Abstract
ObjectiveObesity is a recognized risk factor for the progression to severe forms of COVID-19, yet the mechanisms of the association are unclear.MethodsSubcutaneous abdominal adipose tissue specimens of subjects deceased from COVID-19 (n = 23) were compared to those of controls dying abruptly from causes other than infectious (accidental trauma, sudden cardiac death). Alterations of lung parenchyma consistent with moderate to severe disease were detected in all COVID-19 cases, not in controls. Investigations included: histopathologic features, detection of virus antigens and genome, characterization of infiltrating leukocytes, transcription levels of immune-related genes.ResultsBy RT-PCR, the SARS-CoV-2 genome was detected in the adipose tissue of 13/23 (56%) cases of the COVID-19 cohort. The virus nucleocapsid antigen was detected in the cytoplasm of 1–5% adipocytes in 12/12 COVID-19 cases that were virus-positive by PCR in the adipose tissue (one case could not be assessed due insufficient tissue). The adipose tissue of COVID-19 cases showed leukocyte infiltrates and upregulation of the interferon-alpha pathway. After adjusting for age and sex, the activation score of IFN-alpha was directly related with transcription levels of the ACE2 gene, a key entry factor of SARS-CoV-2.ConclusionsIn lethal COVID-19 cases, the SARS-CoV-2 nucleocapsid antigen has been detected in a sizeable proportion of adipocytes, showing that the virus may directly infect the parenchymal cells of subcutaneous fat. Infection appears to activate the IFN alpha pathway and to attract infiltrating leukocytes. Due to the huge numbers of adipocytes in adults, the adipose tissue represents a significant reservoir for SARS-CoV-2 and an important source of inflammatory mediators.
Highlights
The white adipose tissue (WAT) communicates with other tissues to regulate metabolism both centrally and peripherally through secretion of adipocyte-derived peptide hormones, inflammatory mediators and signaling lipids [1–3]
Among COVID-19 cases, the virus genome was detected in abdominal WAT of 13/23 (56%) subjects
Uninfected controls and COVID-19 cases whose WAT was SARS-CoV-2-negative by PCR were not stained by antibodies to the virus nucleocapsid antigen
Summary
The white adipose tissue (WAT) communicates with other tissues to regulate metabolism both centrally and peripherally through secretion of adipocyte-derived peptide hormones, inflammatory mediators and signaling lipids [1–3]. In addition to releasing regulators of glucose and lipid metabolism, WAT cells (adipocytes, stromal cells, resident innate lymphoid cells, dendritic cells, monocyte-derived macrophages) produce hormones (e.g., leptin, adiponectin, resistin, apelin), growth factors (e.g., FGF21, BMPs, TGF-beta, VEGFs, PDGF) and cytokines (e.g., TNF, IL6, IL13, CCL2)[1, 2]. Obesity could contribute in multiple ways to the evolution of infection: (a) down-modulating the antiviral responses [6]; (b) releasing lipids that promote endothelial dysfunction and sustain intravascular coagulation [7]; (c) disrupting leptin and insulin signaling, intensifying the inflammatory response [8]; (d) promoting enhanced expression of SARS-CoV-2 receptors [9]; (e) representing a large reservoir for virus replication with increased shedding of virus and inflammatory mediators [10]
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