Coronavirus disease-19: The multi-level, multi-faceted vasculopathy

Abstract

Background and aims: The new coronavirus disease (COVID-19) is a systemic disease. Mounting evidence depict signs and symptoms involving multiple organs, most of which supported by pathological data. A plausible link to these manifestations is vascular and endothelial dysfunction/damage. However, much of the current knowledge relies on opinion and incipient evidence. We aim to objectively appraise current evidence on the association between COVID-19 and vascular disease, specifically endotheliitis and vasculitis.

Methods: Two researchers independently entered the search terms COVID-19 OR SARS-CoV-2 AND vasculitis, endotheliitis OR endothelium in the following online platforms: MedRxiv and LitCovid (PubMed). The search period was set from November 1, 2019 to August 28, 2020. Manuscripts with unavailable full texts, not in English, mainly on pre-clinical data, presenting only study designs or not directly related to the topics of this review were excluded. Retrospective and prospective studies, especially longitudinal ones, were given priority to the purpose of this review. Since there was paucity of prospective controlled evidence, case reports/series were also considered.

Results: A total of 318 manuscripts were initially found. Sixty-seven (21%) were excluded: 59 (18.5%) met exclusion criteria and 8 (2.5%) were duplicates. One hundred and forty-two manuscripts (44,6%) did not provide original data and were also excluded: 35 (11%) were comments, 108 (33.9%) reviews; 1 (0.3%) position paper. One hundred and seven (33.6%) studies were considered for the present scoping review: 81 (25,5%) case reports/series; 18 (5.7%) prospective; 8 (2.5%) retrospective. Viral inclusions in endothelial cells, mononuclear cell infiltrates in the intima of small vessels and markers of endothelial cell apoptosis were demonstrated. Specificities of COVID-19 may lead to diverse vascular manifestations in different levels of the vascular bed.

Conclusions: Evidence indicates that COVID-19 targets vasculature and endothelium. However, high quality data is still lacking and studies with prospective designs and appropriately matched controls are needed.

Keywords: Coagulation; Coronavirus; Endotheliitis; Inflammation; Vascular reactivity.

Graphical abstract

Fig. 1

Flow diagram showing main appraised studies after application of inclusion and exclusion criteria.

Fig. 2

Biomarkers and clinical features of vascular damage and associated inflammation, thrombosis and vascular reactivity responses in COVID-19 according to retrospective and prospective studies in human subjects published to date. Evidence of increase in vascular damage (particularly the endothelium) seems to associate with exacerbated inflammation, thrombosis and vascular reactivity. The arrow indicates a likely positive correlation between these features. These biomarkers and clinical characteristics were extracted from the studies with the best available evidence after the application of inclusion and exclusion criteria of the present review. The studies from which the biomarkers and clinical characteristics were extracted are presented in Table 1 and obtained as outlined in Fig. 1.