Inflammation and vascular remodeling in COVID-19 hearts.

A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + -macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations.

Guduchi Ghanavati (Ayurveda medication) improves the perceived immunity in individuals at risk of SARS-CoV-2: A Multicentred, controlled, before-and-after study.

Introduction During the COVID-19 pandemic in India, Ayurvedic medication (Guduchi Ghanavati, GG) was prescribed by Ayurveda physicians for prevention and management. This study aimed to evaluate the prophylactic effect of GG in individuals with moderate to very high risk of SARS-CoV-2. Methods A multicenter, controlled, quasi-experimental, before-and-after study was conducted on individuals at moderate to very high risk of SARS-COV-2 exposure. In the intervention group (n = 15,992), participants received GG 1 g daily for 28 days in conjunction with standard preventive guidelines (SPG), while in the control group (n = 4953), participants were asked to follow SPG only. Outcomes were the incidence of COVID-19, perceived immune status, quality of life, and safety. The perceived immune status was assessed using a brief Likert-scale questionnaire having common immune-related complaints. Results Of the 20,945 enrolled, 20,574 completed the trial (intervention: 15,729, control: 4845). The percentage of participants who reported the incidence of COVID-19 was marginally lower in the GG+SPG group (41, 0.26%) than in the SPG group (16, 0.33%), leading to 21% (95% CI, -40% to 55%) efficacy of GG. However, the decrease in incidence percentage was statistically insignificant due to the trivial incidences reported. The scores of perceived immune status quality of life improved significantly from baseline in the GG+SPG group (p < 0.001) compared to the SPG group. Conclusion GG is safe and improves perception of immune status in individuals at risk of developing SRAS-CoV-2. However, these findings are inadequate to establish that GG lowers the incidence of COVID-19 necessitating to conduct RCTs in high-risk populations. Clinical Trial Registration CTRI/2020/06/025,525.

3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography.

For the first time, we have used phase-contrast X-ray tomography to characterize the three-dimensional (3d) structure of cardiac tissue from patients who succumbed to Covid-19. By extending conventional histopathological examination by a third dimension, the delicate pathological changes of the vascular system of severe Covid-19 progressions can be analyzed, fully quantified and compared to other types of viral myocarditis and controls. To this end, cardiac samples with a cross-section of 3.5mm were scanned at a laboratory setup as well as at a parallel beam setup at a synchrotron radiation facility the synchrotron in a parallel beam configuration. The vascular network was segmented by a deep learning architecture suitable for 3d datasets (V-net), trained by sparse manual annotations. Pathological alterations of vessels, concerning the variation of diameters and the amount of small holes, were observed, indicative of elevated occurrence of intussusceptive angiogenesis, also confirmed by high-resolution cone beam X-ray tomography and scanning electron microscopy. Furthermore, we implemented a fully automated analysis of the tissue structure in the form of shape measures based on the structure tensor. The corresponding distributions show that the histopathology of Covid-19 differs from both influenza and typical coxsackie virus myocarditis.