Jae-Hoon Ko1,2, Hyeri Seok1, Sun Young Cho1, Young Eun Ha1, Jin Yang Baek3, So Hyun Kim3, Yae-Jean Kim4, Jin Kyeong Park5, Chi Ryang Chung5, Eun-Suk Kang6, Duck Cho6, Marcel A Müller7,8, Christian Drosten7,8, Cheol-In Kang1, Doo Ryeon Chung1,3, Jae-Hoon Song1,3, Kyong Ran Peck1. 1. Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 2. Present address: Division of Infectious Diseases, Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea. 3. Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, Republic of Korea. 4. Division of Infectious Diseases, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 5. Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 6. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 7. Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany. 8. German Centre for Infection Research, Braunschweig, Germany.
Abstract
BACKGROUND: The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. METHODS: Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. RESULTS: Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. CONCLUSIONS: For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.
BACKGROUND: The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. METHODS: Serological responses of CP-infused MERSpatients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. RESULTS: Three of thirteen MERSpatients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. CONCLUSIONS: For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.
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