Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

doi:10.1016/j.ijid.2018.05.003

. 2018 Jul:72:8-10.

doi: 10.1016/j.ijid.2018.05.003. Epub 2018 May 9.

Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

Wan Beom Park¹, Leo L M Poon², Su-Jin Choi³, Pyoeng Gyun Choe⁴, Kyoung-Ho Song⁴, Ji Hwan Bang⁴, Eu Suk Kim⁴, Hong Bin Kim⁴, Sang Won Park⁴, Nam Joong Kim¹, Malik Peiris⁵, Myoung-Don Oh⁶

Affiliations

¹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Laboratory of Infection and Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea.
² School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong, China.
³ Laboratory of Infection and Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea.
⁴ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
⁵ School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address: malik@hku.hk.
⁶ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Laboratory of Infection and Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea. Electronic address: mdohmd@snu.ac.kr.

PMID: 29753119
PMCID: PMC7110884
DOI: 10.1016/j.ijid.2018.05.003

Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

Wan Beom Park et al. Int J Infect Dis. 2018 Jul.

. 2018 Jul:72:8-10.

doi: 10.1016/j.ijid.2018.05.003. Epub 2018 May 9.

Authors

Affiliations

¹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Laboratory of Infection and Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea.
² School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong, China.
³ Laboratory of Infection and Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea.
⁴ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
⁵ School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address: malik@hku.hk.
⁶ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Laboratory of Infection and Immunity, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea. Electronic address: mdohmd@snu.ac.kr.

PMID: 29753119
PMCID: PMC7110884
DOI: 10.1016/j.ijid.2018.05.003

Abstract

Background: Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. The detection of MERS-CoV sub-genomic mRNAs indicates that the virus is replicative. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens.

Methods: Upper and lower respiratory samples were obtained from 17 MERS-CoV-infected patients. MERS-CoV sub-genomic mRNA was detected by reverse transcription PCR (RT-PCR) and MERS-CoV genomic RNA by real-time RT-PCR.

Results: In sputum and transtracheal aspirate, sub-genomic mRNA was detected for up to 4 weeks after symptoms developed, which correlated with the detection of genomic RNA. In oropharyngeal and nasopharyngeal swab specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate.

Conclusions: These findings suggest that MERS-CoV does not replicate well in the upper respiratory tract.

Keywords: Coronavirus infections; Messenger; RNA; Respiratory system.

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Figures

**Figure 1**
Detection of Middle East respiratory syndrome coronavirus (MERS-CoV) sub-genomic mRNA in (A) sputum and transtracheal aspirates; (B) throat swabs; (C) nasopharyngeal swabs. A pink dot denotes a positive RT-PCR result for MERS-CoV sub-genomic mRNA, while a gray dot indicates a negative result. The blue lines indicate the duration from symptom onset to the last positive result for MERS-CoV genomic RNA. Patients A–I were in the severe group and patients J–Q were in the mild group. Among the severe group subjects, patients A–E received ventilator therapy, while patients F–I did not. 5UTR-S and 5UTR-N denote the sub-genomic mRNA of spike protein and nucleocapsid protein, respectively.

**Figure 2**
Middle East respiratory syndrome coronavirus (MERS-CoV) genomic RNA (*upE*) titers in sputum and transtracheal aspirates with vs. without sub-genomic mRNA detection. Solid lines indicate the mean and standard error of the mean. The dashed line indicates the detection limit.

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References

1. Corman V.M., Albarrak A.M., Omrani A.S., Albarrak M.M., Farah M.E., Almasri M. Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection. Clin Infect Dis. 2016;62:477–483. - PMC - PubMed
1. Memish Z.A., Assiri A.M., Al-Tawfiq J.A. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. Int J Infect Dis. 2014;29:307–308. - PMC - PubMed
1. Min C.K., Cheon S., Ha N.Y., Sohn K.M., Kim Y., Aigerim A. Comparative and kinetic analysis of viral shedding and immunological responses in mers patients representing a broad spectrum of disease severity. Sci Rep. 2016;6 - PMC - PubMed
1. Oh M.D., Park W.B., Choe P.G., Choi S.J., Kim J.I., Chae J. Viral load kinetics of MERS coronavirus infection. N Engl J Med. 2016;375:1303–1305. - PubMed
1. Park W.B., Perera R.A., Choe P.G., Lau E.H., Choi S.J., Chun J.Y. Kinetics of serologic responses to mers coronavirus infection in humans, South Korea. Emerg Infect Dis. 2015;21:2186–2189. - PMC - PubMed

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[1] Corman V.M., Albarrak A.M., Omrani A.S., Albarrak M.M., Farah M.E., Almasri M. Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection. Clin Infect Dis. 2016;62:477–483. - PMC - PubMed

[2] Corman V.M., Albarrak A.M., Omrani A.S., Albarrak M.M., Farah M.E., Almasri M. Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection. Clin Infect Dis. 2016;62:477–483. - PMC - PubMed

[3] Memish Z.A., Assiri A.M., Al-Tawfiq J.A. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. Int J Infect Dis. 2014;29:307–308. - PMC - PubMed

[4] Memish Z.A., Assiri A.M., Al-Tawfiq J.A. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. Int J Infect Dis. 2014;29:307–308. - PMC - PubMed

[5] Min C.K., Cheon S., Ha N.Y., Sohn K.M., Kim Y., Aigerim A. Comparative and kinetic analysis of viral shedding and immunological responses in mers patients representing a broad spectrum of disease severity. Sci Rep. 2016;6 - PMC - PubMed

[6] Min C.K., Cheon S., Ha N.Y., Sohn K.M., Kim Y., Aigerim A. Comparative and kinetic analysis of viral shedding and immunological responses in mers patients representing a broad spectrum of disease severity. Sci Rep. 2016;6 - PMC - PubMed

[7] Oh M.D., Park W.B., Choe P.G., Choi S.J., Kim J.I., Chae J. Viral load kinetics of MERS coronavirus infection. N Engl J Med. 2016;375:1303–1305. - PubMed

[8] Oh M.D., Park W.B., Choe P.G., Choi S.J., Kim J.I., Chae J. Viral load kinetics of MERS coronavirus infection. N Engl J Med. 2016;375:1303–1305. - PubMed

[9] Park W.B., Perera R.A., Choe P.G., Lau E.H., Choi S.J., Chun J.Y. Kinetics of serologic responses to mers coronavirus infection in humans, South Korea. Emerg Infect Dis. 2015;21:2186–2189. - PMC - PubMed

[10] Park W.B., Perera R.A., Choe P.G., Lau E.H., Choi S.J., Chun J.Y. Kinetics of serologic responses to mers coronavirus infection in humans, South Korea. Emerg Infect Dis. 2015;21:2186–2189. - PMC - PubMed

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Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

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Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

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