Respiratory Tract Samples, Viral Load, and Genome Fraction Yield in Patients With Middle East Respiratory Syndrome

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Abstract

Background. Analysis of clinical samples from patients with new viral infections is critical to confirm the diagnosis, to specify the viral load, and to sequence data necessary for characterizing the viral kinetics, transmission, and evolution. We analyzed samples from 112 patients infected with the recently discovered Middle East respiratory syndrome coronavirus (MERS-CoV).

Methods. Respiratory tract samples from cases of MERS-CoV infection confirmed by polymerase chain reaction (PCR) were investigated to determine the MERS-CoV load and fraction of the MERS-CoV genome. These values were analyzed to determine associations with clinical sample type.

Results. Samples from 112 individuals in which MERS-CoV was detected by PCR were analyzed, of which 13 were sputum samples, 64 were nasopharyngeal swab specimens, 30 were tracheal aspirates, and 3 were bronchoalveolar lavage specimens; 2 samples were of unknown origin. Tracheal aspirates yielded significantly higher MERS-CoV loads, compared with nasopharyngeal swab specimens ( P = .005) and sputum specimens ( P = .0001). Tracheal aspirates had viral loads similar to those in bronchoalveolar lavage samples ( P = .3079). Bronchoalveolar lavage samples and tracheal aspirates had significantly higher genome fraction than nasopharyngeal swab specimens ( P = .0095 and P = .0002, respectively) and sputum samples ( P = .0009 and P = .0001, respectively). The genome yield from tracheal aspirates and bronchoalveolar lavage samples were similar ( P = .1174).

Conclusions. Lower respiratory tract samples yield significantly higher MERS-CoV loads and genome fractions than upper respiratory tract samples.

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Most cited references 21

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Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Theo M. Bestebroer, Albert Osterhaus, Sander van Boheemen … (2012)

A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.

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Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

Abdullah Assiri, Jaffar Al-Tawfiq, Abdullah A Al-Rabeeah … (2013)

Summary Background Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. Methods We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. Findings 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Interpretation Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. Funding None.

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Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus

Abdullah Assiri, Allison McGeer, Trish M. Perl … (2013)

In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.

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Author and article information

Journal

Journal ID (nlm-ta): J Infect Dis

Journal ID (iso-abbrev): J. Infect. Dis

Journal ID (publisher-id): jid

Journal ID (hwp): jinfdis

Title: The Journal of Infectious Diseases

Publisher: Oxford University Press

ISSN (Print): 0022-1899

ISSN (Electronic): 1537-6613

Publication date (Print): 15 November 2014

Publication date (Electronic): 15 May 2014

Volume: 210

Issue: 10

Pages: 1590-1594

Affiliations

[1 ] Global Centre for Mass Gatherings Medicine and Ministry of Health, Riyadh, Kingdom of Saudi Arabia and College of Medicine, Alfaisal University,

[2 ] Regional Laboratory, Ministry of Health

[3 ] Prince Sultan Military Medical City

[4 ] Pediatric Infectious Diseases, King Saud University , Riyadh

[5 ] Saudi Aramco Medical Services Organization, Dhahran

[6 ] Regional Laboratory, Ministry of Health

[7 ] Special Infectious Diseases Agents Unit, King Fahad Medical Research Center, King Abdualziz University , Jeddah

[8 ] Regional Laboratory, Ministry of Health , Madinah

[9 ] Regional Laboratory, Ministry of Health , Dammam, Kingdom of Saudi Arabia

[10 ] Indiana University School of Medicine , Indianapolis

[11 ] Institute of Virology, University of Bonn Medical Center , Germany

[12 ] Wellcome Trust Sanger Institute , Hinxton,

[13 ] Division of Infection and Immunity, University College London (UCL), and UCL Hospitals National Health Service Foundation Trust , United Kingdom

Author notes

Correspondence: Ziad A. Memish, MD, FRCP(Can), FRCP(Edin), FRCP(Lond), FACP, WHO Collaborating Center for Mass Gathering Medicine, Ministry of Health, Riyadh 11176, Kingdom of Saudi Arabia ( zmemish@ 123456yahoo.com ).

Article

Publisher ID: jiu292

DOI: 10.1093/infdis/jiu292

PMC ID: 7107391

PubMed ID: 24837403

SO-VID: d81db3a5-889e-4cf0-9fb9-7024d6bc7ce5

Copyright © © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ 123456oup.com .

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This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

History

Date received : 28 March 2014

Date accepted : 6 May 2014

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Respiratory Tract Samples, Viral Load, and Genome Fraction Yield in Patients With Middle East Respiratory Syndrome

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European Respiratory Society: COVID-19

Most cited references 21

Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus

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