Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

Berislav Bošnjak,Stefan Pöhlmann,Nina Gödecke,Jörg Martens,Reinhold Förster,Günter Bernhardt,Marius M Hoeper,Rainer Blasczyk,Saskia C Stein ,Wolfram Puppe,Thomas F Schulz,Anne Cossmann,Hannah Kleine-Weber,Georg M N Behrens,Christian Schultze-Florey ,Stefanie Willenzon,Isabelle Pink,Inga Ravens,Anna-Lena Cordes ,Mustafa Yılmaz ,Christiane Ritter,Markus Hoffmann

doi:10.1038/s41423-020-00573-9

Abstract

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

Highlights

Within 6 months since its emergence, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread rapidly worldwide
Most individuals with mild COVID-19 disease develop anti-SARSCoV-2 antibodies Between March 23rd and May 11th 2020, we enrolled as a first step 50 convalescent COVID-19 patients diagnosed with SARS-CoV-2 infection by RT-PCR and 12 healthy control subjects who were not exposed to SARS-CoV-2
We validated this assay by comparing data from the surrogate virus neutralization test (sVNT) with those derived from a classical pVNT and found a strong correlation between the results obtained with these two tests, which is in line with the results of Tan et al.[30]

Summary

Introduction

Within 6 months since its emergence, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread rapidly worldwide. COVID-19 consists of a spectrum of clinical syndromes ranging from asymptomatic cases to mild, flu-like disease to severe illness requiring hospitalization mainly due to pulmonary complications.[1,2,3] SARS-CoV-2 primarily targets the respiratory system, new data indicate that COVID-19 affects the vascular system, causing thrombotic microangiopathy and thrombosis in multiple organs, including the lungs.[4,5,6] It is not surprising, that patients with pre-existing cardiovascular diseases, hypertension, and other comorbidities are at particular risk.[7]. This early immune response is accompanied by severe lymphopenia,[12,13] increasing data indicate that successful recovery from COVID-19 relies on antibody and T-cell responses.[12,14,15,16,17]

Methods

Results

Conclusion