Human Lung Organoids Link Molecular Mechanisms to COVID-19 Susceptibility

In a review published in Clinical and Experimental Medicine, researchers evaluated the use of human lung organoids for modeling age- and comorbidity-related differences in susceptibility to SARS-CoV-2 infection and linking molecular mechanisms to epidemiological patterns. While the COVID-19 pandemic demonstrated notable variability in disease severity—with older adults and individuals with chronic obstructive pulmonary disease, cardiovascular disease, and metabolic disorders experiencing increased vulnerability—traditional two-dimensional cell cultures and animal models have displayed limited capacity to accurately replicate human lung physiology.

Human lung organoids have emerged as an alternative platform capable of modeling human-specific cellular architecture, host-virus interactions, and disease-relevant biological responses. Investigations highlighted in the review show that lung organoid models can replicate critical hallmarks of SARS-CoV-2 infection, such as viral replication, epithelial injury, and innate immune activation, while also serving as a flexible testbed for evaluating antiviral and host-directed therapeutics under physiologically relevant conditions.

However, direct SARS-CoV-2 studies comparing lung organoids derived from younger and older donors remain limited. Current understanding of age-related mechanisms relies primarily on human tissue analyses, immune-integrated organoids, and age-stratified respiratory epithelial models rather than definitive age-stratified lung organoid experiments. Consequently, the authors conclude that while human lung organoids represent valuable mechanistic tools that strengthen the biological plausibility of epidemiological associations, translational evidence remains incomplete for donor age and several common systemic comorbidities.

Subject of Research: Human lung organoids in modeling COVID-19 susceptibility

Article Title: Human lung organoids as a translational bridge between molecular mechanisms and epidemiological patterns in COVID-19 susceptibility

Article References: Kow, C. S., Ng, N. C.-S., Mohd Rashidin, P. N. U. B., Long, C. M., & Candasamy, M. (2026). Human lung organoids as a translational bridge between molecular mechanisms and epidemiological patterns in COVID-19 susceptibility. Clinical and Experimental Medicine. https://doi.org/10.1007/s10238-026-02379-x

Image Credits: AI Generated

DOI: 10.1007/s10238-026-02379-x

Keywords: COVID-19, SARS-CoV-2, lung organoids, viral susceptibility, translational models, respiratory epithelium, comorbidities, aging, Human, lung, organoids, translational