Abstract
While there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.
Highlights
severe acute respiratory syndrome (SARS)-CoV-2 causes severe, acute, and often fatal diseases in humans and is considered a global public threat[1,2,3,4]
We found that certain IgG fractions from convalescent plasma or serum samples completely inhibited the infectivity, replication, and cytopathicity of SARS-CoV-2; the strength of neutralization significantly varied from one case to another
When we determined neutralization activity in all the 43 COVID-19 patients at multiple time points; upon admission, during hospitalization, and after discharge, we identified three distinct patterns in temporal changes in neutralization activity: (i) Pattern 1, in which no significant neutralizing activity was seen throughout our observation periods, (ii) Pattern 2, in which substantial neutralization activity was seen by day 20–30 after disease onset and/or persisted during our observation periods up to 92 days after disease onset, and (iii) Pattern 3, in which significant neutralization activity was seen but decreased by > 60% within 9–50 days after the peaks seen in neutralization
Summary
SARS-CoV-2 causes severe, acute, and often fatal diseases in humans and is considered a global public threat[1,2,3,4]. Since passive transfer of antibodies has been shown to protect non-human primates from the lethal challenges with Ebola virus, such plasma therapy has been used to treat patients with Ebola virus disease, severe acute respiratory syndrome (SARS) and H1N1 influenza[6,7,8,9]. Disease severity*1*1 Characteristics Age, years Sex Men Women Clinical course Respiratory support None Oxygen inhalation Mechanical ventilation ECMO*2 Pneumonia Yes No Outcome Discharged Deceased Neutralizing activity*3 Yes No. in the present study, in order to examine the presence and persistence of neutralizing activity in the plasma or serum samples obtained from 43 COVID-19-convalescent cases employing cell-based assays and various virologic endpoints. We found that certain IgG fractions from convalescent plasma or serum samples completely inhibited the infectivity, replication, and cytopathicity of SARS-CoV-2; the strength of neutralization significantly varied from one case to another. The present data strongly suggest that neutralizing activity of plasma should be titrated prior to plasma collection and neutralizing plasma should be collected soon after the determination of neutralizing activity and that only plasma that contains good amounts of neutralizing antibodies should be administered to patients with COVID-19
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