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Authors:J. Wu et al.  

Journal/ Pre-Print:medRxiv 

Key Words:antibody response 

Research Highlights

  1. Symptomatic COVID-19 patients exhibit an early and rapid IgM and IgG-S/N response peaking at week 3-5, followed by contraction phase where IgM disappears below detection level around week 10-13, whilst IgG-S/N stabilizes at relative high levels for at least six months after disease onset. 

  1. SARS-CoV-2 is controlled in COVID-19 patients with high levels of IgM-S/N and IgG-S/N at early time points of disease. 

  1. IgG-RBD-S titers correlated closely with the capacity to neutralize SARS-CoV-2 

Summary 

The authors have quantified IgM and IgG antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients of which 17 patients were sampled repetitively. IgM-S reached a peak of 94% at week 5 and then rapidly decreased to 0% at week 13. IgM-N a peak of 72% at week 3 and undetectable at week 10. IgG-S 97% at week 3 and remained relative high until week 26. IgG-N rose rapidly to 87% of the patients at week 2 and stayed at very high levels thereafter. Significant higher IgG S/N responses were observed in patients with non-severe symptoms at week 2High neutralizing activity was only found in conjunction with high IgG-S titersand not in plasma with high IgG-N titers or unilateral IgM responses.  

Impact for SARS-CoV2/COVID19 research efforts  

Understanding the immune response to SARS-CoV2/COVID19  

Study Type 

  • In vitro study 

  • Patient Case study 

Strengths and limitations of the paper 

Novelty: One of many recent papers longitudinally analysing antibody levels following SARS-CoV-2 infection (e.g. Long et al. Nat Med 2020, Wajnberg et al. 2020; Seow et al. 2020, and Iyer et al.) but follows patients the longest (up to 26 weeks post symptom onset). 

Standing in the field:How long-lasting antibody levels are post infection is currently a matter of scientific debate (Iyer et al; J. Seuw et al.) 

Appropriate statistics:Yes  

Viral model used:Strain BetaCoV/Wuhan/WIV04/2019, National Virus Resource Center number: IVCAS 6.7512 was used to test neutralization capacity of patient plasma. 

Translatability:This preprint shows that anti-viral antibody levels in symptomatic COVID-19 patients seems to follow a prototypical progression with an early expansion phase peaking around week 3followed by an contraction phase after which IgM disappears below detection levels at week 10-13 and a sustained memory phase for IgG up to end of study at 26 weeks. This has important implications both for the design of effective vaccines and long-term protective immunity following primary infection. 

Main limitations:  

  • They only focus on symptomatic patients, similar to another recent preprint (Iyer et al. 2020). 

  • As noted by the authors, due to restrictions samples at 9-11 weeks were limited and not all samples could be assessed for their neutralizing activity  

  • Only data of 15 donors that were repetitive sampled was used, in contrast to J. Seuw et al. that sampled 65 RT-qPCR confirmed SARS-CoV-2-infected individuals over sequential time points. 

  • No data on IgA that is also correlated to protective immunity against SARS-CoV-2. 

  • As shown in Figure 1D IgG Ab levels continuously decline albeit at a slow rate. We feel that to conclude that these titers ‘stabilize’ a stop in declination should be observed and we rather conclude that these IgG titers wane off slow but not stabilise.