Limited window for donation of convalescent plasma with high live-virus neutralizing antibodies for COVID-19 immunotherapy

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  

1. 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. 

2.  IgG and IgM titres were detectable until 140 DPO and peaked at 30 DPO. IgG levels were consistently higher, with IgM declining 60 DPO. 

3. 80% of individuals had a virus neutralisation titre >160 (the FDA-recommended value for use in COVID-19 convalescent plasma therapy), until 60 DPO. 

4. 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. 

5. 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. 

6. 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:  

• Understanding serological responses to COVID-19 and optimal donor characteristics enables clinicians to improve convalescent plasma therapy.  

Methodologies: 

• Study Type: Cohort study. 

• Important cell lines/viral models used: Vero E6 cells for virus neutralisation assay. 

• Key Techniques: Virus neutralisation assay, recombinant S ectodomain and RBD ELISAs for IgG and IgM. 

Limitations: 

• No serum IgA analysis.