Adipose Tissue in SARS-CoV-2 Viral Tropism, Viral Replication, and the Concept of a Viral Reservoir: An Update.

Since the onset of the COVID-19 pandemic, obesity has been consistently associated with worse clinical outcomes. In 2020, we hypothesized that adipose tissue (AT) might serve as a viral reservoir and amplifier of immune responses in SARS-CoV-2 infection. Five years on, accumulating evidence supports this hypothesis. Recent autopsy and in vitro studies support that SARS-CoV-2 disseminates to and may replicate within human adipocytes. While several studies have detected SARS-CoV-2 RNA and proteins in AT, the recovery of infectious virus from this tissue has not yet been demonstrated. This remains a critical gap in our understanding of SARS-CoV-2 viral tropism and replication within adipocytes. Viral entry is mediated via angiotensin-converting enzyme-2 and neuropilin-1 receptors. Infected AT exhibits immune cell infiltration and cytokine activation, implicating it in systemic inflammation. Persistent viral RNA in AT correlates with prolonged metabolic dysfunction. These findings highlight the dual role of AT as a potential viral reservoir and immunometabolic organ. Understanding these mechanisms is critical to mitigating the long-term impact of COVID-19 and guiding responses to future pandemics involving metabolically active tissues.