Investigating Factors of False-Positive Results of Aspergillus Galactomannan Assay: A Case–Control Study in Intensive Care Units

Background: Studies on false-positive galactomannan (GM) enzyme immunoassay (EIA) results and treatment for critically ill patients are scarce.Objectives: The study aimed to determine the false-positive rate of GM-EIA and to probe the risk factors of false positivity among patients in the intensive care units (ICUs).Methods: A case–control approach was conducted to review adult patients who had at least one GM-EIA result and were admitted to the ICU. Those who had no fungal culture were excluded. The clinical characteristics and critical care between patients with false-positive and true-negative GM index (GMI) were compared.Results: Of 206 patients enrolled and with GM-EIA results, 20 (9.7%) were considered to have false-positive antigenemia, including 9 in bronchoalveolar lavages (BAL) and 11 in serum. A total of 148 (71.8%) were true-negatives. After paired grouping of 1:4, factors researched in the previous studies showed no significant difference. However, compared with the true-negatives, patients with positive GM test results but were incompatible with the diagnosis of invasive aspergillosis were more prone to the risk of false positivity due to the use of colistin inhalation. It seemed to be the only factor that significantly increased the risk of false positivity after multivariate analysis (adjusted odds ratio, 35.68; 95% CI, 3.77–337.51, p = 0.002).Conclusions: Colistin inhalation treatment may contribute to false-positive GM-EIA results. The positive GMI among patients receiving colistin nebulization should be interpreted with caution.

Updating the Signal-to-cutoff Level to Reduce Anti-hepatitis C Virus False Positivity

Background: Anti-hepatitis C virus (anti-HCV) is the only screening test being used in the diagnosis of hepatitis C. In this study, we examined anti-HCV positivity rates in our hospital. Objectives: The aim of administering the anti-HCV test was to distinguish patients with hepatitis C infection from false positivity in patients with reactive results. Methods: The anti-HCV tests were performed at Fatih Sultan Mehmet Training and Research Hospital in Istanbul, Turkey, between January 1, 2015 and December 31, 2019. The patients were evaluated retrospectively in terms of age, gender, anti-HCV titer, the clinic for which the examination was requested, the reason for the examination, and the history of hepatitis C. Results: In this study, 511 patients who had two negative polymerase chain reaction (PCR) results were evaluated as false positive cases and enrolled. The cut-off value was found to be 7.5 IU/ml, with the highest sensitivity of 94.4% and specificity of 94.5% (area under the curve [AUC]: 0.982). The lowest anti-HCV titer (5.2) was from patients without acute hepatitis, who were HCV-RNA positive and diagnosed with chronic hepatitis C. Conclusions: It may be more appropriate to report anti-HCV cut-off value of 0 - 5 as negative, 5 - 7.5 as borderline, and > 7.5 as positive. Working with a more acceptable cut-off level with a greater number of tests can help identify patients with asymptomatic HCV infection. Also, it can possibly reduce the cost due to a decrease in the number of PCR tests administered.

High prevalence of false positive SARS-CoV2 serology in a cohort of patients with liver autoimmune diseases

Aim Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with (reverse transcription-polymerase chain reaction) RT-PCR of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. The presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as well. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category.

Unexpected False-Positive Rates in Pediatric SARS-CoV-2 Serology Using the EUROIMMUN Anti-SARS-CoV-2 ELISA IgG Assay

Objectives Serologic assay performance studies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-​2) in pediatric populations are lacking, and few seroprevalence studies have routinely incorporated orthogonal testing to improve accuracy. Methods Remnant serum samples for routine bloodwork from 2,338 pediatric patients at UPMC Children’s Hospital of Pittsburgh were assessed using the EUROIMMUN Anti-SARS-CoV-2 ELISA IgG (EuroIGG) assay. Reactive cases with sufficient volume were also tested using 3 additional commercial assays. Results Eighty-five specimens were reactive according to the EuroIGG, yielding 3.64% (95% confidence interval [CI], 2.91%-4.48%) seropositivity, of which 73 specimens had sufficient remaining volume for confirmation by orthogonal testing. Overall, 19.18% (95% CI, 10.18%-28.18%) of samples were positive on a second and/or third orthogonal assay. This 80.82% false positivity rate is disproportionate to the expected false positivity rate of 50% given our pediatric population prevalence and assay performance. Conclusions In pediatric populations, false-positive SARS-CoV-2 serology may be more common than assay and prevalence parameters would predict, and further studies are needed to establish the performance of SARS-CoV-2 serology in children.

Introducing the Brief Reverse Correlation

The reverse correlation (RC) is an innovative method to capture visual mental representations (i.e., classification images, CIs) of social targets that has become increasingly popular in social psychology. Because CIs of high quality are difficult to obtain without a large number of trials, the majority of past research relied on CIs extracted from samples of participants (average CIs). This strategy, however, leads to inflated false positivity rates. Using the representation from each participant (individual CIs) offers one solution to this problem. Still, this approach requires large numbers of trials and is thus economically costly, time demanding, demotivating for the participants, or simply impractical. We introduce a new version of the reverse correlation method, namely the Brief-RC. The Brief-RC increases the quality of individual (and average) CIs and reduces the overall task length by increasing the number of stimuli (i.e., noisy faces) presented at each trial. In two experiments, assessments by external judges confirm that the new method delivers equally good (Experiment 1) or higher-quality (Experiment 2) outcomes than the traditional method for the same number of trials, time length, and number of stimuli. The Brief-RC may thus facilitate the production of higher-quality individual CIs and alleviate the risk of false positivity rate.

Diagnostic Reliability of Architect Anti-HCV Tests and Diagnostic Cost of False Positivity; A Single Center Study in Turkey.

Background:Although the sensitivity of third generation anti-HCV CIA tests is high, false positivity rates, especially in populations with low HCV infection endemicity, are still high. Objectives:We aimed to determine the S/Co cut-off value of anti-HCV in the diagnosis of real positive patients based on the CIA test kit absorbance routinely used in our laboratory and to reveal the potential cost effectiveness of confirmatory tests for false positive samples. Methods:All anti-HCV CIA test results which were performed in the microbiology laboratory of our hospital between 2016-2019 were retrospectively screened and S/Co values of the patients were recorded. Among these, the results that were confirmed with HCV-RNA real-time PCR test were included. Patients who were previously diagnosed and treated were excluded. Results:A total of 257 patients, who were tested for HCV-RNA after reactive anti-HCV test results, were included in the study. Of the cases, 84(32.68%) had positive HCV-RNA. According to the ROC analysis, the optimal S/Co value was 8.58 with the sensitivity and specificity values 95.24% and 85.55%, respectively. According to this 8.58S/Co value, anti-HCV test was reactive in 105 cases and 80(76.2%) of these cases had active HCV infection. In order to prevent the false-negativity, the additional cost of using 1.0S/Co value to our institution was 4114.64USD, meaning that we spent 1028.66USD to diagnose per true-case of active HCV infection when using 1.0S/Co value. In our institution, approximately 6.25 working hours are spent to finalize the HCV-RNA PCR test. The hours spent for S/Co of 1.0 and 8.58 were 1606.25 and 658.25, respectively. Conclusions:False positive anti-HCV results are an economic burden on health economics of countries. At least, different S/Co values might be used in accordance with the purpose of the screening (like blood donors or pre-operative screening) and prevalence of HCV infection in different laboratories and different populations.