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Volume 26, Number 6—June 2020

Pharmacologic Treatments and Supportive Care for Middle East Respiratory Syndrome

Taylor Kain, Patrick J. Lindsay, Neill K.J. Adhikari, Yaseen M. Arabi, Maria D. Van Kerkhove, and Robert A. FowlerComments to Author 
Author affiliations: University of Toronto, Toronto, Ontario, Canada (T. Kain, P.J. Lindsay, N.K.J. Adhikari, R.A. Fowler); Harvard University, Boston, Massachusetts, USA (P.J. Lindsay); Sunnybrook Health Sciences Center, Toronto (N.K.J. Adhikari, R.A. Fowler); King Saud Bin Abdulaziz University for Health Center, Riyadh, Saudi Arabia (Y.M. Arabi); King Abdullah International Medical Research Center, Riyadh (Y.M. Arabi); World Health Organization, Geneva, Switzerland (M.D. Van Kerkhove)

Main Article

Table 2

Underlying conditions, age of study populations, overall mortality rates, and mortality rates by intervention (where applicable) for studies included in a systematic review of evidence for MERS treatment with pharmacologic and supportive therapies, by type of study*

Reference Age, y Underlying conditions
≥1 Diabetes mellitus CKD Mortality rate
Intervention Comparison Total
Nonrandomized, single-arm intervention study with historical comparisons
(12) 66 (median) NR 15 (47%) 16 (50%)
6 (19%) on dialysis IFN-β1a vs IFN-α2a 64% IFN-β1a 85% IFN-α2a 69%
(13) 46 (median ECMO); 50 (median no ECMO) NR 18 (51%) 5 (14%) ECMO 65% 100% 83%
66 y (mean)
30 (68%)
11 (26%)
RBV + IFN-α2a
14d: 30%; 28d: 70%
14d: 71%,28d: 83%
52% at 14 d; 77% at 28 d
Prospective cohort study
(15) 49 (mean) 11 (47%) 4 (13%)
NS 1 (25%) 1 (3%)
NS 0 (0%) NA NA NA 20%
57 (median)
5 (63%)
Retrospective cohort study
(17) 58 (mean steroids); 55 (mean no steroids) 132 (87%) steroids
115 (73%) no steroids 87 (58%) steroids
69 (44%) no steroids 43 (29%) steroids
47 (30%) no steroids Steroids 90-d 74%
Hospital 78% 58% 90-d
Hospital 58% 66%
(18) 58 (median) 265 (80%)
NS 199 (75%) 162 (49%)
NS 124 (77%) 100 (30%)
NS 80 (80%) MERS vs non-MERS SARI 66% 31% NA
(19) 59 (median) NR 17 (55%)
NS 13 (77%) 6 (19%)
NS 4 (75%) NA NA NA 70%
(20) 45 (median) NR 9 (31%)
NS 7 (78%) 8 (28%)
NS 8 (100%) NA NA NA 35%
(21) 54 (median) 12 (86%) 6 (43%) 6 (42%)
3 (21%) on dialysis NA NA NA 64% 90 d,
43% 28 d
(22) 54 (median) 36 (71%) 17 (33%)
NS 8 (47%) 14 (28%) had ESRD
NS 8 (57%) NA NA NA 37%
(23) 48 (mean) NR NR NR NA NA NA 25%
(24) 56 (median macrolides); 58 (median no macrolides) 106 (78%) vs. 175 (82%) 72 (53%) vs. 98 (46%) 41 (30%) vs. 68 (32%) Macrolides 60% 70% 66%
(25) 60 (median NIV); 58 (median IMV) 88 (84%) vs. 164 (83%) 62 (59%) vs. 95 (48%) 31 (30%) vs. 68 (35%) NIV 69% 76% 73%
58 (median RBV/IFN); 58 (no RBV/IFN)
121 (84%) vs. 160 (78%)
84 (58%) vs. 86 (42%)
53 (37%) vs. 56 (27%)
Case series without evaluation of treatment
(27) 58 (mean) 5 (100%) 4 (80%) 5 (100%) NA NA NA 100%
(28) 59 (median) NR 8 (67%) 5 (42%) NA NA NA 58% at 90 d, 42% at 28 d
(29) 57 vs 52 (median) NR 52 (49%) 21 (20%) NA 39% 54% 51%
(30) 59 (mean) 3 (50%) 0 (0%) 0 (0%) NA NA NA 60%
(31) 58 (mean) NR NR NR NA NA NA 63% (0% in included patients)

*CKD, chronic kidney disease; ESRD, end-stage renal disease; HCW, health-care workers; IFN, interferon; IMV, invasive mechanical ventilation; MERS, Middle East respiratory syndrome; NIV, noninvasive ventilation; NR, not reported; NS, nonsurvivors; NA, not applicable; RBV, ribavirin; SARI, severe acute respiratory infection.

Main Article

  1. ProMED-mail. Novel coronavirus—Saudi Arabia: human isolate. 2012 [cited 2018 Oct 29].
  2. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV). 2018 [cited 2019 Oct 10].
  3. World Health Organization. Epidemic and pandemic prone diseases—MERS situation update. 2018 [cited 2019 Oct 10].
  4. Zaki  AM, van Boheemen  S, Bestebroer  TM, Osterhaus  AD, Fouchier  RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:181420. DOIPubMedGoogle Scholar
  5. 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;13:75261. DOIPubMedGoogle Scholar
  6. Centers for Disease Control and Prevention. Fact sheet about Middle East respiratory syndrome (MERS). 2018 [cited 2018 Aug 1].
  7. Falzarano  D, de Wit  E, Martellaro  C, Callison  J, Munster  VJ, Feldmann  H. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci Rep. 2013;3:1686. DOIPubMedGoogle Scholar
  8. Falzarano  D, de Wit  E, Rasmussen  AL, Feldmann  F, Okumura  A, Scott  DP, et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med. 2013;19:13137. DOIPubMedGoogle Scholar
  9. Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:33641. DOIPubMedGoogle Scholar
  10. Sterne  JA, Hernán  MA, Reeves  BC, Savović  J, Berkman  ND, Viswanathan  M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. DOIPubMedGoogle Scholar
  11. Guyatt  GH, Oxman  AD, Vist  GE, Kunz  R, Falck-Ytter  Y, Alonso-Coello  P, et al.; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:9246. DOIPubMedGoogle Scholar
  12. 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;70:212932. DOIPubMedGoogle Scholar
  13. Alshahrani  MS, Sindi  A, Alshamsi  F, Al-Omari  A, El Tahan  M, Alahmadi  B, et al. Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus. Ann Intensive Care. 2018;8:3. DOIPubMedGoogle Scholar
  14. Omrani  AS, Saad  MM, Baig  K, Bahloul  A, Abdul-Matin  M, Alaidaroos  AY, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14:10905. DOIPubMedGoogle Scholar
  15. Hong  KH, Choi  JP, Hong  SH, Lee  J, Kwon  JS, Kim  SM, et al. Predictors of mortality in Middle East respiratory syndrome (MERS). Thorax. 2018;73:2869. DOIPubMedGoogle Scholar
  16. Al-Hameed  F, Wahla  AS, Siddiqui  S, Ghabashi  A, Al-Shomrani  M, Al-Thaqafi  A, et al. Characteristics and outcomes of Middle East respiratory syndrome coronavirus patients admitted to an intensive care unit in Jeddah, Saudi Arabia. J Intensive Care Med. 2016;31:3448. DOIPubMedGoogle Scholar
  17. Arabi  YM, Mandourah  Y, Al-Hameed  F, Sindi  AA, Almekhlafi  GA, Hussein  MA, et al.; Saudi Critical Care Trial Group. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197:75767. DOIPubMedGoogle Scholar
  18. 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;45:168395. DOIPubMedGoogle Scholar
  19. Almekhlafi  GA, Albarrak  MM, Mandourah  Y, Hassan  S, Alwan  A, Abudayah  A, et al. Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients. Crit Care. 2016;20:123. DOIPubMedGoogle Scholar
  20. Sherbini  N, Iskandrani  A, Kharaba  A, Khalid  G, Abduljawad  M, Al-Jahdali  H. Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data. J Epidemiol Glob Health. 2017;7:2936. DOIPubMedGoogle Scholar
  21. Khalid  I, Alraddadi  BM, Dairi  Y, Khalid  TJ, Kadri  M, Alshukairi  AN, et al. Acute management and long-term survival among subjects with Middle East respiratory syndrome coronavirus pneumonia and ARDS. Respir Care. 2016;61:3408. DOIPubMedGoogle Scholar
  22. Al Ghamdi  M, Alghamdi  KM, Ghandoora  Y, Alzahrani  A, Salah  F, Alsulami  A, et al. Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC Infect Dis. 2016;16:174. DOIPubMedGoogle Scholar
  23. Alfaraj  SH, Al-Tawfiq  JA, Assiri  AY, Alzahrani  NA, Alanazi  AA, Memish  ZA. Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study. Travel Med Infect Dis. 2019;29:4850. DOIPubMedGoogle Scholar
  24. Arabi  YM, Deeb  AM, Al-Hameed  F, Mandourah  Y, Almekhlafi  GA, Sindi  AA, et al.; Saudi Critical Care Trials group. Macrolides in critically ill patients with Middle East Respiratory Syndrome. Int J Infect Dis. 2019;81:18490. DOIPubMedGoogle Scholar
  25. Alraddadi  BM, Qushmaq  I, Al-Hameed  FM, Mandourah  Y, Almekhlafi  GA, Jose  J, et al.; Saudi Critical Care Trials Group. Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome. Influenza Other Respir Viruses. 2019;13:38290. DOIPubMedGoogle Scholar
  26. Arabi  YM, Shalhoub  S, Mandourah  Y, Al-Hameed  F, Al-Omari  A, Al Qasim  E, et al. Ribavirin and interferon therapy for critically ill patients with Middle East respiratory syndrome: a multicenter observational study. Clin Infect Dis. 2019;•••:ciz544. DOIPubMedGoogle Scholar
  27. Al-Tawfiq  JA, Momattin  H, Dib  J, Memish  ZA. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis. 2014;20:426. DOIPubMedGoogle Scholar
  28. Arabi  YM, Arifi  AA, Balkhy  HH, Najm  H, Aldawood  AS, Ghabashi  A, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:38997. DOIPubMedGoogle Scholar
  29. Alhumaid  S, Tobaiqy  M, Albagshi  M, Alrubaya  A, Algharib  F, Aldera  A, et al. MERS-CoV transmitted from animal-to-human vs MERS-CoV transmitted from human-to-human: comparison of virulence and therapeutic outcomes in a Saudi hospital. Trop J Pharm Res. 2018;17:115564. DOIGoogle Scholar
  30. Khalid  M, Khan  B, Al Rabiah  F, Alismaili  R, Saleemi  S, Rehan-Khaliq  AM, et al. Middle Eastern Respiratory Syndrome Corona Virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia. Ann Saudi Med. 2014;34:396400. DOIPubMedGoogle Scholar
  31. Al-Dorzi  HM, Aldawood  AS, Khan  R, Baharoon  S, Alchin  JD, Matroud  AA, et al. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study. Ann Intensive Care. 2016;6:10112. DOIPubMedGoogle Scholar
  32. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV) maps and epicurves Oct 2015. 2015 [cited 2019 Jul 25].
  33. Amsden  GW. Anti-inflammatory effects of macrolides—an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother. 2005;55:1021. DOIPubMedGoogle Scholar
  34. Morra  ME, Van Thanh  L, Kamel  MG, Ghazy  AA, Altibi  AMA, Dat  LM, et al. Clinical outcomes of current medical approaches for Middle East respiratory syndrome: A systematic review and meta-analysis. Rev Med Virol. 2018;28:e1977. DOIPubMedGoogle Scholar
  35. Momattin  H, Al-Ali  AY, Al-Tawfiq  JA. A systematic review of therapeutic agents for the treatment of Middle East respiratory syndrome coronavirus (MERS-CoV). Travel Med Infect Dis. 2019;30:918. DOIPubMedGoogle Scholar
  36. Beigel  JH, Voell  J, Kumar  P, Raviprakash  K, Wu  H, Jiao  JA, et al. A randomized placebo-controlled phase 1 safety and tolerability study of a novel human anti-MERS coronavirus polyclonal intravenous immunoglobulin produced from transchromosomic cattle. Lancet Infect Dis. 2018;18:4108. DOIPubMedGoogle Scholar
  37. Modjarrad  K, Roberts  CC, Mills  KT, Castellano  AR, Paolino  K, Muthumani  K, et al. Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis. 2019;19:101322. DOIPubMedGoogle Scholar
  38. Xu  J, Jia  W, Wang  P, Zhang  S, Shi  X, Wang  X, et al. Antibodies and vaccines against Middle East respiratory syndrome coronavirus. Emerg Microbes Infect. 2019;8:84156. DOIPubMedGoogle Scholar
  39. Han  HJ, Liu  JW, Yu  H, Yu  XJ. Neutralizing monoclonal antibodies as promising therapeutics against Middle East respiratory syndrome coronavirus infection. Viruses. 2018;10:68090. DOIPubMedGoogle Scholar
  40. Wuhan Municipal Health Commission. Report of clustering pneumonia of unknown etiology in Wuhan City. 2019 [cited 2020 Feb 15].
  41. Aguanno  R, Elldrissi  A, Elkholy  AA, Embarek  PB, Gardner  E, Grant  R, et al.; FAO-OIE-WHO MERS Technical Working Group. MERS: Progress on the global response, remaining challenges and the way forward. Antiviral Res. 2018;159:3544. DOIPubMedGoogle Scholar
  42. World Health Organization. WHO consultation on MERS-CoV therapeutics and vaccine evaluation. 2018 [cited 2020 Mar 14].

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