A #Learning-based #Model to Evaluate #Hospitalization #Priority in #COVID19 Pandemics (Patterns, abstract)

[Source: Patterns, full page: (LINK). Abstract, edited.]

A Learning-based Model to Evaluate Hospitalization Priority in COVID-19 Pandemics

Yichao Zheng, Yinheng Zhu, Mengqi Ji, Rongpin Wang, Xinfeng Liu, Mudan Zhang, Choo Hui Qin, Lu Fang, Shaohua Ma

Open Access | Published: August 03, 2020 | DOI: https://doi.org/10.1016/j.patter.2020.100092

 

Highlights

  1. A model was developed to evaluate hospitalization priority in COVID-19 pandemics.
  2. This model used easily accessible biomarkers to evaluate the risk of severe COVID-19.
  3. The evaluation can be rapidly proceeded using an online program.
  4. Performance of different algorithms in evaluation of COVID-19 severity was explored.

 

Summary

The emergence of novel coronavirus disease 2019 (COVID-19) is placing an increasing burden on the healthcare systems. Although the majority of infected patients have non-severe symptoms and can be managed at home, some individuals may develop severe disease and are demanding the hospital admission. Therefore, it becomes paramount to efficiently assess the severity of COVID-19 and identify hospitalization priority with precision. In this respect, a 4-variable assessment model, including lymphocyte, lactate dehydrogenase (LDH), C-reactive protein (CRP) and neutrophil, is established and validated using the XGBoost algorithm. This model is found effective to identify severe COVID-19 cases on admission, with a sensitivity of 84.6%, a specificity of 84.6%, and an accuracy of 100% to predict the disease progression toward rapid deterioration. It also suggests that a computation-derived formula of clinical measures is practically applicable for the healthcare administrators to distribute hospitalization resources to the most needed in epidemics and pandemics.

Accepted: July 29, 2020 – Received in revised form: June 30, 2020 – Received: May 12, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.patter.2020.100092

Copyright © 2020

Keywords: SARS-CoV-2; COVID-19.

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Fruitful neutralizing #antibody #pipeline brings hope to defeat #SARS-Cov-2 (Trends Pharmacol Sci., abstract)

[Source: Trends of Pharmacological Sciences, full page: (LINK). Abstract, edited.]

Fruitful neutralizing antibody pipeline brings hope to defeat SARS-Cov-2

Alex Renn, Ying Fu, Xin Hu, Matthew D. Hall, Anton Simeonov

Published: July 31, 2020 | DOI: https://doi.org/10.1016/j.tips.2020.07.004

 

Highlights

  • We are currently experiencing an explosion of antibody research against COVID-19 that include neutralizing antibodies against SARS-CoV-2 and therapeutic antibodies against COVID-19 associated hyperinflammation.
  • 8 neutralizing antibodies against SARS-CoV-2, LY-CoV555, JS016, REGN-COV2, TY027, BRII-196, BRII-198, CT-P59 and SCTA01, have now entered clinical trials (as of July 28th, 2020).
  • SARS-CoV-2 may develop resistance to neutralizing antibodies through accumulating spontaneous mutations.
  • The neutralizing antibodies also may show antibody-dependent enhancement (ADE) and amplify disease progression.

 

Abstract

With the recent spread of SARS-CoV-2 infecting over 16 million people worldwide as of July 28th, 2020, causing more than 650,000 deaths, there is a desperate need for therapeutic agents and vaccines. Building on the knowledge of the previous outbreaks of SARS-CoV-1 and MERS, the development of therapeutic antibodies and vaccines for COVID-19 is taking place at an unprecedented speed. In this review, the current efforts made toward developing neutralizing antibodies against COVID-19 are summarized. We also highlight the importance of having such a fruitful antibody development pipeline that will be helpful in combatting the potential escape plans of SARS-CoV-2 including somatic mutations and antibody-dependent enhancement (ADE).

Keywords: SARS-CoV-2; COVID-19; Monoclonal antibodies; Immunology.

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#SARS-CoV-2 RNA Dependent RNA polymerase (#RdRp) – A #drug #repurposing study (Heliyon, abstract)

[Source: Heliyon, full page: (LINK). Abstract, edited.]

SARS-CoV-2 RNA Dependent RNA polymerase (RdRp) – A drug repurposing study

Jamshaid Ahmad, Saima Ikram, Fawad Ahmad, Irshad Ur Rehman, Maryam Mushtaq

Open Access | Published: July 23, 2020 | DOI: https://doi.org/10.1016/j.heliyon.2020.e04502

 

Abstract

The outbreak of SARS-CoV-2 in December 2019 in China subsequently lead to a pandemic. Lack of vaccine and specific anti-viral drugs started a global health disaster. For a sustained control and protection, development of potential anti-viral drugs is one of the targeted approach. Although, designing and developing a panel of new drugs molecules are always encouraged. However, in the current emergency, drug repurposing study is one of the most effective and fast track option. The crystal structure of a SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) RNA Dependent RNA Polymerase (RdRp) has recently been deciphered through X-ray crystallography. The single-chain of core RNA Dependent RNA Polymerase relies on virus-encoded cofactors nsp7 and two units of nsp8 for its optimum function. This study explored the FDA approved database of 7922 molecules and screened against the core polymerase along with cofactors. Here we report a panel of FDA approved drugs that show substantial interactions with key amino acid residues of the active site. Interestingly, some of the identified drugs (Ornipressin, Lypressin, Examorelin, Polymyxin B1) bind strongly within the binding pockets of both forms of RdRp. Besides, we found strong candidates for the complex form as well which include Nacortocin, Cistinexine, Cisatracurium (among others). These drugs have the potential to be considered while contriving therapeutic options.

Keywords: SARS-CoV-2; COVID-19; Antivirals.

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#Coronavirus Disease 2019 (#COVID19) #Outbreak in a #SanFrancisco #Homeless #Shelter (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Coronavirus Disease 2019 (COVID-19) Outbreak in a San Francisco Homeless Shelter

Elizabeth Imbert, MD, MPH, Patrick M Kinley, Ashley Scarborough, MPH, Caroline Cawley, MPH, Madeline Sankaran, MPH, Sarah N Cox, MSPH, Margot Kushel, MD, Juliet Stoltey, MD, MPH, Stephanie Cohen, MD, MPH, Jonathan D Fuchs, MD, MPH, SF COVID-19 Response Team

Clinical Infectious Diseases, ciaa1071, https://doi.org/10.1093/cid/ciaa1071

Published: 03 August 2020

 

Abstract

We report the public health response to a COVID-19 outbreak in a San Francisco shelter where 67% of residents and 17% of staff tested positive for SARS-CoV-2. We describe the limited utility of case investigation, person-based contact tracing and symptom screening, and the benefits of mass testing in outbreak response.

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Institutional Outbreaks; USA; California.

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#Nosocomial #outbreak of #SARS-CoV-2 infection in a #haematological #unit – high #mortality rate in infected patients with haematologic #malignancies (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology | Available online 1 August 2020, 104574 | In Press, Journal Pre-proof

Nosocomial outbreak of SARS-CoV-2 infection in a haematological unit – high mortality rate in infected patients with haematologic malignancies

Monika M Biernat a, Aleksander Zińczuk b, Paweł Biernat c, Aleksandra Bogucka-Fedorczuk d, Jacek Kwiatkowski e, Elżbieta Kalicińsk a,f, Dominik Marciniak g, Krzysztof Simon h, Tomasz Wróbel i

a Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow  Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; b Department of Forensic Medicine, Wroclaw Medical University, Infectious Diseases Unit, Gromkowski Regional Hospital in Wrocław, Mikulicz-Radecki Street 4, Koszarowa Street 5, 51-149 50-345, Wroclaw, Poland; c Department of Drugs Form Technology, Wroclaw Medical University, Borowska Street 211A, 50-556, Wroclaw, Poland; d Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; e Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; f Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Wroclaw, Poland; g Department of Drugs Form Technology, Wroclaw Medical University, Borowska Street 211A, 50-556, Wroclaw, Poland; h Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Koszarowa Street 5, 51-149, Wroclaw, Poland; i Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow  Transplantation, Wroclaw Medical University, Pasteura Street 4, 50-367, Poland

Received 27 July 2020, Accepted 30 July 2020, Available online 1 August 2020.

DOI: https://doi.org/10.1016/j.jcv.2020.104574

 

Highlights

  • Higher mortality rate in COVID-19 patients with haematologic diseases.
  • Haematologic patients with COVID-19 have 50% less chance of survival.
  • Probability of death was higher in patients older than 40 yrs of age with AML/MDS.

 

Abstract

Background

Here we report nosocomial outbreak of COVID-19 among patients in a haematological unit. To our knowledge this is the first report from Central Europe comparing morbidity and mortality in infected and non-infected patients after exposure to SARS-CoV-2.

Methods

The outbreak involved 39 individuals: 19 patients and 20 health care workers. The SARS-CoV-2 test by nasopharyngeal swabs was performed by real-time RT-PCR. Exposed patients were divided into two groups: quarantine patients with and without COVID-19. All patients were prospectively examined at the following time points: 0, 7 days, 14 days, 21 days and 28 days after confirmation or exclusion of SARS-CoV-2.

Results

Infection was confirmed in a total of 5/20 health care workers and 10/19 patients. Among the patients positive for SARS-CoV-2 infection, the mortality rate was 36.8%. The probability of death in patients infected with SARS-CoV-2 increased 8-fold (p = 0.03). Bacterial, fungal, and viral co-infection significantly decreased survival in these patients (p < 0.05). Additionally, the probability of death was much higher in patients older than 40 years of age (p = 0.032).

Conclusion

This study showed significantly higher mortality rate in COVID-19 patients with haematologic diseases compared to the non-infected patient group. Haematologic patients with COVID-19 have 50% less chance of survival.

Keywords: SARS-CoV-2; COVID-19; Cancer; Hematology; Poland.

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#COVID19 in Hospitalized Adults Living with #HIV (Open Forum Infect Dis,. abstract)

[Source: Open Forum Infectious Diseases, full page: (LINK). Abstract, edited.]

COVID-19 in Hospitalized Adults Living with HIV

Kate Stoeckle, MD, Carrie D Johnston, MD, Deanna P Jannat-Khah, DrPH, Samuel C Williams, BA, Tanya M Ellman, MD, Mary A Vogler, MD, Roy M Gulick, MD, Marshall J Glesby, MD, Justin J Choi, MD

Open Forum Infectious Diseases, ofaa327, https://doi.org/10.1093/ofid/ofaa327

Published: 01 August 2020

 

Abstract

Background

The spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain.

Methods

We conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020 and May 15, 2020. We matched 30 people living with HIV (PLWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PLWH and control patients.

Results

In our study, the median age was 60.5 years (IQR 56.6–70.0), 20% were female, 27% were White, 30% were Black, and 24% were of Hispanic/Latino ethnicity. There were no significant differences between PLWH and control patients in presenting symptoms, duration of symptoms prior to hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PLWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality.

Conclusions

The clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PLWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation.

coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus

Topic: hiv – adult – coinfection – sars-cov-2 – covid-19

Issue Section: Major Article

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© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: SARS-CoV-2; COVID-19; HIV/AIDS.

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#Functional #neuraminidase #inhibitor #resistance motifs in #avian #influenza A(#H5Nx) viruses (Antiviral Res., abstract)

[Source: Antiviral Research, full page: (LINK). Abstract, edited.]

Antiviral Research | Available online 1 August 2020, 104886 | In Press, Journal Pre-proof | Research paper

Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses

Dagmara Bialy, Holly Shelton, The Pirbright Institute, Pirbright, United Kingdom

Received 24 March 2020, Revised 13 July 2020, Accepted 16 July 2020, Available online 1 August 2020.

DOI: https://doi.org/10.1016/j.antiviral.2020.104886

 

Highlights

  • A R292K residue change in NA reduces susceptibility to NA inhibitor drugs (NAIs) in H5N6 and H5N2 avian influenza viruses.
  • All four mutations (E119V, H274Y, R292K and N294S) reducing susceptibility to NAIs in H5N6 viruses also reduced viral NA activity.
  • Reduced susceptibility to NA inhibitors in H5N6 did not attenuate virus replication efficiency in chicken cells or eggs.
  • A reduction of the viral HA affinity for sialic acid was observed in H5N6 viruses with reduced NA activity.

 

Abstract

Neuraminidase inhibitors (NAIs) are antiviral agents recommended worldwide to treat or prevent influenza virus infections in humans. Past influenza virus pandemics seeded by zoonotic infection by avian influenza viruses (AIV) as well as the increasing number of human infections with AIV have shown the importance of having information about resistance to NAIs by avian NAs that could cross the species barrier. In this study we introduced four NAI resistance-associated mutations (N2 numbering) previously found in human infections into the NA of three current AIV subtypes of the H5Nx genotype that threaten the poultry industry and human health: highly pathogenic H5N8, H5N6 and H5N2. Using the established MUNANA assay we showed that a R292K substitution in H5N6 and H5N2 viruses significantly reduced susceptibility to three licenced NAIs: oseltamivir, zanamivir and peramivir. In contrast the mutations E119V, H274Y and N294S had more variable effects with NAI susceptibility being drug- and strain-specific. We measured the replicative fitness of NAI resistant H5N6 viruses and found that they replicated to comparable or significantly higher titres in primary chicken cells and in embryonated hens’ eggs as compared to wild type – despite the NA activity of the viral neuraminidase proteins being reduced. The R292K and N294S drug resistant H5N6 viruses had single amino acid substitutions in their haemagglutinin (HA): Y98F and A189T, respectively (H3 numbering) which reduced receptor binding properties possibly balancing the reduced NA activity seen. Our results demonstrate that the H5Nx viruses can support drug resistance mutations that confer reduced susceptibility to licenced NAIs and that these H5N6 viruses did not show diminished replicative fitness in avian cell cultures. Our results support the requirement for on-going surveillance of these strains in bird populations to include motifs associated with human drug resistance.

Keywords: Avian Influenza; H5N2; H5N6; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir.

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#Immunoserologic #detection and #diagnostic relevance of cross-reactive auto-antibodies in #COVID19 patients (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunoserologic detection and diagnostic relevance of cross-reactive auto-antibodies in COVID-19 patients

María Teresa Schiaffino, Marisa Di Natale, Elena García-Martínez, Joaquín Navarro, José Luis Muñoz-Blanco, Pablo Demelo-Rodríguez, Paloma Sánchez-Mateos

The Journal of Infectious Diseases, jiaa485, https://doi.org/10.1093/infdis/jiaa485

Published: 01 August 2020

 

Abstract

During the COVID-19 pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients. The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections. We describe 12 patients positive for the cross-reactive Ab, compared to a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion. Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for auto-reactive mediated complications such as thrombotic or neurologic events.

COVID-19, Autoimmunity, Autoantibody, Immunofluorescence, Molecular Mimicry

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.

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The first 100 days of #SARS-CoV-2 #control in #Vietnam (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

The first 100 days of SARS-CoV-2 control in Vietnam

Quang Thai Pham, Maia A Rabaa, Huy Luong Duong, Quang Tan Dang, Dai Quang Tran, Ha-Linh Quach, Ngoc-Anh Thi Hoang, Cong Dinh Phung, Duy Nghia Ngu, Anh Tu Tran, Ngoc Quang La, My Phuc Tran, Chau Vinh, Cong Khanh Nguyen, Duc Anh Dang, Nhu Duong Tran, Guy Thwaites, H Rogier van Doorn, Marc Choisy, OUCRU COVID-19 Research Group

Clinical Infectious Diseases, ciaa1130, https://doi.org/10.1093/cid/ciaa1130

Published: 01 August 2020

 

Abstract

Background

One hundred days after SARS-CoV-2 was first reported in Vietnam on January 23rd, 270 cases were confirmed, with no deaths. We describe the control measures used by the Government and their relationship with imported and domestically-acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control.

Methods

Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of Government control measures, including numbers of tests and quarantined individuals, were analysed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of pre-symptomatic transmission events and time-varying reproduction numbers.

Results

A national lockdown was implemented between April 1st and 22nd. Around 200 000 people were quarantined and 266 122 RT-PCR tests conducted. Population mobility decreased progressively before lockdown. 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3·24 days, and 27·5% (95% confidence interval, 15·7%-40·0%) of transmissions occurred pre-symptomatically. Limited transmission amounted to a maximum reproduction number of 1·15 (95% confidence interval, 0·37-2·36). No community transmission has been detected since April 15th.

Conclusions

Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial pre-symptomatic transmission.

COVID-19, SARS-CoV-2, Vietnam, asymptomatic, epidemic control

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: SARS-CoV-2; COVID-19; Vietnam.

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