Animals ; Antibodies, Neutralizing/biosynthesis* ; Antibodies, Viral/biosynthesis* ; Body Weight/immunology* ; COVID-19/virology* ; Disease Models, Animal ; Disease Progression ; Humans ; Immunohistochemistry ; Lung/virology* ; Male ; Mesocricetus ; Nasal Cavity/virology* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Severity of Illness Index ; Viral Load

Biomarkers/blood* ; COVID-19/diagnosis* ; Chemokine CXCL10/blood* ; Humans ; Lung Diseases/virology* ; Severity of Illness Index

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.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*

Since December 2019, the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has spread to many countries around the world, developing into a global pandemic with increasing numbers of deaths reported worldwide. To data, although some vaccines have been developed, there are no ideal drugs to treat novel coronavirus pneumonia (coronavirus disease 2019 (COVID-19)). By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide, this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2. We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage (DAD) of the lungs and microthrombus formation, resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure. Although direct evidence of viral infection can also be found in other organs and tissues, the viral load is relatively small. The conclusion that the injuries of the extra-pulmonary organs are directly caused by the virus needs further investigation.
COVID-19/physiopathology* ; Human Body ; Humans ; Immune Evasion ; Lung/virology* ; Viral Load

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.
Administration, Oral ; COVID-19/virology* ; Drugs, Chinese Herbal/therapeutic use* ; Exudates and Transudates ; Female ; Humans ; Inflammation/etiology* ; Lung/pathology* ; Magnoliopsida ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Pulmonary Fibrosis/etiology* ; SARS-CoV-2

We present an unusual case of a patient with bilateral-lung transplantation due to severe coronavirus disease 2019 (COVID-19), who subsequently suffered complications with acute myocardial infarction and underwent primary percutaneous coronary intervention (PCI).
Aged ; Betacoronavirus ; China ; Coronavirus Infections ; complications ; Humans ; Lung Diseases ; surgery ; virology ; Lung Transplantation ; Male ; Pandemics ; Percutaneous Coronary Intervention ; Pneumonia, Viral ; complications ; ST Elevation Myocardial Infarction ; surgery ; virology

BACKGROUND: With the rapid spread of novel coronavirus pneumonia (NCP) worldwide and the escalation of prevention and control efforts, the routine medical needs of patients have been restricted. The aims were to investigate medical needs of lung cancer patients and their mental health status during the epidemic periods, so as to provide rational recommendations for subsequent diagnosis and treatment. METHODS: The questionnaire was sent in the form of an electronic questionnaire at 7am on 4th, March, 2020, until 7am 6th, March, 2020, 368 questionnaires were recollected from 25 provinces (autonomous regions/municipalities) in 48 h. RESULTS: Of the 368 patients, 18 patients were excluded as they didn't receive anti-tumor treatment, and 350 patients were included in the final analysis. 229 cases were treated with oral targeted drugs, and 121 cases were treated with chemotherapy or immunotherapy. 41.3% of patients treated with intravenous chemotherapy or immunotherapy experienced treatment discontinuation, and the proportion of treatment discontinuation in chemotherapy or immunotherapy was higher than those treated with oral targeted drugs (21.0%). Whether oral targeted drugs or intravenous chemotherapy or immunotherapy, more than 60% of patients experienced delays in imaging examinations. Nearly one third of patients developed new symptoms or exacerbation of existing symptoms. 26.6%-28.9% of patients have changed their treatment plans through online consultation. During novel coronavirus pneumonia, 40%-75% of lung cancer patients have mental health problems, and more than 95% of patients support government's prevention and control measures. CONCLUSIONS During the emergence of NCP, the medical needs of patients with lung cancer have not been enough, especially those who discontinued chemotherapy or immunotherapy. When medical institution resumes work, priority should be given to them. At the same time, mental health problems of patients should be valued and resolved timely.
Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Betacoronavirus ; physiology ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; virology ; Female ; Humans ; Lung Neoplasms ; drug therapy ; psychology ; Male ; Middle Aged ; Pandemics ; Pneumonia ; epidemiology ; virology ; Pneumonia, Viral ; epidemiology ; virology ; Retrospective Studies

Adaptation, Physiological ; Adenosine Monophosphate ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Administration, Intranasal ; Alanine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Betacoronavirus ; genetics ; physiology ; Chlorocebus aethiops ; Coronavirus Infections ; drug therapy ; virology ; Disease Models, Animal ; Female ; Host Specificity ; genetics ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation, Missense ; Nasal Mucosa ; virology ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; RNA, Viral ; administration & dosage ; genetics ; Turbinates ; virology ; Vero Cells ; Viral Load ; Virus Replication

The coronavirus disease 2019 (COVID-19) is a new infectious disease, which has a strong virus transmission power and complex transmission routes. This disease is prone to outbreak of cluster infection. It is difficult for medical workers to provide a better perioperative treatment for surgery patient with COVID-19 while avoiding hospital spread effectively. The perioperative management for such patients needs to fully consider the possible lung injury factors caused by anesthesia and surgery. It also needs to choose the suitable timing of the operation, carry out preoperative infection screening and evaluation, and implement lung protection strategies during and after the operation to avoid aggravating the lung injury. Meanwhile, it is necessary to pay more attention to infection prevention and control in order to avoid nosocomial infection.
Betacoronavirus ; Coronavirus Infections ; therapy ; Cross Infection ; prevention & control ; Humans ; Lung ; pathology ; virology ; Pandemics ; Perioperative Care ; Pneumonia, Viral ; therapy

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Fatal Outcome ; Hemorrhage/virology* ; Humans ; Lung/pathology* ; Myocardium/pathology* ; Pandemics ; Pneumonia, Viral/pathology* ; Retrospective Studies ; SARS-CoV-2