Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte–associated protein 4 (CTLA-4) or the programmed cell death 1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the preexistence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long-lasting disease control, yet one-third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.

Cancer immunotherapy using checkpoint blockade

Background: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, Eur...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.201807-1255ST

Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

/pdf/post-acute-covid-19-syndrome-1bat2sg5js.pdf

Post-acute COVID-19 syndrome.

The Coronavirus Disease 2019 (COVID-19) pandemic continues to have a devastating effect on the health and well-being of the global population. A critical step in the fight against COVID-19 is effective screening of infected patients, with one of the key screening approaches being radiology examination using chest radiography. It was found in early studies that patients present abnormalities in chest radiography images that are characteristic of those infected with COVID-19. Motivated by this and inspired by the open source efforts of the research community, in this study we introduce COVID-Net, a deep convolutional neural network design tailored for the detection of COVID-19 cases from chest X-ray (CXR) images that is open source and available to the general public. To the best of the authors' knowledge, COVID-Net is one of the first open source network designs for COVID-19 detection from CXR images at the time of initial release. We also introduce COVIDx, an open access benchmark dataset that we generated comprising of 13,975 CXR images across 13,870 patient patient cases, with the largest number of publicly available COVID-19 positive cases to the best of the authors' knowledge. Furthermore, we investigate how COVID-Net makes predictions using an explainability method in an attempt to not only gain deeper insights into critical factors associated with COVID cases, which can aid clinicians in improved screening, but also audit COVID-Net in a responsible and transparent manner to validate that it is making decisions based on relevant information from the CXR images. By no means a production-ready solution, the hope is that the open access COVID-Net, along with the description on constructing the open source COVIDx dataset, will be leveraged and build upon by both researchers and citizen data scientists alike to accelerate the development of highly accurate yet practical deep learning solutions for detecting COVID-19 cases and accelerate treatment of those who need it the most.

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COVID-Net: a tailored deep convolutional neural network design for detection of COVID-19 cases from chest X-ray images.

The Automated E-ILD CT Algorithm Is More Prognostic Than FVC in the Serial Assessment of Patients With Non-IPF Fibrotic Interstitial Lung Disease

OBJECTIVES
To compare the experience of COVID-protected and mixed cohort pathways in COVID-19 transmission at a tertiary referral hospital for elective CT-guided lung biopsy and ablation during the COVID-19 pandemic.


METHODS
From September 2020 to August 2021 patients admitted for elective thoracic intervention were treated at a tertiary hospital (Site 1). Site one received patients for extracorporeal membrane oxygenation (ECMO) and invasive ventilation in the treatment of COVID-19. Shared imaging, theatre, and hallway facilities were used.From April 2020 to August 2020 patients admitted for elective thoracic intervention were treated at a COVID-protected hospital (Site 2). No patients with suspected or confirmed COVID-19 were treated at Site 2.Patients were surveyed for clinical and laboratory signs of COVID-19 infection up to 30 days post-procedure.


RESULTS
At Site 1, 2 patients (2.4%) tested positive for COVID-19 at 10 and 14 days post-procedure.At Site two there were no COVID-19 positive cases within 30 days of undergoing elective thoracic intervention.


CONCLUSION
A mixed-site method for infection control could represent a pragmatic approach to the management of elective procedures during the COVID-19 pandemic or for similar illnesses.


ADVANCES IN KNOWLEDGE
Mixed-cohort infection control is possible in the prevention of nosocomial COVID-19 infection.

COVID-Protected pathways for image guided lung cancer intervention during the COVID-19 pandemic: A cohort study.

EP11.03-003 Adenocarcinoma Grade Correlates with PD-L1 and TP53, but not EGFR/KRAS Status and Diagnostic Yield: Analysis of 346 Cases

/pdf/an-unusual-case-of-intravascular-oral-nodular-fasciitis-a-2u2mkggg.pdf

An Unusual Case of Intravascular Oral Nodular Fasciitis: A Case Report/Review

IIM-ILD follows a varied clinical course. Serological profile can help predict clinical phenotype, but impact on ILD prognosis is less clear.This multicentre UK cohort study examines whether serological profile can predict mortality and change in lung function over time.Patients with IIM-ILD were identified in 3 NHS trusts from local databases. Adults with ILD meeting IIM diagnostic criteria or Interstitial Pneumonia with Autoimmune Features (IPAF) with Myositis Specific Antibodies (MSA) were included. Baseline characteristics from time of presentation were compared across antibody groups and across survivors/deceased at 2 years. Survival analysis looking at time to death (or lung transplant) for duration of available follow-up was modelled by Cox-Proportional Hazards comparing each antibody individually to all others. Models were adjusted for age, gender, ethnicity, presence of overlap CTD/malignancy, smoking and site. Regression models were also used to observe trends in lung function parameters over time.Of 430 included patients, 68% were female, 46% were of White ethnicity. 81% met IIM criteria, 19% were IPAF. Mean follow up duration was 4.3 years. Common antibodies were to Ro52, Jo1, PL12, MDA5 (n=195, 126, 44 & 32 respectively). 10% had evidence of pulmonary hypertension within 1 year of diagnosis, 4% had malignancy within 3 years.Baseline characteristics of survivors vs fatal cases at 2 years showed survivors were younger (51.4 vs 61.7 years), more likely to have never smoked (69% vs 44%), less likely to have been hospitalised at diagnosis (15% vs 52%) and had a lower Charleson Comorbidity Index. Survivors had lower CRP, higher CK & higher baseline FEV1/FVC/TLCO. Imbalance in age, BMI, CK and comorbidity status were seen across antibody groups.MDA5 had the highest adjusted hazard ratio (HR) for mortality of 4.59 (95%CI 2.10-10.01). Kaplan-Meier curve shows high early mortality in this group. Anti-synthetase antibodies (ARS) carried a reduced risk of mortality (HR 0.63), however individually Jo1 had low HR (0.61, 95%CI 0.4-0.87) and PL7 had high HR (2.07, 95%CI 1.44-2.99). RNP showed worse prognosis on adjusted analysis (HR 1.88, 95%CI 1.25-2.84) (Table 1).Regression models suggest that compared to other antibodies, %pred FVC in MDA5 improves over the first 3 years, in PL7 it drops, and in Jo1 it is no different (Figure 1). MDA5 % pred FEV1 also showed improvement, but in Ku it was lower than other antibodies from 21 months. There were no significant differences in % pred TLCO between antibodies.Table 1.AntibodynDeaths/TransplantUnivariate HRp valueMultivariate HRp valueJo1126210.56 (0.35, 0.91)0.0200.61 (0.42, 0.87)0.006PL1244100.90 (0.47, 1.73)0.7481.06 (0.90, 1.26)0.482PL726112.29 (1.22, 4.31)0.0102.07 (1.44, 2.99)<0.001EJ16*0.63 (0.15, 2.56)0.5170.65 (0.30, 1.41)0.271OJ9*0.51 (0.07, 3.68)0.5050.36 (0.01, 8.50)0.529Mi219*1.31 (0.48, 3.58)0.6030.89 (0.27, 2.90)0.848SRP16*1.00 (0.32, 3.17)1.0000.82 (0.18, 3.73)0.797MDA532112.90 (1.53, 5.49)0.0014.59 (2.10, 10.01)<0.001PMScl4080.89 (0.43, 1.85)0.7640.66 (0.40, 1.09)0.105RNP30121.48 (0.80, 2.72)0.2081.88 (1.25, 2.84)0.003Ku13*1.16 (0.37, 3.66)0.8041.78 (0.36, 8.77)0.477Negative3270.96 (0.45, 2.08)0.9240.90 (0.49, 1.65)0.740Ro52195401.13 (0.75, 1.70)0.5681.15 (0.74, 1.80)0.525All ARS215390.58 (0.38, 0.87)0.0090.63 (0.52, 0.77)<0.001* counts of < 5 suppressed for anonymityFigure 1.There is strong evidence that antibody status associates with clinical outcomes, both in terms of progression of lung disease and mortality, suggesting pathogenetic differences. MDA5 predicts a high risk of death early on in disease course, whilst Jo1 associates with lower mortality. PL7 and RNP were additional antibodies associating with higher mortality. Difference between Jo1 and PL7 highlights variation within anti-synthetase syndrome. Paradoxically, if an MDA5 positive person survived the early disease phase, there was evidence that lung function can recover, which may reflect different MDA5 subpopulations.NIL.NIL.Jennifer Hannah: None declared, Alexandra Lawrence: None declared, Jennifer Martinovic: None declared, Marium Naqvi: None declared, Saadia Sasha Ali: None declared, Carmel Stock: None declared, Cara Owens: None declared, Anand Devaraj Consultant of: Boehringer Ingelhime, Brainomix, Louise Pollard: None declared, Sangita Agarwal: None declared, Belén Atienza-Mateo: None declared, Amit Patel: None declared, Alex West: None declared, Kate Tinsley: None declared, Hasti Robbie: None declared, Felix Chua: None declared, Boris Lams: None declared, Athol Wells Speakers bureau: Boehringer Ingelheim, Roche, Veracyte, Consultant of: Boehringer Ingelheim, Roche, Veracyte, Sam Norton: None declared, James Galloway: None declared, Elisabetta Renzoni: None declared, Patrick Gordon Speakers bureau: UCB, Consultant of: Eli Lilly, Galapagos, Grant/research support from: Corbus Pharmaceuticals.

/pdf/pos1235-antibody-predictors-of-prognosis-in-idiopathic-1aoyykzo.pdf

Anand Devaraj

Papers

The Automated E-ILD CT Algorithm Is More Prognostic Than FVC in the Serial Assessment of Patients With Non-IPF Fibrotic Interstitial Lung Disease

COVID-Protected pathways for image guided lung cancer intervention during the COVID-19 pandemic: A cohort study.

EP11.03-003 Adenocarcinoma Grade Correlates with PD-L1 and TP53, but not EGFR/KRAS Status and Diagnostic Yield: Analysis of 346 Cases

An Unusual Case of Intravascular Oral Nodular Fasciitis: A Case Report/Review

Pos1235 antibody predictors of prognosis in idiopathic inflammatory myopathy associated interstitial lung disease