr; Ludovic Desvignes; Kamal Khanna; Yonghua Li; Rosemary Schluger; Samaan Rafeq; Destiny Collazo; Yaa Kyeremateng; Nancy Amoroso; Deepak Pradhan; Sanchita Das; Laura Evans; Timothy M Uyeki; Elodie Ghedin; Gregg J Silverman; Leopoldo N Segal; Shari B Brosnahan

doi:10.1183/23120541.00789-2023

Impaired immune responses in the airways are associated with poor outcome in critically ill COVID-19 patients

ERJ Open Res. 2024 Jul 8;10(4):00789-2023. doi: 10.1183/23120541.00789-2023. eCollection 2024 Jul.

Authors

Clea R Barnett^{1

2}, Kelsey Krolikowski^{1

2}, Radu Postelnicu^{1

2}, Vikramjit Mukherjee^{1

2}, Imran Sulaiman^{1

2}, Matthew Chung³, Luis Angel^{1

2}, Jun-Chieh J Tsay^{1

2

4}, Benjamin G Wu^{1

2

4}, Stephen T Yeung⁵, Ralf Duerr^{2

5

6}, Ludovic Desvignes⁵, Kamal Khanna⁵, Yonghua Li^{1

2}, Rosemary Schluger^{1

2}, Samaan Rafeq^{1

2}, Destiny Collazo^{1

2}, Yaa Kyeremateng^{1

2}, Nancy Amoroso^{1

2}, Deepak Pradhan^{1

2}, Sanchita Das⁷, Laura Evans⁸, Timothy M Uyeki⁹, Elodie Ghedin³, Gregg J Silverman¹⁰, Leopoldo N Segal^{1

2

11}, Shari B Brosnahan^{1

2}

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
² Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
³ Systems Genomics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁴ Division of Pulmonary and Critical Care Medicine, VA New York Harbor Healthcare System, New York, NY, USA.
⁵ Department of Microbiology, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA.
⁶ Vaccine Center, NYU Grossman School of Medicine, New York, NY, USA.
⁷ Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁸ Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.
⁹ Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
¹⁰ Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
¹¹ Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, NYU Langone Health, New York, NY, USA.

Abstract

Introduction: Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study.

Material and methods: We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load.

Results: While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p<0.05), while there was no such association with antibody levels in the systemic circulation.

Discussion: Our data highlight the critical role of local adaptive immunity in the airways as a key defence mechanism against primary SARS-CoV-2 infection.

Abstract

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