The central executive network moderates the relationship between posttraumatic stress symptom severity and gastrointestinal related issues.

Although most adults experience at least one traumatic event in their lifetime, a smaller proportion will go on to be clinically diagnosed with post-traumatic stress disorder (PTSD). Persons diagnosed with PTSD have a greater likelihood of developing gastrointestinal (GI) disorders. However, the extent to which subclinical levels of post-traumatic stress (PTS) correspond with the incidence of GI issues in a normative sample is unclear. Resting state fMRI, medical history, psychological survey, and anthropometric data were acquired from the Enhanced Nathan Kline Institute-Rockland Sample (n = 378; age range 18-85.6 years). The primary aim of this study was to test the main effect of subclinical PTS symptom severity on the number of endorsed GI issues. The secondary aim was to test the moderating effect of high versus low resting state functional connectivity (rsFC) of the central executive network (CEN) on the relationship between PTS symptom severity and GI issues. Trauma Symptom Checklist-40 (TSC-40) scores were positively associated with the number of endorsed GI issues (b = -0.038, SE = .009, p < .001). The interaction between TSC-40 scores and rsFC within the CEN was significant on GI issues after controlling for sociodemographic and cardiometabolic variables (b = -0.031, SE = .016, p < .05), such that above average rsFC within the CEN buffered the effect of TSC-40 scores on GI issues. Our findings of higher rsFC within the CEN moderating the magnitude of coincidence in PTS and GI symptom severity may reflect the mitigating role of executive control processes in the putative stress signaling mechanisms that contribute to gut dysbiosis.

Dynamic vagal-mediated connectivity of cortical and subcortical central autonomic hubs predicts chronotropic response to submaximal exercise in healthy adults.

BACKGROUND: Despite accumulation of a substantial body of literature supporting the role of exercise on frontal lobe functioning, relatively less is understood of the interconnectivity of ventromedial prefrontal cortical (vmPFC) regions that underpin cardio-autonomic regulation predict cardiac chronotropic competence (CC) in response to sub-maximal exercise. METHODS: Eligibility of 161 adults (mean age = 48.6, SD = 18.3, 68% female) was based upon completion of resting state brain scan and sub-maximal bike test. Sliding window analysis of the resting state signal was conducted over 45-s windows, with 50% overlap, to assess how changes in photoplethysmography-derived HRV relate to vmPFC functional connectivity with the whole brain. CC was assessed based upon heart rate (HR) changes during submaximal exercise (HR change /HRmax (206-0.88 × age) - HRrest). RESULTS: During states of elevated HRV the vmPFC showed greater rsFC with an 83-voxel region of the hypothalamus (p < 0.001, uncorrected). Beta estimates of vmPFC connectivity extracted from a 6-mm sphere around this region emerged as the strongest predictor of CC (b = 0.283, p <.001) than age, BMI, and resting HRV F(8,144) = 6.30, p <.001. CONCLUSION: Extensive glutamatergic innervation of the hypothalamus by the vmPFC allows for top-down control of the hypothalamus and its various autonomic efferents which facilitate chronotropic response during sub-maximal exercise.

Impact of a Multi-Institutional Initiative to Engage Students and Early-Stage Scholars From Underrepresented Racial and Ethnic Minority Groups in HIV Research: The Centers for AIDS Research Diversity, Equity, and Inclusion Pathway Initiative.

BACKGROUND: The Centers for AIDS Research Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) aims to establish programs to develop pathways for successful careers in HIV science among scholars from underrepresented racial and ethnic populations. This article describes cross-site evaluation outcomes during the first 18 months (July 2021-December 2022) across 15 programs. METHODS: The aims of the evaluation were to characterize participants, describe feasibility, challenges, and successes of the programs and provide a basis for the generalizability of best practices to Diversity, Equity, and Inclusion (DEI) programs in the United States. Two primary data collection methods were used: a quarterly programmatic monitoring process and a centrally managed, individual-level, participant quantitative and qualitative survey. RESULTS: During the first year of evaluation data collection, 1085 racially and ethnically diverse scholars ranging from the high school to postdoctoral levels applied for CDEIPI programs throughout the United States. Of these, 257 (23.7%) were selected to participate based on program capacity and applicant qualifications. Participants were trained by 149 mentors, teachers, and staff. Of the N = 95 participants responding to the individual-level survey, 95.7% agreed or strongly agreed with statements of satisfaction with the program, 96.8% planned to pursue further education, and 73.7% attributed increased interest in a variety of HIV science topics to the program. Qualitative findings suggest strong associations between mentorship, exposure to scientific content, and positive outcomes. CONCLUSIONS: These data provide evidence to support the feasibility and impact of novel DEI programs in HIV research to engage and encourage racially and ethnically diverse scholars to pursue careers in HIV science.

Modulatory effects of transcranial direct current stimulation of right insula on compassion motivation

Background: Compassion motivation is associated with increased heart rate variability (HRV), reflecting a calm and self-soothing physiological state. Recent work, however, suggests that this association is dynamic for the specific components of compassion. Objectives: The present study adopted anodal transcranial direct current stimulation (tDCS) targeting the right insula to see whether this would modulate the sensitivity to suffering and the commitment to engage in helpful actions (i.e., the components of compassion motivation). Method: Ninety-seven healthy individuals underwent 15-min anodal or sham tDCS over the frontotemporal lobe, while watching a video inducing empathic sensitivity and performing a Redistribution Game. Tonic and phasic HRV, dispositional traits, and momentary affects were assessed. Results: Compared to sham condition, anodal stimulation favored significant i) HRV reductions during the video and HRV increases during the Redistribution Game; ii) decreases in self-reported levels of negative affect and increases in positive affect during task when the latter was preceded by the video, without influencing altruistic behavior. Conclusions: Anodal tDCS over the right insula may modulate the engagement phase of compassion by intensifying the psychophysiological sensitivity to signals of distress and protecting from being subjectively overwhelmed by it. (AU)

Does emotion regulation network mediate the effect of social network on psychological distress among older adults?

Socio-emotional interactions are integral for regulating emotions and buffering psychological distress. Social neuroscience perspectives on aging suggest that empathetic interpersonal interactions are supported by the activation of brain regions involved in regulating negative affect. The current study tested whether resting state functional connectivity of a network of brain regions activated during cognitive emotion regulation, i.e., emotion regulation network (ERN), statistically mediates the frequency of social contact with friends or family on psychological distress. Here, a 10-min resting-state functional MRI scan was collected along with self-reported anxiety/depressive, somatic, and thought problems and social networking from 90 community-dwelling older adults (aged 65-85 years). The frequency of social interactions with family, but not friends and neighbors, was associated with lower psychological distress. The magnitude of this effect was reduced by 33.34% to non-significant upon adding resting state ERN connectivity as a mediator. Follow-up whole-brain graph network analyses revealed that efficiency and centrality of the left inferior frontal gyrus and the right middle temporal gyrus relate to greater family interactions and lower distress. These hubs may help to buffer psychological problems in older adults through interactions involving empathetic and cognitive emotion regulation with close family.

Synergistic effects of high early-life stress exposure and HIV infection on reaction time variability.

Addressing comorbidities contributing to cognitive impairment in people living with HIV (PLWH) remains imperative. Prior studies utilizing reaction time intra-individual variability (RT-IIV), a robust behavioral marker of cognitive dysfunction, demonstrate increased cognitive impairment in adults living with HIV who have high early life stress (ELS) exposure relative to those with low-ELS exposure. Yet, it is unknown whether RT-IIV elevations are due to high-ELS alone or both HIV-status and high-ELS. In the current study, we explore the potential additive effects of HIV and high-ELS exposure on RT-IIV to better characterize the independent and combined effects of these factors on RT-IIV among PLWH. We assessed 59 PLWH and 69 HIV-negative healthy control (HC) participants with either low or high ELS on RT-IIV during a working memory task (1-back). We observed a significant interaction between HIV status and ELS exposure on RT-IIV, PLWH who had experienced high ELS demonstrating RT-IIV elevations relative to all other groups. In addition, RT-IIV was significantly associated with ELS exposure in PLWH, but not in the HC group. We also observed associations between RT-IIV and measures of HIV-disease severity (plasma HIV viral load, nadir CD4) among PLWH. Taken as a whole, these findings provide novel evidence of the combined effects of HIV and high-ELS exposure on RT-IIV, and thus suggest HIV-related and ELS-related neural abnormalities may act in an additive or synergistic manner to affect cognition. Such data warrant further investigation into the neurobiological mechanisms associated with HIV and high-ELS exposure that contribute to increased neurocognitive dysfunction among PLWH.

The Evolution of Assessing Central Nervous System Complications in Human Immunodeficiency Virus: Where Do We Go From Here?

In this fifth decade of the human immunodeficiency virus (HIV) epidemic, central nervous system (CNS) complications including cognitive impairment and mental health remain a burden for people with HIV (PWH) on antiretroviral therapy. Despite the persistence of these complications, which often co-occur, the underlying pathophysiology remains elusive and consequently treatments remain limited. To continue to grow our understanding of the underlying mechanisms of CNS complications among PWH, there is a need to reexamine our current approaches, which are now more than 2 decades old. At the 2021 National Institutes of Health-sponsored meeting on Biotypes of CNS Complications in PWH, the Neurobehavioral Working Group addressed the following: (1) challenges inherent to determining CNS complications; (2) heterogeneity in CNS complications; and (3) problems and solutions for examining integrated biotypes. The review below provides a summary of the main points presented and discussed by the Neurobehavioral Working Group at the meeting.

Neutrophil-to-Lymphocyte Ratio Amplifies the Effects of Aging on Decrements in Grip Strength and Its Functional Neural Underpinnings.

The neutrophil-to-lymphocyte ratio (NLR) is a trans-prognostic biomarker of physiologic stress and inflammation linked to muscle weakness in older adults. Generation of grip force coincides with sustained activity in the primary sensorimotor cortex (SM1). The current study investigates whether whole-brain functional connectivity, that is, degree centrality (CD) of SM1 relates to grip strength and whether both functional measures are predicted by advancing age as a function of the NLR. A structural regression model investigated the main and interactive effects of age and NLR on grip strength and CD of SM1 in 589 adults aged 21-85 years (M = 45.87, SD = 18.06). The model including the entire sample had a good fit (χ 2(4) = 1.63, p = .804). In individuals aged 50 years and older, age predicted lower grip strength and SM1 CD as a function of increasing NLR. In a model stratified by sex, the effect of age, NLR, and their interaction on grip strength are significant for older men but not older women. Analyses support CD of SM1 at rest as a neural biomarker of grip strength. Grip and its neural underpinnings decrease with advancing age and increasing NLR in mid to late life. Age-related decrements in grip strength and functional connectivity of brain regions involved in the generation of dynamic grip appear to be accelerated as a function of systemic physiological stress and inflammation, particularly in older men.

Modulatory effects of transcranial direct current stimulation of right insula on compassion motivation.

Background: Compassion motivation is associated with increased heart rate variability (HRV), reflecting a calm and self-soothing physiological state. Recent work, however, suggests that this association is dynamic for the specific components of compassion. Objectives: The present study adopted anodal transcranial direct current stimulation (tDCS) targeting the right insula to see whether this would modulate the sensitivity to suffering and the commitment to engage in helpful actions (i.e., the components of compassion motivation). Method: Ninety-seven healthy individuals underwent 15-min anodal or sham tDCS over the frontotemporal lobe, while watching a video inducing empathic sensitivity and performing a Redistribution Game. Tonic and phasic HRV, dispositional traits, and momentary affects were assessed. Results: Compared to sham condition, anodal stimulation favored significant i) HRV reductions during the video and HRV increases during the Redistribution Game; ii) decreases in self-reported levels of negative affect and increases in positive affect during task when the latter was preceded by the video, without influencing altruistic behavior. Conclusions: Anodal tDCS over the right insula may modulate the engagement phase of compassion by intensifying the psychophysiological sensitivity to signals of distress and protecting from being subjectively overwhelmed by it.

Circulating endothelial and angiogenic cells predict hippocampal volume as a function of HIV status.

Circulating endothelial cells (CECs) and myeloid angiogenic cells (MACs) have the capacity to stabilize human blood vessels in vivo. Evidence suggests that these cells are depleted in dementia and in persons living with HIV (PWH), who have a higher prevalence of dementia and other cognitive deficits associated with aging. However, the associations of CECs and MACs with MRI-based measures of aging brain health, such as hippocampal gray matter volume, have not been previously demonstrated. The present study examined differences in these associations in 51 postmenopausal women with and without HIV infection. Gray matter volume was quantified using MRI. CECs and MACs were enumerated using fluorescence-activated cell sorting. Analyses examined the association of these cell counts with left and right hippocampal gray matter volume while controlling for age and hypertension status. The main finding was an interaction suggesting that compared to controls, postmenopausal PWH with greater levels of CECs and MACs had significantly greater hippocampus GMV. Further research is necessary to examine potential underlying pathophysiological mechanisms in HIV infection linking morpho-functional circulatory reparative processes with more diminished hippocampal volume in postmenopausal women.

Anterior Insula Activation During Cardiac Interoception Relates to Depressive Symptom Severity in HIV-Positive and HIV-Negative Postmenopausal Women.

OBJECTIVE: This study aimed to determine whether subclinical symptoms of depression in postmenopausal women are associated with blood oxygen level-dependent (BOLD) activity within the anterior insula during cardiac interoceptive awareness and whether this association differs for persons living with the human immunodeficiency virus (PWH). METHOD: Twenty-three postmenopausal (mean [standard deviation] age = 56.5 [4.8] years) and 27 HIV-negative women (mean [standard deviation] age = 56.4 [8.0]) underwent functional magnetic resonance imaging while performing a heartbeat detection task. BOLD activation within the bilateral anterior insula based on the contrast of a heartbeat detection condition with and without a distracting tone was entered along with age, HIV status, and psychological stress into two multivariate regression models with self-reported depressive symptom severity as the outcome. RESULTS: Depressive symptoms did not vary by HIV status, nor was there a main effect or interaction for PWH on insula BOLD activation. Depressive symptoms were positively associated with psychological stress for the left ( ß = 0.310, t (49) = 2.352, p = .023) and right brain models ( ß = 0.296, t (49) = 2.265, p = .028) as well as the magnitude of BOLD activation in the left insula ( ß = 0.290, t (49) = 2.218, p = .032) and right insula ( ß = 0.318, t (49) = 2.453, p = .018), respectively. Exploratory analyses revealed that greater magnitude of BOLD activation attributed to exteroceptive noise (tone) was also correlated with self-reported distrust and preoccupation with interoceptive sensations. CONCLUSIONS: Results support an active interference model for interoceptive awareness wherein greater BOLD signal in the anterior insula in the presence of distracting exteroceptive stimuli may reflect greater prediction error, a feature of depression.

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era.

OBJECTIVE: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiome-gut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. METHODS: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. RESULTS: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). CONCLUSIONS: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiome-gut-brain axis pathways among PWH in the modern antiretroviral therapy era.

Rapid detection of SARS-CoV-2 RNA in saliva via Cas13.

Rapid nucleic acid testing is central to infectious disease surveillance. Here, we report an assay for rapid COVID-19 testing and its implementation in a prototype microfluidic device. The assay, which we named DISCoVER (for diagnostics with coronavirus enzymatic reporting), involves extraction-free sample lysis via shelf-stable and low-cost reagents, multiplexed isothermal RNA amplification followed by T7 transcription, and Cas13-mediated cleavage of a quenched fluorophore. The device consists of a single-use gravity-driven microfluidic cartridge inserted into a compact instrument for automated running of the assay and readout of fluorescence within 60 min. DISCoVER can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva with a sensitivity of 40 copies µl-1, and was 94% sensitive and 100% specific when validated (against quantitative PCR) using total RNA extracted from 63 nasal-swab samples (33 SARS-CoV-2-positive, with cycle-threshold values of 13-35). The device correctly identified all tested clinical saliva samples (10 SARS-CoV-2-positive out of 13, with cycle-threshold values of 23-31). Rapid point-of-care nucleic acid testing may broaden the use of molecular diagnostics.

HIV-related drivers of sexual compulsivity and sexuality in sexual minority men who use methamphetamine.

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and sexual sensation seeking. This 15-month longitudinal study enrolled 110 sexual minority men (SMM) living with HIV who had biologically confirmed meth use (i.e., reactive urine or hair toxicology results). Peripheral venous blood samples collected at baseline, 6 months, 12 months, and 15 months were used to measure a detectable viral load (> 40 copies/mL), the kynurenine/tryptophan (K/T) ratio, and the phenylalanine/tyrosine (P/T) ratio. The K/T and P/T ratios index dysregulated serotonin and catecholamine (e.g., dopamine) synthesis, respectively. In a cross-lagged panel model, a detectable viral load at 6 months predicted greater sexual compulsivity at 12 months after adjusting for prior levels of sexual compulsivity and recent stimulant use (ß = 0.26, p = 0.046). A greater P/T ratio at baseline predicted decreased sexual sensation seeking at 6 months (ß = - 0.25, p = 0.004) after adjusting for baseline sexual sensation seeking and recent stimulant use. Taken together, HIV replication and dysregulated catecholamine synthesis could potentiate sexual compulsivity while decreasing sexual pleasure in SMM who use meth.

Learning to forget: Hippocampal-amygdala connectivity partially mediates the effect of sexual trauma severity on verbal recall in older women undiagnosed with posttraumatic stress disorder.

Verbal learning deficits are common among sexually traumatized women who have not been formally diagnosed with posttraumatic stress disorder (PTSD). Aberrant resting-state functional connectivity (rsFC) of the amygdala and hippocampus are implicated in PTSD and verbal memory impairment. We tested rsFC between bilateral dentate gyrus (DG) and both centromedial (CM) and basolateral (BL) nuclei of the amygdala as statistical mediators for the effect of sexual trauma-related symptom severity on delayed verbal recall performance in 63 older women (age: 60-85 years) undiagnosed with PTSD. Participant data were drawn from the NKI-Rockland Study. Individuals completed a 10-min resting-state scan, Rey Auditory Verbal Learning Test (RAVLT), and the Sexual Abuse Trauma Index (SATI) from the Trauma Symptom Checklist. Z-scores indicating rsFC of DG with BL and CM amygdala seeds were evaluated in two separate mediation models. Higher SATI scores were associated with lower RAVLT after controlling for age, ß = -.23, 95% CI [.48, .03], p = .039. This effect was negated upon adding a negative path from SATI to rsFC of left DG and right CM, ß = -.29, 95% CI [-.52, -.02], p = .022, and a positive path from that seed pair to RAVLT List A recall, ß = .28, 95% CI [.03, 0.48], p = .015. Chi-square fit indices supported partial mediation by this seed pair, p = .762. In the absence of PTSD sexual trauma symptoms partially relate to verbal learning deficits as a function of aberrant rsFC between left hippocampus DG and right amygdala CM nuclei.

Neutrophil to lymphocyte ratio is a transdiagnostic biomarker of depression and structural and functional brain alterations in older adults.

The neutrophil to lymphocyte ratio (N:L) is an emergent transdiagnostic biomarker shown to predict peripheral inflammation as well as neuropsychiatric impairment. The afferent signaling of inflammation to the central nervous system has been implicated in the pathophysiology of sickness behavior and depression. Here, the N:L was compared to structural and functional limbic alterations found concomitant with depression within a geriatric cohort. Venous blood was collected for a complete blood count, and magnetic resonance imaging as well as phenotypic data were collected from the 66 community-dwelling older adults (aged 65-86 years). The N:L was regressed on gray matter volume and resting-state functional connectivity (rsFC) of the subgenual anterior cingulate (sgACC). Thresholded parameter estimates were extracted from structural and functional brain scans and bivariate associations tested with scores on the geriatric depression scale. Greater N:L predicted lower volume of hypothalamus and rsFC of sgACC with ventromedial prefrontal cortex. Both parameters were correlated (p < 0.05) with greater symptomology in those reporting moderate to severe levels of depression. These findings support the N:L as a transdiagnostic biomarker of limbic alteration underpinning mood disturbance in non-treated older adults.

Cognition, Coping, and Psychological Distress in HIV.

Interrelationships among HIV-associated neurocognitive dysfunction, avoidant coping, cognitively-oriented coping, and psychological distress were examined using structural equation modeling in an ethnically diverse sample of 209 adults predominantly in the mid-range of illness. Global neurocognitive deficits, assessed with the HIV-dementia scale, were associated with higher levels of avoidant coping, lower levels of cognitive coping, and a higher avoidant/cognitive coping ratio, which were each in turn associated with higher psychological distress measured by a latent factor comprising symptoms of depression, anxiety, and HIV-related distressing thoughts. There were significant indirect effects through avoidant coping and a higher avoidant/cognitive coping ratio. Results suggest the presence of HIV-associated neurocognitive deficits may interfere with the utilization of cognitive-based coping strategies and increase reliance on  more maladaptive strategies, which in turn may translate to elevated reports of  psychological distress. Findings may help inform interventions aimed at reducing avoidant coping and psychological distress, two factors associated with accelerated HIV disease progression.

Association of cardiometabolic health factors with age-related executive function and episodic memory.

Although decline of cognitive abilities in late life is regarded as a common facet of aging, there is inter-individual variability in this decline. Possible contributors are cardiometabolic risk factors associated with cerebrovascular dysfunction, but a dearth in unifying health-cognition models confound exactly how these risk factors mediate age-related changes in executive function (EF) and episodic memory. This study investigated the indirect effect of age on these cognitive abilities via cardiometabolic risk factors using a structural equation modeling approach. Participants included 738 adults (64% female) ranging from 21 to 85 years of age (M = 47.47, SD = 18.28). An exploratory factor analysis was applied to an EF battery yielding a two-factor solution, consisting of inhibition and cognitive flexibility, that showed acceptable fit (χ2(48) = 101.84, p < .001, CFI = .980, RMSEA = .039, SRMR = .035). The EF latent factors were then included in a confirmatory factor analysis exploring the indirect role of age on episodic memory and EF via blood pressure, cholesterol, triglycerides and body mass index. The theoretical model demonstrated acceptable fit, χ2(108) = 204.071, p < .001, CFI = .972, RMSEA = .035, SRMR = .035. Blood pressure was associated with lower cognitive flexibility (ß = -.20, p < .001) and there was a significant indirect effect of age on episodic memory through cognitive flexibility (ß = .07, p = .021). Results support the "Executive Decline Hypothesis" of age-related episodic memory decline and specifically implicate lower blood pressure control and cognitive flexibility in these changes.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided RNA recognition that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper their detection sensitivity and speed. Here, we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 molecules per µl of RNA in 20 min. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA extracted from respiratory swab samples with quantitative reverse transcriptase PCR (qRT-PCR)-derived cycle threshold (Ct) values up to 33, using a compact detector. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables sensitive, direct RNA detection in a format that is amenable to point-of-care infection diagnosis as well as to a wide range of other diagnostic or research applications.