Luqian Zhan,1,* Ye Zhang,2,* Yanwei Li,3 Chenhui Lin,3 Heyu Zhang,3 Yuntao Liu,3 Jincai He3 

1Department of Neurology, Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Third Department of Cerebrovascular Disease, Cangzhou Central Hospital, Cangzhou, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jincai He; Yuntao Liu, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email hjc@wmu.edu.cn; 18267850815@163.com

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.

Keywords: COVID-19, Omicron, stroke, mediation analysis, APTT ratio