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Authors: Lee et al. 

Journal/ Pre-PrintmedXriv 

Key Words: Immunology, Antibodies, Convalescent plasma therapy  

Research Highlights 

  1. Sera with high SARS-CoV-2 antibody levels (> 960 ELISA titres) showed maximal activity, but not all high titre sera contained neutralizing antibody (Ab) at FDA recommended levels, particularly at high stringency thresholds 

  1. No specific antibody titre level was shown to be an absolute predictor of neutralizing activity, especially if using a more stringent threshold.  

  1. Neutralizing antibody activity was not correlated with ELISA titres in all donors. 

Summary 

SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients were evaluated using plaque reduction neutralization tests at low (PRNT50) and high (PRNT90) stringency thresholds. A trend toward more neutralization with higher Ab titres was observed. However, only 50% of the sera at the highest Ab titre had neutralizing titres of 160 (as recommended by the FDA for convalescent plasma therapy) or greater when measured by PRNT90. Neutralizing activity was shown to increase with time post symptom onset (PSO), reaching a peak at 31-35 days PSO, at which point the number of sera having neutralizing titres of at least 160 was around 93% (PRNT50) and 54% (PRNT90). Beyond 35 days, the number of sera with high PRNT90 titres decreased significantly, with only 24% showing FDA recommended neutralizing titre levels. 

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Treatment of SARS-CoV2/COVID19 positive individuals 

Study Type  

  • In vitro study 

  • Patient Case study 

Strengths and limitations of the paper 

Novelty: Shows that even high antibody titres are not necessarily containing neutralizing antibodies  

Standing in the field:Confirms some previously reported findings in regard to titre levels of recovered COVID-19 patients (Wu et al. 2020), while at the same time not showing the same level of correlation between antibody levels and neutralizing activity as some other reports (Wu et al. 2020) 

Appropriate statistics:Yes 

Viral model used:Sera of COVID-19 recovered individuals 

Translatability: The results of this paper highlight the importance of screening not just for titre levels but also of neutralizing activity in order to select effective convalescent plasma and suggest that there is an optimal window for choosing the most effective sera for treatment 

Main limitations:  

  • They use two different cohorts from two different hospitals using different assays to measure antibody levels (ELISA and MIA). While showing in the paper that ELISA and MIA overall provide very similar results it would have been nice to stratify the separate sets better and not just combine them in most data sets shown. Also, not all donors were necessarily PCR confirmed to have been infected by SARS-CoV-2. 

  • Another caveat for the main message of this preprint (as also pointed out by the authors) is that it is actually not yet known what antibody titre and neutralizing activity levels are required to provide protection against SARS-CoV-2 (re)infection