Humoral and cellular BNT162b2 mRNA-based booster vaccine-induced immunity in patients with multiple myeloma and persistence of neutralising antibodies: results of a prospective single-centre cohort study.

BACKGROUND: Currently available messenger ribonucleic acid (mRNA)-based vaccines against coronavirus disease (COVID-19) have been shown to be effective even in highly immunocompromised hosts, including patients with multiple myeloma. However, vaccination failure can be observed in all patient groups. METHODS: This prospective study longitudinally assessed the humoral and cellular responses to a third booster dose of BNT162b2 mRNA-based vaccine in patients with myeloma (n = 59) and healthy controls (n = 22) by measuring the levels of anti-spike (S) antibodies (electro-chemiluminescence immunoassay) including neutralising antibodies and specific T-cells (enzyme-linked immunospot assay) following booster administration. RESULTS: The third booster dose showed a high immunogenicity on the serological level among the patients with multiple myeloma (median anti-S level = 41 binding antibody units [BAUs]/ml pre-booster vs 3902 BAU/ml post-booster, p <0.001; increase in the median neutralising antibody level from 19.8% to 97%, p <0.0001). Four of five (80%) patients with a complete lack of any serological response (anti-S immunoglobulin level <0.8 BAU/ml) after two vaccine doses developed detectable anti-S antibodies after booster vaccination (median anti-S level = 88 BAU/ml post-booster). T-cell responses were largely preserved among the patients with multiple myeloma with no difference from the healthy controls following baseline vaccination (median spot-forming units [SFU]/106 of peripheral blood mononuclear cells = 193 vs 175, p = 0.711); these responses were augmented significantly after booster administration among the patients with multiple myeloma (median SFU/106 of peripheral blood mononuclear cells = 235 vs 443, p <0.001). However, the vaccination responses remained highly heterogeneous and diminished over time, with insufficient serological responses occurring even after booster vaccination in a few patients irrespective of the treatment intensity. CONCLUSIONS: Our data demonstrate improvements in humoral and cellular immunity following booster vaccination and support the assessment of the humoral vaccine response in patients with multiple myeloma until a threshold for protection against severe COVID-19 is validated. This strategy can allow the identification of patients who might benefit from additional protective measures (e.g. pre-exposure prophylaxis via passive immunisation).

The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model.

BACKGROUND: The effects of the com quorum sensing system during colonisation and invasion of Streptococcus pneumoniae (Spn) are poorly understood. METHODS: We developed an ex vivo model of differentiated human airway epithelial (HAE) cells with beating ciliae, mucus production and tight junctions to study Spn colonisation and translocation. HAE cells were inoculated with Spn wild-type TIGR4 (wtSpn) or its isogenic ΔcomC quorum sensing-deficient mutant. RESULTS: Colonisation density of ΔcomC mutant was lower after 6 h but higher at 19 h and 30 h compared to wtSpn. Translocation correlated inversely with colonisation density. Transepithelial electric resistance (TEER) decreased after pneumococcal inoculation and correlated with increased translocation. Confocal imaging illustrated prominent microcolony formation with wtSpn but disintegration of microcolony structures with ΔcomC mutant. ΔcomC mutant showed greater cytotoxicity than wtSpn, suggesting that cytotoxicity was likely not the mechanism leading to translocation. There was greater density- and time-dependent increase of inflammatory cytokines including NLRP3 inflammasome-related IL-18 after infection with ΔcomC compared with wtSpn. ComC inactivation was associated with increased pneumolysin expression. CONCLUSIONS: ComC system allows a higher organisational level of population structure resulting in microcolony formation, increased early colonisation and subsequent translocation. We propose that ComC inactivation unleashes a very different and possibly more virulent phenotype that merits further investigation.

Safety Evaluation of a Medical Congress Held During the COVID-19 Pandemic-A Prospective Cohort.

Objectives: During the COVID-19 pandemic, few scientific congresses have been held on-site. We prospectively evaluated the safety concept of the congress of the Swiss Societies of Infectious Diseases and Hospital Hygiene. Methods: The congress was held in Geneva (Switzerland) while local COVID-19 incidence (with SARS-CoV-2 wild type circulating) was 65/100,000 population (September 2020). A rigorous safety concept was implemented. Congress attendees filled out a questionnaire to assess risk perception, exposures, symptoms and diagnoses of SARS-CoV-2 before, during and after the congress. Dried blood spots were taken on-site and 4 weeks later to detect SARS-CoV-2 seroconversions. Results: Of 365 congress attendees, 196 (54%) either answered the questionnaire (N = 150) or provided baseline and follow-up blood samples (N = 168). None of the participants reported a positive PCR in the 2 weeks after the congress. Five of 168 (3%) participants were seropositive at follow-up, all of which had already been positive at baseline. Conclusion: Findings indicate that congresses with a rigorous safety concept may take place, even in areas with moderately-high COVID-19 activity. Whether this holds true in vaccinated populations and with more transmissible viral variants circulating remains unclear.

Characteristics of Three Different Chemiluminescence Assays for Testing for SARS-CoV-2 Antibodies.

Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multigroup study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 (n = 145), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, n = 191, and healthcare workers, n = 1002). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of the Epstein-Barr virus (EBV) (n = 9), cytomegalovirus (CMV) (n = 7), and endemic common-cold coronavirus infections (n = 12) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers' cut-offs, the sensitivities were 90%, 95% confidence interval [84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8] (CMIA), 99.7% [99.3,99.9] (LIA), and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers' cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers' cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.