Obesity causes various structural, hemodynamic, and metabolic alterations in the kidney. Most of these are likely to be compensatory responses to the systemic increase in metabolic demand that is seen with obesity. In some cases, however, renal injury becomes clinically apparent as a result of compensatory failure. Obesity-related glomerulopathy is the best known of such disease states. Factors that may sensitize obese individuals to renal compensatory failure and associated injury include the severity and number of obesity-associated conditions or complications, including components of metabolic syndrome, and the mismatch of body size to nephron mass, due to nephron reductions of congenital or acquired origin.
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.
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