Sigma metrics in laboratory medicine: A call for harmonization.

BACKGROUND AND AIM: Sigma metrics are applied in clinical laboratories to assess the quality of analytical processes. A parameter associated to a Sigma > 6 is considered "world class" whereas a Sigma < 3 is "poor" or "unacceptable". The aim of this retrospective study was to quantify the impact of different approaches for Sigma metrics calculation. MATERIAL AND METHODS: Two IQC levels of 20 different parameters were evaluated for a 12-month period. Sigma metrics were calculated using the formula: (allowable total error (TEa) (%) - bias (%))/(coefficient of variation (CV) (%)). Method precision was calculated monthly or annually. The bias was obtained from peer comparison program (PCP) or external quality assessment program (EQAP), and 9 different TEa sources were included. RESULTS: There was a substantial monthly variation of Sigma metrics for all combinations, with a median variation of 32% (IQR, 25.6-41.3%). Variation across multiple analyzers and IQC levels were also observed. Furthermore, TEa source had the highest impact on Sigma calculation with proportions of Sigma > 6 ranging from 17.5% to 84.4%. The nature of bias was less decisive. CONCLUSION: In absence of a clear consensus, we recommend that laboratories calculate Sigma metrics on a sufficiently long period of time (>6 months) and carefully evaluate the choice of TEa source.

Neutralizing Antibodies in COVID-19 Patients and Vaccine Recipients after Two Doses of BNT162b2.

The evaluation of the neutralizing capacity of anti-SARS-CoV-2 antibodies is important because they represent real protective immunity. In this study we aimed to measure and compare the neutralizing antibodies (NAbs) in COVID-19 patients and in vaccinated individuals. One-hundred and fifty long-term samples from 75 COVID-19 patients were analyzed with a surrogate virus neutralization test (sVNT) and compared to six different SARS-CoV-2 serology assays. The agreement between the sVNT and pseudovirus VNT (pVNT) results was found to be excellent (i.e., 97.2%). The NAb response was also assessed in 90 individuals who had received the complete dose regimen of BNT162b2. In COVID-19 patients, a stronger response was observed in moderate-severe versus mild patients (p-value = 0.0006). A slow decay in NAbs was noted in samples for up to 300 days after diagnosis, especially in moderate-severe patients (r = -0.35, p-value = 0.03). In the vaccinated population, 83.3% of COVID-19-naive individuals had positive NAbs 14 days after the first dose and all were positive 7 days after the second dose, i.e., at day 28. In previously infected individuals, all were already positive for NAbs at day 14. At each time point, a stronger response was observed for previously infected individuals (p-value < 0.05). The NAb response remained stable for up to 56 days in all participants. Vaccinated participants had significantly higher NAb titers compared to COVID patients. In previously infected vaccine recipients, one dose might be sufficient to generate sufficient neutralizing antibodies.