【病毒外文文献】2017 The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus

Accepted Manuscript The Impact of Co infection of Influenza A Virus on the on Severity of Middle East Respiratory Syndrome Coronavirus Sarah H Alfaraj Jaffar A Al Tawfiq Nojoom A Alzahrani Talal Altwaijri Ziad A Memish PII S0163 4453 17 30048 8 DOI 10 1016 j jinf 2017 02 001 Reference YJINF 3882 To appear in Journal of Infection Received Date 28 January 2017 Accepted Date 2 February 2017 Please cite this article as Alfaraj SH Al Tawfiq JA Alzahrani NA Altwaijri T Memish ZA The Impact of Co infection of Influenza A Virus on the on Severity of Middle East Respiratory Syndrome Coronavirus Journal of Infection 2017 doi 10 1016 j jinf 2017 02 001 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting typesetting and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content and all legal disclaimers that apply to the journal pertain M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 1 The Impact of Co infection of Influenza A Virus on the on Severity of Middle East Respiratory Syndrome Coronavirus Sarah H Alfaraj1 Jaffar A Al Tawfiq 2 3 Nojoom A Alzahrani4 Talal Altwaijri 5 Ziad A Memish6 7 1Corona Center Infectious Diseases Division Department of Pediatric Prince Mohamed Bin Abdulaziz Hospital Ministry of Health Riyadh Saudi Arabia 2Johns Hopkins Aramco Healthcare Dhahran Kingdom of Saudi Arabia 3Indiana University School of Medicine Indianapolis IN USA 4Corona Center Practitioner Corona Center Department Prince Mohamed Bin Abdulaziz Hospital Ministry of Health Riyadh Saudi Arabia 5Department of Surgery Prince Mohamed Bin Abdulaziz Hospital Ministry of Health Riyadh Saudi Arabia 6School of Public Health Emory University Atlanta GA USA 7Infectious Diseases Division Department of Medicine Prince Mohamed Bin Abdulaziz Hospital Ministry of Health Riyadh Saudi Arabia Key word Middle East Respiratory Syndrome Coronavirus MERS CoV Influenza Co infection All authors have no conflict of interest to report M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 2 Ho and colleagues recently drew attention to the consequences of co infection with Influenza and HIV 1 We present four cases of combined infection with influenza and Middle East Respiratory Syndrome Coronavirus MERS CoV infection Nasopharyngeal swabs or tracheal aspirates were tested for MERS CoV using real time reverse transcription polymerase chain reaction RT PCR 2 3 Samples were tested for Influenza A B and H1N1 by rapid molecular test GenEXper for detection of flu A B and 2009 H1N1 Cepheid CASE 1 A 39 year old male health care worker an engineer who became ill seven days before admission He had fever 38 C cough and sore throat He also had no nausea vomiting diarrhea and shortness of breathing SOB He had no history of travel or contact with positive case or camels He was febrile with a temperature of 39 50C Chest X ray showed non homogenous opacity at the lower right lung zone A nasopharyngeal swab was positive for MERS CoV with Ct value UPE GENE 34 ORF1A 34 Table 1 The test was negative for influenza but a repeat swab after 48 hrs was negative for MERS CoV and positive for H1N1 The patient received azithromycin ceftriaxone and oseltamivir The patient was discharged home after two negative swabs of MERS CoV and being asymptomatic for 48 hours CASE 2 A 61 year old female with diabetes mellitus and dyslipidemia was admitted with a three day history of shortness of breath and productive cough She also had no nausea vomiting and diarrhea She has no history of travel or contact with positive case or camels She was afebrile with a temperature of 370C Chest x ray showed patchy opacities involving middle and lower zones of both lung fields M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 3 A nasopharyngeal swab was positive for MERS CoV with Ct value upE gene 34 ORF1A 35 and negative for influenza A repeated swab after 48 hrs was negative for MERS CoV but positive for H1N1 She required BIPAP and she was subsequently intubated and was started on mechanical ventilation She was extubated after 13 days The patient received piperacillin tazobactam and erythromycin The patient was discharged home after she had 2 negative swabs of MERS CoV and being asymptomatic for 48 hours CASE 3 A 29 year old housekeeper female was admitted with two days history of fever and cough She had no nausea vomiting diarrhoea nor shortness of breathing She had a history of contact with MERS CoV positive case She was afebrile with a temperature of 36 90C Chest x ray was normal A nasopharyngeal swab collected upon presentation was positive for MERS CoV with CT value upE gene 32 ORF1A 32 The swab was negative for influenza A repeated swab after 48hrs was positive MERS CoV and positive for H1N1 The patient received oseltamivir azithromycin and ceftriaxone The patient was discharged home after she had 2 negative swab of MERS CoV and she was asymptomatic for 48 hours CASE 4 The patient was a 73 year old female with a history of hypothyroidism heart failure lymphoma and lung fibrosis She has no history of travel or contact with positive case or camels Four days prior to her presentation she had productive cough and shortness of breath She had no fever diarrhea vomiting or nausea She was afebrile with a temperature of 36 70C Chest X ray showed bilateral diffuse Figure 1 A nasopharyngeal swab was positive for MERS CoV with Ct value upE gene 37 ORF1A 36 and negative for Influenza A repeat swab after 3 days was M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 negative for MERS CoV but positive for influenza A The patient was treated with piperacillin tazobactam for six days and oseltemavir for 5 Days The patient was discharged home after two negative MERS CoV and she was asymptomatic for 48 hours These patients highlight the co infection with MERS CoV and influenza The exact reason to have a negative influenza test at the time of positive MERS CoV is not completely understood It is possible that the presence of MERS CoV inhibits the PCR reaction for influenza virus However an earlier case of MERS CoV tested initially positive for influenza A H1N1 pdm09 4 On the other hand the positivity of nasal swabs for influenza is specimen and method dependent 5 Thus initially negative influenza tests could be a false test result Positive results for viral respiratory pathogens should not preclude testing for MERS CoV because co infection can occur 6 Only a small number of MERS cases had co infection with influenza A parainfluenza herpes simplex and Streptococcus pneumoniae 7 In one case a co infection with Herpes simplex virus type 1 DNA13 and rhinovirus RNA14 were detected by RT PCR 8 The investigation of the first 47 cases showed no co infection with MERS CoV 2 There is a controversy regarding the risk of increased or decreased severity of co infections For example co infections with Respiratory Syncytial Virus RSV and human meta pneumovirus hMPV causes more severe infection than either virus alone with longer hospitalization and oxygen requirement 9 Other studies did not demonstrate these effects 10 The association and the impact of co infection with MERS CoV and influenza viruses deserve further evaluation and studies M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 References 1 Ho A Aston SJ Mitchell T Alaerts M Menyere M Mallewa J et al The impact of HIV on the burden and severity of influenza illness in Malawian adults The bash flu study J Infect 2015 71 687 8 doi 10 1016 j jinf 2015 09 030 2 Assiri A Al Tawfiq JA Al Rabeeah AA Al Rabiah FA Al Hajjar S Al Barrak A et al Epidemiological demographic and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia A descriptive study Lancet Infect Dis 2013 13 752 61 doi 10 1016 S1473 3099 13 70204 4 3 Corman VM M ller MA Costabel U Timm J Binger T Meyer B et al Assays for laboratory confirmation of novel human coronavirus hCoV EMC infections Euro Surveill 2012 17 49 4 Health Protection Agency HPA UK Novel Coronavirus Investigation team Evidence of person to person transmission within a family cluster of novel coronavirus infections United Kingdom February 2013 Euro Surveill 2013 18 20427 5 Cunha BA Dumont M Abruzzo E An adult returned traveler from Dubai hospitalized with an influenza like illness ILI Middle East Respiratory Syndrome MERS or influenza Infection control implications from a near MERS case Infect Control Hosp Epidemiol 2015 36 858 60 doi 10 1017 ice 2015 91 6 Saudi Ministry of Health Case Definition and Surveillance Guidance for MERS CoV Testing in Saudi 2014 M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 6 http www moh gov sa en Documents MoHCaseDefinitionMERSCoVVersionMay13201 4 pdf accessed January 17 2017 7 World Health Organization WHO guidelines for investigation of cases of human infection with Middle East Respiratory Syndrome Coronavirus MERS CoV 2013 http www who int csr disease coronavirus infections MERS CoV investigation guideli ne Jul13 pdf accessed January 17 2017 8 Drosten C Seilmaier M Corman VM Hartmann W Scheible G Sack S et al Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection Lancet Infect Dis 2013 13 745 51 doi 10 1016 S1473 3099 13 70154 3 9 Konig B Konig W Arnold R Werchau H Ihorst G Forster J Prospective Study of Human Metapneumovirus Infection in Children Less Than 3 Years of Age J Clin Microbiol 2004 42 4632 5 doi 10 1128 JCM 42 10 4632 4635 2004 10 Debiaggi M Canducci F Ceresola ER Clementi M The role of infections and coinfections with newly identified and emerging respiratory viruses in children Virol J 2012 9 247 doi 10 1186 1743 422X 9 247 M A N U S C R I P T A C C E P T E D A CCEPTED MANUSCRIPT 7 Table 1 A Summary of the Four Cases of Co Infection of MERS CoV and Influenza Age Gender Symptoms Comorbidity Sample Type Viral Load CT Value upE gene Co Infection CXR Intensive Care Outcome Days ill before Hospitalisation Oxygen requirement 1 39 Male Fever cough sore throat None NPS 34 H1N1 Non homogenous opacity in lower right lung zone clear both NO Discharged home 7 Nil 2 61 Female Productive cough SOB DM hypothyroidism NPS 35 H1N1 Patchy opacities involving middle and lower zones of both lung fields YES Discharged home 3 Ventilator for 13 days 3 29 Female Fever cough None NPS 32 H1N1 Normal NO Discharged home 2 Nil 4 73 Female SOB productive cough CHF hypothyroidism NPS 36 Influenza A Bilateral diffuse infiltrate NO Discharged home 4 Nasal Canula NPS nasopharyngeal swab DM diabetes mellitus SOB shortness of breath CHF congestive heart failure M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 8 Figure 1 A Chest Radiograph showing bilateral diffuse opacities