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BMJ Open Respir Res ; 8(1)2021 09.
Article in English | MEDLINE | ID: covidwho-1438096


INTRODUCTION: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). METHODS AND ANALYSIS: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. ETHICS AND DISSEMINATION: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. CONCLUSION: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.

COVID-19/complications , Lung Diseases, Interstitial , Humans , Longitudinal Studies , Lung Diseases, Interstitial/epidemiology , Observational Studies as Topic , Pandemics , Prospective Studies , United Kingdom/epidemiology
Lancet Rheumatol ; 3(6): e394-e395, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1146614
Lancet Rheumatol ; 3(3): e171-e172, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1053910
Eur Respir Rev ; 29(157)2020 Sep 30.
Article in English | MEDLINE | ID: covidwho-810447


Novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has rapidly spread throughout the world, resulting in a pandemic with high mortality. There are no effective treatments for the management of severe COVID-19 and current therapeutic trials are focused on antiviral therapy and attenuation of hyper-inflammation with anti-cytokine therapy. Severe COVID-19 pneumonia shares some pathological similarities with severe bacterial pneumonia and sepsis. In particular, it disrupts the haemostatic balance, which results in a procoagulant state locally in the lungs and systemically. This culminates in the formation of microthrombi, disseminated intravascular coagulation and multi-organ failure. The deleterious effects of exaggerated inflammatory responses and activation of coagulation have been investigated in bacterial pneumonia and sepsis and there is recognition that although these pathways are important for the host immune response to pathogens, they can lead to bystander tissue injury and are negatively associated with survival. In the past two decades, evidence from preclinical studies has led to the emergence of potential anticoagulant therapeutic strategies for the treatment of patients with pneumonia, sepsis and acute respiratory distress syndrome, and some of these anticoagulant approaches have been trialled in humans. Here, we review the evidence from preclinical studies and clinical trials of anticoagulant treatment strategies in bacterial pneumonia and sepsis, and discuss the importance of these findings in the context of COVID-19.

Anticoagulants/therapeutic use , Betacoronavirus , Blood Coagulation/physiology , Coronavirus Infections/blood , Pneumonia, Bacterial/blood , Pneumonia, Viral/blood , Sepsis/blood , Biomarkers/blood , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , SARS-CoV-2
Lancet Rheumatol ; 2(10): e589-e590, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-741637
Lancet Respir Med ; 8(8): 822-830, 2020 08.
Article in English | MEDLINE | ID: covidwho-599200


The COVID-19 pandemic is a global public health crisis, with considerable mortality and morbidity exerting pressure on health-care resources, including critical care. An excessive host inflammatory response in a subgroup of patients with severe COVID-19 might contribute to the development of acute respiratory distress syndrome (ARDS) and multiorgan failure. Timely therapeutic intervention with immunomodulation in patients with hyperinflammation could prevent disease progression to ARDS and obviate the need for invasive ventilation. Granulocyte macrophage colony-stimulating factor (GM-CSF) is an immunoregulatory cytokine with a pivotal role in initiation and perpetuation of inflammatory diseases. GM-CSF could link T-cell-driven acute pulmonary inflammation with an autocrine, self-amplifying cytokine loop leading to monocyte and macrophage activation. This axis has been targeted in cytokine storm syndromes and chronic inflammatory disorders. Here, we consider the scientific rationale for therapeutic targeting of GM-CSF in COVID-19-associated hyperinflammation. Since GM-CSF also has a key role in homoeostasis and host defence, we discuss potential risks associated with inhibition of GM-CSF in the context of viral infection and the challenges of doing clinical trials in this setting, highlighting in particular the need for a patient risk-stratification algorithm.

Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Immunologic Factors/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome/prevention & control , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Disease Progression , Humans , Immunomodulation , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Respiratory Distress Syndrome/virology , SARS-CoV-2