Analysis of Humoral Immune Responses in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Henß, Lisa; Scholz, Tatjana; Rhein, Christine von; Wieters, Imke; Borgans, Frauke; Eberhardt, Fabian; Zacharowski, Kai; Ciesek, Sandra; Rohde, Gernot; Vehreschild, Maria J.G.T.; Stephan, Christoph; Wolf, Timo; Hofmann-Winkler, Heike; Scheiblauer, Heinrich; Schnierle, Barbara S.

doi:10.1093/infdis/jiaa680

Cited by 74 publications

(60 citation statements)

References 22 publications

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“…Validation studies by end-users are important to assess the performance characteristics of these new commercial assays, and to determine the correlation between EIAs and neutralising antibody titres. To date, a small number of studies have validated a range of commercially available SARS-CoV-2 serological assays against a live-virus neutralisation test [ 11 , 12 , 13 , 14 , 15 ]. Assays assessed in these publications incorporate automated platforms as well as serology-based point of care tests and have some, but limited, crossover with the comparison of EIAs in the present study.…”

Section: Introductionmentioning

confidence: 99%

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

Walker

Naing

Stella

et al. 2021

Viruses

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Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.

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Section: Introductionmentioning

confidence: 99%

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

Walker

Naing

Stella

et al. 2021

Viruses

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“…There are several reports that cross-protection against SARS-CoV-2 might contribute to this phenomenon; for example, Grifoni [3], Le Bert [4] and Mateus [5] have described T cell responses to SARS-CoV-2 in unexposed human individuals. In a recent manuscript, Henss [6] have stated that "disease severity seemed to correlate with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection". In a survey of 1,186 convalescent patients with mild COVID-19 [7], contact to small children has been reported frequently (30.1% of participants).…”

Section: Introductionmentioning

confidence: 99%

Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19

Dugas

Grote-Westrick

Merle

et al. 2020

Preprint

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Most COVID-19 patients experience a mild disease; a minority suffers from critical disease.We report about a biomarker validation study regarding 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France.Patients with critical disease had significantly less anti-HCoV OC43 nucleocapsid protein antibodies compared to other COVID-19 patients (p=0.007). In multivariate analysis, OC43 negative inpatients had an increased risk of critical disease, higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis.Our results indicate that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment. We expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination, especially with other risk factors prevailing.

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“…The frequency of donation was dependent on multiple factors including antibody titer, availability of the donor and tolerance of apheresis procedure itself. There are data indicating a relationship between the severity of disease symptoms and the antibody titer [ 32 ]. Therefore, as part of the recruitment process, potential donors (n = 108) for our center were interviewed regarding their disease symptoms.…”

Section: Resultsmentioning

confidence: 99%

Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality

et al. 2020

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The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2–6°C) for up to 5 days or frozen (-30°C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100–1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.

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Analysis of Humoral Immune Responses in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Cited by 74 publications

References 22 publications

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19

Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality

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