Abstract
PURPOSE: Acute ischemic stroke (AIS) patients with COVID-19 have severe neurological symptoms and high mortality. It remains unclear how COVID-19 causes unfavorable outcomes. This study aimed to explore the possible mechanism focusing on inflammation and coagulation. PATIENTS AND METHODS: 109 AIS patients were recruited and followed up 3 months after stroke. We used binary logistic regression to investigate if COVID-19 infection is an independent prognostic factor. To analyze the link between inflammation, coagulation, and neurological outcomes, we used mediation analysis. RESULTS: Compared to the non-COVID-19 group, the COVID-19 group had significantly higher fibrinogen (FIB) (P < 0.001), APTT ratio (P < 0.001), D-dimer (P < 0.001), CRP (P < 0.001). Patients with unfavorable outcomes had a higher incidence of COVID-19 infection (P = 0.002), along with elevated levels of INR (P = 0.005), D-dimer (P < 0.001), and CRP (P = 0.012). The significant association between 3-month functional outcomes and COVID-19 tends to be insignificant (P = 0.294) after adding the covariates of inflammation and coagulation. The mediation analyses showed the APTT ratio mediated the association between COVID-19 and the 3-month outcome (percent mediation = 56.3%). The integrated pathway analysis implicated that the path of COVID-19 infection→CRP→APTT ratio→3-month outcome was significant (percent mediation = 18.7%). CONCLUSION: AIS with COVID-19 had a poorer prognosis. We delineated a more accurate mechanism by which COVID-19 influences functional outcomes: COVID-19 infection→inflammation→endogenous coagulation pathway→poor stroke outcome. This study provided new insight into the pathway mechanisms of AIS with COVID-19.