Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.

Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection induced more severe cell death in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection and drug discovery.

Observe the clinical curative effect of Tanreqing injection of antibiotics in the treatment of pulmonary infection in the elderly / 中国生化药物杂志

Objective To observe the clinical curative effect of Tanreqing injection of antibiotics in the treatment of pulmonary infection in the elderly.Methods 120 cases of elderly patients with pulmonary infection from June 2015 to June 2016 in our hospital were selected, randomly divided into observation group and control group,60 cases in each group, the observation group treated with Tanreqing injection and oxygen, anti-inflammatory, expectorant therapy,the control group treated only with oxygen, anti-inflammatory, expectorant therapy, the clinical symptoms and therapeutic effects were compared between the two groups.Results After seven days of treatment, PaO2 , SaO2 and pH of the observation group were higher than those of the control group (P<0.05), the levels of PaCO2, CRP, IL-6, IL-13, LTB4 and WBC were lower than those in the control group (P<0.05); After 14 days of treatment, CRP, IL-6, IL-13 and LTB4 in the observation group were lower than those in the control group (P<0.05); The total effective rate was 75.00%in the observation group and 58.33%in the control group after 14 days of treatment.There was significant difference between the two groups (P<0.05).Conclusion Tanreqing injection combined with western medicine antibiotic treatment of elderly patients with pulmonary infection was significant,can significantly improve the clinical symptoms of patients and improve clinical efficacy .