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1.
Nat Rev Drug Discov ; 21(1): 60-78, 2022 01.
Article in English | MEDLINE | ID: covidwho-2008294

ABSTRACT

Integrins are cell adhesion and signalling proteins crucial to a wide range of biological functions. Effective marketed treatments have successfully targeted integrins αIIbß3, α4ß7/α4ß1 and αLß2 for cardiovascular diseases, inflammatory bowel disease/multiple sclerosis and dry eye disease, respectively. Yet, clinical development of others, notably within the RGD-binding subfamily of αv integrins, including αvß3, have faced significant challenges in the fields of cancer, ophthalmology and osteoporosis. New inhibitors of the related integrins αvß6 and αvß1 have recently come to the fore and are being investigated clinically for the treatment of fibrotic diseases, including idiopathic pulmonary fibrosis and nonalcoholic steatohepatitis. The design of integrin drugs may now be at a turning point, with opportunities to learn from previous clinical trials, to explore new modalities and to incorporate new findings in pharmacological and structural biology. This Review intertwines research from biological, clinical and medicinal chemistry disciplines to discuss historical and current RGD-binding integrin drug discovery, with an emphasis on small-molecule inhibitors of the αv integrins.


Subject(s)
Integrins/antagonists & inhibitors , Integrins/metabolism , Small Molecule Libraries/pharmacology , Small Molecule Libraries/therapeutic use , Animals , Drug Discovery/methods , Humans , Protein Binding/drug effects
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330329

ABSTRACT

Introduction Shared characteristics between COVID-19 and pulmonary fibrosis, including symptoms, genetic architecture, and circulating biomarkers, suggests interstitial lung disease (ILD) development may be associated with SARS-CoV-2 infection. Methods The UKILD Post-COVID study planned interim analysis was designed to stratify risk groups and estimate the prevalence of Post-COVID Interstitial Lung Damage (ILDam) using the Post-HOSPitalisation COVID-19 (PHOSP-COVID) Study. Demographics, radiological patterns and missing data were assessed descriptively. Bayes binomial regression was used to estimate the risk ratio of persistent lung damage >10% involvement in linked, clinically indicated CT scans. Indexing thresholds of percent predicted DLco, chest X-ray findings and severity of admission were used to generate risk strata. Number of cases within strata were used to estimate the amount of suspected Post-COVID ILDam. Results A total 3702 people were included in the UKILD interim cohort, 2406 completed an early follow-up research visit within 240 days of discharge and 1296 had follow-up through routine clinical review. We linked the cohort to 87 clinically indicated CTs with visually scored radiological patterns (median 119 days;interquartile range 83 to 155, max 240), of which 74 people had ILDam. ILDam was associated with abnormal chest X-ray (RR 1.21 95%CrI 1.05;1.40), percent predicted DLco<80% (RR 1.25 95%CrI 1.00;1.56) and severe admission (RR 1.27 95%CrI 1.07;1.55). A risk index based on these features suggested 6.9% of the interim cohort had moderate to very-high risk of Post-COVID ILDam. Comparable radiological patterns were observed in repeat scans >90 days in a subset of participants. Conclusion These interim data highlight that ILDam was not uncommon in clinically indicated thoracic CT up to 8 months following SARS-CoV-2 hospitalisation. Whether the ILDam will progress to ILD is currently unknown, however health services should radiologically and physiologically monitor individuals who have Post-COVID ILDam risk factors.

4.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326588

ABSTRACT

Reports of new-onset diabetes and diabetic ketoacidosis in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2, the virus that causes COVID-19, is directly cytotoxic to pancreatic islet beta cells. This would require binding and entry of SARS-CoV-2 into host beta cells via cell surface co-expression of ACE2 and TMPRSS2, the putative receptor and effector protease, respectively. To define ACE2 and TMPRSS2 expression in the human pancreas, we examined six transcriptional datasets from primary human islet cells and assessed protein expression by immunofluorescence in pancreata from donors with and without diabetes. ACE2 and TMPRSS2 transcripts were low or undetectable in pancreatic islet endocrine cells as determined by bulk or single cell RNA sequencing, and neither protein was detected in alpha or beta cells from these donors. Instead, ACE2 protein was expressed in the islet and exocrine tissue microvasculature and also found in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. The absence of significant ACE2 and TMPRSS2 co-expression in islet endocrine cells reduces the likelihood that SARS-CoV-2 directly infects pancreatic islet beta cells through these cell entry proteins.

5.
Lancet Respir Med ; 9(11): 1275-1287, 2021 11.
Article in English | MEDLINE | ID: covidwho-1514340

ABSTRACT

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.


Subject(s)
COVID-19 , Health Status , Mental Health , Acute Disease , Adult , Aged , COVID-19/complications , Cognition , Comorbidity , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology
6.
Thorax ; 76(Suppl 2):A68-A69, 2021.
Article in English | ProQuest Central | ID: covidwho-1506087

ABSTRACT

P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.

7.
Nat Commun ; 12(1): 4314, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1310804

ABSTRACT

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.


Subject(s)
Lung Diseases/genetics , SARS-CoV-2/physiology , Transcriptome , Virus Internalization , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/genetics , COVID-19/pathology , Chronic Disease , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Immunity, Innate/genetics , Inflammation/genetics , Lung/metabolism , Lung/pathology , Lung Diseases/pathology , SARS-CoV-2/pathogenicity , Virus Replication/genetics
8.
International Journal of Behavioral Nutrition & Physical Activity ; 18(1):57, 2021.
Article in English | MEDLINE | ID: covidwho-1209333

ABSTRACT

BACKGROUND: The 2008 Great Recession significantly impacted economies and individuals globally, with potential impacts on food systems and dietary intake. We systematically reviewed evidence on the impact of the Great Recession on individuals' dietary intake globally and whether disadvantaged individuals were disproportionately affected. METHODS: We searched seven databases and relevant grey literature through June 2020. Longitudinal quantitative studies with the 2008 recession as the exposure and any measure of dietary intake (energy intake, dietary quality, and food/macronutrient consumption) as the outcome were eligible for inclusion. Eligibility was independently assessed by two reviewers. The Newcastle Ottawa Scale was used for quality and risk of bias assessment. We undertook a random effects meta-analysis for changes in energy intake. Harvest plots were used to display and summarise study results for other outcomes. The study was registered with PROSPERO (CRD42019135864). RESULTS: Forty-one studies including 2.6 million people met our inclusion criteria and were heterogenous in both methods and results. Ten studies reported energy intake, 11 dietary quality, 34 food intake, and 13 macronutrient consumption. The Great Recession was associated with a mean reduction of 103.0 cal per adult equivalent per day (95% Confidence Interval: - 132.1, - 73.9) in high-income countries (5 studies) and an increase of 105.5 cal per adult per day (95% Confidence Interval: 72.8, 138.2) in middle-income countries (2 studies) following random effects meta-analysis. We found reductions in fruit and vegetable intake. We also found reductions in intake of fast food, sugary products, and soft drinks. Impacts on macronutrients and dietary quality were inconclusive, though suggestive of a decrease in dietary quality. The Great Recession had greater impacts on dietary intake for disadvantaged individuals. CONCLUSIONS: The 2008 recession was associated with diverse impacts on diets. Calorie intake decreased in high income countries but increased in middle income countries. Fruit and vegetable consumption reduced, especially for more disadvantaged individuals, which may negatively affect health. Fast food, sugary products, and soft drink consumption also decreased which may confer health benefits. Implementing effective policies to mitigate adverse nutritional changes and encourage positive changes during the COVID-19 pandemic and other major economic shocks should be prioritised.

9.
Techne: Research in Philosophy and Technology ; 25(1):162-183, 2021.
Article in English | Scopus | ID: covidwho-1187124

ABSTRACT

Few sectors are more affected by COVID-19 than higher education. There is growing recognition that reopening the densely populated communities of higher education will require surveillance technologies, but many of these technologies pose threats to the privacy of the very students, faculty, and staff they are meant to protect. The authors have a history of working with our institution’s governing bodies to provide ethical guidance on the use of technologies, especially including those with significant implications for privacy. Here, we draw on that experience to provide guidelines for using surveillance technologies to reopen college campuses safely and responsibly, even under the specter of covid. We aim to generalize our recommendations, so they are sensitive to the practical realities and constraints that universities face. © 2021 Philosophy Documentation Center. All rights reserved.

10.
Thorax ; 76(SUPPL 1):A159-A160, 2021.
Article in English | EMBASE | ID: covidwho-1146642

ABSTRACT

Home handheld spirometry enables repeated measurements of forced vital capacity (FVC), offering opportunities for longitudinal evaluation in interstitial lung disease (ILD). Whilst recent studies have not blinded participants to their home spirometry performance, they support feasibility in participants with idiopathic pulmonary fibrosis (IPF). However little data exists for the utility of home spirometry in non-IPF ILD. We assess correlation, agreement and non-inferiority of blinded daily home spirometry over three months relative to hospital spirometry, informing the feasibility of remote monitoring as a primary endpoint in clinical settings. We utilised interim data from the ongoing INJUSTIS study (NCT03670576). Participants with fibrotic ILD were offered a handheld spirometer linked via bluetooth to a smartphone application and asked to perform daily, blinded FVC for three months. Hospital spirometry was concurrently obtained at baseline and three months. Home FVC values were based on week averages at study timepoints. Correlation, Bland-Altman plots and equivalence tests were used to compare baseline, 3 month and delta. Sensitivity analysis was performed where test dates matched. 82 participants with ILD were included. Mean age was 69.8±8 years, 72.3% were male and mean FVC was 2.96 ±0.88L. Median adherence to daily spirometry was 79.5%, four participants had an adherence <10%. At the time of (Table presented) censorship, 35 participants had 3 month data for both home and hospital spirometry, 45 participants had date-matched values. High correlation was observed between home and hospital spirometry at baseline (r=0.86) and three-months (r=0.81), changes in 3 month DFVC were not correlated (r=-0.09). At least 90% of home spirometry values were within agreement limits of hospital values at baseline (mean difference -0.31L/min,95%CI -0.39;-0.22), three-months (-0.13L/min,95%CI -0.31;0.05) and 3 month DFVC (-0.03L/min,95%CI 0.13;0.20). Home values more frequently underestimated hospital values but non-inferiority was confirmed within 400 ml. Home spirometry in fibrotic ILD is feasible and non-inferior to hospital spirometry. This is particularly relevant in the context of the current covid-19 pandemic, where an urgent need has arisen to consider remote monitoring of lung function. Adherence to daily spirometry was high in blinded participants, but variability in home values was observed when using week-averages, supporting importance of longitudinal modelling for clinical endpoint precision.

11.
EBioMedicine ; 65: 103277, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1131243

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease, characterized by progressive lung scarring. Severe COVID-19 is associated with substantial pneumonitis and has a number of shared major risk factors with IPF. This study aimed to determine the genetic correlation between IPF and severe COVID-19 and assess a potential causal role of genetically increased risk of IPF on COVID-19 severity. METHODS: The genetic correlation between IPF and COVID-19 severity was estimated with linkage disequilibrium (LD) score regression. We performed a Mendelian randomization (MR) study for IPF causality in COVID-19. Genetic variants associated with IPF susceptibility (P<5 × 10-8) in previous genome-wide association studies (GWAS) were used as instrumental variables (IVs). Effect estimates of those IVs on COVID-19 severity were gathered from the GWAS meta-analysis by the COVID-19 Host Genetics Initiative (4,336 cases & 623,902 controls). FINDINGS: We detected a positive genetic correlation of IPF with COVID-19 severity (rg=0·31 [95% CI 0·04-0·57], P = 0·023). The MR estimates for severe COVID-19 did not reveal any genetic association (OR 1·05, [95% CI 0·92-1·20], P = 0·43). However, outlier analysis revealed that the IPF risk allele rs35705950 at MUC5B had a different effect compared with the other variants. When rs35705950 was excluded, MR results provided evidence that genetically increased risk of IPF has a causal effect on COVID-19 severity (OR 1·21, [95% CI 1·06-1·38], P = 4·24 × 10-3). Furthermore, the IPF risk-allele at MUC5B showed an apparent protective effect against COVID-19 hospitalization only in older adults (OR 0·86, [95% CI 0·73-1·00], P = 2·99 × 10-2) . INTERPRETATION: The strongest genetic determinant of IPF, rs35705950 at MUC5B, seems to confer protection against COVID-19, whereas the combined effect of all other IPF risk loci seem to confer risk of COVID-19 severity. The observed effect of rs35705950 could either be due to protective effects of mucin over-production on the airways or a consequence of selection bias due to (1) a patient group that is heavily enriched for the rs35705950 T undertaking strict self-isolation and/or (2) due to survival bias of the rs35705950 non-IPF risk allele carriers. Due to the diverse impact of IPF causal variants on SARS-CoV-2 infection, with a possible selection bias as an explanation, further investigation is needed to address this apparent paradox between variance at MUC5B and other IPF genetic risk factors. FUNDING: Novo Nordisk Foundation and Oak Foundation.


Subject(s)
COVID-19/pathology , Genetic Predisposition to Disease/genetics , Idiopathic Pulmonary Fibrosis/pathology , COVID-19/genetics , Genome-Wide Association Study , Humans , Idiopathic Pulmonary Fibrosis/genetics , Lung/pathology , Mucin-5B/genetics , Polymorphism, Single Nucleotide/genetics , Risk , SARS-CoV-2 , Severity of Illness Index
13.
Journal of the National Medical Association ; 112(5):S44, 2020.
Article in English | EMBASE | ID: covidwho-988459

ABSTRACT

Dr. Melvin Jenkins is a pioneer of the NMA Pediatric Section, having several firsts in research, academics, and clinical care. In recognition of his numerous accomplishments, the Pediatric Section named its annual luncheon “The Melvin E. Jenkins, MD Annual Lecture and Luncheon,” to be given by the president-elect of the American Academy of Pediatrics (AAP). This year’s presentation by President-Elect Dr. Lee Beers included a discussion of the importance of early childhood brain development and early experiences to lifelong health and wellness. Both positive and adverse early experiences can shape development, and there are concrete actions and interventions which can promote early positive experiences. However, despite buffering by many familial and community strengths and supports, children of color are at increased risk for adverse early experiences, in large part due to interpersonal, institutional and systemic racism. The significant impacts of the COVID-19 pandemic on young children, with a special emphasis on the amplifying effects on children and families of color were discussed. Early childhood brain development impacts long term health outcomes, and the promotion of positive early childhood experiences can influence more equitable outcomes for children and families, particularly children of color. The AAP Equity Agenda was introduced and discussed by AAP President Dr. Sara Goza and AAP CEO Mark Del Monte, specifically on how to support pediatricians as they address the impacts of racism on their patients and on the professional practice of medicine. Finally, the history of the relationship between the AAP and NMA Pediatric Section, and specifically the importance of addressing past wrongs and strengthening the collaboration, was highlighted by Dr. Renee Jenkins. Reference: The National Academies Press, Communities in Action, Pathways to Health Equity The Impact of Racism on Child and Adolescent Health, Pediatrics 2019, Trent et al.

15.
bioRxiv ; 2021 Jan 04.
Article in English | MEDLINE | ID: covidwho-900764

ABSTRACT

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD epithelial cells expressed higher levels of genes linked directly to the efficiency of viral replication and innate immune response. Additionally, we identified basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.

16.
Thorax ; 75(11): 1009-1016, 2020 11.
Article in English | MEDLINE | ID: covidwho-729414

ABSTRACT

The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/therapy , Lung Diseases/therapy , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Respiration Disorders/therapy , Algorithms , COVID-19 , Coronavirus Infections/diagnosis , Humans , Lung Diseases/diagnosis , Lung Diseases/virology , Pandemics , Pneumonia, Viral/diagnosis , Respiration Disorders/diagnosis , Respiration Disorders/virology , SARS-CoV-2
17.
Lancet Respir Med ; 8(8): 807-815, 2020 08.
Article in English | MEDLINE | ID: covidwho-276695

ABSTRACT

In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million people had been confirmed infected, with over 1 million in the USA alone, and over 215 000 deaths. The symptoms associated with COVID-19 are diverse, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome. The major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF who contract SARS-CoV-2 infection, and the scientific rationale for their continuation or cessation, is poorly defined. Furthermore, several licensed and potential antifibrotic compounds have been assessed in models of acute lung injury and viral pneumonia. Data from previous coronavirus infections such as severe acute respiratory syndrome and Middle East respiratory syndrome, as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection. Antifibrotic therapies that are available or in development could have value in preventing severe COVID-19 in patients with IPF, have the potential to treat severe COVID-19 in patients without IPF, and might have a role in preventing fibrosis after SARS-CoV-2 infection.


Subject(s)
Antifibrinolytic Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Pulmonary Fibrosis/drug therapy , COVID-19 , Coronavirus Infections/complications , Humans , Pandemics , Pneumonia, Viral/complications , Pulmonary Fibrosis/virology , SARS-CoV-2
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