#Coinfection in #SARS‐CoV‐2 infected Patients: Where Are #Influenza Virus and #Rhinovirus / #Enterovirus? (J Med Virol., abstract)

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

Co‐infection in SARS‐CoV‐2 infected Patients: Where Are Influenza Virus and Rhinovirus/Enterovirus?

Michael D. Nowak, Emilia Mia Sordillo,  Melissa R. Gitman,  Alberto E Paniz Mondolfi

First published: 30 April 2020 | DOI:  https://doi.org/10.1002/jmv.25953

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.25953



Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has been declared a global pandemic. Our goal was to determine whether coinfections with other respiratory pathogens occur in a significant subset of SARS‐CoV‐2 infected patients in the greater New York City metropolitan area. During the period from March 16, 2020 through April 20, 2020, our laboratory detected SARS‐CoV‐2 infection in 8,990 patients of a total 18,704 tested by real‐time reverse‐transcription‐polymerase‐chain‐reaction amplification (SARS‐CoV‐2 Test, cobas® 6800 system, RocheDiagnostics). Amongst the patients who tested positive for SARS‐CoV‐2, 1,204 were also tested for other respiratory viruses, and concurrent infection was found in only 36 (< 3%). In comparison, coinfection with at least one non‐SARS‐CoV‐2 respiratory viral pathogen was found in 13.1% of patients who tested negative for SARS‐CoV‐2. Additionally, in patients who tested negative for SARS‐CoV‐2, the most common respiratory virus co‐infections were those commonly seen circulating in the community including rhinovirus/enterovirus, influenza viruses and coronavirus NL63, whereas non‐SARS‐CoV‐2 coronaviridae were the most common concurrent respiratory viruses found in SARS‐CoV‐2 –positive patients. Additional studies are needed to establish whether simultaneous viral infection in SARS‐CoV‐2 patients could potential drive viral interference or influence disease outcomes.

This article is protected by copyright. All rights reserved.

Keywords: Seasonal Influenza; Rhinovirus; Coronavirus; SARS-CoV-2; COVID-19; Enterovirus; Viral interference.


Characteristics of #Patients with Acute Flaccid #Myelitis [#AFM], #USA, 2015–2018 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / CME ACTIVITY – Research

Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015–2018

Nilay McLaren, Adriana Lopez, Sarah Kidd, John X. Zhang, W. Allan Nix, Ruth Link-Gelles, Adria Lee, and Janell A. Routh

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA



Observed peaks of acute flaccid myelitis (AFM) cases have occurred biennially since 2014 in the United States. We aimed to determine if AFM etiology differed between peak and nonpeak years, considering that clinical features of AFM differ by virus etiology. We compared clinical and laboratory characteristics of AFM cases that occurred during peak (2016 and 2018, n = 366) and nonpeak (2015 and 2017, n = 50) years. AFM patients in peak years were younger (5.2 years) than those in nonpeak years (8.3 years). A higher percentage of patients in peak years than nonpeak years had pleocytosis (86% vs. 60%), upper extremity involvement (33% vs. 16%), and an illness preceding limb weakness (90% vs. 62%) and were positive for enterovirus or rhinovirus RNA (38% vs. 16%). Enterovirus D68 infection was associated with AFM only in peak years. Our findings suggest AFM etiology differs between peak and nonpeak years.

Keywords: EV-D68; Enterovirus; Rhinovirus; AFM; USA.


Novel #Scoring #System for Differentiating #Parechovirus-A3 and #Enterovirus #Infection in #Neonates and Young #Infants (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 7 January 2020, 104256 / In Press, Journal Pre-proof

Novel Scoring System for Differentiating Parechovirus-A3 and Enterovirus Infection in Neonates and Young Infants

Authors: Ryohei Izumita a, Yuta Aizawa a, Rie Habuka a, Kanako Watanabe b, Taketo Otsuka a, Nobutaka Kitamura c, Kohei Akazawa d, Akihiko Saitoh a

{a} Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan; {b} Department of Laboratory Science, Niigata University Graduate School of Health Sciences, Niigata, Japan; {c} Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan; {d} Department of Medical Informatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Received 10 April 2019, Revised 20 August 2019, Accepted 30 December 2019, Available online 7 January 2020. DOI: https://doi.org/10.1016/j.jcv.2019.104256



  • PeV-A3 and EVs are the most common viruses causing severe diseases in young infants.
  • PeV-A3 patients had some severer symptoms and signs compared to EVs patients.
  • PeV-A3 patients tended to have a lower WBC count in blood and no CSF pleocytosis.
  • The scoring system with these findings were successful to distinguish 2 infections.


Keywords: Parechovirus A3; Enterovirus; Pediatrics.


#Development of an #EV71 #vaccine efficacy #test using human scavenger receptor B2 transgenic mice (J Virol., abstract)

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

Development of an enterovirus 71 vaccine efficacy test using human scavenger receptor B2 transgenic mice

Ayumi Imura, Yui Sudaka, Ayako Takashino, Kanami Tamura, Kyousuke Kobayashi, Noriyo Nagata, Hidekazu Nishimura, Katsumi Mizuta, Satoshi Koike

DOI: 10.1128/JVI.01921-19



Enterovirus 71 (EV71) is a causative agent of hand-foot-mouth disease, and it sometimes causes severe neurological disease. Development of effective vaccines and animal models to evaluate vaccine candidates are needed. However, the animal models currently used for vaccine efficacy testing, monkeys and neonatal mice, have economic, ethical, and practical drawbacks. In addition, EV71 strains prepared for lethal challenge often develop decreased virulence during propagation in cell culture. To overcome these problems, we used a mouse model expressing human scavenger receptor B2 (hSCARB2) that showed life-long susceptibility to EV71. We selected virulent EV71 strains belonging to the subgenogroups B4, B5, C1, C2, and C4 and propagated them using a culture method for EV71 without an apparent reduction in virulence. Here, we describe a novel EV71 vaccine efficacy test based on these hSCARB2 transgenic (Tg) mice and these virulent viruses. Adult Tg mice were immunized subcutaneously with formalin-inactivated EV71. The vaccine elicited sufficient levels of neutralizing antibodies in the immunized mice. The mice were subjected to lethal challenge with virulent viruses via intravenous injection. Survival, clinical signs, and body weight changes were observed for 2 weeks. Most immunized mice survived without clinical signs or histopathological lesions. The viral replication in immunized mice was much lower than that in nonimmunized mice. Mice immunized with the EV71 vaccine were only partially protected against lethal challenge with coxsackievirus A16. These results indicate that this new model is useful for in vivo EV71 vaccine efficacy testing.



The development of new vaccines for EV71 relies on the availability of small animal models suitable for in vivo efficacy testing. Monkeys and neonatal mice have been used, but the use of these animals has several drawbacks, including high costs, limited susceptibility, and poor experimental reproducibility. In addition, the related ethical issues are considerable. The new efficacy test based on hSCARB2 Tg mice and virulent EV71 strains propagated in genetically modified cell lines presented here can overcome these disadvantages and is expected to accelerate the development of new EV71 vaccines.

Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords: EV-71; Vaccines; Coxsackievirus A16; Animal models.


#Clinical characteristics of #EVA71 #neurological disease during an #outbreak in #children in #Colorado, #USA, in 2018: an observational cohort study (Lancet Infect Dis., abstract)

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

Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study

Kevin Messacar, MD, Emily Spence-Davizon, MPH, Christina Osborne, MD, Craig Press, MD, Teri L Schreiner, MD, Jan Martin, MD, Ricka Messer, MD, John Maloney, MD, Alexis Burakoff, MD, Meghan Barnes, MSPH, Shannon Rogers, MS, Adriana S Lopez, MPH, Janell Routh, MD, Susan I Gerber, MD, M Steven Oberste, PhD, W Allan Nix, BS, Prof Mark J Abzug, MD, Prof Kenneth L Tyler, MD, Rachel Herlihy, MD, Samuel R Dominguez, MD

Published: December 16, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30632-2




In May, 2018, Children’s Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak.


In this retrospective observational cohort study, children (younger than 18 years) who presented to Children’s Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018.


Between March 10 and Nov 10, 2018, 74 children presenting to Children’s Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0–31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1–2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover.


This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance.



Keywords: Enterovirus; EV-A71; Neurology; Pediatrics; AFM; Meningitis; Encephalitis; USA; Colorado.


Next generation #sequencing of #human #enterovirus strains from an #outbreak of #EVA71 shows applicability to outbreak investigations (J Clin Invest., abstract)

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

Journal of Clinical Virology / Available online 17 November 2019, 104216 / In Press, Journal Pre-proof

Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations

Sacha Stelzer-Braid a,b, Matthew Wynn a, Richard Chatoor a, Matthew Scotchc d,e, Vidiya Ramachandran f, Hooi-Ling Teoh g, h, Michelle A.Farrarg h, Hugo Sampaio g,h, Peter Ian Andrews g,h, Maria E.Craig a,h, C. Raina Mac Intyre c,i,j, Hemalatha Varadhan k, Alison Kesson l, Philip N.Britton l,m, James Newcomb e,n, William D.Rawlinson a,b,h

{a} Virology Research Laboratory, Serology and Virology Division (SAViD), NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW 2031, Australia; {b} School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; {c} College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; {d} Center for Environmental Health Engineering, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; {e} School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW 2033, Australia; {f} Serology and Virology Division (SAViD), NSW Health Pathology East, Department of Microbiology, Prince of Wales Hospital, Sydney, NSW 2031, Australia; {g} Department of Neurology, Sydney Children’s Hospital, Sydney, Australia; {h} School of Women’s and Children’s Health, University of New South Wales Medicine, Sydney, NSW 2052, Australia; {i} Biosecurity Program, Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia; {j} Watts College of Public Service and Community Solutions, Arizona State University, Phoenix, AZ 85004, USA; {k} NSW Health Pathology, John Hunter Hospital, Newcastle, United Kingdom; {l} Department of Infectious Diseases and Microbiology, The Children’s Hospital at Westmead, Australia; {m} Marie Bashir Institute, University of Sydney, Australia; {n} Pathology North, Royal North Shore Hospital, St Leonards, Australia

Received 24 April 2019, Revised 8 October 2019, Accepted 11 November 2019, Available online 17 November 2019.

DOI: https://doi.org/10.1016/j.jcv.2019.104216



  • Near full-length genome analysis using next generation sequencing identified EV-A71 and other enterovirus A and B subtypes circulating.
  • The Sydney EV-A71 2013 strain was very similar to EV-A71 circulating in China and Vietnam during the previous year.
  • Strains causing more severe clinical manifestations grouped together phylogenetically.




The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications.


To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype.

Study design

We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses.


We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community.


This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.

Keywords: Enterovirus – EV-A71 – Phylogeny – Hand, foot and mouth disease – Whole genome sequencing – Australia

© 2019 Published by Elsevier B.V.

Keywords: HFMD; Enterovirus; EV-A71; Australia.


National #Epidemiology and #Evolutionary #History of Four #HFMD -Related #Enteroviruses in #China from 2008 to 2016 (Virol Sin., abstract)

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

National Epidemiology and Evolutionary History of Four Hand, Foot and Mouth Disease-Related Enteroviruses in China from 2008 to 2016

Authors: Xuemin Fu, Zhenzhou Wan, Yanpeng Li, Yihong Hu, Xia Jin, Chiyu Zhang

Research Article / First Online: 29 October 2019



Hand, foot and mouth disease (HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71 (EVA71) and coxsackievirus A16 (CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level. In this study, we performed systematic epidemiological analyses of HFMD-related enteroviruses using the data of 64 published papers that met the inclusion criteria, and conducted phylogenetic analyses based on 12,080 partial VP1 sequences identified in China before 31st June 2018. We found that EVA71 prevalence has decreased sharply but other enteroviruses have increased rapidly from 2008 to 2016 and that one subtype of each enterovirus is represented during the epidemic. In addition, four genotypes EVA71_C4, CVA16_B1, CVA6_D and CVA10_C are the most predominant enterovirus strains and collectively they cause over 90% of all HFMD cases in China according to the phylogenetic trees using representative partial VP1 sequences. These four major enterovirus genotypes have different geographical distributions, and they may co-circulate with other genotypes and serotypes. These results suggest that more molecular epidemiological studies should be performed on several enteroviruses simultaneously, and such information should have implications for virological surveillance, disease management, vaccine development and policy-making on the prevention and control of HFMD.

Keywords: Enterovirus – Hand, foot and mouth disease (HFMD) – Molecular epidemiology – Evolution – Genotype


Electronic supplementary material

The online version of this article ( https://doi.org/10.1007/s12250-019-00169-2) contains supplementary material, which is available to authorized users.

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We thank Zhihang Zheng and Rong Xu at Institut Pasteur of Shanghai, CAS for their technique help in this study. This work was supported by the TOTAL foundation, and the Grants from the National Science and Technology Major Project of China (2017ZX10103009-002), the “One Belt One Road” Project (153831KYSB20170043) of the Chinese Academy of Sciences, the 133 Project of Institut Pasteur of Shanghai, CAS.

Author Contributions

CZ conceived and designed the study. XF, ZW, XJ and YH collected the data. XF, ZW, and YL performed the analyses. CZ, XF and ZW analyzed and interpreted the data. XF and CZ drafted the manuscript, and XJ contributed to critical revision of the manuscript. All authors have read and approved the contents of the final manuscript.


Compliance with Ethical Standards

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: HFMD; Enterovirus; EV-A71; Coxsackievirus A16; China.