Annexin A1 Is Associated with Adverse Clinical Outcomes in Patients with COVID-19

Severe coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation, vascular damage, and hypercoagulability. Insufficient responses of Annexin A1 (AnxA1), a pro-resolving inhibitor of neutrophil infiltration and activation, might contribute to a severe course of the disease. We longitudinally evaluated AnxA1 ' s role in terms of inflammation, vascular damage, and clinical outcomes in a large prospective cohort of patients with COVID-19. AnxA1 was measured at presentation and during follow-up in the sera of 220 consecutive patients who presented at our hospital during the first wave. AnxA1 was significantly higher in the moderate and severe cases of COVID-19 compared to the healthy controls. Elevated AnxA1 was associated with markers of inflammation and endothelial damage. AnxA1 was significantly higher in patients with thrombotic events and ICU admission. Multivariable logistic regression indicated baseline AnxA1 (per ten units) as a predictor of thrombotic events. Linear mixed models predicted that AnxA1 tended to increase more steeply over time in patients without adverse events, with a statistically significant rise in patients without thrombotic events. These findings might reflect an insufficient increase in AnxA1 as a response to the excessive hyperinflammation in COVID-19. Future studies should evaluate whether hyperinflammation could be reduced through the administration of human recombinant AnxA1 or Ac2-26 peptide.

Automated summary

Severe COVID-19 is characterized by hyperinflammation, vascular damage, and hypercoagulability. This study found that insufficient responses of Annexin A1 (AnxA1), a pro-resolving inhibitor, might contribute to the severe course of the disease. AnxA1 levels were significantly higher in moderate and severe COVID-19 cases compared to healthy controls, and elevated AnxA1 levels were associated with markers of inflammation and endothelial damage. AnxA1 was also higher in patients with thrombotic events and ICU admission. Baseline AnxA1 was identified as a predictor of thrombotic events, and the increase in AnxA1 over time was steeper in patients without adverse events.