Clinical Infectious Diseases. for the initial characterization of CCP. Hma-Qubec, the agency responsible for the blood supply in Quebec, Canada, is involved in the collection and testing of CCP used in a randomized open-label trial of Convalescent Plasma for Hospitalized Adults with Acute COVID-19 Respiratory Illness (CONCOR-1, clinicaltrials.gov identifier #NCT04348656) designed to determine the effect of CCP at reducing the risk of intubation or death in adult patients hospitalized for COVID-19. Potential donors were recruited after at least 14 days of resolution of COVID-19 symptoms (see supplemental Methods for additional information, available on the Web site). Initial diagnosis had been confirmed by public health authorities through either polymerase chain reaction or epidemiologic contact. All participants met the donor selection criteria for Omtriptolide plasma donation in use at Hma-Qubec and consented to the study. Omtriptolide Seropositivity (presence of antibodies against SARS-CoV-2 RBD) was determined using a semiquantitative ELISA (supplemental Methods) adapted from previous work.15,16 Consistent with previous reports on the rate of seroconversion of COVID-19 patients,17-19 the overall proportion of our convalescent plasma donors (n = 282) that were tested seronegative at the time of donation was 6.9%. However, this proportion increased to about 15% when considering only donors who had waited for more than 11 to 12 weeks after symptom onset before donating (supplemental Table). This prompted us to perform a longitudinal analysis of the anti-RBD antibody response in CCP donors (11 males and 4 females; median age, 56 years; range, 20-67 years) who donated at least 4 times, during a time interval after symptom onset ranging from 33 to 77 days for the first donation to 66 to 114 days for the last donation. These donors reported symptoms of different intensity (from mild/moderate to severe), although none of them were hospitalized for COVID-19. Changes from baseline measurements were modeled with the use of a linear mixed-effects model for repeated measures based on a participant-level analysis with Omtriptolide fixed effects for sex, age, and time since symptom onset (for more details, see supplemental Methods). As shown in Figure 1A, the level of anti-RBD antibodies at the first donation varies greatly between donors. However, a decrease in anti-RBD antibody level between first and last TEF2 donation was observed for all donors. To better illustrate the evolution of the anti-RBD antibody response over time, the relative level of anti-RDB antibodies was calculated at each time point using the first time point as reference (Figure 1B). In some donors, an increase was observed Omtriptolide after their first donation, but this was always followed by a decline in anti-RBD antibodies Omtriptolide at later time points. To rule out the possibility that the decline observed in all donors was a consequence of repeated donations, we determined the correlation between the number of donations and the overall decline in anti-RBD level, as defined using the maximal optical density (OD) and the OD at the last donation (ODlast donation/ODmax). As shown in Figure 1C, the decrease in anti-RBD levels did not correlate with the number of donations (= .417, = .1221). We then compared the decrease in anti-RBD level as a function of the time elapsed between the onset of symptoms and the time of the last donation (Figure 1D). The results revealed a significant correlation between these 2 parameters (= .821, = .0002), indicating that the anti-RBD response wanes over time of convalescence rather than because of repeated donations. Open in a separate window Figure 1. Longitudinal analysis of the anti-RBD antibody response in 15 repeat CCP donors. Males.
Clinical Infectious Diseases