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Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naive patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-gamma release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.

Introduction: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed. Methods: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Ass42), amyloid-beta40 (Ass40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed. Results: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Ass42/Ass40 (H(2) = 7.50, p = 0.02) and pTau181/Ass42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Ass42 and an SCD versus MCI difference for Ass42/Ass40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Ass42, Ass40, and NFL concentrations. Conclusion: Plasma pTau181 and NFL, as well as the ratios Ass42/Ass40 and pTau181/Ass42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies.

Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2 neutralization, with these elite neutralizers also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity, and gender as key factors predicting SARS-CoV-2-neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% of individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a rather long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19.

Background: The investigation of the antibody response to SARS-CoV-2 represents a key aspect in facing the COVID-19 pandemic. In the present study, we compared the new Immundiagnostik IDK (R) anti-SARS-CoV-2 S1 IgG assay with four widely-used commercial serological assays for the detection of antibodies targeting S (spike) and NC (nucleocapsid) proteins. Methods: Serum samples were taken from an unbiased group of convalescent patients and from a negative control group. Sample were simultaneously analyzed by the new Immundiagnostik IDK(R) anti-SARS-CoV-2 S1 IgG assay, by the DiaSorin LIAISON(R) SARS-CoV-2 S1/S2 IgG assay, and by the Euroimmun anti-SARS-CoV-2 S1 IgG ELISA. Antibodies binding NC were detected by the Abbott SARS-CoV-2 IgG assay and by the pan-immunoglobulin immunoassay Roche Elecsys(R) anti-SARS-CoV-2. Moreover, we investigated samples of a group of COVID-19 convalescent subjects that were primarily tested S1 IgG non-reactive. Samples were also tested by live virus and pseudovirus neutralization tests. Results: Overall, the IDK (R) anti-SARS-CoV-2 S1 IgG assay showed the highest sensitivity among the evaluated spike (S) protein-based assays. Additionally, the Immundiagnostik assay correlated well with serum-neutralizing activity. Conclusions: The novel IDK(R) anti-SARS-CoV-2 S1 IgG assay showed high sensitivity and specificity, representing a valid option for use in the routine diagnostic.

Objectives: Coronavirus disease 2019 (COVID-19) is currently a worldwide major health threat. Recognizing hypoxia in patients early on can have a considerable effect on therapy success and survival rate. Methods: We collected data using a standard blood gas analyzer from 50 patients and analyzed measurements of partial pressure of carbon dioxide-pCO(2), partial pressure of oxygen-pO(2) and oxygen saturation-sO(2), bicarbonate concentrations-HCO3- as well as ionized calcium concentrations. We further examined PCR test results for SARS-CoV-2 of the patients and analyzed differences between patients tested positive and those tested negative for the virus. Results: Venous pCO(2) was significantly higher whereas pO(2) and sO(2) were significantly lower in patients who tested positive for SARS-CoV-2. The pH, and ionized calcium concentrations of patients tested positive for the virus were significantly lower than in those tested negative. Conclusions: Symptomatic SARS-CoV-2-positive patients upon admission to the emergency room exhibit lower venous blood levels of oxygen, pH, and calcium and higher levels of carbon dioxide compared to symptomatic SARS-CoV2-negative patients. This blood gas analysis constellation could help in identifying SARS-CoV-2-positive patients more rapidly and identifying early signs of hypoxia.

Point-of-care testing (POCT) has been an essential service in hospitals for many years with a main focus on reliability, classical laboratory quality criteria and easy handling. Hospital information technology (IT) security regulations, however, have not yet been adapted to the specificities of POCT. Following the POCT Symposium in Munich, the 1st Round Table POCT-IT-Security Meeting held in October 2019 in Cologne addressed these issues and managed to establish first consensus results in the essential fields of user, data and update management, as well as network connections and user-friendliness. First practical steps include optimizing the user management by connection to a directory service and definition of access control (including emergency authorization). Patient data economy on analyzers in combination with data and data transmission encryption as well as technically secure communication protocols are relevant steps in the fields of data management and network connections. An update management needs to be contractually defined for remote services and generally includes testing in a protocol-based scenario. Providing an organizational structure for POCT-IT security is a necessary prerequisite, as are continuous training and awareness for this topic with a strong focus on usability.

Objective: We investigated whether COMP may modify cartilage metabolism and play a role as an endogenous disease aggravating factor in OA. Materials and methods: Full-length and momomeric COMP was recombinantly expressed in human embryonic kidney cells and purified it via affinity chromatography. Purified COMP was used to stimulate either primary human chondrocytes or cartilage explants. Changes in the expression profiles of inflammatory genes, differentiation markers and growth factors were examined by immunoassay and by quantitative real-time reverse-transcription polymerase chain reaction. Results: Incubation of primary human chondrocytes or cartilage explants in the presence of COMP did not induce statistically significant changes in the expression of IL-6, MMP1, MMP13, collagen I, collagen II, collagen X, TGF-beta 1 and BMP-2. Conclusions: In contrast to collagen II and matrilin-3, COMP lacks the ability to trigger a proinflammatory response in chondrocytes, although it carries an RGD motif and can bind to integrins. COMP is a well-accepted biomarker for osteoarthritis but increased COMP levels do not necessarily correlate with inflammation.