Prevalence of Powassan Virus Seropositivity Among People with History of Lyme Disease and Non-Lyme Community Controls in the Northeastern United States.

Introduction: Lyme disease (LD) affects ∼476,000 people each year in the United States. Symptoms are variable and include rash and flu-like symptoms. Reasons for the wide variation in disease outcomes are unknown. Powassan virus (POWV) is a tick-borne flavivirus that causes disease ranging from asymptomatic infection to encephalitis, neurologic damage, and death. POWV and LD geographic case distributions overlap, with Ixodes species ticks as the common vectors. Clinical ramifications of coinfection or sequential infection are unknown. Objectives: This study's primary objective was to determine the prevalence of POWV-reactive antibodies in sera samples collected from previously studied cohorts of individuals with self-reported LD history residing in the Northeastern United States. As a secondary objective, we studied clinical differences between people with self-reported LD history and low versus high POWV antibody levels. Methods: We used an enzyme-linked immunosorbent assay (ELISA) to quantify IgG directed at the POWV envelope (E) protein domain III in 538 samples from individuals with self-reported LD history and 16 community controls. The samples were also tested with an ELISA assay to quantify IgG directed at the POWV NS1 protein. Results: The percentage of individuals with LD history and possible evidence of POWV exposure varied depending on the assay utilized. We found no significant difference in clinical symptoms between those with low or high POWV IgG levels in the in-house assay. Congruence of the EDIII and NS1 assays was low with only 12% of those positive in the in-house EDIII ELISA testing positive in the POWV NS1 ELISA. Conclusions: The results highlight the difficulty in flavivirus diagnostic testing, particularly in the retrospective detection of flavivirus exposure. The findings suggest that a prospective study with symptomatic patients using approved clinical testing is necessary to address the incidence and clinical implications of LD and POWV co-infection or sequential infection.

Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.

Neuropsychiatric Symptoms and Tick-Borne Diseases.

In North America, Lyme disease (LD) is primarily caused by the spirochetal bacterium Borrelia burgdorferi, transmitted to humans by Ixodes species tick bites, at an estimated rate of 476,000 patients diagnosed per year. Acute LD often manifests with flu-like symptoms and an expanding rash known as erythema migrans (EM) and less often with neurologic, neuropsychiatric, arthritic, or cardiac features. Most acute cases of Lyme disease are effectively treated with antibiotics, but 10-20% of individuals may experience recurrent or persistent symptoms. This chapter focuses on the neuropsychiatric aspects of Lyme disease, as these are less widely recognized by physicians and often overlooked. Broader education about the potential complexity, severity, and diverse manifestations of tick-borne diseases is needed.

Kundalini Yoga for Post-Treatment Lyme Disease: A Preliminary Randomized Study.

This study examined the adherence to and the potential benefit of Kundalini yoga (KY) for post-treatment Lyme disease syndrome (PTLDS). Participants were randomly assigned to 8 weeks of a KY small-group intervention or a waitlist control (WLC). Adherence was measured as attendance at KY group sessions. Primary outcomes assessed pain, pain interference, fatigue, and global health. Secondary outcomes assessed multisystem symptom burden, mood, sleep, physical and social functioning, cognition, and mindfulness. Linear mixed models were used to test changes in outcomes over time as a function of group assignment; intercepts for participants were modeled as random effects. Although the target sample size was 40 participants, the study concluded with 29 participants due to recruitment challenges. No KY participants dropped out of the study, and participants attended 75% of group sessions on average, but WLC retention was poor (57%). Regarding primary outcomes, there was no significant interaction between group and time. Regarding secondary outcomes, there was a significant interaction between group and time for multisystem symptom burden (p < 0.05) and cognition (p < 0.01); KY participants reported improved multisystem symptom burden and cognition over the course of the study compared to WLC participants. To enhance recruitment and retention, future trials may consider expanding geographic access and including supportive procedures for WLC participants. This preliminary study supports the need for a larger study to determine if KY reduces multisystem symptom burden and enhances cognition among people with PTLDS.

Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.

Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential. One-Sentence Summary: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.

Borrelia miyamotoi Serology in a Clinical Population With Persistent Symptoms and Suspected Tick-Borne Illness.

Eighty-two patients seeking consultation for long-term sequalae after suspected tick-borne illness were consecutively tested for Borrelia miyamotoi antibodies using a recombinant glycerophosphodiester phosphodiesterase (GlpQ) enzyme immunoassay. Twenty-one of the 82 patients (26%) tested positive on the GlpQ IgG ELISA. Nearly all of the patients (98%) had no prior B. miyamotoi testing, indicating that clinicians rarely test for this emerging tick-borne pathogen. Compared to patients who solely tested positive for Lyme disease antibodies, patients with B. miyamotoi antibodies presented with significantly more sleepiness and pain. A prospective study is needed to ascertain the relationship between the presence of B. miyamotoi antibodies and persistent symptoms.

Brain-based mediation of non-conscious reduction of phobic avoidance in young women during functional MRI: a randomised controlled experiment.

BACKGROUND: Exposure therapy is the treatment of choice for anxiety disorders but requires people to confront feared situations and can be distressing. We tested the hypothesis that exposure without conscious awareness would reduce fear in participants with specific phobia by harnessing the neural circuitry supporting the automatic extinction of fear. METHODS: In this single-centre, randomised controlled experiment, we recruited women aged 18-29 years from an ethnically diverse, community-based population in northeastern USA, between Sept 1, 2013, and Aug 1, 2016. Eligible participants classified as having phobia met the DSM-5 criteria for specific phobia but not for any other disorder, had scores in the top 10% of respondents to the Fear of Spiders Questionnaire, and exhibited impairing avoidance of a live tarantula. Eligible controls met no criteria for any disorder, were in the bottom 30% of questionnaire respondents, and displayed no avoidance of the tarantula. The randomisation schedule was generated with the open source Research Randomizer Tool. A research assistant randomly assigned participants to the active intervention of very brief exposure (VBE)-the repeated presentation of masked phobic stimuli (ie, spiders)-or the control intervention which used masked flowers (VBF). VBE and VBF were given code numbers to prevent staff from knowing which intervention they were administering. During a 10 min functional MRI (fMRI) task, each participant was exposed to 16 blocks of ten masked target stimuli (spiders or flowers), alternating with 16 blocks of ten masked neutral stimuli. A few minutes after fMRI, participants with spider phobia approached the tarantula again so we could measure changes in phobic behaviour. The primary outcome was real-time changes in brain activity measured by fMRI. All analyses were done by intention to treat. RESULTS: We recruited 82 women, of whom 42 had spider phobia and 40 were controls. VBE generated stronger neural activity in participants with spider phobia than in controls, particularly in regions supporting emotion, emotion regulation, and attention systems, such as the inferior frontal cortex (Cohen's d 0·95, 95% CI 0·93-0·98, Bayesian posterior probability 99·5%) and the caudate nucleus (1·16, 1·14-1·18, 100·0%). In participants with phobia, VBE also generated stronger activity in these regions than did VBF (eg, dorsal anterior cingulate cortex Cohen's d 0·80, 95% CI 0·78-0·80, Bayesian posterior probability 98·5%; caudate nucleus 1·0, 0·98-1·02, 99·5%). VBE reduced avoidance of the live tarantula in participants with phobia. Regions supporting fear extinction (including ventral medial prefrontal cortex) and emotional salience processing mediated this effect. No adverse events occurred. INTERPRETATION: VBE reduced fear non-consciously in participants with spider phobia by recruiting brain regions supporting automatic fear extinction, emotion regulation, and top-down attentional processing. Future studies should explore the use of VBE in other fear-based disorders. FUNDING: National Institutes of Mental Health and Brain & Behavior Research Foundation.

Less is more: Neural activity during very brief and clearly visible exposure to phobic stimuli.

Research on automatic processes in fear has emphasized the provocation of fear responses rather than their attenuation. We have previously shown that the repeated presentation of feared images without conscious awareness via backward masking reduces avoidance of a live tarantula in spider-phobic participants. Herein we investigated the neural basis for these adaptive effects of masked exposure. 21 spider-phobic and 21 control participants, identified by a psychiatric interview, fear questionnaire, and approaching a live tarantula, viewed stimuli in each of three conditions: (1) very brief exposure (VBE) to masked images of spiders, severely limited awareness; (2) clearly visible exposure (CVE) to spiders, full awareness; and (3) masked images of flowers (control), severely limited awareness. Only VBE to masked spiders generated neural activity more strongly in phobic than in control participants, within subcortical fear, attention, higher-order language, and vision systems. Moreover, VBE activated regions that support fear processing in phobic participants without causing them to experience fear consciously. Counter-intuitively, CVE to the same spiders generated stronger neural activity in control rather than phobic participants within these and other systems. CVE deactivated regions supporting fear regulation and caused phobic participants to experience fear. CVE-induced activations also correlated with measures of explicit fear ratings, whereas VBE-induced activations correlated with measures of implicit fear (color-naming interference of spider words). These multiple dissociations between the effects of VBE and CVE to spiders suggest that limiting awareness of exposure to phobic stimuli through visual masking paradoxically facilitates their processing, while simultaneously minimizing the experience of fear. Hum Brain Mapp 38:2466-2481, 2017. © 2017 Wiley Periodicals, Inc.