The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly burdened global public health. However, the tropism of SARS-CoV-2 within the human body remains not fully understood. In this review, we overview the literature on SARS-CoV-2 infection across various human organs and tissues. We summarize the relevant specimen types, techniques for examining SARS-CoV-2 tropism, and findings at both organ/tissue and cellular levels. To systematically evaluate the evidence supporting SARS-CoV-2 tissue tropism, we establish a hierarchical classification system based on two key criteria: (1) specimen origin and (2) detection methodology. Clinical specimens obtained directly from COVID-19 patients provide the most definitive evidence, whereas organoid-derived specimens and animal models indicate potential infectivity under artificial conditions. In terms of detection methods, we prioritize viral particle identification over viral protein or RNA detection, as the latter requires further confirmation to establish productive infection. Our findings indicate that SARS-CoV-2 potentially targets multiple human organ systems, including the respiratory tract, lungs, kidneys, heart, blood vessels, pancreas, small intestine, liver, and salivary glands. By contrast, viral tropism for the central nervous system and the reproductive system remains uncertain and requires further validation. At the cellular level, we identify specific target cell types vulnerable to infection, including ciliated epithelial cells, alveolar type II pneumocytes, enterocytes, cardiomyocytes, vascular endothelial cells, renal tubular epithelial cells, and pancreatic acinar cells. Furthermore, we analyze the correlation between angiotensin-converting enzyme 2 receptor distribution patterns and viral tropism, as well as potential variations in tissue specificity among different viral variants. We expect this review to provide a comprehensive landscape of SARS-CoV-2 tropism and enhance our understanding of the life cycle and consequences of SARS-CoV-2 infection within the human body.

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