Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

Kinetics of Anti-SARS-CoV-2 IgG among healthcare workers in a General Hospital.

SARS-CoV-2 is a newly-discovered positive-sense RNA virus, the cause of coronavirus disease 2019 (COVID-19) currently spreading worldwide. The SARS-CoV-2 S glycoprotein is considered a main target for neutralizing antibodies. In order to better understand the kinetics of the antibody response, we evaluated the relation between two consecutive antibody titers determined over an average period of four months. A total of 628 subjects were included in the study. A significant reduction of the antibody titers over time was found: Ab Titer 1: 8.1 Arbitrary Units (AU)/mL (IQR: 4.8-29.3); Ab Titer 2: 6.2 AU/mL (IQR: 0-28.5); p<0.0001. A Receiver Operator Characteristic curve analysis showed an Area Under the Curve (AUC) of 0.973 (95% CI: 0.962-0.984; p<0.0001) with an Ab titer 1 threshold of 110 AU/mL to predict an Ab Titer 2 ≥50 AU/mL with 100% specificity. Likewise, an AUC of 0.952 (95% CI: 0.930-0.974; p<0.0001) with an Ab titer 1 threshold of 185 AU/mL was found to predict an Ab Titer 2 ≥100 AU/mL. This study showed that the SARS-CoV-2 S1/S2 IgG median titer declined over an average period of four months and that the first IgG determination thresholds found can help predict IgG values after the same interval.

Diagnostic accuracy of a commercial multiplex PCR for the diagnosis of meningitis and encephalitis in an Italian general hospital.

Infectious meningitis and encephalitis are potentially life-threatening conditions caused mostly by bacterial and viral agents. Rapid diagnosis and prompt treatment are associated with a more favorable outcome. In recent years nucleic acid amplification tests have been developed to speed detection and identification of pathogens directly from cerebrospinal fluid (CSF). The aim of this study was to compare the diagnostic accuracy of a commercially available multiplex PCR assay for etiological diagnosis of infectious meningitis directly from CSF samples with culture. A secondary endpoint was to look for a possible screening threshold based on main CSF indices and urgent blood test results, to define CSF samples with low pre-test probability of PCR and/or culture-positive result. We performed a secondary analysis of results of CSF samples already processed as part of routine clinical care from February 2016 to December 2018. In all, 109 CSF samples were included in the study and a total of 14 bacteria were identified by either PCR, culture or both methods, along with nine samples positive for viruses. The comparison of PCR results with culture showed no significant difference: 7/109 (6.4%) vs 13/109 (11.9%) respectively, p=0.07. After exclusion of the isolates not detectable by the multiplex PCR panel, the diagnostic accuracy was: 100% (95% confidence interval (CI): 54.1% to 100%) sensitivity; 98.9% (95% CI: 93.5% to 99.9%) specificity; 85.7% (95% CI: 42% to 99.2%) positive predictive value; 100% (95% CI: 95.1% to 100%) negative predictive value; 96 (95% CI: 13.6 to 674.6) LR+; Zero LR-; Cohen's kappa: 0.918, p<0.0001. CSF protein value ≤ 28 mg/dl and CSF glucose/blood glucose ratio ≥0.78 were associated with both PCR-negative result for bacteria or viruses and culture-negative result. The multiplex PCR evaluated in this study showed a very good diagnostic performance compared to culture, and the thresholds found can be a useful tool to best choose which samples to test.

Multicenter comparison of automated procalcitonin immunoassays.

OBJECTIVES: A multicenter study to compare results of BRAHMS Kryptor PCT with those obtained using four BRAHMS-partnered procalcitonin (PCT) automated immunoassays (DiaSorin Liaison, BioMérieux Vidas, Roche Cobas E601 and Siemens Advia Centaur) and the Diazyme immunotubidimetric assay implemented on four clinical chemistry platforms (Abbott Architect c16000, Siemens Advia 2400, Roche Cobas C501 and Beckman Coulter AU5800). DESIGN AND METHODS: One hundred serum samples from in-patients with PCT values between 0.10 and 58.7 ng/mL were divided into aliquots and tested with the nine different reagents and analyzers. BRAHMS PCT Kryptor results were used as reference. RESULTS: Compared to BRAHMS PCT Kryptor, significant differences in results were observed on Vidas, Advia Centaur, Architect, Cobas C501 and AU5800. However, the correlation coeffiecients (r) with BRAHMS PCT Kryptor were between 0.899 and 0.988. The mean bias was less than ±1.02 ng/mL, except for Vidas (2.70 ng/mL). The agreement at three clinically relevant cut-offs was optimal: between 83-98% at 0.50 ng/mL, 90-97% at 2.0 ng/mL, and 98% at 10 ng/mL. The comparison of Diazyme PCT across the four clinical chemistry analyzers yielded high correlation coefficients (r between 0.952 and 0.976), a mean bias less than ±0.9 ng/mL, acceptable agreement at 0.5 ng/mL (>82%), and high concordance at the 2.0 ng/mL (>97%) and 10 ng/mL (>98%) cut-offs. CONCLUSIONS: The methods and applications evaluated in this multicenter study are aligned with BRAHMS PCT Kryptor and can be used for predicting the risk of progression to systemic inflammation in patients with bacterial infections using the conventional PCT diagnostic thresholds.

Usefulness of suPAR in the risk stratification of patients with sepsis admitted to the emergency department.

To investigate the role of suPAR in patients with sepsis admitted to the Emergency Department (ED). We performed multicentre prospective trial including patients admitted to the ED of three different Italian hospitals. Patients were studied upon admission on day 1, 2, 4 and 7. They were subdivided into two groups: sepsis (group 1) and severe sepsis or septic shock (group 2). The two groups were comparable for age, gender and CRP level on day 1. Patients with severe sepsis or septic shock displayed significantly higher baseline levels of suPAR, PCT and lactate. In both groups, suPAR decreased across the time (p < 0.0005). Group 1 was not different from group 2 (p = 0.545) in mortality at 7 days, while group 2 had higher mortality at 30 days than group 1 (p = 0.022). At the multivariate analysis, lactate1 (p = 0.012) and age (p = 0.019) were independent predictors of mortality at 7 days, whereas suPAR1 (p = 0.023) and age (p = 0.032) were independent predictors of mortality at 30 days. Lactate and suPAR resulted the most predictive biomarkers in the risk stratification of patients with suspected infection initially admitted to the ED, according to their role in predicting 7- and 30-day mortality, respectively.

Aberrant expression of CD8 in B-cell non-Hodgkin lymphoma: a multicenter study of 951 bone marrow samples with lymphomatous infiltration.

T-cell antigen expression can be observed in B-cell non-Hodgkin lymphoma (B-NHL). Although CD5 is expressed in B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma, the presence of other T-cell antigens is less common. This article reports a retrospective multicenter analysis in which flow cytometry was used to evaluate aberrant CD8 expression on the pathologic B cells of 951 bone marrow samples from patients with various types of B-NHL. In a total of 18 patients, CD8 was coexpressed: 10 had B-CLL; 1, small lymphocytic lymphoma (SLL); 1, marginal zone lymphoma; 1, lymphoplasmacytic lymphoma; 2, diffuse large B-cell lymphoma; and 3, follicular lymphoma. There was a 1.89% overall frequency of CD8 coexpression in which B-CLL/SLL had a higher frequency (3.03%) than did the other B-cell neoplasms (1.18%). Most cases were characterized by a favorable outcome.