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

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.

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

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

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).