COVID-19 patients commonly present with neurological signs of central nervous system (CNS) and/or peripheral nervous system dysfunction. However, which neural cells are permissive to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been controversial. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively permissive to SARS-CoV-2 infection both in vitro and upon transplantation in vivo, and that SARS-CoV-2 infection triggers a DA neuron inflammatory and cellular senescence response. A high-throughput screen in hPSC-derived DA neurons identified several FDA approved drugs, including riluzole, metformin, and imatinib, that can rescue the cellular senescence phenotype and prevent SARS-CoV-2 infection. RNA-seq analysis of human ventral midbrain tissue from COVID-19 patients, using formalin-fixed paraffin-embedded autopsy samples, confirmed the induction of an inflammatory and cellular senescence signature and identified low levels of SARS-CoV-2 transcripts. Our findings demonstrate that hPSC-derived DA neurons can serve as a disease model to study neuronal susceptibility to SARS-CoV-2 and to identify candidate neuroprotective drugs for COVID-19 patients. The susceptibility of hPSC-derived DA neurons to SARS-CoV-2 and the observed inflammatory and senescence transcriptional responses suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Infectious diseases have become significant events that threaten global public health and economic development. Since the 20th century, multiple outbreaks of infectious diseases have gradually deepened humanity's understanding of viral infections, prevention and treatment. Organoids possess a high degree of similarity to human physiological states and have strong self‐organising capabilities. Research on infectious diseases based on organoids offers significant advantages in terms of availability, editability and diversity. In this perspective, we briefly introduce the development of organoids, focusing on historically significant infectious diseases that have caused fatal harm to human health, such as HIV, ZIKV, SARS‐CoV‐2 and MPXV. We further summarise relevant research on the pathogenic mechanisms of these viruses based on organoid models, host reactivity, and therapeutic strategies. Finally, we list the latest research techniques combined with organoid models, discuss the challenges faced in the development of organoids and look forward to the future prospects of organoids in vaccine and drug development.

Organoid technology, as a revolutionary biomedical tool, has shown immense potential in haematological research in recent years. By using three‐dimensional (3D) cell culture systems constructed from pluripotent stem cells (PSCs) or adult stem cells (ASCs), organoids can highly mimic the characteristics of in vivo organs, thereby offering significant potential for investigating human organ development, disease processes and treatment strategies. This review introduces the development of organoids and focuses on their progress in haematological research, including haematopoietic‐related organoids, immune‐related organoids and organoids used for studying blood system diseases. It discusses the prospects, challenges and future outlook of organoids in the field of haematology. This review aims to provide the latest advancements and future directions of organoid technology in haematological research, offering references and insights into further exploration in this field.

While COVID‐19 affects multiple organ systems, the human respiratory system is the primary viral target and main site for disease progression. In this study, spatial transcriptional assays (NanoString CosMx) are utilized to analyze both explant and autopsy samples from non‐COVID and COVID‐19 lungs, identifying the activation of proinflammatory macrophages in COVID‐19 explants. It is further developed immuno‐lung organoids comprising hPSC‐derived alveolar and airway organoids co‐cultured with macrophages to investigate the impact and underlying mechanisms of macrophage‐mediated lung damage following SARS‐CoV‐2 infection. The findings demonstrate that proinflammatory macrophages induce lung cell senescence through the THBS1–(ITGA3+ITGB1) signaling axis, a mechanism further validated using spatial transcriptomics. This study not only establishes physiologically relevant immuno‐lung organoid models for modeling macrophage‐mediated tissue damage, but also identifies a previous unrecognized role of the THBS1‐(ITGA3+ITGB1) pathway in driving lung cell senescence during infectious disease.