309. TB Quantiferon Testing Predicts Mortality in Patients with COVID-19

Background Finding reliable clinical predictors for severity of COVID-19 has been challenging. Interferon gamma (IFNG) plays an important role in viral replication. QuantiFERON-TB (QFT) test relies on IFNG release in response to antigens. A positive or negative test signifies adequate IFNG response, whereas an indeterminate result is obtained when such a response is lacking. In this study, we have attempted to see if an indeterminate QFT result can provide prognostic information on patients with COVID–19. Survival Probability in patients with Covid - 19 and an indeterminate TB Quantiferon test result Methods This is a retrospective study of patients who were admitted at our institute with COVID–19 and had a QFT done within one month of the positive SARS-CoV-2 nucleic acid amplification test result. Patient charts were analyzed for clinical course and outcomes, including in-hospital mortality (primary outcome), 90-day mortality, respiratory failure, requirement for intubation and other complications that would portend a more severe disease course. Results A total of 120 patient charts were analyzed, out of which 43 (35.8%) had an indeterminate QFT. All the indeterminate results were due to an inadequate mitogen response. The indeterminate QFT group had a 41.86% (18/43) in-hospital mortality vs. 9.09% (7/77) in the negative or positive QFT group (p-value of < 0.001). The 90-day mortality was similar between the two groups. Patients with indeterminate QFT also had a higher incidence of respiratory failure (97.7% vs. 75.3%; p-value = 0.020), requirement for mechanical ventilation (55.8% vs. 23.4%; p-value < 0.001), requirement of ECMO (25.58% vs. 0%; p-vale < 0.001), requirement of pressor (48.83% vs. 14.28%; p-value < 0.001) and requirement for renal replacement therapy (32.5% vs. 1.3%; p-value < 0.001), when compared to patients with a negative or positive QFT. Patients in indeterminate group had a higher hospital length of stay than the other group (p-value = 0.035). Conclusion Our study indicates that patients with COVID-19 who fail to mount an adequate IFNG mitogen response in QFT assay have worse clinical outcomes and a more complicated and protracted clinical course. Evaluating cell-mediated immune responses through commercially available IFNG release assays may yield a promising strategy to predict COVID-19 clinical outcomes. Disclosures All Authors: No reported disclosures

Sporotrichosis: Review of Innate and Acquired Immune Mechanisms

Context: Different factors such as the site of infection, the etiological agent, and the immune system can modify the antifungal response of the host. Differences in Sporothrix schenckii strains’ virulence and the host’s immune competency may be involved in the development of sporotrichosis. Nevertheless, the mechanisms related to the disease’s development and progression remain not fully elucidated. Nowadays, no model outweighs the usefulness of mice in biological studies. In these models, transient controlled immunity is created by depressed inflammatory cells during the acute phase of the disease. This is also related to nitric oxide-induced T-cell apoptosis and the lack of a mitogen response. Evidence Acquisition: The recognition of the lipid components of S. schenckii can induce and prolong inflammation. This recognition occurs mainly through the Toll-like receptor (TLR)-4 or the inflammasome. At the same time, TLR-2-mediated identification of fungal exoantigen can serve as an immune evasion process, continuing and worsening the infection. Cell-mediated immune mechanisms have a predominant influence on modulating the clinical expression of sporotrichosis, which is mainly related to Th1/Th17 immunity. Conclusions: In this study, we aimed to explore the innate and acquired immune mechanisms involved in sporotrichosis, as well as the most commonly used animal models for experimental studies.

High Proportion of Indeterminate Qua.jpegERON-TB Gold In-Tube Results in an Inpatient Population Is Related to Host Factors and Preanalytical Steps

Background. Qua.jpegERON-TB Gold In-Tube test (QFT-GIT) can be used as an alternative to tuberculin skin testing (TST) for the targeted testing of latent tuberculosis. Due to many shortcomings with TST, QFT-GIT usage is increasing. QFT-GIT implementation in the inpatient setting remains unclear. Methods. We retrospectively ide.jpegied patients admitted to a tertiary care academic center who received either a TST or a QFT-GIT in the 18 months prior to and after QFT-GIT implementation in March 2012. Risk factors associated with indeterminate results were evaluated. Results. The proportion of inpatients receiving a test for tuberculosis infection doubled following QFT-GIT implementation (1.4% vs 2.9%). After QFT-GIT became available, 75% of tested people received a QFT-GIT and 25% received a TST. We found indeterminate test results in 19.8%. Independent predictors of indeterminate results were female sex (adjusted odds ratio [AOR], 1.64), lymphopenia (AOR, 2.21), hypoalbuminemia (AOR, 6.81) and sample collection by nonphlebotomists (AOR, 3.0, vs phlebotomists). Of patients who had indeterminate results, 42% had a subsequent indeterminate result on repeat testing. All indeterminate results were due to a low mitogen response. Conclusions. QFT-GIT testing in the inpatient setting is associated with a high proportion of indeterminate results that is associated with host factors and preanalytical errors. Careful selection of patients to be tested and training on sample processing for QFT-GIT testing should be considered to decrease indeterminate results.

Effect of Acetylcholine on Mitogen Response of Peripheral Lymphocytes Isolated From Rats Exposed to Chronic Stress

The purpose of this study was to clarify the effects of acetylcholine (Ach) on lymphocyte function in rats under chronic stress. The authors isolated peripheral lymphocytes from rats 5 weeks after stress treatment and then measured interleukin-2 (IL-2) production after stimulation with concanavalin A or phytohemagglutinin-L. Although mitogen-induced IL-2 production of the stress group was lower than that of the control group, the addition of Ach significantly increased mitogen-induced IL-2 production in both groups. This effect of Ach was inhibited by atropine in the control group only. The changes (increasing rates) in mitogen-induced IL-2 production from basal condition showed a negative correlation with serum corticosterone concentrations. The authors observed no correlation between the effects of Ach (changes in mitogen-induced IL-2 production with Ach compared to those without Ach) and serum corticosterone concentration. These findings suggest that stimulation of the parasympathetic nervous system improves lymphocyte function during chronic stress.