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

Background: Visceral 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. Results: Although 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. Conclusions: This study describes for the first time novel COVID-19-related features possibly underlying the unfavorable prognosis in obese SARS-CoV2-infected-subjects.

Predictors of Worse Prognosis in Young Adults Hospitalized with COVID-19 Pneumonia: A Multi-Center Italian Study (COVID-UNDER50) (preprint)

Background: Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in overall COVID-19 population, but limited information are available on their specific roles in young adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics, and role of selected prognostic predictors, in particular obesity, in a large cohort of young hospitalized patients with COVID-19 pneumonia.Methods: Nine Pulmonology Units, across North and Centre of Italy, were involved in this retrospective study. Demographic and clinical characteristics as well as radiological features were registered for all cases. Comorbidity were classified according to their known or potential association with COVID-19.Findings: A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 73 patients (27.7%), and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only significant predictors for MV in a full model adjusted for comorbidities and markers of severity. Pre-existing comorbidities, such as hypertension, diabetes and asthma, and increased D-dimer level were significantly associated with higher mortality risk, regardless of age, body mass index, and MV.Interpretation: Obesity in young adults is, per se, a strong, independent, predictor of a more complicated COVID-19, without, however, influencing in-hospital mortality. On the other hand, selected comorbidities, mainly hypertension, diabetes and asthma, significantly impact survival even in a young population, and prompt recognition of these conditions as well as a closer surveillance of this subgroup are highly recommended.Funding: none.Declaration of Interests: Prof. Bonifazi reports speaker fees from Boehringer Ingelheim and Roche, outside the submitted work; Dr. Harari reports personal fees from Roche, grants and personal fees from Actelion and Boehringer Ingelheim, outside the submitted work.Ethics Approval Statement: Anonymized data of patients included in the study cohort were retrospectively collected from electronic medical records. The study protocol complies to the ethical guidelines of the 1975 Declaration of Helsinki and it was notified and approved by the coordinator ethics committee (n. 2020131) and by each local ethics committee and the need for patient’s informed consent was waived.