Table 1.

Recent evidences of 3D lung cultures as robust platforms for studying the pathogenesis of SARS-CoV-2 and testing new therapeutic approaches for COVID-19

Approach	Main findings	Reference
Organoid lung model from human pluripotent stem cells infected with SARS-CoV-2	Robust induction of chemokines and cytokines. Pre- or post-treatment with imatinib and mycophenolic acid decreased SARS-CoV-2 infection	Han et al. [108]
Organoid as a model of distal lung disease for COVID-19	The basal and human alveolar epithelial type II apical-out organoids were infected by SARS-CoV-2, pointing to club cells as a new target population	Salahudeen et al. [109]
SARS-CoV-2 infected airway organoid	Investigation of the effects of viral particles in different cell types, viral replication kinetics and genetic changes, differential expression of genes, and cell profile before and after viral infection	Elbadawi et al. [111]
Organoid as a model of distal lung disease for COVID-19	Recognition of cell functional heterogeneity and progenitor identification with a progressive proliferating human tissue	Suzuki et al. [112]
Organoid lung model from human pluripotent stem cells infected with SARS-CoV-2	Evident induction of cytokines and chemokine. The treatment of the organoid with imatinib and mycophenolic acid decreased the infection by SARs-CoV-2	Han et al. [108]
Bronchial organoid composed of cryopreserved human bronchial epithelial cells	After the organoid infection by SARS-CoV-2, an intracellular viral genome, progeny virus, cytotoxicity, pyknotic cells, and moderate increase of the interferon type I was observed. The treatment of organoid with camostat promoted a reduction in the viral copies	Suzuki et al. [112]
3D cell culture technique for human alveolar type 2 3D cell cultures infected with SARS-CoV-2	A rapid viral replication and modulation of the innate endogenous immune response was observed. Also, it was possible to identify an effective complete cell infection from a single viral entry	Youk et al. [113]
3D cell culture technique for human alveolar type 3 3D cell cultures infected with SARS-CoV-2	Cellular and transcriptional changes occurred, pointing to cellular tropism in viral replication and transcription as well as a consequent host cell response	Youk et al. [113]
Normal human distal alveolar organoids infected with SARS-CoV-2	Pretreatment with hydroxychloroquine and remdesivir significantly reduced viral replication, however, this effect was more pronounced with remdesivir	Mulay et al. [114]
Lung-on-a-chip composed of human lung airway epithelium cells	Amodiaquine and toremifene significantly inhibited entry of the pseudotyped SARS-CoV-2 virus	Si et al. [36]