Résumé
Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL/6 mice were acutely exposed for 3d to either ambient PM (NIST particles) and/or noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM particularly affects the lungs. Noise also increased levels of circulating stress hormones adrenaline and noradrenaline, while PM increased levels of circulating cytokines CD68 and MCP-1. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.Copyright © 2023
Résumé
Objective: SARS-CoV2 infection can lead to several clinical scenarios, named COVID-19, ranging from mild manifestations to acute respiratory distress syndrome (ARDS), coagulation alterations and endothelial dysfunction. The functional impairment of the microcirculation seems play a key role in the pathophysiology and clinical consequences of COVID-19. However, to date there is no evidence of structural microvascular damage related to COVID-19. Design and method: The aim of this study is to investigate microvascular alterations by adaptive optics and vide-ocapillaroscopy in patients recently admitted for COVID-19 and re-evaluated one year later. Methods: We enrolled 153 patients admitted between February and April 2020 at the Hospital of Montichiari (Brescia) and at the Internal Medicine Department of ASST Spedali Civili - University of Brescia for respiratory failure due to SARSCoV2- related interstitial pneumonia. Patients were evaluated two months after nalysed sation and after one year. All patients underwent a venous blood sampling for hematochemical tests, evaluation of retinal arteriolar morphology by adaptive optics, assessment of basal and total capillary density (BCD and TCD respectively) at the dorsum of the fourth finger of the non-dominant hand by videocapillaroscopy. Results: Fifty patients with completed follow-up were nalysed. An increase of internal lumen (93.8 ± 13.3 vs. 97.3 ± 14.2 micron, p < 0.001) and a reduction of wall to lumen ratio (WLR 0.30 ± 0.03 vs. 0.27 ± 0.03, p < 0.001) were observed at the follow up visit after one year (Figure). No significant differences were observed in BCD in the dorsum of the finger after one year, whereas a significant reduction in TCD was observed (p < 0.001). Microvascular changes were independent of body mass index and the presence of hypertension or diabetes mellitus. Conclusions: Preliminary data from this study show that patients with SARSCov2 infection present an improvement of microvascular structure after one year from the disease, such as a reduction in WLR of retinal arterioles. This suggests that COVID19 might induce structural alterations in the microcirculation which contribute to vascular damage. These changes do not seem to be influenced by the weight, presence of hypertension or diabetes.
Résumé
Background: SARS-CoV2 infection has been associated to a wide range of clinical scenarios, named COVID-19, ranging from acute respiratory distress syndrome to blood coagulation abnormalities and vascular manifestations related to hyper-inflammation. Recent focus has been addressed to study of microvascular alterations which may explain COVID-19 pathophysiology. Alterations in microvascular structure, identified as increased wall to lumen ratio (WLR) of retinal arterioles, have been extensively described in patients with cardiovascular diseases, such as hypertension or diabetes mellitus. Both inflammation and immune system dysregulation seem to play a role in the pathogenesis of these morphological changes. Purpose: Aim of this study was to evaluate through Adaptive Optics microvascular differences of retinal arterioles between patients experienced COVID-19 and controls. Methods: Patients were hospitalized between 28th February and 15th April at a Internal Medicine ward in a tertiary care hospital. All patients tested positive for a SARS-CoV-2 nasopharyngeal swab at admission and showed signs of pneumonia and respiratory insufficiency. Adaptive Optics, which allows a non-invasive evaluation of retinal arteriole structure, and blood chemistry exams were performed as part of follow up visits between 2 to 3 months after hospitalization. Baseline characteristics were collected through medical records. COVID-19 patients were compared to age-and sex-matched healthy subjects referred to our center between 2018 and 2019. Results: A total of 80 patients were included in this study (of which 40 were COVID-19 patients). Apart from smoking habit, other baseline characteristics (sex, age, cardiovascular risk factors and main comorbidities) did not differ between the two groups. At follow up visit COVID-19 patients showed lower values for leukocytes (6.2 vs. 7.5x103/μL, p=0.015) and lymphocytes (1.9 vs. 2.8x103/μL, p=0.002). Creatinine values were higher in patients who suffered from COVID-19 (1.0 vs 0.8 mg/dl, p=0.004-Figure 1, panel A). Adaptive Optics showed no differences in terms of internal lumen, wall thickness and WLR of retinal arterioles. However, the wall cross-sectional area (WCSA) was found to be higher in COVID-19 patients (p=0.039-Figure 1, panel B). Hypertension significantly affected both WCSA and WLR between COVID-19 and healthy individuals, while diabetes only impacted on WLR (Figure 2). Conclusion: Previous studies described the presence of leukopenia and lymphopenia during the acute phase of SARS-CoV2 infection. Our study demonstrates that these alterations persist several weeks after symptoms onset. Adaptive Optics showed microvascular alterations occurring in these patients: in particular, higher wall cross-sectional area of retinal arterioles were observed in patients after COVID-19 hospitalization, reflecting the complex pathogenic mechanisms which may explain the wide range of symptoms and clinical severity.