Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 25, Number 4—April 2019
Research

Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia

Hail M. Al-Abdely1, Claire M. Midgley1Comments to Author , Abdulrahim M. Alkhamis, Glen R. Abedi, Xiaoyan Lu, Alison M. Binder, Khalid H. Alanazi, Azaibi Tamin, Weam M. Banjar, Sandra Lester, Osman Abdalla, Rebecca M. Dahl, Mutaz Mohammed, Suvang Trivedi, Homoud S. Algarni, Senthilkumar K. Sakthivel, Abdullah Algwizani, Fahad Bafaqeeh, Abdullah Alzahrani, Ali Abraheem Alsharef, Raafat F. Alhakeem, Hani A. Aziz Jokhdar, Sameeh S. Ghazal, Natalie J. Thornburg, Dean D. Erdman, Abdullah M. Assiri, John T. WatsonComments to Author , and Susan I. Gerber
Author affiliations: Ministry of Health, Riyadh, Saudi Arabia (H.M. Al-Abdely, A.M. Alkhamis, K.H. Alanazi, W.M. Banjar, O. Abdalla, M. Mohammed, H.S. Algarni, A. Alzahrani, A.A. Alsharef, R.F. Alhakeem, H.A.A. Jokhdar, A.M. Assiri); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (C.M. Midgley, G.R. Abedi, X. Lu, A.M. Binder, A. Tamin, S. Lester, R.M. Dahl, S.K. Sakthivel, N.J. Thornburg, D.D. Erdman, J.T. Watson, S.I. Gerber); Princess Nourah Bint Abdulrahman University, Riyadh (W.M. Banjar); Prince Mohammed Bin Abdulaziz Hospital, Riyadh (A. Algwizani, F. Bafaqeeh, S.S. Ghazal)

Main Article

Figure 1

Timeline of clinical course and MERS-CoV detection, by patient, Saudi Arabia, August 1, 2015–August 31, 2016. Findings are presented by time since illness onset (day 0). Patients are grouped by illness severity and outcome. For each patient, day of admission, discharge or death, period of mechanical ventilation (if applicable), and MERS-CoV detection are depicted. For a subset of patients with sufficient data, the peak RNA level (or the minimum upstream of the envelope cycle threshold value) is

Figure 1. Timeline of clinical course and MERS-CoV detection, by patient, Saudi Arabia, August 1, 2015–August 31, 2016. Findings are presented by time since illness onset (day 0). Patients are grouped by illness severity and outcome. For each patient, day of admission, discharge or death, period of mechanical ventilation (if applicable), and MERS-CoV detection are depicted. For a subset of patients with sufficient data, the peak RNA level (or the minimum upstream of the envelope cycle threshold value) is depicted. Peak RNA was based on upper respiratory tract specimen results among group 1 patients and Pt 29, and lower respiratory tract specimen results in group 2 and group 3 patients. The date of death is shown for group 3 patients. Pt 11 and Pt 32 did not report any symptoms throughout their hospitalization. Pt 30 was hospitalized and mechanically ventilated before MERS onset because of a road traffic accident; this patient was excluded from severity and clinical course analyses. Pt 23 has been described previously (36). The first positive MERS-CoV rRT-PCR for Pt 20 was collected 1 day before symptom onset. BiPAP, bilevel positive airway pressure; CoV, coronavirus; MERS, Middle East respiratory syndrome; Pt, patient; rRT-PCR, real-time reverse transcription PCR.

Main Article

References
  1. Assiri  A, McGeer  A, Perl  TM, Price  CS, Al Rabeeah  AA, Cummings  DA, et al.; KSA MERS-CoV Investigation Team. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407–16. DOIPubMedGoogle Scholar
  2. Oboho  IK, Tomczyk  SM, Al-Asmari  AM, Banjar  AA, Al-Mugti  H, Aloraini  MS, et al. 2014 MERS-CoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372:846–54. DOIPubMedGoogle Scholar
  3. Arabi  YM, Al-Omari  A, Mandourah  Y, Al-Hameed  F, Sindi  AA, Alraddadi  B, et al.; Saudi Critical Care Trial Group. Critically ill patients with the Middle East respiratory syndrome: a multicenter retrospective cohort study. Crit Care Med. 2017;45:1683–95. DOIPubMedGoogle Scholar
  4. Arabi  YM, Balkhy  HH, Hayden  FG, Bouchama  A, Luke  T, Baillie  JK, et al. Middle East respiratory syndrome. N Engl J Med. 2017;376:584–94. DOIPubMedGoogle Scholar
  5. Ko  JH, Park  GE, Lee  JY, Lee  JY, Cho  SY, Ha  YE, et al. Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients. J Infect. 2016;73:468–75. DOIPubMedGoogle Scholar
  6. Senga  M, Arabi  YM, Fowler  RA. Clinical spectrum of the Middle East respiratory syndrome coronavirus (MERS-CoV). J Infect Public Health. 2017;10:191–4. DOIPubMedGoogle Scholar
  7. 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. DOIPubMedGoogle Scholar
  8. Saad  M, Omrani  AS, Baig  K, Bahloul  A, Elzein  F, Matin  MA, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301–6. DOIPubMedGoogle Scholar
  9. World Health Organization. Middle East respiratory syndrome coronaviurs (MERS-CoV) fact sheet [cited 2017 Oct 30]. https://www.who.int/en/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)
  10. Assiri  AM, Biggs  HM, Abedi  GR, Lu  X, Bin Saeed  A, Abdalla  O, et al. Increase in Middle East Respiratory syndrome-coronavirus cases in Saudi Arabia linked to hospital outbreak with continued circulation of recombinant virus, July 1–August 31, 2015. Open Forum Infect Dis. 2016;3:ofw165.
  11. Assiri  A, Abedi  GR, Bin Saeed  AA, Abdalla  MA, al-Masry  M, Choudhry  AJ, et al. Multifacility outbreak of Middle East respiratory syndrome in Taif, Saudi Arabia. Emerg Infect Dis. 2016;22:32–40. DOIPubMedGoogle Scholar
  12. Drosten  C, Meyer  B, Müller  MA, Corman  VM, Al-Masri  M, Hossain  R, et al. Transmission of MERS-coronavirus in household contacts. N Engl J Med. 2014;371:828–35. DOIPubMedGoogle Scholar
  13. Alraddadi  BM, Watson  JT, Almarashi  A, Abedi  GR, Turkistani  A, Sadran  M, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49–55. DOIPubMedGoogle Scholar
  14. World Health Organization. Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection—interim guidance [cited 2017 Oct 30]. https://www.who.int/csr/disease/coronavirus_infections/ipc-mers-cov/en
  15. World Health Organization. Management of asymptomatic persons who are RT-PCR positive for Middle East respiratory syndrome coronavirus (MERS-CoV) [cited 2018 Sep 20]. https://www.who.int/csr/disease/coronavirus_infections/management_of_asymptomatic_patients/en
  16. Memish  ZA, Assiri  AM, Al-Tawfiq  JA. 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;29:307–8. DOIPubMedGoogle Scholar
  17. Poissy  J, Goffard  A, Parmentier-Decrucq  E, Favory  R, Kauv  M, Kipnis  E, et al.; MERS-CoV Biology Group. Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases. J Clin Virol. 2014;61:275–8. DOIPubMedGoogle Scholar
  18. Oh  MD, Park  WB, Choe  PG, Choi  SJ, Kim  JI, Chae  J, et al. Viral load kinetics of MERS coronavirus infection. N Engl J Med. 2016;375:1303–5. DOIPubMedGoogle Scholar
  19. Corman  VM, Albarrak  AM, Omrani  AS, Albarrak  MM, Farah  ME, Almasri  M, et al. Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection. Clin Infect Dis. 2016;62:477–83.PubMedGoogle Scholar
  20. Memish  ZA, Al-Tawfiq  JA, Makhdoom  HQ, Assiri  A, Alhakeem  RF, Albarrak  A, et al. Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome. J Infect Dis. 2014;210:1590–4. DOIPubMedGoogle Scholar
  21. Feikin  DR, Alraddadi  B, Qutub  M, Shabouni  O, Curns  A, Oboho  IK, et al. Association of higher MERS-CoV virus load with severe disease and death, Saudi Arabia, 2014. Emerg Infect Dis. 2015;21:2029–35. DOIPubMedGoogle Scholar
  22. Guery  B, Poissy  J, el Mansouf  L, Séjourné  C, Ettahar  N, Lemaire  X, et al.; MERS-CoV study group. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet. 2013;381:2265–72. DOIPubMedGoogle Scholar
  23. 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. DOIPubMedGoogle Scholar
  24. Kim  SY, Park  SJ, Cho  SY, Cha  RH, Jee  HG, Kim  G, et al. Viral RNA in blood as indicator of severe outcome in Middle East respiratory syndrome coronavirus infection. Emerg Infect Dis. 2016;22:1813–6. DOIPubMedGoogle Scholar
  25. Min  CK, Cheon  S, Ha  NY, Sohn  KM, Kim  Y, Aigerim  A, et al. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci Rep. 2016;6:25359. DOIPubMedGoogle Scholar
  26. Shalhoub  S, Farahat  F, Al-Jiffri  A, Simhairi  R, Shamma  O, Siddiqi  N, et al. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother. 2015;70:2129–32. DOIPubMedGoogle Scholar
  27. Zhou  J, Li  C, Zhao  G, Chu  H, Wang  D, Yan  HH, et al. Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus. Sci Adv. 2017;3:eaao4966. PMID 29152574
  28. Choe  PG, Perera  RAPM, Park  WB, Song  KH, Bang  JH, Kim  ES, et al. MERS-CoV antibody responses 1 year after symptom onset, South Korea, 2015. Emerg Infect Dis. 2017;23:1079–84. DOIPubMedGoogle Scholar
  29. Shin  HS, Kim  Y, Kim  G, Lee  JY, Jeong  I, Joh  JS, et al. Immune responses to MERS coronavirus during the acute and convalescent phases of human infection. Clin Infect Dis. 2018.
  30. Park  WB, Perera  RA, Choe  PG, Lau  EH, Choi  SJ, Chun  JY, et al. Kinetics of serologic responses to MERS coronavirus infection in humans, South Korea. Emerg Infect Dis. 2015;21:2186–9. DOIPubMedGoogle Scholar
  31. Ko  JH, Müller  MA, Seok  H, Park  GE, Lee  JY, Cho  SY, et al. Serologic responses of 42 MERS-coronavirus-infected patients according to the disease severity. Diagn Microbiol Infect Dis. 2017;89:106–11. DOIPubMedGoogle Scholar
  32. Payne  DC, Iblan  I, Rha  B, Alqasrawi  S, Haddadin  A, Al Nsour  M, et al. Persistence of antibodies against Middle East respiratory syndrome coronavirus. Emerg Infect Dis. 2016;22:1824–6. DOIPubMedGoogle Scholar
  33. Saeed  AA, Abedi  GR, Alzahrani  AG, Salameh  I, Abdirizak  F, Alhakeem  R, et al. Surveillance and testing for Middle East respiratory syndrome coronavirus, Saudi Arabia, April 2015–February 2016. Emerg Infect Dis. 2017;23:682–5. DOIPubMedGoogle Scholar
  34. Corman  VM, Ölschläger  S, Wendtner  CM, Drexler  JF, Hess  M, Drosten  C. Performance and clinical validation of the RealStar MERS-CoV Kit for detection of Middle East respiratory syndrome coronavirus RNA. J Clin Virol. 2014;60:168–71. DOIPubMedGoogle Scholar
  35. Lu  X, Whitaker  B, Sakthivel  SK, Kamili  S, Rose  LE, Lowe  L, et al. Real-time reverse transcription-PCR assay panel for Middle East respiratory syndrome coronavirus. J Clin Microbiol. 2014;52:67–75. DOIPubMedGoogle Scholar
  36. Al-Abdely  HM, Midgley  CM, Alkhamis  AM, Abedi  GR, Tamin  A, Binder  AM, et al. Infectious MERS-CoV isolated from a mildly ill patient, Saudi Arabia. Open Forum Infect Dis. 2018;5:ofy111.
  37. Al-Abdallat  MM, Payne  DC, Alqasrawi  S, Rha  B, Tohme  RA, Abedi  GR, et al.; Jordan MERS-CoV Investigation Team. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59:1225–33. DOIPubMedGoogle Scholar
  38. Trivedi  S, Miao  C, Al-Abdallat  MM, Haddadin  A, Alqasrawi  S, Iblan  I, et al. Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection. J Med Virol. 2018;90:367–71. DOIPubMedGoogle Scholar
  39. Assiri  AM, Midgley  CM, Abedi  GR, Bin Saeed  A, Almasri  MM, Lu  X, et al. Epidemiology of a novel recombinant Middle East respiratory syndrome coronavirus in humans in Saudi Arabia. J Infect Dis. 2016;214:712–21. DOIPubMedGoogle Scholar
  40. Sabir  JS, Lam  TT, Ahmed  MM, Li  L, Shen  Y, Abo-Aba  SE, et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science. 2016;351:81–4. DOIPubMedGoogle Scholar
  41. World Health Organization. Diabetes country profile, Saudi Arabia [cited 2017 Dec 26]. https://www.who.int/diabetes/country-profiles/sau_en.pdf
  42. International Diabetes Federation. Age-adjusted prevalence of diabetes (20–79), Saudi Arabia, 2017 [cited 2017 Dec 26]. http://www.diabetesatlas.org/across-the-globe.html
  43. Badawi  A, Ryoo  SG. Prevalence of diabetes in the 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus: a systematic review and meta-analysis. J Public Health Res. 2016;5:733. DOIPubMedGoogle Scholar
  44. Banik  GR, Alqahtani  AS, Booy  R, Rashid  H. Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia. Virol Sin. 2016;31:81–4. DOIPubMedGoogle Scholar
  45. Choi  WS, Kang  CI, Kim  Y, Choi  JP, Joh  JS, Shin  HS, et al.; Korean Society of Infectious Diseases. Clinical presentation and outcomes of Middle East respiratory syndrome in the Republic of Korea. Infect Chemother. 2016;48:118–26. DOIPubMedGoogle Scholar
  46. Kim  ES, Choe  PG, Park  WB, Oh  HS, Kim  EJ, Nam  EY, et al. Clinical progression and cytokine profiles of Middle East respiratory syndrome coronavirus infection. J Korean Med Sci. 2016;31:1717–25. DOIPubMedGoogle Scholar
  47. Kim  KH, Tandi  TE, Choi  JW, Moon  JM, Kim  MS. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications. J Hosp Infect. 2017;95:207–13. DOIPubMedGoogle Scholar

Main Article

1These first authors contributed equally to this article.

Page created: March 18, 2019
Page updated: March 18, 2019
Page reviewed: March 18, 2019
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external