Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Rijkers, Ger T.; Murk, Jean Luc; Wintermans, Bas; Looy, Bieke van; Berge, Marcel van den; Veenemans, Jacobien; Stohr, Joep; Reusken, Chantal; Pol, Pieter van der; Reimerink, Johan

doi:10.1093/infdis/jiaa463

Cited by 158 publications

(147 citation statements)

References 14 publications

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“…In summary, we observed that severe patients showed a strong antibody response in line with other observations (18,26,28,52,67). Levels of IgA and IgG in asymptomatic individuals returned to levels comparable to those measured in healthy contacts 6-8 weeks from the first positive swab.…”

Section: Adaptive Immunitysupporting

confidence: 90%

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

et al. 2020

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SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focused on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. In order to understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up, flow-cytometric and serological analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: 28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; eight patients with Mild COVID-19 disease and eight cases of Severe COVID-19 disease. Our data show that high frequency of NK cells and early and transient increase of specific IgA, IgM and, to a lower extent, IgG are associated with asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and different kinetics of antibodies are detected in mild COVID-19. The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.

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Section: Adaptive Immunitysupporting

confidence: 90%

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

et al. 2020

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“…This indicates a specificity of 99.2 (95% CI: 96.9-99.9) and 99.6 (95% CI: 97.5-99.9) for a 20% and 30% cut-off, respectively ( Figure 1B, 2A and Table 3). Furthermore, we analysed the relationship between the severity of COVID-19 disease and the clinical sensitivity of the sVNT as stronger immune responses were observed in severe vs mild cases 14,15 . We observed that the assay sensitivity increased with an increased disease severity, being higher in hospitalised patients vs outpatients, regardless of the time of sampling.…”

Section: Resultsmentioning

confidence: 99%

Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT)

Meyer

Reimerink²,

Torriani

et al. 2020

Emerging Microbes & Infections

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125

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To understand SARS-CoV-2 immunity after natural infection or vaccination, functional assays such as virus neutralising assays are needed. So far, assays to detect SARS-CoV-2 neutralising antibodies rely on cellculture based infection assays either using wild type SARS-CoV-2 or pseudotyped viruses. Such assays are labour-intensive, require appropriate biosafety facilities and are difficult to standardize. Recently, a new surrogate virus neutralisation test (sVNT) was described that uses the principle of an ELISA to measure the neutralisation capacity of anti-SARS-CoV-2 antibodies directed against the receptor binding domain. Here, we performed an independent evaluation of the robustness, specificity and sensitivity on an extensive panel of sera from 269 PCR-confirmed COVID-19 cases and 259 unmatched samples collected before 2020 and compared it to cell-based neutralisation assays. We found a high specificity of 99.2 (95%CI: 96.9-99.9) and overall sensitivity of 80.3 (95%CI: 74.9-84.8) for the sVNT. Clinical sensitivity increased between early (<14 days post symptom onset or post diagnosis, dpos/dpd) and late sera (>14 dpos/dpd) from 75.0 (64.7-83.2) to 83.1 (76.5-88.1). Also, higher severity was associated with an increase in clinical sensitivity. Upon comparison with cell-based neutralisation assays we determined an analytical sensitivity of 74.3 (56.4-86.9) and 98.2 (89.4-99.9) for titres ≥10 to <40 and ≥40 to <160, respectively. Only samples with a titre ≥160 were always positive in the sVNT. In conclusion, the sVNT can be used as an additional assay to determine the immune status of COVID-19 infected of vaccinated individuals but its value needs to be assessed for each specific context.

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“…20 ). A similar approach based on intensiometric detection of split NanoLuc complementation was recently published as a preprint 55 , but the ratiometric detection enabled by the RAPPID assay is preferred for quantitative measurements, which are important when studying the time-dependence of the antibody response and the correlation between antibody titers and immunological protection 56,57 . Collectively, these results illustrate that the RAPPID platform is highly versatile and can be reengineered to suit a variety of applications related to antibody detection, including quantitative measurements of antibodies that bind discontinuous epitopes, therapeutic antibodies and their ADAs, and anti-SARS-CoV-2 antibodies.…”

Section: Resultsmentioning

confidence: 99%

RAPPID: a platform of ratiometric bioluminescent sensors for homogeneous immunoassays

Rosier

Aalen

et al. 2020

Preprint

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Heterogeneous immunoassays such as ELISA have become indispensable in modern bioanalysis, yet translation into easy-to-use point-of-care assays is hindered by their dependence on external calibration and multiple washing and incubation steps. Here, we introduce RAPPID (Ratiometric Plug-and-Play Immunodiagnostics), a "mix-and-measure" homogeneous immunoassay platform that combines highly specific antibody-based detection with a ratiometric bioluminescent readout that can be detected using a basic digital camera. The concept entails analyte-induced complementation of split NanoLuc luciferase fragments, photoconjugated to an antibody sandwich pair via protein G adapters. We also introduce the use of a calibrator luciferase that provides a robust ratiometric signal, allowing direct in-sample calibration and quantitative measurements in complex media such as blood plasma. We developed RAPPID sensors that allow low-picomolar detection of several protein biomarkers, anti-drug antibodies, therapeutic antibodies, and both SARS-CoV-2 spike protein and anti-SARS-CoV-2 antibodies. RAPPID combines ratiometric bioluminescent detection with antibody-based target recognition into an easy-to-implement standardized workflow, and therefore represents an attractive, fast, and low-cost alternative to traditional immunoassays, both in an academic setting and in clinical laboratories for point-of-care applications.

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Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Cited by 158 publications

References 14 publications

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT)

RAPPID: a platform of ratiometric bioluminescent sensors for homogeneous immunoassays

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