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1: Clinical characteristics of 2019 novel coronavirus infection in China
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Posted 09 Feb 2020

Clinical characteristics of 2019 novel coronavirus infection in China
211,101 downloads medRxiv respiratory medicine

Wei-jie Guan, Zheng-yi Ni, Yu Hu, Wen-hua Liang, Chun-quan Ou, Jian-xing He, Lei Liu, Hong Shan, Chun-liang Lei, David S.C. Hui, Bin Du, Lan-juan Li, Guang Zeng, Kwok-Yung Yuen, Ru-chong Chen, Chun-li Tang, Tao Wang, Ping-yan Chen, Jie Xiang, Shi-yue Li, Jin-lin Wang, Zi-jing Liang, Yi-xiang Peng, Li Wei, Yong Liu, Ya-hua Hu, Peng Peng, Jian-ming Wang, Ji-yang Liu, Zhong Chen, Gang Li, Zhi-jian Zheng, Shao-qin Qiu, Jie Luo, Chang-jiang Ye, Shao-yong Zhu, Nan-shan Zhong, on behalf of China Medical Treatment Expert Group for 2019-nCoV

BackgroundSince December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. MethodsWe extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. ResultsThe median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). ConclusionsThe 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

2: High Resolution CHEST CT(HRCT) Evaluation in Patients Hospitalized with COVID-19 Infection
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Posted 28 May 2020

High Resolution CHEST CT(HRCT) Evaluation in Patients Hospitalized with COVID-19 Infection
47,565 downloads medRxiv respiratory medicine

Maulin Patel, Junad Chowdhury, Matthew Zheng, Osheen Abramian, Steven Verga, Huaqing Zhao, Nicole Patlakh, David Fleece, Nicholas Montecalvo, Gary Cohen, Maruti Kumaran, Chandra Dass, Gerard Criner

Abstract Introduction: Currently the main diagnostic modality for COVID-19 (Coronavirus disease-2019) is reverse transcriptase polymerase chain reaction (RT-PCR) via nasopharyngeal swab which has high false negative rates. We evaluated the performance of high-resolution computed tomography (HRCT) imaging in the diagnosis of suspected COVID-19 infection compared to RT-PCR nasopharyngeal swab alone in patients hospitalized for suspected COVID-19 infection. Methods: This was a retrospective analysis of 324 consecutive patients admitted to Temple University Hospital. All hospitalized patients who had RT-PCR testing and HRCT were included in the study. HRCTs were classified as Category 1, 2 or 3. Patients were then divided into four groups based on HRCT category and RT-PCR swab results for analysis. Results: The average age of patients was 59.4 (+15.2) years and 123 (38.9%) were female. Predominant ethnicity was African American 148 (46.11%). 161 patients tested positive by RT-PCR, while 41 tested positive by HRCT. 167 (52.02%) had category 1 scan, 63 (19.63%) had category 2 scan and 91 (28.35%) had category 3 HRCT scans. There was substantial agreement between our radiologists for HRCT classification ({kappa} = 0.64). Sensitivity and specificity of HRCT classification system was 77.6 and 73.7 respectively. Ferritin, LDH, AST and ALT were higher in Group 1 and D-dimers levels was higher in Group 3; differences however were not statistically significant. Conclusion: Due to its high infectivity and asymptomatic transmission, until a highly sensitive and specific COVID-19 test is developed, HRCT should be incorporated into the assessment of patients who are hospitalized with suspected COVID-19.

3: Heparin therapy improving hypoxia in COVID-19 patients - a case series
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Posted 20 Apr 2020

Heparin therapy improving hypoxia in COVID-19 patients - a case series
36,864 downloads medRxiv respiratory medicine

Elnara Marcia Negri, Bruna Piloto, Luciana Kato Morinaga, Carlos Viana Poyares Jardim, Shari Anne El-Dash Lamy, Marcelo U. Ferreira, Elbio Antonio D'Amico, Daniel Deheinzelin

INTRODUCTION: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting intravascular coagulation as a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in Sao Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. RESULTS AND DISCUSSION: PaO2/FiO2 ratio increased significantly over the 72 hours following the start of anticoagulation, from 254(SD 90) to 325(SD 80), p=0.013, and 81% of the patients were discharged home within a mean time of 11.4 (SD 7.9) days. Most mechanically ventilated patients (67%) were extubated within 12.5(SD 5.7) days. There were no bleeding complications or fatal events. Even though this uncontrolled case series does not offer absolute proof of DIC as the underlying mechanism of respiratory failure in COVID-19, patients positive response to tailored dose heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these very sick patients while we await the results of further prospective controlled studies.

4: Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis
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Posted 27 Feb 2020

Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis
26,252 downloads medRxiv respiratory medicine

Wei-jie Guan, Wen-hua Liang, Yi Zhao, Heng-rui Liang, Zi-sheng Chen, Yi-min Li, Xiao-qing Liu, Ru-chong Chen, Chun-li Tang, Tao Wang, Chun-quan Ou, Li Li, Ping-yan Chen, Ling Sang, Wei Wang, Jian-fu Li, Cai-chen Li, Li-min Ou, Bo Cheng, Shan Xiong, Zheng-yi Ni, Jie Xiang, Yu Hu, Lei Liu, Hong Shan, Chun-liang Lei, Yi-xiang Peng, Li Wei, Yong Liu, Ya-hua Hu, Peng Peng, Jian-ming Wang, Ji-yang Liu, Zhong Chen, Gang Li, Zhi-jian Zheng, Shao-qin Qiu, Jie Luo, Chang-jiang Ye, Shao-yong Zhu, Lin-ling Cheng, Feng Ye, Shi-yue Li, Jin-ping Zheng, Nuo-fu Zhang, Nan-shan Zhong, Jian-xing He, on behalf of China Medical Treatment Expert Group for COVID-19

ObjectiveTo evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19). DesignRetrospective case studies Setting575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020. Main outcomes and measuresEpidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. ResultsOf the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P<0.05). After adjusting for age and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities. ConclusionComorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes. HighlightsO_ST_ABSWhat is already known on this topicC_ST_ABS- Since November 2019, the rapid outbreak of coronavirus disease 2019 (COVID-19) has recently become a public health emergency of international concern. There have been 79,331 laboratory-confirmed cases and 2,595 deaths globally as of February 25th, 2020 - Previous studies have demonstrated the association between comorbidities and other severe acute respiratory diseases including SARS and MERS. - No study with a nationwide representative cohort has demonstrated the spectrum of comorbidities and the impact of comorbidities on the clinical outcomes in patients with COVID-19. What this study adds- In this nationwide study with 1,590 patients with COVID-19, comorbidities were identified in 399 patients. Comorbidities of COVID-19 mainly included hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency. - The presence of as well as the number of comorbidities predicted the poor clinical outcomes (admission to intensive care unit, invasive ventilation, or death) of COVID-19. - Comorbidities should be taken into account when estimating the clinical outcomes of patients with COVID-19 on hospital admission.

5: Patient outcomes after hospitalisation with COVID-19 and implications for follow-up; results from a prospective UK cohort.
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Posted 14 Aug 2020

Patient outcomes after hospitalisation with COVID-19 and implications for follow-up; results from a prospective UK cohort.
19,597 downloads medRxiv respiratory medicine

David Arnold, Fergus W Hamilton, Alice Milne, Anna Morley, Jason Viner, Marie Attwood, Alan Noel, Samuel Gunning, Jessica Hatrick, Sassa Hamilton, Karen T Elvers, Catherine Hyams, Anna Bibby, Ed Moran, Huzaifa Adamali, James Dodd, Nick A Maskell, Shaney L Barratt

Background: COVID19 causes a wide spectrum of disease. However, the incidence and severity of sequelae after the acute infection is uncertain. Data measuring the longer-term impact of COVID19 on symptoms, radiology and pulmonary function are urgently needed to inform patients and plan follow up services. Methods: Consecutive patients hospitalised with COVID19 were prospectively recruited to an observational cohort with outcomes recorded at 28 days. All were invited to a systematic follow up at 12 weeks, including chest radiograph, spirometry, exercise test, blood tests, and health-related quality of life (HRQoL) questionnaires. Findings: Between 30th March and 3rd June 2020, 163 patients with COVID19 were recruited. Median hospital length of stay was 5 days (IQR 2 to 8) and 30 patients required ITU or NIV, 19 patients died. At 12 weeks post admission, 134 were available for follow up and 110 attended. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) with reduced HRQoL. Only patients with disease sufficiently severe to warrant oxygen therapy in hospital had abnormal radiology, clinical examination or spirometry at follow up. Thirteen (12%) patients had an abnormal chest X-ray with improvement in all but 2 from admission. Eleven (10%) had restrictive spirometry. Blood test abnormalities had returned to baseline in the majority (104/110). Interpretation: Patients with COVID19 remain highly symptomatic at 12 weeks, however, clinical abnormalities requiring action are infrequent, especially in those without a supplementary oxygen requirement during their acute illness. This has significant implications for physicians assessing patients with persistent symptoms, suggesting that a more holistic approach focussing on rehabilitation and general wellbeing is paramount. Funding: Southmead Hospital Charity

6: Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China
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Posted 06 Mar 2020

Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China
10,125 downloads medRxiv respiratory medicine

Min Cao, Dandan Zhang, Youhua Wang, Yunfei Lu, Xiangdong Zhu, Ying Li, Honghao Xue, Yunxiao Lin, Min Zhang, Yiguo Sun, Zongguo Yang, Jia Shi, Yi Wang, Chang Zhou, Yidan Dong, Longping Peng, Ping Liu, Steven M. Dudek, Zhen Xiao, Hongzhou Lu

BackgroundSince mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai. MethodsCases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. ResultsOf 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5{degrees} C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. ConclusionsIn this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5{degrees}C, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease.

7: Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support
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Posted 03 Apr 2020

Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support
7,320 downloads medRxiv respiratory medicine

Giuseppe Gritti, Federico Raimondi, Diego Ripamonti, Ivano Riva, Francesco Landi, Leonardo Alborghetti, Marco Frigeni, Marianna Damiani, Caterina Micò, Stefano Fagiuoli, Roberto Cosentini, Ferdinando Luca Lorini, Lucia Gandini, Luca Novelli, Jonathan P Morgan, Benjamin M.J. Owens, Karan Kanhai, Gordana Tonkovic Reljanovic, Marco Rizzi, Fabiano Di Marco, Alessandro Rambaldi

COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SAR-CoV-2), resulting in symptoms, such as fever, cough, and shortness of breath. The SARS-CoV-2 virus has also been suggested to initiate a cytokine storm in patients with COVID-19 evidenced by elevated cytokines, such as interleukin-6 (IL-6) and C-reactive protein (CRP). We report preliminary data from 21 patients with COVID-19 who developed pneumonia/acute respiratory distress syndrome (ARDS) and participated in a compassionate-use program at Papa Giovanni XXIII hospital in Bergamo, Italy. All 21 patients received intravenous siltuximab - a chimeric mAb that binds to and blocks the effect of IL-6 - at a dose ranging between 700 to 1,200 mg (median 900 mg). The median age of patients treated was 64 years, and all patients were followed for a median of eight days. Serum CRP levels reduced in all 16 patients with available data following treatment. An improvement in the clinical condition was observed in 33% (7/21) of patients, 43% (9/21) of patients stabilized as evidenced by no clinically relevant change in their condition, and 24% (5/21) experienced a worsening in their condition. Of those patients who experienced a worsening in their condition, one patient died, and one patient experienced a cerebrovascular event. This analysis is presented to inform the medical community of the potential role of siltuximab in treating patients with ARDS secondary to SARS-CoV-2 infection, and a cohort study with patients treated with standard therapy in our hospital is ongoing, and will report the 30-day mortality rates upon completion.

8: Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China
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Posted 06 Mar 2020

Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China
6,801 downloads medRxiv respiratory medicine

Guqin Zhang, Chang Hu, Linjie Luo, Fang Fang, Yongfeng Chen, Jianguo Li, Zhiyong Peng, Huaqin Pan

RationaleIn late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease. ObjectivesTo study the epidemiology, clinical features and outcomes of patients with COVID-19. Methodswe performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. Measurements and Main ResultsThe median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. ConclusionsThe COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

9: Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition
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Posted 29 Feb 2020

Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition
6,462 downloads medRxiv respiratory medicine

Jing Li, Yinghua Zhang, Fang Wang, Bing Liu, Hui Li, Guodong Tang, Zhigang Chang, Aihua Liu, Chunyi Fu, Jing Gao

ObjectiveTo compare the sex differences in the clinical findings among patients with severe coronavirus disease 2019 (COVID-19). MethodsWe retrospectively collected data of 47 patients diagnosed as severe type of COVID-19 from February 8 to 22, 2020, including demographics, illness history, physical examination, laboratory test, management, and compared differences between men and women. ResultsOf the 47 patients, 28 (59.6%) were men. The median age was 62 years, and 30 (63.8%) had comorbidities. The initial symptoms were mainly fever (34 [72.3%]), cough (36 [76.6%]), myalgia (5 [10.6%]) and fatigue (7 [14.9%]). Procalcitonin level was higher in men than in women (0.08 vs. 0.04ng/ml, p=0.002). N-terminal-pro brain natriuretic peptide increased in 16 (57.1%) men and 5 (26.3%) women (p=0.037). Five men (17.9%) had detected positive influenza A antibody, but no women. During 2-week admission, 5 (17.9%) men and 1 (5.3%) woman were reclassified into the critical type due to deterioration. Mortality was 3.6% in men and 0 in women respectively. Four (21.1%) women and one man (3.6%) recovered and discharged from hospital. ConclusionSex differences may exist in COVID-19 patients of severe type. Men are likely to have more complicated clinical condition and worse in-hospital outcomes as compared to women.

10: A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China
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Posted 27 Mar 2020

A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China
5,921 downloads medRxiv respiratory medicine

Ying Zhou, Zhen Yang, Yanan Guo, Shuang Geng, Gao Shan, Shenglan Ye, Yi Hu, Yafei Wang

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, Hubei, China. This study sought to elucidate a novel predictor of disease severity in patients with coronavirus disease-19 (COVID-19) cased by SARS-CoV-2. MethodsPatients enrolled in this study were all hospitalized with COVID-19 in the Central Hospital of Wuhan, China. Clinical features, chronic comorbidities, demographic data, and laboratory and radiological data were reviewed. The outcomes of patients with severe pneumonia and those with non-severe pneumonia were compared using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) to explore clinical characteristics and risk factors. The receiver operating characteristic curve was used to screen optimal predictors from the risk factors and the predictive power was verified by internal validation. ResultsA total of 377 patients diagnosed with COVID-19 were enrolled in this study, including 117 with severe pneumonia and 260 with non-severe pneumonia. The independent risk factors for severe pneumonia were age [odds ratio (OR): 1.059, 95% confidence interval (CI): 1.036-1.082; p < 0.001], N/L (OR: 1.322, 95% CI: 1.180-1.481; p < 0.001), CRP (OR: 1.231, 95% CI: 1.129-1.341; p = 0.002), and D-dimer (OR: 1.059, 95% CI: 1.013-1.107; p = 0.011). We identified a product of N/L*CRP*D-dimer as having an important predictive value for the severity of COVID-19. The cutoff value was 5.32. The negative predictive value of less than 5.32 for the N/L*CRP*D-dimer was 93.75%, while the positive predictive value was 46.03% in the test sets. The sensitivity and specificity were 89.47% and 67.42%. In the training sets, the negative and positive predictive values were 93.80% and 41.32%, respectively, with a specificity of 70.76% and a sensitivity of 89.87%. ConclusionsA product of N/L*CRP*D-dimer may be an important predictor of disease severity in patients with COVID-19.

11: Rapid Open Development and Clinical Validation of Multiple New 3D-Printed Nasopharyngeal Swabs in Response to the COVID-19 Pandemic
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Posted 17 Apr 2020

Rapid Open Development and Clinical Validation of Multiple New 3D-Printed Nasopharyngeal Swabs in Response to the COVID-19 Pandemic
5,312 downloads medRxiv respiratory medicine

Cody J Callahan, Rose Lee, Kate Zulauf, Lauren Tamburello, Keneth P Smith, Joe Previtera, Annie Cheng, Alex Green, Ahmed Abdul Azim, Amanda Yano, Nancy Doraiswami, James Kirby, Ramy Arnaout

Abstract The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck in the way of high-sensitivity virological testing for COVID-19. To address this crisis, we designed and executed an innovative, radically cooperative, rapid-response translational-research program that brought together healthcare workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a rigorous multi-step preclinical evaluation on 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital's drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control ({kappa}=0.85-0.89). Cycle-threshold (Ct) values were not significantly different between each prototype and the control, supporting the new swabs' non-inferiority (Mann-Whitney U [MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. The swabs are available to order (http://printedswabs.org). Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.

12: Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis
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Posted 27 Mar 2020

Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis
4,391 downloads medRxiv respiratory medicine

Jaber S Alqahtani, Tope Oyelade, Abdulelah M Aldhahir, Saeed M. Alghamdi, Mater Almehmadi, Abdullah S Alqahtani, Shumonta Quaderi, Swapna Mandal, John R Hurst

BackgroundCoronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarised the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers. MethodsWe systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesised a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI). ResultsIn total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 6.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4- 2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%. ConclusionAlthough COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

13: Current tobacco smoking and risk from COVID-19: results from a population symptom app in over 2.4 million people
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Posted 21 May 2020

Current tobacco smoking and risk from COVID-19: results from a population symptom app in over 2.4 million people
4,277 downloads medRxiv respiratory medicine

Nicholas S Hopkinson, Niccolò Rossi, Julia El-Sayed Moustafa, Anthony Laverty, Jennifer K Quint, Maxim Freidin, Alessia Visconti, Benjamin Murray, Marc Modat, Sebastien Ourselin, Kerrin Small, Richard Davies, Jonathan Wolf, Timothy Spector, Claire J Steves, Mario Falchi

Background: The association between current tobacco smoking, the risk of developing COVID-19 and the severity of illness is an important information gap. Methods: UK users of the COVID Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, were asked to log symptoms daily from 24th March 2020 to 23rd April 2020. Participants reporting that they did not feel physically normal were taken through a series of questions, including 14 potential COVID-19 symptoms and any hospital attendance. The main study outcome was the association between current smoking and the development of classic symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness. The number of concurrent COVID-19 symptoms was used as a proxy for severity. In addition, association of subcutaneous adipose tissue expression of ACE2, both the receptor for SARS-CoV-2 and a potential mediator of disease severity, with smoking status was assessed in a subset of 541 twins from the TwinsUK cohort. Results: Data were available on 2,401,982 participants, mean(SD) age 43.6(15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834,437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to develop symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR[95%CI] 1.14[1.10 to 1.18]; >5 symptoms 1.29[1.26 to 1.31]; >10 symptoms 1.50[1.42 to 1.58]. Smoking was associated with reduced ACE2 expression in adipose tissue (Beta(SE)= -0.395(0.149); p=7.01x10-3). Interpretation: These data are consistent with smokers having an increased risk from COVID-19.

14: Predictors of CPAP outcome in hospitalised COVID-19 patients
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Posted 16 Jun 2020

Predictors of CPAP outcome in hospitalised COVID-19 patients
4,099 downloads medRxiv respiratory medicine

Yasser Noeman Ahmed, Sriya Gokaraju, Duncan Powrie, Dora Amran, Iman El Sayed, Ashraf Roshdy

Introduction: Throughout March - April 2020, many patients with COVID-19 presented to Southend University Hospital with Acute Hypoxaemic Respiratory Failure (AHRF). Patients were managed in a Specialist Respiratory High Dependency Unit. We present our experience on the usage of continuous positive airway pressure (CPAP) therapy and possible indicators of its success in this patient group. Methods: Data from patients (n=89) requiring mechanical ventilation during the months of March to April 2020, were retrospectively collected and analysed. 37 patients received IMV (Invasive Mechanical Ventilation) without a CPAP trial beforehand. 52 patients underwent a CPAP trial, of which 21 patients successfully avoided intubation and ITU admission. Results: The 52 patients, prior to receiving CPAP had significant respiratory failure as evidenced by a low PaO2: FiO2 (PFR) (mean +/- SD 123 +/- 60 mmHg) and mean SpO2:FiO2 (SFR) (mean +/- SD: 140+/- 50). The main indicators of CPAP success were: higher SFR before and after CPAP, lower respiratory rate (RR) , lower Neutrophil to Lymphocyte ratio (NLR) and higher PFR prior to CPAP. Discussion: CPAP proved successful in 40% of COVID-19 patients presenting with AHRF. SFR, PFR, RR and NLR are predictors of such success. SFR can be used for effective real time monitoring of patients before and after CPAP to identify likelihood of success. Based on our results, we have suggested a modified CPAP management protocol in COVID-19. These findings can guide future studies and will allow improved triage of patients to either CPAP or IMV, in the event of a future COVID peak.

15: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes
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Posted 01 May 2020

Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes
3,956 downloads medRxiv respiratory medicine

Radu Crisan-Dabija, Cristina Grigorescu, Cristina Alice Pavel, Bogdan Artene, Iolanda Valentina Popa, Andrei Cernomaz, Alexandru Burlacu

Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.

16: Reduced ICU demand with early CPAP and proning in COVID-19 at Bradford: a single centre cohort
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Posted 09 Jun 2020

Reduced ICU demand with early CPAP and proning in COVID-19 at Bradford: a single centre cohort
3,838 downloads medRxiv respiratory medicine

Tom Lawton, Kate M Wilkinson, Aaron Corp, Rabeia Javid, Laura MacNally, Michael McCooe, Elizabeth Newton

Background Guidance in COVID-19 respiratory failure has favoured early intubation, with concerns over the use of CPAP. We adopted early CPAP and self-proning, and evaluated the safety and efficacy of this approach. Methods This retrospective observational study included all patients with a positive COVID-19 PCR, and others with high clinical suspicion. Our protocol advised early CPAP and self-proning for severe cases, aiming to prevent rather than respond to deterioration. CPAP was provided outside critical care by ward staff supported by physiotherapists and an intensive critical care outreach program. Data were analysed descriptively and compared against a large UK cohort (ISARIC). Results 559 patients admitted before 1/May/20 were included. 376 were discharged alive, and 183 died. 165 patients (29.5%) received CPAP, 40 (7.2%) were admitted to critical care and 28 (5.0%) were ventilated. Hospital mortality was 32.7%, and 50% for critical care. Following CPAP, 62% of patients with S:F or P:F ratios indicating moderate or severe ARDS, who were candidates for escalation, avoided intubation. Figures for critical care admission, intubation and hospital mortality are lower than ISARIC, whilst critical care mortality is similar. Following ISARIC proportions we would have admitted 92 patients to critical care and intubated 55. Using the described protocol, we intubated 28 patients from 40 admissions, and remained within our expanded critical care capacity. Conclusion Bradford's protocol produced good results despite our population having high levels of co-morbidity and ethnicities associated with poor outcomes. In particular we avoided overloading critical care capacity. We advocate this approach as both effective and safe.

17: Integrated single cell analysis of human lung fibrosis resolves cellular origins of predictive protein signatures in body fluids
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Posted 27 Jan 2020

Integrated single cell analysis of human lung fibrosis resolves cellular origins of predictive protein signatures in body fluids
3,810 downloads medRxiv respiratory medicine

Christoph H Mayr, Lukas M. Simon, Gabriela Leuschner, Meshal Ansari, Philipp E. Geyer, Ilias Angelidis, Maximilian Strunz, Pawandeep Singh, Nikolaus Kneidinger, Frank Reichenberger, Edith Silbernagel, Stephan Böhm, Heiko Adler, Anne Hilgendorff, Michael Lindner, Antje Prasse, Jürgen Behr, Matthias Mann, Oliver Eickelberg, Fabian J Theis, Herbert B Schiller

Single cell genomics enables characterization of disease specific cell states, while improvements in mass spectrometry workflows bring the clinical use of body fluid proteomics within reach. The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we leverage single cell RNA-seq and proteomic analysis of large pulmonary fibrosis patient cohorts to identify disease specific changes on the cellular level and their corresponding reflection in body fluid proteomes. We discovered and validated transcriptional changes in 45 cell types across three patient cohorts that translated into distinct changes in the bronchoalveolar lavage fluid and plasma proteome. These protein signatures correlated with diagnosis, lung function, smoking and injury status. Specifically, the altered expression of a novel marker of lung health, CRTAC1, in alveolar epithelium is robustly reflected in patient plasma. Our findings have direct implications for future non-invasive prediction and monitoring of pathological cell state changes in patient organs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/20018358v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@174e5b2org.highwire.dtl.DTLVardef@1940cf1org.highwire.dtl.DTLVardef@dda827org.highwire.dtl.DTLVardef@4aab59_HPS_FORMAT_FIGEXP M_FIG C_FIG

18: COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid.
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Posted 25 May 2020

COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid.
3,698 downloads medRxiv respiratory medicine

Sarah Heili-Frades, Pablo Minguez, Ignacio Mahillo-Fernandez, Tomas Prieto-Rumeau, Antonio Herrero Gonzalez, Lorena de la Fuente, Maria Jesus Rodriguez Nieto, German Peces-Barba Romero, Mario Peces-Barba, Maria del Pilar Carballosa de Miguel, Itziar Fernandez Ormaechea, Alba Naya Prieto, Farah Ezzine de Blas, Luis Jimenez Hiscock, Cesar Perez Calvo, Arnoldo Santos, Luis Enrique Munoz Alameda, Fredeswinda Romero Bueno, Miguel Gorgolas Hernandez-Mora, Alfonso Cabello Ubeda, Beatriz Alvarez Alvarez, Elizabet Petkova, Nerea Carrasco, Dolores Martin Rios, Nicolas Gonzalez Mangado, Olga Sanchez Pernaute

There is limited information describing features and outcomes of patients requiring hospitalization for COVID19 disease and still no treatments have clearly demonstrated efficacy. Demographics and clinical variables on admission, as well as laboratory markers and therapeutic interventions were extracted from electronic Clinical Records (eCR) in 4712 SARS-CoV2 infected patients attending 4 public Hospitals in Madrid. Patients were stratified according to age and stage of severity. Using multivariate logistic regression analysis, cut-off points that best discriminated mortality were obtained for each of the studied variables. Principal components analysis and a neural network (NN) algorithm were applied. A high mortality incidence associated to age >70, comorbidities (hypertension, neurological disorders and diabetes), altered vitals such as fever, heart rhythm disturbances or elevated systolic blood pressure, and alterations in several laboratory tests. Remarkably, analysis of therapeutic options either taken individually or in combination drew a universal relationship between the use of Cyclosporine A and better outcomes as also a benefit of tocilizumab and/or corticosteroids in critically ill patients. We present a large Spanish population-based study addressing factors influencing survival in current SARS CoV2 pandemic, with particular emphasis on the effectivity of treatments. In addition, we have generated an NN capable of identifying severity predictors of SARS CoV2. A rapid extraction and management of data protocol from eCR and artificial intelligence in-house implementations allowed us to perform almost real time monitoring of the outbreak evolution.

19: Accuracy of Smartphone Integrated Pulse Oximetry Meets Full FDA Clearance Standards for Clinical Use.
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Posted 18 Feb 2021

Accuracy of Smartphone Integrated Pulse Oximetry Meets Full FDA Clearance Standards for Clinical Use.
3,631 downloads medRxiv respiratory medicine

Sara H Browne, Mike Bernstein, Philip E. Bickler

Background: Pulse oximetry is used as an assessment tool to gauge the severity of COVID-19 infection and identify patients at risk of poor outcomes. The pandemic highlights the need for accurate pulse oximetry, particularly at home, as infection rates increase in multiple global regions, including the UK, USA, and South Africa. Over 100 million Samsung smartphones containing dedicated biosensors (Maxim Integrated Inc, San Jose, CA) and preloaded Apps to perform pulse oximetry, are in use globally. We performed detailed in human hypoxia testing on the Samsung S9 smartphone to determine if this integrated hardware meets full FDA/ISO requirements for clinical pulse oximetry. Methods: The accuracy of integrated pulse oximetry in the Samsung 9+ smartphone during stable oxygen saturation (SaO2) between 70% and 100% was evaluated in 12 healthy subjects. Inspired oxygen, nitrogen, and carbon dioxide partial pressures were monitored and adjusted via a partial rebreathing circuit to achieve stable target SaO2 plateaus between 70% and 100%. Arterial blood samples were taken at each plateau, and saturation measured on each blood sample using ABL-90FLEX blood gas analyzer. Bias, calculated from smartphone readings minus the corresponding arterial blood sample, was reported as root mean square deviation (RMSD). Findings: The RMSD of the over 257 data points based on blood sample analysis obtained from 12 human volunteers tested was 2.6%. Interpretation: Evaluation of the smartphone pulse oximeter performance is within requirements of <3.5% RMSD blood oxygen saturation (SpO2) value for FDA/ISO clearance for clinical pulse oximetry. This is the first report of smartphone derived pulse oximetry measurements that meet full FDA/ISO accuracy certification requirements. Both Samsung S9 and S10 contain the same integrated pulse oximeter, thus over 100 million smartphones in current global circulation could be used to obtain clinically accurate spot SpO2 measurements to support at home assessment of COVID-19 patients.

20: COVID-19 Critical Illness Pathophysiology Driven by Diffuse Pulmonary Thrombi and Pulmonary Endothelial Dysfunction Responsive to Thrombolysis
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Posted 21 Apr 2020

COVID-19 Critical Illness Pathophysiology Driven by Diffuse Pulmonary Thrombi and Pulmonary Endothelial Dysfunction Responsive to Thrombolysis
3,573 downloads medRxiv respiratory medicine

Hooman D Poor, Corey E. Ventetuolo, Thomas Tolbert, Glen Chun, Gregory Serrao, Amanda Zeidman, Neha S. Dangayach, Jeffrey Olin, Roopa Kohli-Seth, Charles A Powell

Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated D-dimers and higher rates of venous thromboembolism. We present five cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.

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