Objective Obesity is a recognized risk factor for the progression to severe forms of COVID-19, yet the mechanisms of the association are unclear. Methods Subcutaneous 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. Results By 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. Conclusions In 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.
【저자키워드】 COVID-19, Pathogenesis, interferon, virus, Autopsy, Immune transcriptome, BMI, 【초록키워드】 SARS-CoV-2, interferon-alpha, obesity, Genome, Transcription, interferon, progression, risk factor, RT-PCR, Adults, PCR, Features, SARS-CoV-2 genome, Control, death, pathway, Alpha, IFN, moderate, mechanism, trauma, nucleocapsid antigen, Adipose tissue, association, leukocytes, IFN-alpha, Inflammatory mediators, investigation, Deceased, severe disease, COVID-19 cases, lung parenchyma, sudden cardiac death, ACE2 gene, mediators, cytoplasm, moderate to severe, leukocyte, subcutaneous fat, characterization, Subcutaneous, Activation, cardiac death, tissue, subject, COVID-19 case, causes, alteration, specimen, upregulation, severe forms of COVID-19, adipocytes, COVID-19 cohort, adipose, immune-related genes, virus antigens, infect, adipocyte, fat, objective, controls, Cell, Result, proportion, form, appear, cause, activate, infiltrating, age and sex, parenchymal, the SARS-CoV-2, the SARS-CoV-2 genome, virus antigen, 【제목키워드】 SARS-CoV-2, Activation, adipocyte,