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1.
Nature ; 602(7896): 321-327, 2022 02.
Article in English | MEDLINE | ID: covidwho-1585831

ABSTRACT

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.


Subject(s)
COVID-19/blood , COVID-19/immunology , Dendritic Cells/immunology , Interferons/immunology , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Bronchi/immunology , Bronchi/virology , COVID-19/pathology , Chicago , Cohort Studies , Disease Progression , Epithelial Cells/cytology , Epithelial Cells/immunology , Epithelial Cells/virology , Female , Humans , Immunity, Innate , London , Male , Nasal Mucosa/immunology , Nasal Mucosa/virology , SARS-CoV-2/growth & development , Single-Cell Analysis , Trachea/virology , Young Adult
3.
ATS Sch ; 2(2): 236-248, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1365983

ABSTRACT

Background: The impact of the coronavirus disease (COVID-19) pandemic extends beyond the realms of patient care and healthcare resource use to include medical education; however, the repercussions of COVID-19 on the quality of training and trainee perceptions have yet to be explored. Objective: The purpose of this study was to determine the degree of interventional pulmonology (IP) fellows' involvement in the care of COVID-19 and its impact on fellows' clinical education, procedure skills, and postgraduation employment search. Methods: An internet-based survey was validated and distributed among IP fellows in North American fellowship training programs. Results: Of 40 eligible fellows, 38 (95%) completed the survey. A majority of fellows (76%) reported involvement in the care of patients with COVID-19. Fellows training in the Northeast United States reported involvement in the care of a higher number of patients with COVID-19 than in other regions (median, 30 [interquartile range, 20-50] vs. 10 [5-13], respectively; P < 0.01). Fifty-two percent of fellows reported redeployment outside IP during COVID-19, mostly into intensive care units. IP procedure volume decreased by 21% during COVID-19 compared with pre-COVID-19 volume. This decrease was mainly accounted for by a reduction in bronchoscopies. A majority of fellows (82%) reported retainment of outpatient clinics during COVID-19 with the transition from face-to-face to telehealth-predominant format. Continuation of academic and research activities during COVID-19 was reported by 86% and 82% of fellows, respectively. After graduation, all fellows reported having secured employment positions. Conclusion: Although IP fellows were extensively involved in the care of patients with COVID-19, most IP programs retained educational activities through the COVID-19 outbreak. The impact of the decrease in procedure volume on trainee competency would be best addressed individually within each training program. These data may assist in focusing efforts regarding the education of medical trainees during the current and future healthcare crises.

5.
Nature ; 590(7847): 635-641, 2021 02.
Article in English | MEDLINE | ID: covidwho-1019856

ABSTRACT

Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.


Subject(s)
COVID-19/immunology , COVID-19/virology , Macrophages, Alveolar/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , COVID-19/genetics , Cohort Studies , Humans , Interferon-gamma/immunology , Interferons/immunology , Interferons/metabolism , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/virology , Pneumonia, Viral/genetics , RNA-Seq , SARS-CoV-2/immunology , Signal Transduction/immunology , Single-Cell Analysis , T-Lymphocytes/metabolism , Time Factors
6.
Chest ; 158(4): 1499-1514, 2020 10.
Article in English | MEDLINE | ID: covidwho-805272

ABSTRACT

BACKGROUND: The role of tracheostomy during the coronavirus disease 2019 (COVID-19) pandemic remains unknown. The goal of this consensus statement is to examine the current evidence for performing tracheostomy in patients with respiratory failure from COVID-19 and offer guidance to physicians on the preparation, timing, and technique while minimizing the risk of infection to health care workers (HCWs). METHODS: A panel including intensivists and interventional pulmonologists from three professional societies representing 13 institutions with experience in managing patients with COVID-19 across a spectrum of health-care environments developed key clinical questions addressing specific topics on tracheostomy in COVID-19. A systematic review of the literature and an established modified Delphi consensus methodology were applied to provide a reliable evidence-based consensus statement and expert panel report. RESULTS: Eight key questions, corresponding to 14 decision points, were rated by the panel. The results were aggregated, resulting in eight main recommendations and five additional remarks intended to guide health-care providers in the decision-making process pertinent to tracheostomy in patients with COVID-19-related respiratory failure. CONCLUSION: This panel suggests performing tracheostomy in patients expected to require prolonged mechanical ventilation. A specific timing of tracheostomy cannot be recommended. There is no evidence for routine repeat reverse transcription polymerase chain reaction testing in patients with confirmed COVID-19 evaluated for tracheostomy. To reduce the risk of infection in HCWs, we recommend performing the procedure using techniques that minimize aerosolization while wearing enhanced personal protective equipment. The recommendations presented in this statement may change as more experience is gained during this pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pneumonia, Viral/therapy , Respiratory Insufficiency/therapy , Tracheostomy , COVID-19 , Clinical Protocols , Consensus , Coronavirus Infections/complications , Coronavirus Infections/transmission , Humans , Pandemics , Patient Selection , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Respiratory Insufficiency/virology , SARS-CoV-2 , Societies, Medical
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