Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia

Yaseen M Arabi, Ali H Hajeer, Thomas Luke, Kanakatte Raviprakash, Hanan Balkhy, Sameera Johani, Abdulaziz Al-Dawood, Saad Al-Qahtani, Awad Al-Omari, Fahad Al-Hameed, Frederick G Hayden, Robert Fowler, Abderrezak Bouchama, Nahoko Shindo, Khalid Al-Khairy, Gail Carson, Yusri Taha, Musharaf Sadat, Mashail Alahmadi, Yaseen M Arabi, Ali H Hajeer, Thomas Luke, Kanakatte Raviprakash, Hanan Balkhy, Sameera Johani, Abdulaziz Al-Dawood, Saad Al-Qahtani, Awad Al-Omari, Fahad Al-Hameed, Frederick G Hayden, Robert Fowler, Abderrezak Bouchama, Nahoko Shindo, Khalid Al-Khairy, Gail Carson, Yusri Taha, Musharaf Sadat, Mashail Alahmadi

Abstract

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Keywords: ELISA; IFA; MERS; MERS-CoV; Middle East respiratory syndrome; Middle East respiratory syndrome coronavirus; Saudi Arabia; antibody titers; convalescent phase; convalescent plasma; convalescent-phase plasma; feasibility study; humans; immunotherapy; indirect immunofluorescent antibody assay; intensive care; microneutralization; neutralizing antibodies; respiratory infections; seroreactive; viruses.

Figures

Figure 1
Figure 1
Antibody test results for 443 persons in a study determining the feasibility of using convalescent plasma immunotherapy for Middle East respiratory coronavirus (MERS-CoV) infection, Saudi Arabia. rRT-PCR, real-time reverse transcription PCR.
Figure 2
Figure 2
Clinical and laboratory timeline for a Middle East respiratory coronavirus–infected patient with high ELISA, indirect immunofluorescent antibody (IFA), and microneutralization (MN) titers. The highest titers were measured while the patient had active infection and was critically ill. The ELISA optical density ratio and IFA and MN titers declined as the patient recovered. ICU, intensive care unit; rRT-PCR, real-time reverse transcription PCR; ward, hospital ward; −, negative; +, positive.
Figure 3
Figure 3
Correlation between ELISA optical density and antibody assay results in a study determining the feasibility of using convalescent plasma immunotherapy for Middle East respiratory coronavirus infection, Saudi Arabia. A) Correlation between ELISA and microneutralization assay results (Pearson correlation coefficient 0.70, p = 0.001). B) Correlation between ELISA and indirect immunofluorescent antibody (IFA) assay results (Pearson correlation coefficient 0.55, p = 0.015). C) Correlation between IFA and microneutralization assay results. (Pearson correlation coefficient 0.38, p = 0.12).

References

    1. 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;367:1814–20. 10.1056/NEJMoa1211721
    1. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV) [cited 2016 Jun 26].
    1. Korea Centers for Disease Control and Prevention. Middle East respiratory syndrome coronavirus outbreak in the Republic of Korea, 2015. Osong Public Health Res Perspect. 2015;6:269–78. 10.1016/j.phrp.2015.08.006
    1. Public Health England, International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Treatment of MERS-CoV: information for clinicians. Clinical decision-making support for treatment of MERS-CoV patients. V3.0 [cited 2016 Apr 29].
    1. Hung IF, To KK, Lee CK, Lee KL, Yan WW, Chan K, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013;144:464–73. 10.1378/chest.12-2907
    1. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3:e343. 10.1371/journal.pmed.0030343
    1. Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52:447–56. 10.1093/cid/ciq106
    1. Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145:599–609. 10.7326/0003-4819-145-8-200610170-00139
    1. Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24:44–6 .10.1007/s10096-004-1271-9
    1. Kong LK, Zhou BP. Successful treatment of avian influenza with convalescent plasma. Hong Kong Med J. 2006;12:489.
    1. Mair-Jenkins J, Saavedra-Campos M, Baillie K, Cleary P, Khaw FM, Lim WS, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015;211:80–90. 10.1093/infdis/jiu396
    1. Zhao J, Perera RA, Kayali G, Meyerholz D, Perlman S, Peiris M. Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection. J Virol. 2015;89:6117–20. 10.1128/JVI.00446-15
    1. Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, et al. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015;4:709. 10.1186/s40064-015-1490-9
    1. Centers for Disease Control and Prevention. CDC laboratory testing for Middle East respiratory syndrome coronavirus (MERS-CoV) [cited 2015 Sep 22].
    1. World Health Organization. Laboratory testing for Middle East respiratory syndrome coronavirus: interim recommendations (revised); September 2014. [cited 2015 Sep 22].
    1. Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, et al. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016;8:326ra21. 10.1126/scitranslmed.aaf1061
    1. World Health Organization. Guidelines on assessing donor suitability for blood donation [cited 2015 Sep 22].
    1. WHO Blood Regulators Network (BRN). Position paper on collection and use of convalescent plasma or serum as an element in Middle East respiratory syndrome coronavirus response [cited 2015 Sep 22].
    1. Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill. 2012;17:20285.
    1. 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. 10.1056/NEJMoa1405858
    1. Müller MA, Meyer B, Corman VM, Al-Masri M, Turkestani A, Ritz D, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect Dis. 2015;15:559–64. 10.1016/S1473-3099(15)70090-3
    1. Mou H, Raj VS, van Kuppeveld FJ, Rottier PJ, Haagmans BL, Bosch BJ. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J Virol. 2013;87:9379–83. 10.1128/JVI.01277-13
    1. Chu DK, Poon LL, Gomaa MM, Shehata MM, Perera RA, Abu Zeid D, et al. MERS coronaviruses in dromedary camels, Egypt. Emerg Infect Dis. 2014;20:1049–53. 10.3201/eid2006.140299
    1. Gierer S, Hofmann-Winkler H, Albuali WH, Bertram S, Al-Rubaish AM, Yousef AA, et al. Lack of MERS coronavirus neutralizing antibodies in humans, Eastern Province, Saudi Arabia. Emerg Infect Dis. 2013;19:2034–6. 10.3201/eid1912.130701
    1. Aburizaiza AS, Mattes FM, Azhar EI, Hassan AM, Memish ZA, Muth D, et al. Investigation of anti-middle East respiratory syndrome antibodies in blood donors and slaughterhouse workers in Jeddah and Makkah, Saudi Arabia, fall 2012. J Infect Dis. 2014;209:243–6. 10.1093/infdis/jit589
    1. Memish ZA, Alsahly A, Masri MA, Heil GL, Anderson BD, Peiris M, et al. Sparse evidence of MERS-CoV infection among animal workers living in southern Saudi Arabia during 2012. Influenza Other Respir Viruses. 2015;9:64–7. 10.1111/irv.12287
    1. Cao WC, Liu W, Zhang PH, Zhang F, Richardus JH. Disappearance of antibodies to SARS-associated coronavirus after recovery. N Engl J Med. 2007;357:1162–3. 10.1056/NEJMc070348
    1. Xie L, Liu Y, Fan B, Xiao Y, Tian Q, Chen L, et al. Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respir Res. 2005;6:5. 10.1186/1465-9921-6-5
    1. Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990;105:435–46. 10.1017/S0950268800048019
    1. Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, Burbelo PD, et al. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio. 2014;5:e00884–14. 10.1128/mBio.01002-14
    1. The Wall Street Journal. South Korea tries old weapon to fight MERS [cited 2015 Sep 22].
    1. Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, et al. Pre- and postexposure efficacy of fully human antibodies against spike protein in a novel humanized mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2015;112:8738–43. 10.1073/pnas.1510830112

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir