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ObjectiveTo follow serological immune responses of front-line healthcare workers after PCR-confirmed COVID-19 for a mean of 30 weeks, describe the time-course of SARS-CoV-2 spike protein-specific IgG, IgA and IgM levels and to identify associations of the immune response with symptoms, demographic parameters and severity of disease.MethodsAnti-SARS-CoV-2 S protein-specific IgG, IgA and IgM antibodies were measured at three time points during the 30-week follow-up. COVID-19-specific symptoms were assessed with standardized questionnaires.Results95% of the participants mounted an IgG response with only modest decline after week 12. IgG-type antibodies were still detectable in almost 90% of the subjects at 30 weeks. IgA and IgM responses were less robust and antibody titers decreased more rapidly. At 30 weeks, only 25% still had detectable IgA-type and none had IgM-type antibodies. Higher age and higher disease severity were independently associated with higher IgG antibody levels, albeit with wide variations.ConclusionSerological immune responses after COVID-19 show considerable inter-individual variability, but show an association with increasing age and higher severity of disease. IgG-type anti-SARS-CoV-2 antibodies remain positive in 90% of the individuals 30 weeks after onset of symptoms.

BackgroundThe long-term course of immunity among individuals with a history of COVID-19, in particular among those who received a booster vaccination, has not been well defined so far.MethodsSARS-CoV-2-specific antibody levels were measured by ELISA over 1 year among 136 health care workers infected during the first COVID-19 wave and in a subgroup after booster vaccination approximately 1 year later. Furthermore, spike-protein-reactive memory T cells were quantified approximately 7 months after the infection and after booster vaccination. Thirty healthy individuals without history of COVID-19 who were routinely vaccinated served as controls.ResultsLevels of SARS-CoV-2-specific IgM- and IgA-antibodies showed a rapid decay over time, whereas IgG-antibody levels decreased more slowly. Among individuals with history of COVID-19, booster vaccination induced very high IgG- and to a lesser degree IgA-antibodies. Antibody levels were significantly higher after booster vaccination than after recovery from COVID-19. After vaccination with a two-dose schedule, healthy control subjects developed similar antibody levels as compared to individuals with history of COVID-19 and booster vaccination. SARS-CoV-2-specific memory T cell counts did not correlate with antibody levels. None of the study participants suffered from a reinfection.ConclusionsBooster vaccination induces high antibody levels in individuals with a history of COVID-19 that exceeds by far levels observed after recovery. SARS-CoV-2-specific antibody levels of similar magnitude were achieved in healthy, COVID-19-naïve individuals after routine two-dose vaccination.

BackgroundThe immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied.MethodsWe investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition.ResultsAnti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects.ConclusionsLong-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.

Background In Germany, the telephone patient service 116,117 for callers with non-life-threatening health issues is available 24/7. Based on structured initial assessment, urgency and placement of suitable medical care offer have been offered since 2020. The service has been in increasing demand for several years: Depending on time and residence, this can result in longer waiting times. Methods Prospective, two-armed cohort study with two intervention groups and one control group, alternating between blinding and unblinding for employees of 116,117 regarding prioritization status. Two interventions based on automated voice dialogues (1: Simple self-rating tool, 2: Automated brief query of emergency symptoms). In case of high level of urgency, callers are prioritized. Validation of urgency and need for care is carried out routinely based on structured initial assessment. Discussion By creating and providing a largely reproducible documentation of the implemented solutions for a waiting queue management, the developed approach would be available for comparable projects in the German health care system or in the European context. This potentially leads to a reduction in the use of resources in the development of comparable technical solutions based on automated voice dialogs. Trial registration DRKS00031235, registered on 10th November 2023, https://drks.de/search/de/trial/DRKS00031235 .

The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.

Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.