A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization

Peterhoff, David; Glück, Vivian; Vogel, Mathias; Schuster, Philipp; Schütz, Alexander; Neubert, Philip; Albert, Veruschka; Frisch, Stefanie; Kiessling, Mara; Pervan, Philip; Werner, Maren Caroline Frogner; Ritter, Nicole; Babl, Leon; Deichner, Maria; Hanses, Frank; Lubnow, Matthias; Müller, Thomas; Lunz, Dirk; Hitzenbichler, Florian; Audebert, Franz; Hähnel, Viola; Offner, Robert; Müller, Martina; Schmid, Stephan; Burkhardt, Ralph; Glück, Thomas; Koller, Michael; Niller, Hans Helmut; Graf, Bernhard M.; Salzberger, Bernd; Wenzel, Jürgen J.; Jantsch, Jonathan; Gessner, André; Schmidt, Bárbara; Wagner, Ralf

doi:10.1007/s15010-020-01503-7

Cited by 130 publications

(161 citation statements)

References 39 publications

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“…PLOS ONE [23] and IgG, IgA and IgM sensitivities of 96%, 92% and 98% respectively, for 53 samples >10 days post first positive COVID-19 PCR [24]. One possibility for the variability between all these studies including ours are differences in COVID-19 diagnosis between countries.…”

Section: Plos Onementioning

confidence: 75%

Testing IgG antibodies against the RBD of SARS-CoV-2 is sufficient and necessary for COVID-19 diagnosis

et al. 2020

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The COVID-19 pandemic and the fast global spread of the disease resulted in unprecedented decline in world trade and travel. A critical priority is, therefore, to quickly develop serological diagnostic capacity and identify individuals with past exposure to SARS-CoV-2. In this study serum samples obtained from 309 persons infected by SARS-CoV-2 and 324 of healthy, uninfected individuals as well as serum from 7 COVID-19 patients with 4–7 samples each ranging between 1–92 days post first positive PCR were tested by an “in house” ELISA which detects IgM, IgA and IgG antibodies against the receptor binding domain (RBD) of SARS-CoV-2. Sensitivity of 47%, 80% and 88% and specificity of 100%, 98% and 98% in detection of IgM, IgA and IgG antibodies, respectively, were observed. IgG antibody levels against the RBD were demonstrated to be up regulated between 1–7 days after COVID-19 detection, earlier than both IgM and IgA antibodies. Study of the antibody kinetics of seven COVID 19 patients revealed that while IgG levels are high and maintained for at least 3 months, IgM and IgA levels decline after a 35–50 days following infection. Altogether, these results highlight the usefulness of the RBD based ELISA, which is both easy and cheap to prepare, to identify COVID-19 patients even at the acute phase. Most importantly our results demonstrate that measuring IgG levels alone is both sufficient and necessary to diagnose past exposure to SARS-CoV-2.

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Section: Plos Onementioning

confidence: 75%

Testing IgG antibodies against the RBD of SARS-CoV-2 is sufficient and necessary for COVID-19 diagnosis

et al. 2020

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“…Virus production. We used previously described patient-derived SARS-CoV-2 isolates 86,87 propagated on Vero cells. To make high-titre viral stocks, we used TMPRSS2-Vero E6 cells, which were infected at a multiplicity of infection (MOI) of 0.005 plaque-forming units (p.f.u.)…”

Section: Generation Of Larp1 Knockout Cell Lines Using Crispr-cas9mentioning

confidence: 99%

The SARS-CoV-2 RNA–protein interactome in infected human cells

et al. 2020

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Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.

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“…Moreover, given that many of the SARS-CoV-2 neutralizing epitopes are located in the viral receptor binding domain (RBD) of the Spike (S) protein (21)(22)(23)(24)(25)(26)(27)(28)(29), it is important to evaluate the relationship between RBD-specific IgG titers and neutralizing antibody responses.…”

Section: Introductionmentioning

confidence: 99%

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

Nayak¹,

Gottimukkala²,

Kumar³

et al. 2020

Preprint

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India is one of the countries most affected by the recent COVID-19 pandemic. Characterization of humoral responses to SARS-CoV-2 infection, including immunoglobulin isotype usage, neutralizing activity and memory B cell generation, is necessary to provide critical insights on the formation of immune memory in Indian subjects. In this study, we evaluated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG, IgM, and IgA antibody responses, neutralization of live virus, and RBD-specific memory B cell responses in pre-pandemic healthy versus convalescent COVID-19 individuals from India. We observed substantial heterogeneity in the formation of humoral and B cell memory post COVID-19 recovery. While a vast majority (38/42, 90.47%) of COVID-19 recovered individuals developed SARS-CoV-2 RBD-specific IgG responses, only half of them had appreciable neutralizing antibody titers. RBD-specific IgG titers correlated with these neutralizing antibody titers as well as with RBD-specific memory B cell frequencies. In contrast, IgG titers measured against SARS-CoV-2 whole virus preparation, which includes responses to additional viral proteins besides RBD, did not show robust correlation. Our results suggest that assessing RBD-specific IgG titers can serve as a surrogate assay to determine the neutralizing antibody response. These observations have timely implications for identifying potential plasma therapy donors based on RBD-specific IgG in resource-limited settings where routine performance of neutralization assays remains a challenge.ImportanceOur study provides an understanding of SARS-CoV-2-specific neutralizing antibodies, binding antibodies and memory B cells in COVID-19 convalescent subjects from India. Our study highlights that PCR-confirmed convalescent COVID-19 individuals develop SARS-CoV-2 RBD-specific IgG antibodies, which correlate strongly with their neutralizing antibody titers. RBD-specific IgG titers, thus, can serve as a valuable surrogate measurement for neutralizing antibody responses. These finding have timely significance for selection of appropriate individuals as donors for plasma intervention strategies, as well as determining vaccine efficacy.

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A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization

Cited by 130 publications

References 39 publications

Testing IgG antibodies against the RBD of SARS-CoV-2 is sufficient and necessary for COVID-19 diagnosis

Testing IgG antibodies against the RBD of SARS-CoV-2 is sufficient and necessary for COVID-19 diagnosis

The SARS-CoV-2 RNA–protein interactome in infected human cells

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

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