Severe SARS-CoV-2 infection induces a distinct nasal cytokine profile

  

View ORCID ProfileB Morton, KG Barnes, C Anscombe, K Jere, R Kamng’ona, C Brown, J Nyirenda, T Phiri, N Banda, C Van Der Veer, KS Mndolo, K Mponda,  View ORCID ProfileJ Rylance, C Phiri, J Mallewa, M Nyirenda, G Katha, P Kambiya, J Jafali, HC Mwandumba, SB Gordon, J Cornick,  View ORCID ProfileKC Jambo, Clinical, J Phulusa, M Mkandawire, S Kaimba, H Thole, S Nthala, E Nsomba, L Keyala, P Mandala, B Chinoko, M Gmeiner, V Kaudzu, S Lissauer, B Freyne, P MacPherson, TD Swarthout, PI Iroh Tam, Laboratory, S Sichone, A Ahmadu, O Kanjewa, V Nyasulu, E Chinyama, A Zuza, B Denis, E Storey, N Bondera, D Matchado, A Chande, A Chingota, C Ntwea, L Mkandawire, P Matambo, C Mhango, A Lakudzala, D Tembo, M Chaponda, P Mwenechanya, L Mvaya, J Mandolo, Data and statistics, MYR Henrion, J Chirombo, C Masesa, J Gondwe

doi: https://doi.org/10.1101/2021.02.15.21251753

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.02.15.21251753v1.full.pdf

Abstract

Understanding the host–viral interaction at the nasal mucosa, the primary site of SARS-CoV-2 infection, may provide important insights into COVID-19 pathogenesis. Here, we studied nasal and systemic immune parameters in comprehensively characterised patients hospitalised with suspected or confirmed COVID-19, and healthy community controls. PCR-confirmed COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and more likely to survive to hospital discharge than PCR−/IgG+ and PCR−/IgG− participants. PCR−/IgG+ participants exhibited a nasal and systemic cytokine signature analogous to PCR-confirmed COVID-19 participants, but had an increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. The nasal immune signature in PCR−/IgG+ and PCR-confirmed COVID-19 participants was distinct and predominated by chemokines and neutrophils. These findings demonstrate that severe COVID-19 is associated with inflammatory chemokine and neutrophil predominance in the nasal mucosa, and that PCR−/IgG+ individuals with high COVID-19 clinical suspicion have inflammatory profiles analogous to PCR-confirmed disease.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The authors thank all study participants and the staff of the Queen Elizabeth Central Hospital (QECH) for their support and co-operation during the study. This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [220757/Z/20/Z] (BM). Further support was provided by Wellcome [211433/Z/18/Z] (SBG) and National Institute for Health Research (NIHR) [16/136/46] (KCJ). KCJ is supported by an MRC African Research Leader award [MR/T008822/1]. JR is supported by a Wellcome Trust Career Development Fellowship [211098/Z/18/Z]. KB is supported by a NIH K-award (TW010853). KJ is supported by a Wellcome International Training Fellowship [201945/Z/16/Z]. A Wellcome Strategic award number 206545/Z/17/Z supports the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (SBG). The views expressed are those of the authors and not necessarily those of the UK NHS, the NIHR or the Department of Health and Social Care.

https://www.medrxiv.org/content/10.1101/2021.02.15.21251753v1