Sensitivity of anti-SARS-CoV-2 serological assays in a high-prevalence setting

Müller, Lisa; Ostermann, Philipp Niklas; Walker, Andreas; Wienemann, Tobias; Mertens, Alexander; Adams, Ortwin; Andrée, Marcel; Hauka, Sandra; Lübke, Nadine; Keitel, Verena; Drexler, Ingo; Cristanziano, Veronica Di; Hermsen, Derik; Kaiser, Rolf; Boege, Friedrich; Klein, Florian; Schaal, Heiner; Timm, Jörg; Senff, Tina

doi:10.1007/s10096-021-04169-7

Cited by 53 publications

(45 citation statements)

References 21 publications

(30 reference statements)

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“…By contrast, only a weak correlation between NAbs and anti-SARS-CoV-2 IgA antibodies (Euroimmun, Lübeck) was detected for both assays (cell culture assay: r = 0.55, sVNT assay: r = 0.32, see supplement). While data for the sVNT assay are lacking, a recent study of Müller et al has already shown a good correlation between a cell culture-based NAb assay and anti-SARS-CoV-2 IgG BAb ratios determined by using the Euroimmun ELISA assay [9]. As opposed to our data, the authors also showed a good correlation to anti-SARS-CoV-2 IgA antibody results.…”

Section: Discussioncontrasting

confidence: 98%

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A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories

Fischer

Lichtenberg

Mueller

et al. 2021

Preprint

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The determination of anti-SARS-CoV-2 neutralizing antibodies (NAbs) is of interest in many respects. High NAb titers, for example, are the most important criterion regarding the effectiveness of convalescent plasma therapy. However, common cell culture-based NAb assays are time-consuming and feasible only in special laboratories. Our data reveal the suitability of a novel ELISA-based surrogate virus neutralization test (sVNT) to easily measure the inhibition-capability of NAbs in the plasma of COVID-19 convalescents. We propose a combined strategy to detect plasma samples with high NAb titers (≥ 1:160) reliably and to, simultaneously, reduce the risk of erroneously identifying low-titer specimens. For this approach, results of the sVNT assay are compared to and combined with those acquired from the Euroimmun anti-SARS-CoV-2 IgG assay. Both assays are appropriate for high-throughput screening in standard BSL-2 laboratories. Our measurements further show a long-lasting humoral immunity of at least 11 months after symptom onset.

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Section: Discussioncontrasting

confidence: 98%

“…The experimental procedure was performed as specified by the manufacturer [8]. The cell culture assay was performed as previously described [9]. In brief, a virus stock solution with the SARS-CoV-2 NRW-42 isolate (EPI ISL 425126 [10]) was added to a final concentration of 1000 TCID50/well to heat-inactivated and diluted plasma samples.…”

Section: Resultsmentioning

confidence: 99%

A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories

Fischer

Lichtenberg

Mueller

et al. 2021

Preprint

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“…The ECLIA technique has a good accuracy [3,49,50] and has been recommended for population screening [51]. Anti-SARS-CoV-2 antibodies obtained by ECLIA positively correlate with neutralising antibodies, but their sensitivity should be improved [52,53].…”

Section: Discussionmentioning

confidence: 99%

Persistence of Anti-SARS-CoV-2 Antibodies Six Months after Infection in an Outbreak with Five Hundred COVID-19 Cases in Borriana (Spain): A Prospective Cohort Study

Domènech-Montoliu¹,

Puig-Barberà

Pac-Sa³

et al. 2021

COVID

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In March 2020, several mass gathering events were related to the Falles festival in Borriana (Spain), resulting in a 536 laboratory-confirmed COVID-19 cases outbreak among participants. This article estimates anti-SARS-CoV-2 antibodies persistence six months after and factors associated with antibody response. A prospective population-based cohort study was carried out by the Public Health Centre of Castellon and the Emergency and Clinical Analysis and Microbiology Services of Hospital de la Plana in Vila-real. In October 2020, a seroepidemiologic study was used to estimate the persistence of anti-SARS-CoV-2 antibodies against nucleocapsid protein (N) by an electrochemiluminescence immunoassay (ECLIA) was implemented. We enrolled 484 (90.2%) of the 536 members of the initial outbreak cohort and detected persistent antibodies in 479 (99%) without reinfection episodes. Five participants had a negative antibody test. Factors associated with a negative result were a lower body mass index (BMI), and less contact with other COVID-19 cases. Among the 469 participants with two ECLIA tests, 96 (20.5%) had an increase of antibodies and 373 (79.5%) a decline. Increased antibodies were associated with older age, higher BMI, more severe illness, and low current smokers. Our results show that after a COVID-19 infection, a high proportion of cases maintain detectable anti-SARS-CoV-2 antibodies.

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“…15 Numerous enzyme-linked immunosorbent assay (ELISA) kits to detect antibodies against SARS-CoV-2 are available on the market. Although recent studies demonstrated that there is a good correlation between the immunoglobulin G (IgG) titers, 16,17 a classical neutralization assay is still the method of choice to determine the antiviral activity of serum or plasma antibodies against SARS-CoV-2. 18 According to an EU guidance for COVID-19 convalescent plasma collection and transfusion, it is strongly recommended that defined SARS-CoV-2 neutralizing antibody titers be measured in the donated plasma.…”

Section: Introductionmentioning

confidence: 99%

Convalescent plasma treatment of critically ill intensive care COVID‐19 patients

et al. 2021

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Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may be life‐threatening, and specific antiviral drugs are currently not available. However, first studies indicated that convalescent plasma treatment might improve the clinical outcome of coronavirus disease 2019 (COVID‐19) patients. Study Design and Methods In the current study, we investigated the efficacy of convalescent plasma treatment in eight COVID‐19 patients. All the patients were critically ill, and seven of them were SARS‐CoV‐2 RNA–positive when starting treatment. SARS‐CoV‐2–specific antibodies were determined by an enzyme‐linked immunosorbent assay detecting immunoglobulin G (IgG) antibodies against the S1 protein (Euroimmun), and the neutralizing titers were determined with a cell‐culture‐based neutralization assay. Plasma treatment started between 4 and 23 days after the onset of symptoms. The patients were usually treated by three plasma units, each containing 200–280 ml, which was applied at day 1, 3, and 5. Results Donor sera had on average lower IgG antibody ratios and neutralizing titers than the COVID‐19 patients before the onset of treatment (median ratio of 5.8 and neutralizing titer of 1:320 vs. 7.5 and 1:640, respectively). Nevertheless, we observed an increase of antibody ratios in seven and of neutralizing titers in five patients after treatment; which did, however, not correlate with patient survival. Plasma treatment was effective in three patients, but five deceased despite treatment. Patients who deceased had a later treatment onset than survivors and finally died from multiple organ failure. Conclusion Our data indicate that the efficacy of convalescent plasma treatment of critically ill COVID‐19 patients who already had developed strong antiviral immune responses and organ complications is limited.

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Sensitivity of anti-SARS-CoV-2 serological assays in a high-prevalence setting

Cited by 53 publications

References 21 publications

A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories

A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories

Persistence of Anti-SARS-CoV-2 Antibodies Six Months after Infection in an Outbreak with Five Hundred COVID-19 Cases in Borriana (Spain): A Prospective Cohort Study

Convalescent plasma treatment of critically ill intensive care COVID‐19 patients

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