Thread by @LPearmain

Hugely excited to share our paper (@mannlab) out in #ERJ (@ERSpublications) showing monocyte immune profiles identify unique features of #longCOVID symptoms and define acute hospitalised #COVID19 severity. Interested? 🧵of key messages for scientists, clinicians and patients 1/10

We studied monocyte immune profiles in acute hospitalised COVID19, and at up to 9 months post-COVID19. Healthy individuals, convalescent RSV/influenza, and progressive fibrosing ILD were used as controls (2/10)

Acute #COVID19 CXCR2 and COX-2 expression decreased with severity whilst adhesion (CD62L) and migration (ITGb7) markers increased. Other adhesion and migration molecules (notably PSGL1 and CXCR6) increased across severity. (3/10)

At follow up we analysed immune markers dysregulated in acute #COVID19 and tested persistence and association with symptoms of #longCOVID. We found unique monocyte signatures associated with different symptoms likely indicating different pathological mechanisms (4/10)

Results suggest the CXCR6-CXCL16 axis is important for monocyte recruitment to injured lung (breathless+abnormal radiology) alongside PSGL1 (important for endothelium tethering). Expression profile was replicated in patients with progressive lung fibrosis #PFILD! (5/10)

We also identified a monocyte signature associated with #COVID19 lung injury recovery! TNFa production was ⬆️ in recovery (also ⬆️ in mild acute COVID19), whilst IL-1b returned to ↔️ levels in recovery. IL-1b is ⬇️ in breathless patients and TNFa production is ⬇️ in #PFILD!(6/10)

Fatigue is debilitating in #longCOVID. We identified a fatigue specific monocyte signature where CXCR2 (➕trend CXCR1), which migrates towards CXCL8/IL-8 expression in peripheral tissues, is ⬆️ and prostaglandin generating COX-2 enzyme is ⬇️ (prev associated with CFS/ME…) (7/10)

FUTURE WORK: We will take forward work on lung injury immune signature to #pulmonaryfibrosis. Our work shows soluble serum immune mediators may provide promising biomarkers to endotype patients with #longCOVID enabling treatments/trials focussed at distinct disease mechanisms8/10

Limitations/caveats: There may be multiple mechanisms for a single symptom (e.g. breathlessness). This study included hospitalised COVID19 patients only, so caution must be used extrapolating to all #longCOVID patients. 9/10

This paper was a huge, collaborative team effort special thanks though to: all our patients, co-authors esp incredibly talented 🌟@mannlab🌟, Nick Scott (my joint 1st author, now with @HussellTracy) @PilarRiveraOrt1 and @HanleyPiper lab. ++@The_MRC (for funding me!) 10/10

Further credit to the hugely supportive environment created by @FBMH_UoM @LydiaBeckerIII @MFT_Research, @ManchesterBRC @ManchesterCRF

Link here....erj.ersjournals.com/content/early/…