BRAIN AND BEHAVIOR PREDICTORS OF SARS-CoV-2 INFECTION AMONG PEOPLE WITH HIV

Background: Recent findings from the UK Biobank revealed that healthy adults who later became infected with SARS-CoV-2 had lower brain volumes in regions involved in risk-taking behavior and olfaction compared to individuals who did not become infected. We examined if similar pre-existing differences in brain regions correspond to SARS-CoV-2 infection among people with HIV (PWH) receiving suppressive ART. Method(s): Participants included adult Thai MSM enrolled in the acute HIV (AHI) cohort (RV254/SEARCH010) in Bangkok, Thailand. Participants underwent 3T MRI and clinical assessments (i.e., HIV disease metrics, cognitive testing, and self-reported mood and substance use). ART initiation occurred within 5 days of the MRI (median=same day). Regional brain volumes were summed across hemispheres and corrected for head size. Brain volumes and clinical indices were compared between participants with laboratory confirmed SARS-CoV-2 and those without a diagnosis of SARS-CoV-2 following ART initiation. Machine learning was utilized to identify variables at the time of enrollment into the cohort that predicted subsequent SARS-CoV-2 infection status. Result(s): 112 participants were included in the analysis. All study participants achieved viral suppression after ART and received SARS-CoV-2 vaccinations. Fifty-four participants became infected with SARS-CoV-2 during the observation period (median=79 weeks from ART initiation). Study participants who became infected with SARS-CoV-2 after ART had lower volumes at the time of enrollment in several subcortical brain regions with the most pronounced effect in the pallidum (p=.025). There were no associations between brain volumes and ratings of mood, demographics, or HIV disease indices. SARS-CoV-2 infection was two-fold higher among individuals who reported use of amyl nitrites (i.e., poppers) during chemsex. Machine learning with repeated cross validation revealed that lower orbital and medial frontal lobe, anterior cingulate, pallidum, vermis, and olfactory volumes, worse motor function, and higher education collectively predicted co-infection status (average AUC of 85%). Conclusion(s): Study findings point toward a risk phenotype for SARS-CoV-2 infection among PWH defined by pre-existing differences in brain volumes relevant to risk-taking behavior, emotion, and neuroHIV as well as behavioral factors such as inhalant use and lack of social distancing during chemsex. (Table Presented).

Characteristics and Outcomes of Covid-19 in an Early-Treated Hiv Cohort in Thailand

Background: Emerging data indicate that people with HIV (PWH) are at risk of more severe outcomes from COVID-19. We described the clinical course and laboratory parameters pre-and post-COVID-19 in an early-treated HIV cohort in Thailand. Method(s): RV254 cohort participants were enrolled during Fiebig I-V acute HIV and initiated antiretroviral therapy (ART) within days. They underwent regular blood tests (CD4+ & CD8+ T-cell counts, HIV RNA), neuropsychiatric (NP) assessment (Color Trails 1 & 2, non-dominant hand Grooved Pegboard, Trails Making A), and mood questionnaires (Patient Health Questionnaire-9, Distress Thermometer) post-enrollment longitudinally. Their assessment outcomes pre-and post-COVID-19 were compared using Generalized Estimating Equations (GEE) with a normal distribution and identity link (CD4+, CD8+ T-cell counts, NP parameters) or binomial distribution with log link (HIV RNA), and autoregressive correlation structure. Result(s): Between 4/2021 and 9/2022, 295 participants on ART (98% male, median age 32 [IQR 28-37] were diagnosed with COVID-19. Of these, 16(5%), 38(13%) and 241(82%) were infected with alpha, delta and o variants, determined by the predominant strain circulating in Thailand at the time of infection;238(81%) received >=2 doses of COVID-19 vaccines prior to diagnosis;121(41%) received favipiravir. While 106 (36%) were managed in hospital or 'hospitel', including one intensive care unit admission, only 4(1.4%) received supplemental oxygen and none required mechanical ventilation (mean length of stay: 12 days). The participants were followed a median of 8 [IQR 5-15] weeks post-COVID. Comparing the outcomes pre-and post-COVID, plasma HIV suppression rate remained stable (98% vs. 96%, p=0.212). CD4+ (782 [IQR 708-856] vs. 823 [IQR 748-899], p=0.018) and CD8+ (622 [IQR 563-681] vs. 667 [IQR 605-728], p=0.023) T-cell counts were higher at follow-up after adjusting for age, sex, and duration between COVID-19 diagnosis and follow-up. The increasing trends of CD4+ and CD8+ T-cell were sustained on subsequent visits. Mood scores and NP performance (n=217) were stable at follow-up. Conclusion(s): In this cohort of young PWH on stable ART, we did not observe major clinical adverse events after COVID-19. Increases of CD4+ and CD8+ T-cell counts were observed while mood and NP parameters remained stable. More extensive NP assessment with incorporation of multimodal imaging outcomes and longer follow-up are needed to determine the long-term sequelae of COVID-19 in PWH.

Cognitive, Motor, & Negative Valence Systems in Neurologic Pasc: A Preliminary Study

Background: Nervous system post-acute sequelae of COVID-19 (NS-PASC) include cognitive and mental health symptoms. To further define these, we applied a Research Domain Criteria (RDoC) approach to examine motor, positive valence (PV) and negative valence (NV) systems, and social processing data in The COVID Mind Study of NS-PASC. Method(s): NS-PASC participants (>3 months after COVID-19) referred from a NeuroCOVID Clinic and non-COVID controls from New Haven, CT and Baltimore, MD completed an RDoC test battery for cognition (language, declarative and working memory, cognitive control, perception), motor, PV, NV, and social processes. To date, 3T MRI with diffusion tensor imaging was performed in 11 NS-PASC to assess white matter integrity (global white matter fractional anisotropy [FA]) as a contributor to alterations identified on the RDoC tests. Analysis of Covariance examined group differences after adjusting for sex, race, ethnicity, age, and years of education. Result(s): 25 NS-PASC participants (age 43.4+/-11.3 yrs, 76% female, 402 days after COVID-19 symptom onset) and 29 controls (age 46.2.6+/-13.1 yrs, 66% female) completed the battery. Controls were more racially diverse and less educated than NS-PASC (43% vs. 12% Black, p=0.005;14.5 vs. 16.1 yrs of education, p< 0.05). Means and statistics for RDoC between NS-PASC and controls are shown in Table. NS-PASC performed worse in language, verbal working and declarative memory, and perception and reported greater cognitive control difficulties (e.g., behavioral inhibition, set shifting) without issues on performance-based metrics (Stroop, Trail Making Test-Part B), and had slower motor function. NS-PASC reported more NV issues including greater symptoms of depression, rumination in response to depressive mood, apathy, childhood trauma, anxiety, and perceived stress. There were no differences in PV and social processing. In a subset of NS-PASC participants who underwent MRI, there was a dynamic range of FA values with a mean of 0.509 (IQR 0.481 - 0.536). Conclusion(s): Our findings extend previous PASC studies characterizing cognitive and mental health alterations, indicating that additional RDoC assessments warrant focus, including alterations in motor and the negative valence system. In future analyses, we will examine white matter integrity as a pathophysiologic contributor to these RDoC systems.

Csf & Plasma Soluble Biomarkers in Neuro-Pasc: Preliminary Results from Covid Mind

Background: It is unknown whether individuals with neurological post-acute sequelae of COVID-19 (NeuroPASC) display altered levels of neuroimmune activity or neuronal injury. Method(s): Participants with new or worsened neurologic symptoms at least 3 months after laboratory-confirmed COVID-19 were enrolled in The COVID Mind Study at Yale. Never COVID controls (no history of COVID-19;nucleocapsid (N) antibody negative) were pre-pandemic or prospectively enrolled volunteers. CSF and plasma were assessed for neopterin and for IL-1beta, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, MCP-1, TNFalpha by bead-based multiplex assay;and for anti-SARS-CoV-2 N antibodies by Luminex-based multiplex assay in technical replicate, normalized against bovine serum albumin conjugated beads. Plasma concentrations of D-dimer, C-reactive protein, neurofilament light chain (NFL), and glial fibrillary acid protein (GFAP) were measured using high-sensitivity immunoassays. Group comparisons used non-parametric tests. Result(s): NeuroPASC participants (n=38) were studied 329 (median) days (range 81-742) after first positive test for acute COVID-19. Cognitive impairment (84%) and fatigue (82%) were the most frequent post-COVID symptoms. NeuroPASC and controls (n=22) were median 49 vs 52 yrs old (p=0.9), 74% vs 32% female (p< 0.001), 76% vs 23% white race (p< 0.001), and 6% vs 57% smokers (p< 0.001). CSF white blood cells/mL, CSF protein, and serum:CSF albumin ratio were normal in both groups. CSF TNFalpha (0.66 vs 0.55 pg/ul) and plasma IL12p40 were higher (103.3 vs 42.7);and MCP-1 (503 vs 697 pg/ul) and IL-6 (1.32 vs 1.84 pg/ul;p < 0.05 for IL-6) were lower in NeuroPASC vs controls (p< 0.05);but none of these differences were significant after adjusting for multiple comparisons. Plasma GFAP was elevated in NeuroPASC vs controls (54.4 vs 42.3 pg/ml;adjusted p< 0.03). There were no differences in the other biomarkers tested. 10/31 and 7/31 NeuroPASC had anti-N antibodies in CSF and plasma, respectively. Conclusion(s): When comparing NeuroPASC to never COVID controls, we found no evidence of neuroinflammation (normal CSF cell count, inflammatory cytokines) or blood-brain barrier dysfunction (normal albumin ratio), and no support for ongoing neuronal damage (normal plasma NFL). Future studies should include better gender and race matched controls and should explore the significance of a persistent CNS humoral immune response to SARS-CoV-2 and elevated plasma GFAP after COVID-19. (Figure Presented).

Overview: Scott M. Hammer Workshop for New Investigators and Trainees

Over the past four decades, remarkable progress has been made in understanding HIV epidemiology, pathogenesis, treatment, and prevention from the combined efforts of community members, clinicians, investigators, and funding agencies worldwide. Yet more work and new approaches are needed to achieve the ambitious goal of ending the epidemic and ensuring optimal quality of life for those living with HIV. To encourage and stimulate the next generation of investigators, the CROI Program Committee organizes an annual Workshop for New Investigators and Trainees comprised of expert and comprehensible talks to cover current knowledge and controversies in basic, clinical, and public health investigation into HIV and related infections, and to highlight relevant work to be presented over the ensuing days at CROI. This year, the program will begin with a presentation by Dr Stuart Neil on novel aspects of the molecular virology of HIV-1 and SARS-CoV-2. Following this, Dr Guido Silvestri will cover the immune responses against HIV and SARS-CoV-2. Ms Dawn Averitt, an HIV treatment policy advocate and activist will provide a community perspective on the power of community engagement in research. In the following presentation, Dr Monica Gandhi will review novel therapeutic strategies for HIV. Dr Raphael Landovitz will address advances in different strategies for preventing HIV transmission. Dr John Mellors will review advances in preclinical and clinical approaches for functional or sterilizing HIV-1 cure. The workshop will end with an intervention by Dr Rochelle Walensky, who will discuss career opportunities in research and public health. By completing the workshop, attendees will have achieved a head start toward maximizing the knowledge gained and research ideas arising from CROI 2022.

Case Series: Post-COVID Small Fiber Neuropathy

Objective: To report a case series documenting biopsy-proven small fiber neuropathy (SFN) after COVID-19. Background: Patients recovering from COVID-19 who present with sensory as well as autonomic symptoms, including positional orthostatic tachycardia syndrome (POTS), frequently have negative electrodiagnostic testing. Skin biopsy may be required to reveal SFN. Design/Methods: This is a retrospective case series of patients seen in the Yale Neurology COVID-19 Clinic with positive SARS-CoV-2 PCR or antibody or a clinically consistent illness. After laboratory testing and a negative nerve conduction study, all patients underwent skin biopsy to test for intraepidermal SFN. Case 1: A 40F with pre-diabetes (HbA1c 6.2%) developed burning, numbness, and tingling in the hands and legs and POTS 6 weeks after acute COVID-19. Skin biopsy demonstrated non-length dependent SFN. Complete remission of neuropathy symptoms occurred within days of intravenous immunoglobulin (IVIG) therapy, which has been continued longitudinally. Case 2: A 65F with non-insulin dependent diabetes (HbA1c 8.0%) developed excruciating burning pain in her feet and orthostasis within weeks of acute COVID-19. Skin biopsy demonstrated non-length dependent SFN. She experienced partial relief of symptoms after IVIG and gabapentin. Case 3: A 43F with pre-diabetes (HbA1c 6.0%) developed orthostasis, numbness, paresthesias, and a “sunburned” feeling in her face, back, hands, and feet 2 weeks after acute COVID-19. Skin biopsy demonstrated length-dependent SFN. Symptoms improved over several months of pregabalin treatment, but have not resolved. The patient deferred immunotherapy. Case 4: A 40M developed POTS, numbness, and paresthesias in his face and left leg up to the knee within weeks of a clinical COVID-19 illness. Skin biopsy demonstrated non-length dependent SFN. IVIG therapy has resulted in significant improvement in symptoms. Conclusions: Sensory symptoms and POTS occur post-COVID, and SFN should be considered in the differential. Given the time of onset and response to immunotherapy, post-COVID SFN may have an underlying autoimmune etiology.

SCOTT M. HAMMER WORKSHOP for NEW INVESTIGATORS and TRAINEES

Over the past four decades, remarkable progress has been made in understanding HIV epidemiology, pathogenesis, treatment, and prevention from the combined efforts of community members, clinicians, investigators, and funding agencies worldwide. Yet more work and new approaches are needed to achieve the ambitious goal of ending the epidemic and ensuring optimal quality of life for those living with HIV. To encourage and stimulate the next generation of investigators, the CROI Program Committee organizes an annual Workshop for New Investigators and Trainees comprised of expert and comprehensible talks to cover current knowledge and controversies in basic, clinical, and public health investigation into HIV and related infections, and to highlight relevant work to be presented over the ensuing days at CROI. This year, the presentations will cover HIV and SARS-CoV-2. The program will begin with a presentation by Dr Theodora Hatziioannou on novel aspects of the HIV-1 and SARS-CoV-2 replication cycles, with an emphasis on the similarities and differences between the two viruses. Following this, Dr Penny Moore will cover the immune responses against HIV and SARS-CoV-2. Dr Carlos del Rio will outline the most efficient prevention measures for controlling the COVID-19 pandemic and will review therapeutic strategies and currently available SARS-CoV-2 vaccines. In the next presentation, Dr Adaora Adimora will address advances in different biomedic strategies for the prevention of HIV transmission. Finally, Dr Peter W. Hunt will review advances in preclinical and clinical approaches for functional or sterilizing HIV-1 cure. By the completion of the workshop, attendees will have achieved a head start toward maximizing the knowledge gained and research ideas arising from CROI 2022.

CSF and BLOOD ANALYSES in PARTICIPANTS with POST-COVID-19 NEUROPSYCHIATRIC SYMPTOMS

Background: The pathogenesis of neuropsychiatric symptoms persisting months after acute SARS-CoV-2 infection is poorly understood. We examined clinical and laboratory parameters in participants with post-acute COVID-19 neuropsychiatric symptom to assess for systemic and nervous system immune perturbations. Methods: Participants with a history of laboratory confirmed COVID-19 and ongoing neurologic symptoms were enrolled in an observational study that collected medical history;detailed post-COVID symptom survey;and paired cerebrospinal fluid (CSF) and blood. In addition to standard clinical labs, neopterin and anti-SARS-CoV-2 antibodies (anti-spike, RBD, and nucleocapsid) were measured by ELISA. Non-parametric tests were used to compare CSF and blood findings between the post-COVID participants and pre-COVID-19 era healthy controls. Results: Post-COVID participants (n=27) and controls (n=21) were similar in age (median 51 and 46 years), but there was a greater proportion of females (67% vs 24%;p=0.004) and white participants in the post-COVID cohort (63% vs 24%;p=0.04). The post-COVID study visit was a median of 264 days (IQR 59-332) after acute COVID-19 symptom onset. 35% were hospitalized during their acute illness;12% required intensive care. 33% had previously been treated with medications for mental health conditions. The most frequent neuropsychiatric symptoms were cognitive impairment (67%), mood symptoms (67%), headache (56%), and neuropathy (41%). Blood c-reactive protein, T cell count, and T cell subset frequency (CD4% and CD8%) were similar between groups, while D-dimer was higher in the post-COVID cohort (median 0.48 vs 0.27 mg/L;p = 0.019) (Figure). CSF WBC, protein, neopterin, and CSF/blood albumin ratio were similar between the groups;the frequency of CSF lymphocytes was lower in the post-COVID cohort (p = 0.05) (Figure 1). Antibodies against at least one SARS-CoV-2 antigen were detected in 7/10 CSF and 8/9 blood samples in the post-COVID CSF (antibody reactivity range 1.5 to 55-fold greater than to control antigens). Conclusion: In this small cohort of post-COVID participants with neurologic symptoms, we found limited differences in CSF and blood markers when compared to pre-pandemic healthy controls. Deeper immunophenotyping in a larger number of participants may provide greater insight into subtle differences. The presence of anti-SARS-CoV-2 antibodies in CSF months after acute infection warrants further investigation.

Ischemic stroke, inflammation, and endotheliopathy in COVID-19 patients

Objective: Early reports suggest an increased risk of ischemic stroke during COVID-19 infection. We aimed to identify patients with COVID-19 and ischemic stroke and explore markers of endotheliopathy, inflammation, and hypercoagulability. Background: Novel coronavirus-19 disease (COVID-19) is associated with a diverse array of neurologic complications, including ischemic stroke. Suspected mechanisms include hypercoagulability and endothelial injury, although evidence is sparse in stroke patients. Design/Methods: This was a retrospective, observational cohort study of patients with acute ischemic stroke and COVID-19 (n=21) compared to non-COVID-19 acute ischemic stroke patients (n=11). Timing of stroke onset during COVID-19 course, acute phase reactant levels, cytokine levels, endothelial activation, and hypercoagulability were evaluated with respect to stroke onset and etiology. Results: Twenty-one ischemic stroke patients were diagnosed with COVID-19 during the study period. Both groups had a similar age and burden of vascular risk factors. COVID-19 patients had significantly higher levels of endothelial activation around the time of stroke when compared to controls. The mean Factor VIII level was 332% of normal in the COVID-19 group and 49% in the control group, while von Willebrand Factor antigen and activity were 330% and 285% in the COVID-19 group and 213% and 152% in the control group, respectively. Cytokine storming and a strong inflammatory responses are defining features of severe COVID-19. We demonstrated a temporal correlation between stroke onset and the peak of acute phase reactants. Elevated cytokine levels, IL-6 and soluble IL-2 receptor levels in particular, were significantly associated with embolic stroke of undetermined source (ESUS) in COVID-19 patients when compared with other etiologies. Conclusions: We provide emerging evidence that endotheliopathy and the systemic inflammatory response in patients with vascular risk factors and COVID-19 is associated with ischemic stroke. Further research is needed. Understanding the mechanism of stroke in COVID- 19 patients will be critical in providing primary stroke prevention and treatment.

Low-Field, Portable Magnetic Resonance Imaging at the Bedside to Assess Brain Injury in Patients with Severe COVID-19

Objective: To obtain neuroimaging on patients with COVID-19 using a low-field, portable magnetic resonance imaging (MRI) device. Background: Neuroimaging is a key step in the clinical evaluation of brain injury. Conventional MRI systems operate at high-strength magnetic fields (1.5-3T) that require patient transportation to access-controlled environments. During the COVID-19 pandemic, critically ill patients have had limited neuroimaging due to infection control and safety concerns. We report neuroimaging in patients with severe COVID-19 using a portable MRI device. Design/Methods: A 64mT point-of-care (POC) MRI was used to acquire neuroimaging in Yale New Haven Hospital ICUs from April 2020 through August 2020. COVID-19 patients with neurological symptoms and no MRI contraindications were scanned. Exams were acquired using a standard 110V/15A power outlet. Hospital rooms included vital signs monitors, ventilators, dialysis machines, and intravenous infusion pumps. Images were acquired by trained research staff, without the need for an MRI technician. POC MRI exams were interpreted by two boardcertified physicians (one neuroradiologist and one neurologist). Results: POC MRI exams were obtained on 22 ICU COVID-19 patients (19% female, ages 42-74 years, 86% mechanically ventilated). Glasgow Coma Scale and Richmond Agitation-Sedation Scale at time of scan were 7±3 and-3±2, respectively. T1-weighted (T1W), T2-weighted (T2W), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences were obtained for all patients. Axial scan times were 4:54 minutes, 7:03 minutes, 9:31 minutes, and 9:04 minutes, respectively. Examination time was 35:40 minutes. Abnormal neuroimaging findings were observed in 10 patients: Intracranial hemorrhage (n=2), cerebral infarction (n=4), diffuse cerebral edema (n=1), and leukoencephalopathy (n=3). The device did not interfere with ICU equipment, and no significant adverse events occurred. Conclusions: We report the acquisition of neuroimaging using a low-field, portable MRI at the bedside of patients with severe COVID-19. This approach may hold promise for bedside assessment of neurological injury in settings with imaging access constraints.

Program committee workshop for new investigators and trainees: Session overview

Over the past four decades, remarkable progress has been made in understanding HIV epidemiology, pathogenesis, treatment, and prevention from the combined efforts of community members, clinicians, investigators, and funding agencies worldwide. Yet more work and new approaches are needed to achieve the ambitious goal of ending the epidemic and ensuring optimal quality of life for those living with HIV. To encourage and stimulate the next generation of investigators, the CROI Program Committee organizes an annual Workshop for New Investigators and Trainees comprised of expert and comprehensible talks to cover current knowledge and controversies in basic, clinical and public health investigation into HIV and related infections, and to highlight relevant work to be presented over the ensuing days at CROI. This year, the presentations will cover both HIV and SARS-CoV-2. The program will begin with a presentation by Dr Frank Kirchhoff on novel aspects of the HIV-1 and SARS-CoV-2 replication cycles, with an emphasis on the similarities and differences between the two viruses. Following this, Dr Galit Alter will cover the immune responses (with a particular focus on B- and T-cell responses) against HIV and SARS-CoV-2. Dr Jürgen Rockstroh will outline the most efficient prevention measures for controlling the COVID-19 pandemic and will review new testing technologies as well as therapeutic strategies and currently available SARS-CoV-2 vaccines. In the next presentation, Jean-Michel Molina will address advances in different biomedical strategies for prevention of HIV transmission, with an emphasis on the recent development in preexposure prophylaxis (PrEP) but also some of the emerging strategies to limit SARS-CoV-2 transmission. Finally, Dr Katharine Bar will review advances in characterizing the size and composition of the replication- and rebound-competent HIV-1 reservoirs as well as highlight several preclinical and clinical approaches for functional or sterilizing HIV-1 cure. By the completion of the workshop, attendees will have achieved a head start toward maximizing the knowledge gained and research ideas arising from vCROI 2021.

Divergent and self-reactive immune responses in the CNS of COVID-19 patients

Background: One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. Methods: We examined immune parameters in CSF and blood samples from a cohort of hospitalized patients with COVID-19 and significant neurological complications (n=6), compared to SARS-CoV-2 uninfected controls (Fig1A). Immune cells were characterized by single cell RNA and repertoire sequencing. Intrathecal antibodies were assessed for anti-viral and auto-reactivity by ELISA, mouse brain immunostaining, phage display, and IP-MS. Results: Through single cell and parallel cytokine analyses of CSF and paired plasma, we found divergent T cell responses in the CNS compartment, including increased levels of IL-1B and IL-12-associated innate and adaptive immune cell activation (Fig1B). We found evidence of clonal expansion of B cells in the CSF, with B cell receptor sequences that were unique from those observed in peripheral blood B cells (Fig1C), suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-antibodies. Next, we directly examined whether CSF resident antibodies targeted self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. COVID-19 CSF produced immunoreactive staining of specific anatomic regions of the brain including cortical neurons, olfactory bulb, thalamus, and cerebral vasculature. Finally, we produced a panel of monoclonal antibodies from patients' CSF and peripheral blood, and show that these target both anti-viral and anti-neural antigens-including one CSF-derived mAb specific for the spike protein that also recognizes neural tissue (Fig1D). Conclusion: This immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS in COVID-19 patients with neurologic symptoms. We identified both innate and adaptive anti-viral immune responses, as well as humoral autoimmunity that appears to be unique to the CNS during SARS-CoV-2 infection. These data suggest a potential role for autoimmunity in contributing to neurological symptoms, and merit further investigation to the potential role of autoantibodies in post-acute COVID-19 neurological symptoms.

A survey-based pilot study to assess the effects of covid-19 isolation on older plwh

Background: Public health emergencies increase stress, anxiety, and fear, and older adults and those with pre-existing conditions may be especially vulnerable. We used a survey-based pilot study to explore the psychosocial impact of COVID-19 on older PLWH and correlate the level of COVID-19 related distress with baseline HIV disease metrics. Methods: Participants were PLWH > age 50 who had previously (2017-2020) enrolled in the HARC HIV biorepository study at Yale. 48 PLWH were contacted and 22 participated in this study, conducted Aug-Sep 2020. An 8-part survey was administered to inquire about COVID-19 exposure, financial distress, medication adherence/medical follow-up, social support, substance use, and mood symptoms (Table 1). Cross-sectional analysis was performed on results at the time of survey administration, and longitudinal analysis was performed to compare anxiety (GAD-7), alcohol/drug use (ASSIST), and depression (CES-D) to baseline values obtained pre-pandemic (median 1.3 years prior). Results: Participant demographics are reported in Table 1. 2 participants reported having been diagnosed with COVID-19, 1 of whom had a known COVID-19 positive contact. 68% of participants were retired and reported no changes to their work due to COVID-19, and most reported moderate (4.1 on scale of 0-7) financial distress. Most reported excellent medication adherence, with 77% reporting no missed doses. 95% stated they felt “very well supported” by their primary HIV care providers, with 18% saying their care was improved during COVID-19. Only 18% felt their care was “somewhat worse.” Most participants also scored highly on the social support scale, with an average score of 11 out of 14. There were no significant differences between pre-pandemic and current scores for anxiety, alcohol/drug use, and depression, and there was no correlation between baseline HIV metrics and current level of distress. However, there was an association between COVID-19-associated worsening in GAD-7 score and a history of substance use disorder (p = 0.02). Conclusion: These results suggest that overall, most participants were doing well with excellent medication adherence and no significant changes in scores for anxiety, depression, and substance use, but that older PLWH with a history of substance use disorder had a greater risk for increased anxiety during COVID- 19. These findings can help identify groups who may be the most at-risk to experience distress from a second wave of COVID-19 and put support measures in place.