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Visceral Fat Inflammation and Fat Embolism are associated with Lung's Lipidic Hyaline Membranes in COVID-19 patients

Colleluori, G.; Graciotti, L.; Pesaresi, M.; Di Vincenzo, A.; Perugini, J.; Di Mercurio, E.; Caucci, S.; Bagnarelli, P.; Zingaretti, C. M.; Nisoli, E.; Menzo, S.; Tagliabracci, A.; Ladoux, A.; Dani, C.; Giordano, A.; Cinti, S.

2021-11-01 pathology
10.1101/2021.10.30.466586 bioRxiv
Show abstract

BackgroundVisceral obesity is a critical determinant of severe coronavirus disease-2019 (COVID-19). Methods: In this study, we performed a comprehensive histomorphologic analysis of autoptic visceral adipose tissues (VAT), lungs and livers of 19 COVID-19 and 23 non-COVID-19 subjects. ResultsAlthough there were no between-groups differences in body-mass-index and adipocytes size, higher prevalence of CD68+ macrophages in COVID-19 subjects 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-CoV2 in vitro and displayed lower cell viability. Being VAT inflammation associated with lipids spill-over from dead adipocytes, we studied lipids distribution employing Oil-Red-O staining (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 individuals (p<0.001). Notably, signs of fat embolism were more prevalent among obese (p=0.03) independently of COVID-19 diagnosis, suggesting that such condition may be an obesity complication, exacerbated by SARS-CoV2 infection. Importantly, all infected subjects lungs presented lipids-rich (ORO+) hyaline membranes, formations associated with COVID-19-related pneumonia, present only in one control with non-COVID-19 pneumonia. ConclusionsThis study describes for the first time novel COVID-19-related features possibly underlying the unfavorable prognosis in obese SARS-CoV2-infected-subjects.

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