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Ann Med . Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions

tetano

Editor, Senior Moderator
Ann Med


. 2022 Dec;54(1):3234-3249.
doi: 10.1080/07853890.2022.2136403.
Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions


Pasquale Ambrosino[SUP] 1 [/SUP], Stefano Sanduzzi Zamparelli[SUP] 2 [/SUP], Marco Mosella[SUP] 3 [/SUP], Roberto Formisano[SUP] 1 [/SUP], Antonio Molino[SUP] 2 [/SUP], Giorgio Alfredo Spedicato[SUP] 4 [/SUP], Antimo Papa[SUP] 1 [/SUP], Andrea Motta[SUP] 5 [/SUP], Matteo Nicola Dario Di Minno[SUP] 2 [/SUP], Mauro Maniscalco[SUP] 2 6 [/SUP]



Affiliations

Abstract

Background: Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19.
Methods: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684.
Results: Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: -2.31%; 95% CI: -3.19, -1.44; p < 0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: -1.73%; 95% CI: -3.04, -0.41; p = 0.010). Interestingly, when considering studies separately based on enrolment within or after 3 months of symptom onset, results were further confirmed in both short- (MD: -2.20%; 95% CI: -3.35, -1.05; p < 0.0001) and long-term follow-up (MD: -2.53%; 95% CI: -4.19, -0.86; p = 0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: -2.09; p = 0.037).
Conclusions: Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.Key messagesThe mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated.Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist.Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19.

Keywords: Post-acute COVID-19 syndrome; disability; endothelial dysfunction; exercise; long COVID; rehabilitation.
 
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