Limited window for donation of convalescent plasma with high live-virus neutralizing antibodies for COVID-19 immunotherapy
Cardiff University review therapeutics
First Author: Gontu et al.
Journal/preprint name: bioRxiv
Paper DOI: https://doi.org/10.1101/2020.08.21.261909
Tags: Convalescent plasma, neutralisation, immunotherapy, antibody kinetics.
Summary
Convalescent plasma is used as immunotherapy for COVID-19 patients, however, the optimal timeframe for donation is currently unknown. 175 COVID-19 plasma donors were found to have robust IgM and IgG, and potent neutralisation responses to SARS-CoV-2 100 days post-symptom onset (DPO). Virus neutralisation capacity began to decline 60 DPO. Higher antibody titres were found in sera of those who were >30 years of age and had more severe disease, indicating this population as optimal donors for convalescent plasma. These data aid in understanding the persistence of serological responses to SARS-CoV-2, for immunotherapy in COVID-19 patients.
Research Highlights
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2.3% of 175 convalescent plasma donors had undetectable levels of IgM/IgG to the RBD or ectodomain of the S protein. Whilst, 25.4% had undetectable virus neutralisation titres.
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IgG and IgM titres were detectable until 140 DPO and peaked at 30 DPO. IgG levels were consistently higher, with IgM declining 60 DPO.
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80% of individuals had a virus neutralisation titre >160 (the FDA-recommended value for use in COVID-19 convalescent plasma therapy), until 60 DPO.
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RBD antibodies titres >1350 in early infection (1-30 DPO), were a promising marker for virus neutralisation titres >160. This may help in identifying good convalescent plasma donors.
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Only 8.3% of individuals had an increase in virus neutralisation capacity after the first blood donation, highlighting the importance of fast screening for donors.
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Those with more severe disease had higher antibody titres, as did those over 30 years of age. IgM titres also persisted longer in these groups.
Impact for COVID-19 research:
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Understanding serological responses to COVID-19 and optimal donor characteristics enables clinicians to improve convalescent plasma therapy.
Methodologies:
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Study Type: Cohort study.
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Important cell lines/viral models used: Vero E6 cells for virus neutralisation assay.
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Key Techniques: Virus neutralisation assay, recombinant S ectodomain and RBD ELISAs for IgG and IgM.
Limitations:
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No serum IgA analysis.