COVID-19 is primarily known as a respiratory syndrome, but compelling lines of evidence have suggested the multiorgan involvement in the disease. When taking tissue samples from COVID-19 patients, strict ethical requirements must be met. This restricts the acquirable tissue samples from patients, limiting a thorough examination of tissues from various organs. Currently, the majority of COVID-19 scRNA-seq studies are limited to peripheral blood mononuclear cells (PBMCs), nasal swabs, and bronchoalveolar lavage fluid (BALF). Collection and profiling of tissue from all representative organs could provide a multi-system landscape view of COVID-19.
Recent attempts to elucidate COVID-19 pathophysiology across the human body are praiseworthy. One good tissue source is from autopsy. Remarkably, single-cell atlases of lung, kidney, liver, and heart autopsy tissue samples from COVID-19 donors were released [4, 5]. While these studies provide important insights into the biological effects across organs during severe SARS-CoV-2 infection, limitations still remain. The samples were collected from critical COVID-19 patients, most likely immunosuppressed. The findings from these patients may not be representative to moderate or severe patients. In addition, the time of tissue sampling in autopsy is much later than the time of infection, disease onset, or progression. As a result, the cell compositions and gene expression profiles of these samples might be significantly different from those in living patients.
Alternative sources of human tissues include in vitro tissue culture and organoids. Three-dimensional organoid models can mimic body tissue structure, and have been successfully applied in complex disease studies. A recent scRNA-seq study using kidney organoids revealed the injury and dedifferentiation of SARS-CoV-2 infected cells, and activation of profibrotic signaling pathways [6]. On the other hand, the cell composition and spatial distribution in organoids derived from induced pluripotent stem cells (iPSCs) do not fully resemble those in the adult organs, and the immune response cannot be modelled without an immune system in the organoid [6]. Therefore, the findings should be carefully interpreted for their implications in vivo. Cross-validation of the results from organoids and autopsy samples is highly recommended to examine the consistency.
The third approach is animal models. Animal experiments can control critical factors like viral exposure dose, duration, and route. Moreover, easy access to the tissues from multiple organs at various time points enables the investigation of spatiotemporal cell atlases, and the tracking of SARS-CoV-2 infection and host immune response dynamics from disease onset to recovery or death. Among animal models, non-human primates like macaques are ideal due to their close phylogenetic relationship with humans [7]. Moreover, rodent models like hamsters and transgenic mice are also widely used due to several advantages such as similar disease phenotype, easy breeding, experimental operation, and low cost [8]. Notably, the susceptibility to SARS-CoV-2 infection varies among species, typically with lower rates in non-human animals than humans.