Table 1 Summary of the application of organoids to study SARS-CoV-2

Respiratory organoids

ALOs

hPSC-ALOs

ACE2 in AT2 cells;

TMPRSS2 and FURIN widely expressed^47,48,52,70

AT2 cells^47,48

Apoptosis⁵²;

upregulation of inflammatory, NF-κB signaling, and loss of the mature alveolar population⁵⁰;

induction of chemokine, TNF signaling, IL-17 signaling and cytokine–cytokine receptor interaction pathways⁴⁷

Remdesivir^50,52; antiandrogenic drugs⁵¹; imatinib, mycophenolic acid and quinacrine dihydrochloride⁴⁷; camostat/nafamostat⁴⁸; 25HC⁵⁴

Human neutralizing antibody⁵²;

EK1 peptide⁴⁸

Adult ALOs

ACE2 in AT2 cells⁵⁹;

TMPRSS2 widely expressed⁵⁵

AT2 and club cells^55,56,59

Apoptosis⁵⁹;

upregulation of type I/III interferon response^55,56;

interferon-mediated inflammatory responses, loss of surfactant proteins, apoptosis^57,67;

upregulation of epithelial cell-autonomous pro-inflammatory response⁶⁷

Remdesivir^58,67

AWOs

hPSC-AWOs

ACE2, NRP1 and TMPRSS2 in ciliated cells; FURIN and CTSL widely expressed^52,60

Ciliated cells⁶⁰ and club cells⁵²

Apoptosis⁵²;

downregulation of lipid metabolism⁵²;

upregulation of glycolysis⁵⁰

Remdesivir⁵²; GW6471, xanthohumol, 5-(tetradecyloxy)-2-furoic acid and ND-646 (ref. ⁶⁰)

Human neutralizing antibody⁵²

Adult AWOs

ACE2 in ciliated cells⁶⁰

Induction of ISGs, cytokines and chemokines⁶²;

Humanized decoy antibody (ACE2-Fc)⁶³

IOs

SIOs

hPSC-SLOs

ACE2 and TMPRSS2 in the gastrointestinal tract⁷¹

Enteroendocrine and paneth cells⁷¹

Apoptosis and a robust transcriptomic response, including ISGs⁷¹

Remdesivir⁷¹

Peptides or antibodies toward IFITM⁷²

Adult SLOs

ACE2 in enterocytes⁷⁵

Enterocytes⁷⁵

Induction of cytokines and ISGs attributed to type I and III interferon responses⁷⁵

COs

hPSC-COs

ACE2 in enterocytes⁴⁷

Enterocytes⁴⁷

Induction of cytokines and chemokines⁴⁷

Imatinib, mycophenolic acid and quinacrine dihydrochloride⁴⁷

Adult COs

ACE2 in enterocytes; TMPRSS2, FURIN and CTSL in COs⁷⁷

Enterocytes⁷⁵

Induction of pro-inflammatory pathway and interferon-mediated signaling pathway⁷⁷

ILOs

Adult ILOs

ACE2 in enterocytes^74,75; TMPRSS2, FURIN and CTSL in SLOs⁷⁷

Enterocytes⁷⁵

Induction of pro-inflammatory pathway and interferon-mediated signaling pathway⁷⁷

hPSC-KOs

ACE2 and TMPRSS2 in kidney tubules^82,116

MEDS433 (ref. ⁸³)

Human soluble ACE2 (ref. ⁸²) hrsACE2 (ref. ⁸¹)

hPSC-LOs

ACE2 in hepatocytes⁸⁴

Hepatocytes⁸⁴

Upregulation of cytokine–cytokine receptor interaction, IL-17 signaling, chemokine signaling pathway, TNF signaling and NF-κB signaling pathway; downregulation of cellular metabolism⁸⁴

Adult LOs

ACE2 in cholangiocytes⁸⁵;

TMPRSS2 is broadly expressed⁸⁵

Hepatocytes⁸⁴ and a subset of cholangiocytes⁸⁵

Induction of cytokine–cytokine receptor interaction, IL-17 signaling, chemokine signaling pathway, TNF signaling and NF-κB signaling pathway⁸⁴

Remdesivir⁶³

rsACE2 (ref. ⁶³)

hPSC-BOs

ACE2 is expressed, but low levels of TMPRSS2 were detected⁴⁸

Limited infection in cortical astrocytes⁸⁸

Innate immunity and neurodegeneration genes⁴⁸;

distribution of Tau from axons to soma, and hyperphosphorylation and neuronal death⁹⁰;

metabolic changes⁹¹

ACE2 antibodies⁹¹

hPSC-CPOs

ACE2 in mature choroid plexus cells⁹⁴;

TMPRSS2 and NRP1 in CPOs⁸⁸

Choroid plexus, astrocytes and radial glial progenitors⁹³

Induction of type I interferon astrocytic response⁹⁵;

cell death, inflammatory response and cellular function deficits⁸⁸;

epithelial damage, leakage of blood–brain barrier⁹⁴

Adult TOs

SARS-CoV-2 vaccine

hPSC-ROs

ACE2 and TMPRSS2 in hPSC-ROs⁹⁸

Adult ROs

ACE2 and TMPRSS2 in cornea, limbus, sclera and retinal pigment epithelium⁹⁹

Cornea, limbus, sclera and retinal pigment epithelium⁹⁹

Host immune response, including NF-κB signaling pathway⁹⁹

hPSC-CDOs

Upregulation of pro-inflammatory factors, including IFN-γ, IL-1β and poly(I:C), drive systolic and diastolic cardiac dysfunction¹⁰¹

INCB054329 (ref. ¹⁰¹)

hPSC-CAPOs

hrsACE2 (ref. ⁸¹)