Monocyte Migratory Signatures Identify Acute and Convalescent COVID-19 Patients, and Are Associated with Long COVID-19 Symptoms

Background: Monocytes regulate the development and resolution of lung injury. We previously demonstrated dysregulation of blood monocytes in hospitalised COVID-19 patients. It is unknown whether monocyte abnormalities persist after discharge and their clinical significance to long COVID symptoms Aims: We aimed to assess if monocyte dysfunction in COVID-19 is associated with long COVID symptoms. Methods: Clinical data were collected from 72 patients with acute COVID-19 pneumonitis, 147 COVID-19 convalescent patients (range 8-36 weeks), and 38 healthy controls. Blood monocytes were characterised by flow cytometry. Results: Monocytes from hospitalised, acute COVID-19 patients aberrantly expressed adhesion/migration molecules, including increased monocyte chemoattractant protein 1, chemokine receptor CXCR6 and adhesion molecules integrinβ7, PSGL-1. Notably chemokine receptor CXCR2 (decreased) and CD62L (increased) expression stratified with acute COVID-19 severity. In convalescence, increased monocyte CXCR6 and PSGL1 persisted; associating with patient breathlessness. Cyclo-oxygenase 2 expression was decreased on monocytes during acute COVID-19, stratifying with disease severity, and remained low during convalescence in patients with persistent fatigue. TNFα monocyte production was enhanced in patients with mild disease during the acute phase, and in patients without long COVID symptoms. Conlusions: Persistent changes in monocytes during COVID-19 convalescence are associated with long COVID symptoms, where traditional tests of lung recovery are not. Targeting aberrant monocyte phenotypes throughout the COVID-19 time-course has biomarker & immunomodulatory therapy promise.