Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients.

BACKGROUND: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. METHODS: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. FINDINGS: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. INTERPRETATION: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. FUNDING: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.

Application of the SARS-CoV-2-S1 ACE-2 receptor interaction as the basis of the fully automated assay to detect neutralizing SARS-CoV-2-S1 antibodies in blood samples.

A quantitative, high throughput, fully automated diagnostic method for the detection of neutralizing anti-SARS-CoV-2 antibodies was developed on the Phadia system based on the interaction of SARS-CoV-2 S1 protein and the human ACE-2 receptor. This method was compared to the current state of the art plaque reduction neutralization test (PRNT) and a high correlation between the two methods was observed. Using a large cohort of blood samples from convalescent patients and controls the method displays very high sensitivity and specificity (99,8% and 99.99%, respectively). Neutralizing antibody titers of mRNA-1273 and BNT162b2-vaccinated persons can also be quantified with this method as well. This fully automated method provides the possibility to determine anti-SARS-CoV-2 neutralizing antibody concentrations in just 2  h.

Modelling the concentration of anti-SARS-CoV-2 immunoglobulin G in intravenous immunoglobulin product batches.

BACKGROUND: Plasma-derived intravenous immunoglobulin (IVIg) products contain a dynamic spectrum of immunoglobulin (Ig) G reactivities reflective of the donor population from which they are derived. We sought to model the concentration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG which could be expected in future plasma pool and final-product batches of CSL Behring's immunoglobulin product Privigen. STUDY DESIGN AND METHODS: Data was extracted from accessible databases, including the incidence of coronavirus disease 2019 and SARS-CoV-2 vaccination status, antibody titre in convalescent and vaccinated groups and antibody half-life. Together, these parameters were used to create an integrated mathematical model that could be used to predict anti-SARS-CoV-2 antibody levels in future IVIg preparations. RESULTS: We predict that anti-SARS-CoV-2 IgG concentration will peak in batches produced in mid-October 2021, containing levels in the vicinity of 190-fold that of the mean convalescent (unvaccinated) plasma concentration. An elevated concentration (approximately 35-fold convalescent plasma) is anticipated to be retained in batches produced well into 2022. Measurement of several Privigen batches using the Phadia™ EliA™ SARS-CoV-2-Sp1 IgG binding assay confirmed the early phase of this model. CONCLUSION: The work presented in this paper may have important implications for physicians and patients who use Privigen for indicated diseases.

Determination of neutralising anti-SARS-CoV-2 antibody half-life in COVID-19 convalescent donors.

Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.