Recovery of monocyte exhaustion is associated with resolution of lung injury in COVID-19 convalescence

10.1101/2020.10.10.20207449

medRxiv

8th February 2021

Contributing to research themes:

This research has not been peer-reviewed, and has been posted on pre-print repository medRxiv. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.


Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical syndrome COVID-19 is associated with an exaggerated immune response and monocyte infiltrates in the lungs and other peripheral tissues. It is now increasingly recognised that chronic morbidity persists in some patients. We recently demonstrated profound alterations of monocytes in hospitalised COVID-19 patients. It is currently unclear whether these abnormalities resolve or progress following patient discharge. We show here that blood monocytes in convalescent patients at their 12 week follow up, have a greater propensity to produce pro-inflammatory cytokines TNFα and IL-6, which was consistently higher in patients with resolution of lung injury as indicated by a normal chest X-ray and no shortness of breath (a key symptom of lung injury). Furthermore, monocytes from convalescent patients also displayed enhanced levels of molecules involved in leucocyte migration, including chemokine receptor CXCR6, adhesion molecule CD31/PECAM and integrins VLA-4 and LFA-1. Expression of migration molecules on monocytes was also consistently higher in convalescent patients with a normal chest X-ray. These data suggest persistent changes in innate immune function following recovery from COVID-19 and indicate that immune modulating therapies targeting monocytes and leucocyte migration may be useful in recovering COVID-19 patients with persistent symptoms.

Author list:

N.A. Scott, S.B. Knight, L. Pearmain, O. Brand, D.J. Morgan, C. Jagger, S. Khan, P. Hackney, L. Smith, M. Menon, J. E. Konkel, H. A. Shuwa, M. Franklin, V. Kästele, S. Harbach, S. Brij, A. Ustianowski, A. Uriel, G. Lindergard, N. Diar Bakerly, P. Dark, A.G. Mathioudakis, K.J. Gray, G.M. Lord, T. Felton, C. Brightling, L-P Ho, NIHR Respiratory TRC, CIRCO, K. Piper Hanley, A. Simpson, J.R. Grainger, T. Hussell, E.R. Mann