Key result
In lethal COVID-19 cases, the presence of SARS-CoV-2 in subcutaneous adipose tissue was associated with a significantly reduced survival time from initial symptoms (HR 3.7) compared to patients without virus in adipose tissue.
Observational (n=35)
No
SARS-CoV-2 can directly infect adipocytes in subcutaneous fat, suggesting adipose tissue may serve as a viral reservoir and source of inflammatory mediators in severe COVID-19.
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Autopsy data on adipose tissue in fatal COVID-19 remain hypothesis-generating; prospective studies needed before any clinical implications.
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.
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Basolo et al. (2022) conducted an observational in COVID-19 (n=35). SARS-CoV-2 positivity in subcutaneous adipose tissue vs. SARS-CoV-2 negativity in subcutaneous adipose tissue was evaluated on Survival time from initial symptoms to death (HR 3.7, 95% CI 1.1-12.5, p=0.03). In lethal COVID-19 cases, the presence of SARS-CoV-2 in subcutaneous adipose tissue was associated with a significantly reduced survival time from initial symptoms (HR 3.7) compared to patients without virus in adipose tissue.
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