Abstract
BackgroundTransfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients.MethodsPlasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients.ResultsAnti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients.ConclusionOur results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.
Highlights
The COVID-19 pandemic is exacting a terrible toll on societies and health systems worldwide
Venipuncture blood samples from 93 COVID-19 convalescent plasma (CCP) donors from the San Francisco Bay Area in California who donated CCP at Stanford Blood Center from 4/ 14/2020 to 8/25/2020, as well as from 16 COVID-19 patients admitted to Stanford Hospital were collected in sodium heparinor K2EDTA-coated vacutainers and plasma was used for serology testing, N-antigenemia testing, and rRT-PCR detection of RNAemia
We studied the SARS-CoV-2-specific humoral immune response in 172 CCP samples collected from 93 non-hospitalized outpatients (Table 1)
Summary
The COVID-19 pandemic is exacting a terrible toll on societies and health systems worldwide. Transfusion of COVID-19 convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies may have therapeutic benefit for COVID-19 patients until more efficacious therapeutics are widely available. CCP efficacy in all COVID-19 patients is equivocal [6,7,8], recent studies suggest that high-titer CCP administered to patients early in disease course may be protective [9,10,11,12], a practice recently recommended by the FDA [13]. Since the majority of SARS-CoV-2-infected individuals, and potential CCP donors, are mildly ill outpatients, we have sought to determine the patient characteristics associated with higher antibody titers in these individuals. Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients
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