Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery

Gao, Yiping; Zhou, Wei; Huang, Pei-Na; Liu, Hongyun; Bi, Xiaojun; Zhu, Ying; Sun, Jie; Tang, Qinghua; Li, Li; Zhang, Jun; Zhu, Wan; Cheng, Xingwang; Liu, Yani; Deng, Yansha

doi:10.3389/fmed.2022.809033

Cited by 14 publications

(11 citation statements)

References 35 publications

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“…Although the etiology of PCC is still unknown, recent studies are providing a growing increasing number of evidence that factors like viral persistence, chronic subtle inflammatory events or immune dysregulation, autoimmunity, reactivation of latent infections, deconditioning, mental factors and chronic endothelial dysfunction may all play a role 6 . Specifically, there is particular focus on chronic endotheliopathy and circulating microclots as relevant contributing factors 7 , 8 , that might explain several of the key symptoms documented such as chest pain, musculoskeletal pain, pulmonary hypoperfusion) and the well-established cardiovascular risk following SARS-CoV-2 infection. In addition, other readily available and routinely used parameters like D-Dimers, von Willebrand factors and FVIII and other routine coagulation parameters have also been used as markers of endothelial activation and also assessed in adults with PCC, showing that Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with control 9 .…”

Section: Introductionmentioning

confidence: 99%

Extended coagulation profile of children with Long Covid: a prospective study

Gennaro

Valentini

Sorrentino

et al. 2022

Sci Rep

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Emerging data suggests that endotheliopathy changes can be associated with post covid condition (PCC) in adults. Research on the matter in children is lacking. We analyzed an extended coagulation profile including biomarkers of endothelial damage in children with PCC and compared it with a control group of children that fully recovered post- SARS-CoV-2 infection. A case-control study enrolling children below 18 years of age with previous microbiologically confirmed SARS-CoV-2 infection in a pediatric post-covid unit in Italy ≥ 8 weeks after the initial infection. Samples were taken at 8 and 12 weeks after the SARS-CoV-2 diagnosis and analyzed for coagulation profiling (fibrinogen, prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimers, factor VIII coagulant activity, plasma von Willebrand factor (VWF) antigen and VWF ristocetin cofactor (RC)). We compared coagulation profiles in samples from children identified with PCC (at least one, or three or more symptoms, which could not be explained by an alternative diagnosis, at the 8- and 12-week follow-up assessment using the pediatric Long Covid International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) survey. Seventy-five children were enrolled, 49.3% were females, the median age was 10.2 (IQR 4.9) years. Forty-six (61%) of the children had at least one persisting symptom at the eight weeks post-onset, (PCC8); 39/75 (52%) had persistent symptoms for more than 12 weeks (PCC12) and 15/75(32%) had at least three persisting symptoms (PCC ≥ 3) at 12 weeks. Children with PCC presented more frequently with abnormal D-Dimer levels above the reference range compared to children that had fully recovered at the 8–12 weeks (39.1% vs. 17.2%, p = 0.04), and 12 week follow up or more (41% vs. 17.2%, p = 0.05), and in children with three or more symptoms at 12 weeks follow up compared to those that had recovered (64.3% vs. 22.2%, p = 0.002). For the other coagulation profiles, there were abnormal values detected for VWF, FVIII, RC and Fibrinogen but no significant differences between children with PCC compared to controls. Although the majority of children in our cohort showed coagulation profile within or close to normal ranges, we found that a higher proportion of children with PCC, and specifically those with a more severe spectrum characterized with three or more persisting symptoms, had abnormal D-dimer levels compared to other children that fully recovered from an acute SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

Extended coagulation profile of children with Long Covid: a prospective study

Gennaro

Valentini

Sorrentino

et al. 2022

Sci Rep

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“…Seventeen studies have examined the association of COVID‐19 with endothelial function. 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 Notably, it should be acknowledged that of the 16 studies assessing endothelial dysfunction through FMD, only four studies clearly adjusted FMD measurement for shear stress indices. Τhus, residual confounding regarding the association between endothelial dysfunction and outcomes in acute and post‐recovery COVID‐19 cannot be excluded.…”

Section: Resultsmentioning

confidence: 99%

Clinical implications of vascular dysfunction in acute and convalescent COVID‐19: A systematic review

Mavraganis

Dimopoulou

Bampatsias

et al. 2022

Eur J Clin Investigation

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Background Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID‐19). In this context, vascular impairment in COVID‐19 might be associated with clinical manifestations and could refine risk stratification in these patients. Methods This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post‐recovery COVID‐19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID‐19 and a thorough examination of vascular function. Flow‐mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post‐recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post‐recovery phase. Results All studies except for one in the acute and in the post‐recovery phase showed positive association between vascular dysfunction and COVID‐19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID‐19. Discussion Overall, a detrimental effect of COVID‐19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.

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“…In addition, it has been shown in another observational study that FMD with an optimal cut-off value of 3.43% might predict in-hospital mortality and duration of hospitalization [ 9 ]. Of note, an inverse correlation with inflammatory markers has also been demonstrated, confirming the strong association between low-grade inflammation and endothelial dysfunction, which might be predictive of future development of atherosclerosis [ 10 ]. However, no studies have assessed so far the association of post-COVID-19 endothelial function with future cardiovascular events.…”

mentioning

confidence: 82%