Visceral fat inflammation and fat embolism are associated with lung’s lipidic hyaline membranes in subjects with COVID-19

Abstract

Background Preliminary data suggested that fat embolism could explain the importance of visceral obesity as a critical determinant of coronavirus disease-2019 (COVID-19). Methods We performed a comprehensive histomorphologic analysis of autoptic visceral adipose tissue (VAT), lungs and livers of 19 subjects with COVID-19 (COVID-19+), and 23 people without COVID-19 (controls). Human adipocytes (hMADS) infected with SARS-CoV-2 were also studied. Results Although there were no between-group differences in body-mass-index and adipocytes size, a higher prevalence of CD68+ macrophages among COVID-19+ VAT was detected ( p = 0.005) and accompanied by crown-like structures presence, signs of adipocytes stress and death. Consistently, human adipocytes were successfully infected by SARS-CoV-2 in vitro and displayed lower cell viability. Being VAT inflammation associated with lipids spill-over from dead adipocytes, we studied lipids distribution by ORO. Lipids were observed within lungs and livers interstitial spaces, macrophages, endothelial cells, and vessels lumen, features suggestive of fat embolism syndrome, more prevalent among COVID-19+ ( p < 0.001). Notably, signs of fat embolism were more prevalent among people with obesity ( p = 0.03) independently of COVID-19 diagnosis, suggesting that such condition may be an obesity complication exacerbated by SARS-CoV-2 infection. Importantly, all infected subjects’ lungs presented lipids-rich (ORO+) hyaline membranes, formations associated with COVID-19-related pneumonia, present only in one control patient with non-COVID-19-related pneumonia. Importantly, transition aspects between embolic fat and hyaline membranes were also observed. Conclusions This study confirms the lung fat embolism in COVID-19+ patients and describes for the first time novel COVID-19-related features possibly underlying the unfavorable prognosis in people with COVID-19 and obesity.

Obesity and COVID-19: What are the Consequences?

“…In patients who died from COVID-19, a higher prevalence of CD68-positive M1 macrophages in visceral adipose tissue was observed compared to control patients without COVID-19. As expected, these were accompanied by crown-like structures, signs of adipocyte stress and death [46]. Previously, obesity was shown to increase the duration of type A influenza virus shedding in adults, whereas this was not the case for type B influenza [53].…”

“…blood hypercoagulability [44], and vitamin D deficiency [45], which are furthermore all risk factors for COVID-19 severity [46].…”

Adipose Tissue Inflammation and Pulmonary Dysfunction in Obesity

“…Similarly, there is evidence that dysfunctional adipose tissue and systemic inflammation induced by obesity can contribute to airway inflammation and pulmonary disease [17]. In this context, several studies have shown that pulmonary dysfunction and metabolic disorders in patients with COVID-19 were directly correlated with excess VAT mass [89,90]; in contrast, an inverse correlation was observed with the adiponectin/leptin serum ratio [91]. These findings suggest that an altered adipokine-secretion profile from dysfunctional VAT in obese subjects could promote lung function decline in patients with COVID-19.…”

COVID-19 Medical and Pharmacological Management in the European Countries Compared to Italy: An Overview

“…A systematic review of 60 consecutive forensic and 42 clinical COVID-19 post-mortem cases (>100 autopsies) reported that the major cause of diffuse alveolar damage is an immuno-thrombotic and thromboembolic mechanism driven by SARS-CoV-2-mediated inflammation [ 77 , 82 ]. The recent evidence by Colleluori et al on post-mortem COVID-19 cases assessed that using NSAIDs is paramount to addressing COVID-19 as early as possible, as the inflammation-driven machinery leads to lung fat embolism, causing an unfavorable prognosis of severely affected COVID-19 patients [ 83 ].…”