#Transmission of 2019 novel #Coronavirus to #HCWs in the Early #Epidemic (SSRN, abstract)

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

Transmission of 2019-nCoV to Health-Care Workers in the Early Epidemic

39 Pages Posted: 25 Feb 2020

Feng Wu, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Mengfei Guo, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Shuai Zhang, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Yanling Ma, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Pei Ma, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Limin Duan, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Xuan Wang, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Zhilei Lv, Huazhong University of Science and Technology (Formerly Tongi Medical University) – NHC Key Laboratory of Pulmonary Diseases; Juanjuan Xu, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Jinshuo Fan, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Union Hospital; Guanzhou Ma, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine; Jianhua Yi, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Infectious Diseases; Yu Hu, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Institute of Hematology; Huazhong University of Science and Technology (Formerly Tongi Medical University) – Collaborative Innovation Center of Hematology; Yang Jin, Huazhong University of Science and Technology (Formerly Tongi Medical University) – Department of Respiratory and Critical Care Medicine

 

Abstract

Background:

A large outbreak of pneumonia associated with 2019 novel coronavirus (2019-nCoV) occurred in Wuhan City, Hubei Province, China in December 2019. We have reported the first case of health-care worker infection in Wuhan Union Hospital to public at the earlier stage of the outbreak. Now this report summarizes the initial epidemiological and clinical findings on the basis of the identification of nosocomial 2019- nCoV infection of health-care workers in our 5000-bed tertiary general hospital. We aim to pay tribute to the front-line medical staff fighting against 2019-nCoV pneumonia and provide reference information to protect global health-care workers from 2019-nCoV infection in the epidemic.

Methods:

In this retrospective, single-centre study, we analyzed the firstbatch of 48 hospitalized cases of confirmed 2019-nCoV infection from the health-care workers of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, between January 16, 2020 to January 30, 2020. Included cases were the hospitalized health-care workers with positive symptoms, typical CT findings, and confirmed 2019- nCoV infection by real-time RT-PCR. Data on demographic characteristics, exposure history, clinical features and subjected to preliminary epidemiological assessment. We also investigated the attack rate of 2019- nCoV in the infectious isolation wards and designated fever outpatient clinics.

Findings:

Of the 48 first-batch hospitalized health-care workers with confirmed 2019-nCoV infection (including 17 physicians [35·4%], 28 nurses [58·3%] and three health-care assistants [6·3%]), 32 (66·7%) were female, with an median age of 36 years (IQR 31-41). The median duration from symptom onset to admission was estimated to be 6 days (IQR 5-10). The 48 infected employees were variously from the departments of surgery (23 [47·9%]), internal medicine (16 [33·3%]), pediatrics (2 [4·2%]), gynecology (2 [4·2%]) and other departments (5 [10·4%]) including the radiology unit, clinical laboratory and pharmacy department. 18 out of 48 individuals had direct contact with a patient with confirmed 2019-nCoV infection. Only six of the workers working in high-risk departments were aware of the possibility of exposure to infected patients. During the exposure period, 46 workers protected themselves by only wearing surgical masks; one wore N95 mask and only one physician wore an isolation gown, fit-tested N95 mask, gloves, cap, eye shield and shoe covers. Among the 189 physicians and nurses working in three isolation wards and one fever outpatient clinic, one nurse was infected with 2019- nCoV. Symptoms were of mild nature in most cases. Empirical therapy most commonly included administration of antibiotics, oseltamivir, arbidol, and inhalation of recombinant human interferon α-2b. Oxygen supplementation was used, via a nasal cannula in 21 patients (43·7%) and via a face mask in one patient (2·1%). None of the 48 cases required respiratory support with mechanical ventilation. As of February 8, 30 (62·5%) of 48 patients have been discharged and no fatalities occurred. The median hospital stay of the 30 patients lasted 11 days (IQR, 6·8-16·3). The median time to negative results among the 30 discharged patients was 10·5 days (IQR 7-15·3).

Interpretation:

Our findings confirmed 2019-nCoV could easily spread through direct personal contact in a hospital setting and provided compelling evidence that health-care facilities worldwide need to be prepared for possible transmission of this novel coronavirus. Medical workers engaging in daily interaction with their fellow workers should be personally under effective protection against the infection. The health-care workers developing any possible associated symptoms should seek prompt medical attention and be duly isolated, thereby minimizing secondary transmission of 2019-nCoV in health-care associated outbreaks. Adequate protection against exposure to infected patients can effectively protect health-care workers from 2019-nCoV infection.

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Funding Statement: This study was supported by the State Project for Essential Drug Research and Development, China (no. 2019ZX09301001).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The study was approved by Wuhan Union Hospital Ethics Committee and written informed consent was obtained from subjects involved before they were enrolled and when data were collected retrospectively.

Suggested Citation: Wu, Feng and Guo, Mengfei and Zhang, Shuai and Ma, Yanling and Ma, Pei and Duan, Limin and Wang, Xuan and Lv, Zhilei and Xu, Juanjuan and Fan, Jinshuo and Ma, Guanzhou and Yi, Jianhua and Hu, Yu and Jin, Yang, Transmission of 2019-nCoV to Health-Care Workers in the Early Epidemic (2/13/2020). Available at SSRN: https://ssrn.com/abstract=3542155

Keywords: COVID-19; SARS-CoV-2; HCWs; Antivirals; Arbidol; Oseltamivir.

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#Global #Update on the Susceptibilities of #Human #Influenza Viruses to #NAIs and the #Baloxavir, 2017-2018 (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res, 104718 2020 Jan 28 [Online ahead of print]

Global Update on the Susceptibilities of Human Influenza Viruses to Neuraminidase Inhibitors and the Cap-Dependent Endonuclease Inhibitor Baloxavir, 2017-2018

Emi Takashita 1, Rod S Daniels 2, Seiichiro Fujisaki 3, Vicki Gregory 2, Larisa V Gubareva 4, Weiijuan Huang 5, Aeron C Hurt 6, Angie Lackenby 7, Ha T Nguyen 4, Dmitriy Pereyaslov 8, Merryn Roe 6, Magdi Samaan 9, Kanta Subbarao 6, Herman Tse 10, Dayan Wang 5, Hui-Ling Yen 11, Wenqing Zhang 9, Adam Meijer 12

Affiliations: 1 WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan. Electronic address: emitaka@nih.go.jp. 2 WHO Collaborating Centre for Reference and Research on Influenza, The Francis Crick Institute, Worldwide Influenza Centre, 1 Midland Road, London, NW1 1AT, United Kingdom. 3 WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan. 4 WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, Centers for Diseases Control and Prevention, 1600 Clifton RD NE, MS-G16, Atlanta, GA, 30329, USA. 5 WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China. 6 WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. 7 National Infection Service, Public Health England, London, NW9 5HT, United Kingdom. 8 Division of Communicable Diseases, Health Security, & Environment, World Health Organization Regional Office for Europe, UN City, Marmorvej 51, DK-2100, Copenhagen Ø, Denmark. 9 Global Influenza Programme, World Health Organization, Avenue Appia 20, 1211, Geneva 27, Switzerland. 10 Public Health Laboratory Centre, 382 Nam Cheong Street, Hong Kong SAR, China. 11 School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. 12 National Institute for Public Health and the Environment, PO Box 1, 3720, BA Bilthoven, the Netherlands.

PMID: 32004620 DOI: 10.1016/j.antiviral.2020.104718

 

Abstract

The global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012-13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for the treatment of influenza virus infection in Japan and the United States. For this annual report, the susceptibilities of influenza viruses to NAIs and baloxavir were analyzed. A total of 15409 viruses, collected by World Health Organization (WHO) recognized National Influenza Centers and other laboratories between May 2017 and May 2018, were assessed for phenotypic NAI susceptibility by five WHO Collaborating Centers (CCs). The 50% inhibitory concentration (IC50) was determined for oseltamivir, zanamivir, peramivir and laninamivir. Reduced inhibition (RI) or highly reduced inhibition (HRI) by one or more NAIs was exhibited by 0.8% of viruses tested (n = 122). The frequency of viruses with RI or HRI has remained low since this global analysis began (2012-13: 0.6%; 2013-14: 1.9%; 2014-15: 0.5%; 2015-16: 0.8%; 2016-17: 0.2%). PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23 G/K/R, PA A36V, PA A37T, PA I38 F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions. Five of them were included in phenotypic baloxavir susceptibility analysis by two WHO CCs and IC50 values were determined. The PA variant viruses showed 6-17-fold reduced susceptibility to baloxavir. Overall, in the 2017-18 period the frequency of circulating influenza viruses with reduced susceptibility to NAIs or baloxavir was low, but continued monitoring is important.

Keywords: Baloxavir; Influenza; Neuraminidase inhibitor; Resistance; Surveillance; Susceptibility.

Copyright © 2020. Published by Elsevier B.V.

Conflict of interest statement: Declaration of competing interest None.

Keywords: Antivirals; Drugs Resistance; Influenza A; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Baloxavir.

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Assessing the #susceptibility of highly pathogenic #avian #influenza #H5N1 viruses to #oseltamivir using embryonated chicken #eggs (Indian J Med Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Indian J Med Res. 2019 Nov;150(5):486-491. doi: 10.4103/ijmr.IJMR_845_18.

Assessing the susceptibility of highly pathogenic avian influenza H5N1 viruses to oseltamivir using embryonated chicken eggs.

Tare DS1, Kode SS1, Hurt AC2, Pawar SD3.

Author information: 1 Avian Influenza Group, ICMR-National Institute of Virology-Microbial Containment Complex, Pune, Maharashtra, India. 2 WHO Collaborating Centre for Reference & Research on Influenza (VIDRL), Peter Doherty Institute for Infection & Immunity, Melbourne VIC 3000, Australia. 3 ICMR-National Institute of Virology-Mumbai Unit, Mumbai, Maharashtra, India.

 

Abstract

BACKGROUND & OBJECTIVES:

The susceptibility of influenza viruses to neuraminidase inhibitors (NAIs) is studied using enzyme-based assays, sequence analysis and in vitro and in vivo studies. Oseltamivir carboxylate (OC) is the active prodrug of the NAI oseltamivir. There is lack of information on the use of embryonated chicken eggs for studying susceptibility of highly pathogenic avian influenza (HPAI) H5N1 viruses to antiviral drugs. The aim of the present study was to assess the use of 10 day old embryonated chicken eggs for studying antiviral susceptibility of HPAI H5N1 viruses.

METHODS:

Two HPAI H5N1 viruses isolated from India were used in the study. Fluorescence-based NAI assay was performed to determine antiviral susceptibility of these viruses. In ovo antiviral assays were carried out using 10 day old embryonated chicken eggs. The virus dilutions were incubated with 14 μg/ml of OC and inoculated in the allantoic cavity. In the eggs, 50 per cent egg infectious dose (EID50) titres as well as mortality were quantitated.

RESULTS:

The two viruses used were susceptible to OC in the NAI assay. It was found that there was a significant drop in EID50titres; however, no significant protection from mortality after OC treatment was observed.

INTERPRETATION & CONCLUSIONS:

By measuring viral titres, the egg model was suitable to study the susceptibility of HPAI viruses to antiviral drugs along with NAI assay. The present study highlights the use of eggs as a model to study susceptibility of HPAI viruses to OC.

KEYWORDS: Antivirals – embryonated chicken eggs – H5N1 – highly pathogenic avian influenza – oseltamivir

PMID: 31939392 DOI: 10.4103/ijmr.IJMR_845_18

Keywords: Antivirals; Drugs resistance; Avian Influenza; H5N1; Animal models.

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Evaluating the effects of #oseltamivir phosphate on #platelet counts: a retrospective review (Platelets, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Platelets. 2020 Jan 13:1-5. doi: 10.1080/09537104.2020.1714576. [Epub ahead of print]

Evaluating the effects of oseltamivir phosphate on platelet counts: a retrospective review.

Shaim H1, McCaffrey P1, Trieu JA2, DeAnda A3, Yates SG1.

Author information: 1 Department of Pathology, Division of Transfusion Medicine, University of Texas Medical Branch, Galveston, TX, USA. 2 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. 3 Department of Surgery, Division of Cardiothoracic Surgery, University of Texas Medical Branch, Galveston, TX, USA.

 

Abstract

Desialylation of platelets results in platelet clearance by the Ashwell-Morrell Receptors (AMR) found on hepatocytes. Studies suggest that oseltamivir phosphate inhibits human sialidases, enzymes responsible for desialylation, extending the lifespan of circulating platelets. We thus evaluated, the effects of oseltamivir on platelet count (PC) following treatment. Of the 385 patients evaluated for influenza, 283 (73.5%) were influenza-infected. Of the 283 infected patients, 241 (85.2%) received oseltamivir (I + O+) while 42 patients did not (I + O-). One hundred two non-infected patients received oseltamivir (I-O+). The two groups receiving oseltamivir (I + O+, I-O+), demonstrated a statistically greater increase in the PC (57.53 ± 93.81, p = .013 and 50.79 ± 70.59, p = .023, respectively) relative to the group that did not (18.45 ± 89.33 × 109/L). The observed increase in PC was statistically similar (p = .61) in both groups receiving oseltamivir (I + O+, I-O+), suggesting that this effect is independent of influenza. Comparing clinical characteristics between responders and non-responders to oseltamivir treatment showed that only duration of oseltamivir treatment (AOR = 1.30, 95% CI 1.05-1.61, p = .015) was associated with a positive PC response. Our findings suggest a correlation between oseltamivir treatment and an increase in PCs. Future studies assessing the possible uses of oseltamivir in medical conditions characterized by diminished or defective thrombopoiesis are warranted.

KEYWORDS: Ashwell-Morell Receptor; glycans; oseltamivir; thrombocytopenia

PMID: 31931672 DOI: 10.1080/09537104.2020.1714576

Keywords: Antivirals; Oseltamivir; Platelets; Hematology.

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Early Administration of #Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the #Risk of Influenza B Virus-Associated #Pneumonia in Hospitalized #Pediatric Patients with Influenza B Virus Infection (Pediatr Infect Dis J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pediatr Infect Dis J. 2020 Feb;39(2):e20-e22. doi: 10.1097/INF.0000000000002528.

Early Administration of Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the Risk of Influenza B Virus-Associated Pneumonia in Hospitalized Pediatric Patients with Influenza B Virus Infection.

Dai Z1, Zhang L, Yu Q, Liu L, Yang M, Fan K.

Author information: 1 From the Department of Accident and Emergency, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

 

Abstract

We conducted a retrospective study to identify the risk factors for pneumonia in hospitalized pediatric patients with influenza B infection. Receiving oseltamivir within the first 48 hours of onset and frequent cough was respectively considered as a protective factor and a risk factor for the influenza B virus-associated pneumonia in hospitalized pediatric patients. Early administration of oseltamivir can reduce the risk of influenza B virus-associated pneumonia.

PMID: 31929434 DOI: 10.1097/INF.0000000000002528

Keywords: Seasonal Influenza; Influenza B; Antivirals; Oseltamivir; Pneumonia; Pediatrics.

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#Influenza A/ #H4N2 #mallard #infection experiments further indicate #zanamivir as less prone to induce #environmental #resistance development than #oseltamivir (J Gen Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Gen Virol. 2019 Dec 19. doi: 10.1099/jgv.0.001369. [Epub ahead of print]

Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir.

Tepper V1,2, Nykvist M2, Gillman A3, Skog E3, Wille M4,2, Lindström HS5, Tang C6, Lindberg RH6, Lundkvist Å2, Järhult JD3.

Author information: 1 Institute of Environmental Engineering, ETH Zürich, Switzerland. 2 Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 3 Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 4 Present address: WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. 5 Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, Umeå, Sweden. 6 Department of Chemistry, Umeå University, Umeå, Sweden.

 

Abstract

Neuraminidase inhibitors (NAIs) are the gold standard treatment for influenza A virus (IAV). Oseltamivir is mostly used, followed by zanamivir (ZA). NAIs are not readily degraded in conventional wastewater treatment plants and can be detected in aquatic environments. Waterfowl are natural IAV hosts and replicating IAVs could thus be exposed to NAIs in the environment and develop resistance. Avian IAVs form the genetic basis for new human IAVs, and a resistant IAV with pandemic potential poses a serious public health threat, as NAIs constitute a pandemic preparedness cornerstone. Resistance development in waterfowl IAVs exposed to NAIs in the water environment has previously been investigated in an in vivo mallard model and resistance development was demonstrated in several avian IAVs after the exposure of infected ducks to oseltamivir, and in an H1N1 IAV after exposure to ZA. The N1 and N2 types of IAVs have different characteristics and resistance mutations, and so the present study investigated the exposure of an N2-type IAV (H4N2) in infected mallards to 1, 10 and 100 µg l-1 of ZA in the water environment. Two neuraminidase substitutions emerged, H274N (ZA IC50 increased 5.5-fold) and E119G (ZA IC50 increased 110-fold) at 10 and 100 µg l-1 of ZA, respectively. Reversion towards wild-type was observed for both substitutions in experiments with removed drug pressure, indicating reduced fitness of both resistant viruses. These results corroborate previous findings that the development of resistance to ZA in the environment seems less likely to occur than the development of resistance to oseltamivir, adding information that is useful in planning for prudent drug use and pandemic preparedness.

KEYWORDS: H4N2; LPAI; antiviral resistance; avian influenza; drug residues; environment; influenza A; neuraminidase inhibitor; pandemic preparedness; zanamivir

PMID: 31855133 DOI: 10.1099/jgv.0.001369

Keywords: Avian Influenza; Antivirals; Drugs Resistance; H1N1pdm09; H4N2; Wild Birds.

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#Baloxavir marboxil #treatment of nude mice infected with #influenza A virus (J Infect Dis., abstract)

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

Baloxavir marboxil treatment of nude mice infected with influenza A virus

Maki Kiso, Seiya Yamayoshi, Jurika Murakami, Yoshihiro Kawaoka

The Journal of Infectious Diseases, jiz665, https://doi.org/10.1093/infdis/jiz665

Published: 14 December 2019

 

Abstract

Immunocompromised patients infected with influenza virus require prolonged treatment with neuraminidase inhibitors, because these patients are not able to eradicate the virus from the respiratory tract, leading to the emergence of drug-resistant mutant viruses. Here, we examined the efficacy of baloxavir marboxil in nude mice, which are immunologically deficient. Daily treatment with a suboptimal dose of baloxavir marboxil increased the survival time of the virus-infected nude mice but did not clear the virus from their respiratory organs, resulting in gradual body weight loss after termination of treatment. Despite the prolonged baloxavir marboxil treatment, few resistant mutants were detected.

influenza, baloxavir marboxil, drug resistance, immunocompromised

Issue Section: Brief Report

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Keywords: Antivirals; Drugs Resistance; Influenza A; Oseltamivir; Baloxavir; Animal models.

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