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1.
Nat Biotechnol ; 38(8): 970-979, 2020 08.
Article in English | MEDLINE | ID: covidwho-616612

ABSTRACT

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.


Subject(s)
Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Respiratory System/pathology , Single-Cell Analysis , Transcriptome , Adult , Aged , Bronchoalveolar Lavage Fluid/virology , Cell Communication , Cell Differentiation , Coronavirus Infections/virology , Epithelial Cells/pathology , Epithelial Cells/virology , Female , Humans , Immune System/pathology , Inflammation/immunology , Inflammation/pathology , Longitudinal Studies , Male , Middle Aged , Nasopharynx/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/virology , Respiratory System/immunology , Respiratory System/virology , Severity of Illness Index
2.
Immunity ; 52(6): 905-909, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-324218

ABSTRACT

Respiratory viruses affect us throughout our lives, from infancy to old age, causing illnesses ranging from a common cold to severe pneumonia. They belong to several virus families, and although many features of infection with these diverse viruses are shared, some have unique characteristics. Here we explain what happens when we are infected by respiratory viruses, including SARS-CoV-2, which causes COVID-19.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Respiratory System/physiopathology , Adaptive Immunity , Betacoronavirus/physiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Humans , Immunity, Innate , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Respiratory System/immunology , Respiratory System/virology , Virus Physiological Phenomena , Viruses/classification
3.
Lancet Respir Med ; 8(7): 687-695, 2020 07.
Article in English | MEDLINE | ID: covidwho-197584

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.


Subject(s)
Betacoronavirus/immunology , Conjunctiva/virology , Coronavirus Infections/immunology , Immunity, Innate/immunology , Pneumonia, Viral/immunology , Respiratory System/virology , Viral Tropism/physiology , Virus Replication/physiology , Adult , Aged , Aged, 80 and over , Betacoronavirus/physiology , Conjunctiva/immunology , Conjunctiva/physiopathology , Coronavirus Infections/physiopathology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , Respiratory Mucosa/immunology , Respiratory Mucosa/physiopathology , Respiratory Mucosa/virology , Respiratory System/immunology , Respiratory System/physiopathology
4.
Cell Host Microbe ; 27(6): 883-890.e2, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-165371

ABSTRACT

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Subject(s)
Bronchoalveolar Lavage Fluid/immunology , Coronavirus Infections/immunology , Immunity, Innate , Pneumonia, Viral/immunology , Respiratory System/immunology , Bronchoalveolar Lavage Fluid/cytology , Coronavirus Infections/pathology , Cytokine Release Syndrome , Cytokines/analysis , Host-Pathogen Interactions , Humans , Interferons/metabolism , Pandemics , Pneumonia, Viral/pathology , Respiratory System/pathology
5.
Diabetes Metab Syndr ; 14(4): 489-496, 2020.
Article in English | MEDLINE | ID: covidwho-125331

ABSTRACT

BACKGROUND AND AIMS: COVID-19 is a public world crisis, however, it is a self-limited infection. In COVID-19, the strength of immune and respiratory systems is a critical element. Thus, this review was conducted to demonstrate the short and long term effects of increasing the aerobic capacity on increasing the function and strength of immune and respiratory systems, particularly those essential for overcoming COVID-19 infections and associated disorders. METHODS: This review was carried out by searching in Web of Science, Scopus, EBSCO, Medline databases. The search was conducted over clinical trials and literature and systematic reviews on the effects of increasing the aerobic capacity on the function and strength of specific immune and respiratory elements essential for overcoming COVID-19 infections. RESULTS: This review found that increasing the aerobic capacity could produce short-term safe improvements in the function of immune and respiratory systems, particularly those specific for COVID-19 infections. This could be mainly produced through three mechanisms. Firstly, it could improve immunity by increasing the level and function of immune cells and immunoglobulins, regulating CRP levels, and decreasing anxiety and depression. Secondly, it could improve respiratory system functions by acting as an antibiotic, antioxidant, and antimycotic, restoring normal lung tissue elasticity and strength. Lastly, it could act as a protective barrier to decrease COVID-19 risk factors, which helps to decrease the incidence and progression of COVID-19. CONCLUSION: This review summarizes that increasing the aerobic capacity is recommended because it has potential of improving immune and respiratory functions which would help counter COVID-19.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Exercise , Immunity, Cellular/immunology , Infection Control/methods , Oxygen/metabolism , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Respiratory System/immunology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Pneumonia, Viral/transmission , Pneumonia, Viral/virology
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