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The suppression of the host's innate antiviral immune response by SARS-CoV-2, a contributing factor to the severity of disease, has been considerably studied in recent years. Many of these studies have focused on the actions of the structural proteins of the virus because of their accessibility to host immunological components. However, less is known about SARS-CoV-2 nonstructural and accessory proteins in relation to viral evasion. Herein, we study SARS-CoV-2 nonstructural proteins Orf3a, Orf6, and Nsp9 in a mimicked virus-infected state using poly(I:C), a synthetic analog of viral dsRNA, that elicits the antiviral immune response. Through genome-wide expression profiling, we determined that Orf3a, Orf6, and Nsp9 all modulate the host antiviral signaling transcriptome to varying extents, uniquely suppressing aspects of innate immune signaling. Our data suggest that SARS-CoV-2 Nsp9 hinders viral detection through suppression of RIG-I expression and antagonizes the interferon antiviral cascade by downregulating NF-kB and TBK1. Our data point to unique molecular mechanisms through which the different SARS-CoV-2 proteins suppress immune signaling and promote viral evasion. Nsp9 in particular acts on major elements of the host antiviral pathways to impair the antiviral immune response.
ABSTRACT
[This corrects the article DOI: 10.2196/31862.].
ABSTRACT
Aifred is a clinical decision support system (CDSS) that uses artificial intelligence to assist physicians in selecting treatments for major depressive disorder (MDD) by providing probabilities of remission for different treatment options based on patient characteristics. We evaluated the utility of the CDSS as perceived by physicians participating in simulated clinical interactions. Twenty physicians who were either staff or residents in psychiatry or family medicine completed a study in which they had three 10-minute clinical interactions with standardized patients portraying mild, moderate, and severe episodes of MDD. During these scenarios, physicians were given access to the CDSS, which they could use in their treatment decisions. The perceived utility of the CDSS was assessed through self-report questionnaires, scenario observations, and interviews. 60% of physicians perceived the CDSS to be a useful tool in their treatment-selection process, with family physicians perceiving the greatest utility. Moreover, 50% of physicians would use the tool for all patients with depression, with an additional 35% noting that they would reserve the tool for more severe or treatment-resistant patients. Furthermore, clinicians found the tool to be useful in discussing treatment options with patients. The efficacy of this CDSS and its potential to improve treatment outcomes must be further evaluated in clinical trials.
Subject(s)
Decision Support Systems, Clinical , Depressive Disorder, Major , Physicians , Artificial Intelligence , Depression/therapy , Depressive Disorder, Major/therapy , HumansABSTRACT
BACKGROUND: Approximately two-thirds of patients with major depressive disorder do not achieve remission during their first treatment. There has been increasing interest in the use of digital, artificial intelligence-powered clinical decision support systems (CDSSs) to assist physicians in their treatment selection and management, improving the personalization and use of best practices such as measurement-based care. Previous literature shows that for digital mental health tools to be successful, the tool must be easy for patients and physicians to use and feasible within existing clinical workflows. OBJECTIVE: This study aims to examine the feasibility of an artificial intelligence-powered CDSS, which combines the operationalized 2016 Canadian Network for Mood and Anxiety Treatments guidelines with a neural network-based individualized treatment remission prediction. METHODS: Owing to the COVID-19 pandemic, the study was adapted to be completed entirely remotely. A total of 7 physicians recruited outpatients diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Patients completed a minimum of one visit without the CDSS (baseline) and 2 subsequent visits where the CDSS was used by the physician (visits 1 and 2). The primary outcome of interest was change in appointment length after the introduction of the CDSS as a proxy for feasibility. Feasibility and acceptability data were collected through self-report questionnaires and semistructured interviews. RESULTS: Data were collected between January and November 2020. A total of 17 patients were enrolled in the study; of the 17 patients, 14 (82%) completed the study. There was no significant difference in appointment length between visits (introduction of the tool did not increase appointment length; F2,24=0.805; mean squared error 58.08; P=.46). In total, 92% (12/13) of patients and 71% (5/7) of physicians felt that the tool was easy to use; 62% (8/13) of patients and 71% (5/7) of physicians rated that they trusted the CDSS. Of the 13 patients, 6 (46%) felt that the patient-clinician relationship significantly or somewhat improved, whereas 7 (54%) felt that it did not change. CONCLUSIONS: Our findings confirm that the integration of the tool does not significantly increase appointment length and suggest that the CDSS is easy to use and may have positive effects on the patient-physician relationship for some patients. The CDSS is feasible and ready for effectiveness studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04061642; http://clinicaltrials.gov/ct2/show/NCT04061642.
ABSTRACT
BACKGROUND: Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction. AIMS: Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression. Here, we explore the use of a simulation centre environment in evaluating the usability of Aifred, particularly its impact on the physician-patient interaction. METHOD: Twenty psychiatry and family medicine attending staff and residents were recruited to complete a 2.5-h study at a clinical interaction simulation centre with standardised patients. Each physician had the option of using the CDSS to inform their treatment choice in three 10-min clinical scenarios with standardised patients portraying mild, moderate and severe episodes of major depression. Feasibility and acceptability data were collected through self-report questionnaires, scenario observations, interviews and standardised patient feedback. RESULTS: All 20 participants completed the study. Initial results indicate that the tool was acceptable to clinicians and feasible for use during clinical encounters. Clinicians indicated a willingness to use the tool in real clinical practice, a significant degree of trust in the system's predictions to assist with treatment selection, and reported that the tool helped increase patient understanding of and trust in treatment. The simulation environment allowed for the evaluation of the tool's impact on the physician-patient interaction. CONCLUSIONS: The simulation centre allowed for direct observations of clinician use and impact of the tool on the clinician-patient interaction before clinical studies. It may therefore offer a useful and important environment in the early testing of new technological tools. The present results will inform further tool development and clinician training materials.
