Background Serological immunoassays that can identify protective immunity against SARS‐CoV‐2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed‐design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS‐CoV‐2 proteins and assessed the neutralizing activity of antibodies in patient sera. Methods Consecutive patients admitted with confirmed SARS‐CoV‐2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in‐house enzyme‐linked immunosorbent assay utilizing recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein was developed and compared to three commercially available enzyme‐linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1) and a lateral flow immunoassay (LFI) based on full‐length spike protein. Neutralization assays with live SARS‐CoV‐2 were performed. Results One‐thousand four‐hundred and seventy‐seven individuals were included comprising 112 SARS‐CoV‐2 positives (defined as a positive real‐time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS‐CoV‐2 positive individuals, 96.3% showed full neutralization of live SARS‐CoV‐2 at serum dilutions ≥1:16, while none of the 6 SARS‐CoV‐2 negative sera revealed neutralizing activity. Conclusions ELISAs targeting RBD and S1 protein of SARS‐CoV‐2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS‐CoV‐2.
The simultaneous determination of interleukin-2 (IL-2) and gamma interferon (IFN-␥) in Quanti-FERON-TB test plasma supernatants permitted the detection of shifts in Mycobacterium tuberculosis-specific T-cell signatures. A subset of the 84 subjects tested revealed a significantly elevated IL-2/IFN-␥ ratio, which may be a marker for the successful elimination of M. tuberculosis infection.In countries with low tuberculosis (TB) incidence rates, such as Switzerland, targeted testing for latent Mycobacterium tuberculosis infection (LTBI) among risk groups, such as health care workers (HCW), is an important measure for preventing active TB disease (3, 7). Occupational health programs are increasingly turning to gamma interferon (IFN-␥) release assays (IGRA), such as the QuantiFERON-TB Gold in-tube test (QFT test; Cellestis Inc., Australia), to screen employees for LTBI (4,5,9). Diel et al. prospectively followed QFT testpositive, recent-TB contacts who had refused isoniazid treatment. All contacts who subsequently developed active TB disease within the follow-up period were strong responders in the QFT assay, with IFN-␥ plasma levels above the 10-IU/ml upper limit for the test's enzyme-linked immunosorbent assay (ELISA) (6). These results suggest that a correlation exists between the amount of IFN-␥ released upon M. tuberculosis-specific stimulation of CD4 ϩ T cells and the probability of developing active TB disease.A dynamic relationship between antigen load and distinct IFN-␥ and interleukin-2 (IL-2) profiles of antigen-specific CD4ϩ T cells has been demonstrated in viral infections (10). Typically, antigen clearance is associated with IL-2-dominant functional T-cell signatures. In contrast, high antigen loads are associated with IFN-␥-dominant functional T-cell signatures (10). A similar relationship between the IFN-␥ and IL-2 profiles of M. tuberculosis-specific T cells and antigenic load was reported in patients who were treated for active TB disease (1,2,8). Simultaneous measurement of IFN-␥ and IL-2 secretion at the single-cell level revealed a codominance of CD4 ϩ T cells that secrete only IFN-␥ and those that secrete both IFN-␥ and IL-2 in patients with active TB disease. A shift to dominance of CD4 ϩ T cells secreting both IFN-␥ and IL-2 and of newly detectable CD4 ϩ T cells secreting only IL-2 has been demonstrated both during and following TB treatment. Thus, three main functional patterns were observed: a dominant IL-2 response, a multifunctional (IL-2 and IFN-␥) response, and a dominant IFN-␥ response. Determination of the levels of IL-2 and IFN-␥ secretion has been proposed as an adequate marker for clinical monitoring (10). The net result of functional T-cell signatures would be detectable by assessing the M. tuberculosisspecific IL-2/IFN-␥ ratio in QFT test plasma supernatants. Thus, the simultaneous analysis of both IFN-␥ and IL-2 in QFT test plasma supernatants might provide (i) a more precise basis for assessing an individual's risk of developing active TB disease and (ii) information concerning t...
Two diphtheria outbreaks occurred in a Swiss asylum center from July to October 2022, one is still ongoing. Outbreaks mainly involved minors and included six symptomatic respiratory diphtheria cases requiring antitoxin. Phylogenomic analyses showed evidence of imported and local transmissions of toxigenic strains in respiratory and skin lesion samples. Given the number of cases (n = 20) and the large genetic diversity accumulating in one centre, increased awareness and changes in public health measures are required to prevent and control diphtheria outbreaks.
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