From angiotensin-converting enzyme 2 disruption to thromboinflammatory microvascular disease: A paradigm drawn from COVID-19

Vinci, Robert J.; Pedicino, Daniela; Andreotti, Fernando; Russo, G; d’Aiello, Alessia; Cristofaro, Raimondo De; Crea, Filippo; Liuzzo, Giovanna

doi:10.1016/j.ijcard.2020.11.016

Cited by 17 publications

(22 citation statements)

References 52 publications

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“…These findings could be explained by the multiple pathogenic mechanisms linked to the SARS-CoV-2 infection, including thrombo-inflammatory microangiopathy and angiotensin-converting enzyme (ACE) 2 disruption. 6 , 21 …”

Section: Discussionmentioning

confidence: 99%

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Optical Coherence Tomography Angiography Features in Post-COVID-19 Pneumonia Patients: A Pilot Study

Cennamo

Reibaldi

Montorio

et al. 2021

American Journal of Ophthalmology

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Purpose : To investigate retinal vessel density changes in macular and papillary regions in post SARS-CoV-2 pneumonia patients by means of optical coherence tomography angiography (OCTA). Design : Prospective, observational, cohort study. Methods : Forty eyes of 40 patients (mean age 49.7 ± 12.6) post SARS-CoV-2 infection and 40 healthy subjects were enrolled in this study. Covid-19 patients had to be fully recovered from Covid-19 pneumonia and were evaluated 6 months after Covid-19 infection. The primary outcome was the results of the OCTA study of the following vascular structures: vessel density (VD) in the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), radial peripapillary capillaries (RPC), compared to those of controls. We also evaluated the structural spectral domain (SD)-OCT parameters: ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Results : The patients showed a significant reduction in VD of the SCP in whole image and in the DCP in all sectors compared to healthy subjects (p<0.05). Covid-19 patients featured a reduced VD of the RPC compared to controls (p<0.001). No difference was found in the GCC, while the RNFL was reduced in the COVID-19 group compared to controls (p=0.012). Significant correlations were found between the RNFL and VD of the SCP, DCP, RPC and FAZ area in the Covid-19 group (p<0.05). Conclusion : OCTA showed retinal vascular changes in subjects fully recovered from Covid-19 pneumonia. These findings could be a consequence of a thrombotic microangiopathy that affected retinal structures as well as other systemic organs. OCTA could represent a valid, non-invasive biomarker of early vascular dysfunction after SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

“…Such an impairment of the microcirculatory system may lead to functional disorders in multiple organs. 5 , 6 …”

Section: Introductionmentioning

confidence: 99%

Optical Coherence Tomography Angiography Features in Post-COVID-19 Pneumonia Patients: A Pilot Study

Cennamo

Reibaldi

Montorio

et al. 2021

American Journal of Ophthalmology

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“…Anaphylatoxins also activate endothelial cells, platelets, and monocytes, leading to thrombophilia. 90 Complement activation is also known to be important in thrombotic diseases, including antiphospholipid syndrome and hypocomplementaemia, 91 and COVID-19 thrombosis shares a number of pathophysiologic mechanisms with thrombotic antiphospholipid syndrome. Several case reports describing off-label use of eculizumab, a C5a inhibitor, for patients with COVID-19 and ARDS have been published; one reported recovery of all four patients treated with eculizumab and standard of care in an ICU setting.…”

Section: Antirheumatic Drugs For the Management Of Covid-19mentioning

confidence: 99%

The role of antirheumatics in patients with COVID-19

Nissen

Sciascia

Andrade

et al. 2021

The Lancet Rheumatology

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The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.

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“… 2 In COVID-19, the cytokine storm might evoke and/or potentiate existing or new cardiac functional abnormalities, as well as trigger ACS through a thrombo-inflammatory response. 3 …”

Section: Commentmentioning

confidence: 99%

“…In general, the higher risk of severe COVID-19 disease in diabetes mellitus, obesity, and heart disease might be attributable to synergistic activation of macro- and micro-vascular thrombo-inflammatory pathways associated with both COVID-19 and cardiometabolic disease. 3 It is also plausible that other anti-inflammatory approaches, including anti-TNF-α, may be effective in the course of COVID-19 disease. 6 …”

Section: Commentmentioning

confidence: 99%