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European Union (EU) regulations on in vitro diagnostics (IVD) and on serious cross-border threats to health provide for the establishment of European Reference Laboratories (EURLs) and their harmonization and cooperation with National Reference Laboratories (NRLs). While the EURLs under the IVD Regulation will be operational by 1 October 2024, the EURLs under the Regulation on serious cross-border threats to health will be operational by January 2025. Although NRLs may have been operating for a long time on the basis of national legislation, they should now cooperate with each other and with EURLs in a network of centers of excellence for the authorization and post-market surveillance of IVDs and for the epidemiological surveillance and control of communicable diseases. The term “reference laboratory” has long been used colloquially to refer to many kinds of laboratories, regardless of their tasks, competencies, responsibilities and designation. A literature search and analysis confirmed this by showing that a considerable proportion of scientific publications in 2024 use the term “reference laboratory” inappropriately. In order to clarify the roles and functioning of EURLs and NRLs, we have evaluated the relevant current EU provisions and compared the findings with those of reference laboratories designated by other organizations, calibration (reference) laboratories and referral laboratories, which are simply referred to as “reference laboratories”. With the forthcoming implementation of the EU regulations, at least the goals of providing safe and high-quality IVDs and adequate public health surveillance for communicable diseases appear to be achievable. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in previously SARS-CoV-2–infected adults in the general population of Austria during the Delta wave and with extended follow-up. Methods In a nationwide retrospective cohort study, we calculated age-, sex-, and nursing home residency–adjusted Cox proportional hazard ratios (HRs) of coronavirus disease 2019 (COVID-19) deaths, SARS-CoV-2 infections, and non-COVID-19 deaths from 1 October to 31 December 2021, and secondarily with extended follow-up to 30 June 2022. Relative vaccine effectiveness (rVE) is rVE = (1 – HR) × 100. Results Among 494 646 previously infected adults, 169 543 had received 2 vaccine doses, 133 567 had received 1 dose, and 190 275 were unvaccinated at baseline. We recorded 17 COVID-19 deaths (6 vaccinated, 11 unvaccinated) and 8209 SARS-CoV-2 infections. Absolute risk of COVID-19 deaths was 0.003%. rVE estimates for COVID-19 deaths and reinfections exceeded 75% until the end of 2021 but decreased substantially with extended follow-up. The risk of non-COVID-19 death was lower in those vaccinated versus unvaccinated. Conclusions First and second SARS-CoV-2 vaccine doses appear effective in the short-term, but with diminishing effectiveness over time. The extremely low COVID-19 mortality, regardless of vaccination, indicates strong protection of previous infection against COVID-19 death. Lower non-COVID-19 mortality in the vaccinated population might suggest a healthy vaccinee bias. [ABSTRACT FROM AUTHOR]

Introduction: Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID‐19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections. We estimated the risk of COVID‐19 deaths and SARS‐CoV‐2 infections according to vaccination status in previously infected individuals in Austria. Methods: This is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID‐19 deaths (primary outcome) and SARS‐CoV‐2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1‐HR) X 100. Results: Among 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID‐19 deaths and 89,056 SARS‐CoV‐2 infections. rVE for four versus three vaccine doses was −24% (95% CI: −120 to 30) against COVID‐19 deaths, and 17% (95% CI: 14–19) against SARS‐CoV‐2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow‐up until June 2023. Adjusted HR (95% CI) for all‐cause mortality for four versus three vaccinations was 0.79 (0.74–0.85). Discussion: In previously infected individuals, a fourth vaccination was not associated with COVID‐19 death risk, but with transiently reduced risk of SARS‐CoV‐2 infections and reversal of this effect in longer follow‐up. All‐cause mortality data suggest healthy vaccinee bias. [ABSTRACT FROM AUTHOR]

The differences in C SB t sb values reported for each individual gene target were calculated per participant as [S6 C SB t sb value - S2 C SB t sb value] and ranged from -5.3 to +6.5 cycles. Keywords: Ct value; precision; RT-PCR; SARS-CoV-2; sensitivity; specificity EN Ct value precision RT-PCR SARS-CoV-2 sensitivity specificity e34 e37 4 01/07/22 20220115 NES 220115 To the Editor, In an external quality assessment (EQA) round for SARS-CoV-2 virus genome detection in early 2021, we found first indications of the precision of individual SARS-CoV-2 RT-PCR assays in the linearity of the C SB t sb values obtained for three samples from a dilution series (1:1, 1:10, 1:100) [[1]]. Seven assays reported a C SB t sb value for one of the target genes they used for only one of samples S2 and S6 and none for the second. [Extracted from the article]

Mutation-specific PCR assays have quickly found their way into laboratory diagnostics due to their capacity to be a fast, easy to implement and high-throughput method for the detection of known SARS-CoV-2 variants of concern (VoCs). However, little is known about the performance of such assays in routine laboratory analysis. The results reported in a recent round of an external quality assessment (EQA) scheme for SARS-CoV-2 mutation-specific PCR were retrospectively analyzed. For the determination of individual variant-specific sequences as well as for the interpretation results for certain virus variants, correct, incorrect, and unreported results were evaluated, and their possible causes were investigated. A total of 34 laboratories participated in this study. For five samples containing the VoC Alpha + E484K, Beta, Gamma, Delta, or B.1.1.318 (as a variant of interest), 848 results for SARS-2-CoV mutation detection were reported, 824 (97.2%, range per sample 88–100%) of which were correct. Melting curve assays gave 99% correct results, real-time RT-qPCR 94%, microarray-based assays 100%, and MALDI-TOF MS 96%. A total of 122/167 (73%) reported results for SARS-CoV-2 variant determination were correct. Of the 45 inconclusive or incorrect results, 33 (73%) were due to inadequate selection of targets that did not allow identification of contemporary VoC, 11 (24%) were due to incorrect results, and one (3%) was due to correct results of mutation-specific PCR. Careful and up-to-date selection of the targets used in mutation-specific PCR is essential for successful detection of current SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]