Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.

Limited Awareness of Long COVID Despite Common Experience of Symptoms Among African American/Black, Hispanic/Latino, and Indigenous Adults in Arizona.

OBJECTIVES: Communities of color might disproportionately experience long-term consequences of COVID-19, known as Long COVID. We sought to understand the awareness of and experiences with Long COVID among African American/Black (AA/B), Hispanic/Latino (H/L), and Indigenous (Native) adults (18 + years of age) in Arizona who previously tested positive for COVID-19. METHODS: Between December 2022 and April 2023, the Arizona Community Engagement Alliance (AZCEAL) conducted 12 focus groups and surveys with 65 AA/B, H/L and Native community members. Data from focus groups were analyzed using thematic analysis to identify emerging issues. Survey data provided demographic information about participants and quantitative assessments of Long COVID experiences were used to augment focus group data. RESULTS: Study participants across all three racial/ethnic groups had limited to no awareness of the term Long COVID, yet many described experiencing or witnessing friends and family endure physical symptoms consistent with Long COVID (e.g., brain fog, loss of memory, fatigue) as well as associated mental health issues (e.g., anxiety, worry, post-traumatic stress disorder). Participants identified a need for Long COVID mental health and other health resources, as well as increased access to Long COVID information. CONCLUSION: To prevent Long COVID health inequities among AA/B, H/L, and Native adults living in AZ, health-related organizations and providers should increase access to culturally relevant, community-based Long COVID-specific information, mental health services, and other health resources aimed at serving these populations.

Oral appliance therapy and hypoglossal nerve stimulation as non-positive airway pressure treatment alternatives for obstructive sleep apnea: a narrative expert review.

This perspective on alternatives to positive airway pressure (PAP) therapy for the treatment of obstructive sleep apnea (OSA) summarizes the proceedings of a focus group that was conducted by the Sleep Research Society Foundation. This perspective is from a multidisciplinary panel of experts from sleep medicine, dental sleep medicine, and otolaryngology that aims to identify the current role of oral appliance therapy and hypoglossal nerve stimulation for the treatment of OSA with emphasis on the US practice arena. A secondary aim is to identify-from an implementation science standpoint-the various barriers and facilitators for adoption of non-PAP treatment that includes access to care, multidisciplinary expertise, reimbursement, regulatory aspects, current treatment guidelines, health policies, and other factors related to the delivery of care. The panel has contextualized the review with recent events-such as a large-scale PAP device recall compounded by supply chain woes of the pandemic-and emerging science in the field of OSA and offers solutions for multidisciplinary approaches while identifying knowledge gaps and future research opportunities.

The effect of adding physician recommendation in digitally-enabled outreach for COVID-19 vaccination in socially/economically disadvantaged populations.

INTRODUCTION: People from backgrounds that are economically/socially disadvantaged experienced disproportionately high COVID-19 death rates and had lower vaccination rates. Effective outreach strategies for increasing vaccine uptake during the pandemic are not fully known. Among patients receiving care at a Federally Qualified Health Center, we tested whether community engaged digitally-enabled outreach from a trusted clinician messenger increased COVID vaccine uptake. STUDY DESIGN, SETTING, AND PARTICIPANTS: A 3-parallel-arm randomized controlled trial with a hybrid effectiveness-implementation design was conducted among patients ≥ 18 years old on study enrollment during 2021 with 1,650 assigned in 3:10:20 ratio; 2,328 were later selected for two subsequent implementation rounds. INTERVENTIONS: From April 13 to June 10, 2021, patients were proactively sent a text-messaging invitation to make an appointment for vaccination as part of the routine practice with a link to frequently asked questions (Arm 1, n = 150) with added personalized clinician recommendation alone (Arm 2, n = 500) or with enabled 2-way SMS messaging feature (Arm 3, n = 1,000). Further implementation used messaging addressing vaccine hesitancy (n = 1,323) or adverse reactions to vaccines (n = 1,005). MAIN OUTCOMES AND MEASURES: The primary outcome was the completion of the first SARS-Cov-2 vaccine dose determined at 14, 30 and 90 days after outreach. RESULTS: Of 1,650 patients in effectiveness Arms, 61% was female. Vaccination rates for Arms 1, 2, and 3, were 6% (n = 9), 5.4% (n = 27) and 3.3% (n = 33) at 14 days, and 11.5% (n = 17), 11.6% (n = 58), and 8.5% (n = 85) at 90 days, respectively, which were similar in pairwise comparisons. At 90 days, vaccination rates were similar across the two implementation rounds (3.9% vs. 3.6%) and were similar to the rate (3.3%) among patients who were not selected for intervention arms or implementation rounds (n = 8,671). CONCLUSIONS: Digitally-enabled outreach that included SMS messaging outreach augmented with clinician recommendations did not improve COVID-19 vaccination rates. TRIAL REGISTRATION: This study is registered at ClinicalTrails.gov Identifier: NC-T04952376.

Circadian disruption dysregulates lung gene expression associated with inflammatory lung injury.

Rationale: Circadian systems drive the expression of multiple genes in nearly all cells and coordinate cellular-, tissue-, and system-level processes that are critical to innate immunity regulation. Objective: We examined the effects of circadian rhythm disorganization, produced by light shift exposure, on innate immunity-mediated inflammatory lung responses including vascular permeability and gene expression in a C57BL/6J murine model of inflammatory lung injury. Methods: A total of 32 C57BL/6J mice were assigned to circadian phase shifting (CPS) with intratracheal phosphate-buffered saline (PBS), CPS with intratracheal lipopolysaccharide (LPS), control (normal lighting) condition with intratracheal PBS, and control condition with intratracheal LPS. Bronchoalveolar lavage (BAL) protein, cell counts, tissue immunostaining, and differentially expressed genes (DEGs) were measured in lung tissues at 2 and 10 weeks. Measurements and results: In mice exposed to both CPS and intratracheal LPS, both BAL protein and cell counts were increased at both 2 and 10 weeks compared to mice exposed to LPS alone. Multiple DEGs were identified in CPS-LPS-exposed lung tissues compared to LPS alone and were involved in transcriptional pathways associated with circadian rhythm disruption, regulation of lung permeability, inflammation with Rap1 signaling, and regulation of actin cytoskeleton. The most dysregulated pathways included myosin light chain kinase, MAP kinase, profilin 2, fibroblast growth factor receptor, integrin b4, and p21-activated kinase. Conclusion: Circadian rhythm disruption results in exacerbated immune response and dysregulated expression of cytoskeletal genes involved in the regulation of epithelial and vascular barrier integrity-the mechanistic underpinnings of acute lung injury. Further studies need to explore circadian disorganization as a druggable target.

Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals.

Background: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown. Methods: We enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC. Results: During the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular. Conclusions: We found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC.

A real-world observational study assessing relationships between excessive daytime sleepiness and patient satisfaction in obstructive sleep apnea.

OBJECTIVES/BACKGROUND: To estimate prevalence and severity of excessive daytime sleepiness among patients with obstructive sleep apnea (OSA) who were prescribed treatment; assess perception and satisfaction of OSA-related care; describe relationships between excessive daytime sleepiness, treatment adherence, and patient satisfaction. PATIENTS/METHODS: A national population-based cross-sectional sample of US adults with clinician-diagnosed OSA was surveyed in January 2021 via Evidation Health's Achievement App. Patients completed the Epworth Sleepiness Scale, rated satisfaction with healthcare provider and overall OSA care, and reported treatment adherence. Covariates affecting excessive daytime sleepiness (average weekly sleep duration, treatment adherence, sleepiness-inducing medications, age, sex, body mass index, nasal congestion, smoking status, and comorbidities) were adjusted in multivariate regression models. RESULTS: In 2289 participants (50.3 % women; 44.8 ± 11.1 years), EDS was highly prevalent (42 %), and was experienced by 36 % of patients with high positive airway pressure (PAP) therapy adherence. Each additional hour of nightly PAP use was associated with improved sleepiness (a 0.28-point lower Epworth score; p < 0.001). Excessive daytime sleepiness was associated with lower patient satisfaction with healthcare providers and overall care (OR [95 % CI] 0.62 [0.48-0.80] and 0.50 [0.39-0.64], respectively; p < 0.0001), whereas PAP adherence was associated with higher patient satisfaction (OR [95 % CI] 2.37 [1.64-3.43] and 2.91 [2.03-4.17]; p < 0.0001), after adjusting for confounders. CONCLUSIONS: In a real-world population-based study of patients with OSA, excessive daytime sleepiness was highly prevalent and associated with poor patient satisfaction ratings. Better patient-centered care among patients with OSA may require interventions aimed at addressing excessive daytime sleepiness and treatment adherence.

Vibro-Acoustic Platelet Activation: An Additive Mechanism of Prothrombosis with Applicability to Snoring and Obstructive Sleep Apnea.

Introduction: Obstructive sleep apnea (OSA) and loud snoring are conditions with increased cardiovascular risk and notably an association with stroke. Central in stroke are thrombosis and thromboembolism, all related to and initiaing with platelet activation. Platelet activation in OSA has been felt to be driven by biochemical and inflammatory means, including intermittent catecholamine exposure and transient hypoxia. We hypothesized that snore-associated acoustic vibration (SAAV) is an activator of platelets that synergizes with catecholamines and hypoxia to further amplify platelet activation. Methods: Gel-filtered human platelets were exposed to snoring utilizing a designed vibro-acoustic exposure device, varying the time and intensity of exposure and frequency content. Platelet activation was assessed via thrombin generation using the Platelet Activity State assay and scanning electron microscopy. Comparative activation induced by epinephrine and hypoxia were assessed individually as well as additively with SAAV, as well as the inhibitory effect of aspirin. Results: We demonstrate that snore-associated acoustic vibration is an independent activator of platelets, which is dependent upon the dose of exposure, i.e., intensity x time. In snoring, acoustic vibrations associated with low-frequency sound content (200 Hz) are more activating than those associated with high frequencies (900 Hz) (53.05% vs. 22.08%, p = 0.001). Furthermore, SAAV is additive to both catecholamines and hypoxia-mediated activation, inducing synergistic activation. Finally, aspirin, a known inhibitor of platelet activation, has no significant effect in limiting SAAV platelet activation. Conclusion: Snore-associated acoustic vibration is a mechanical means of platelet activation, which may drive prothrombosis and thrombotic risk clinically observed in loud snoring and OSA.

The Effect of Adding Physician Recommendation in Digitally-Enabled Outreach for COVID-19 Vaccination in Socially/Economically Disadvantaged Populations Subtitle: A Randomized Controlled Trial.

Introduction: People from backgrounds that are economically/socially disadvantaged experienced disproportionately high COVID-19 death rates and had lower vaccination rates. Effective outreach strategies for increasing vaccine uptake during the pandemic are not fully known. Among patients receiving care at a Federally Qualified Health Center, we tested whether community engaged digitally-enabled outreach increased COVID vaccine uptake. Study Design Setting and Participants: A 3-parallel-arm randomized controlled trial with a hybrid effectiveness-implementation design was conducted among patients ≥18 years old on study enrollment during 2021 with 1,650 assigned in 3:10:20 ratio; 2,328 were later selected for two subsequent implementation rounds. Interventions: From April 13 to June 10, 2021, patients were proactively sent a text-messaging invitation to make an appointment for vaccination as part of the routine practice (Arm 1, n=150) with added personalized clinician recommendation alone (Arm 2, n=500) or with an explicit nudge for answers to frequently asked questions (Arm 3, n=1,000). Further implementation used messaging addressing vaccine hesitancy (n=1,323) or adverse reactions to vaccines (n=1,005). Main Outcomes and Measures: The primary outcome was the completion of the first SARS-Cov-2 vaccine dose determined at 14, 30 and 90 days after outreach. Results: Of 1,650 patients in effectiveness Arms, 61% was female. Vaccination rates for Arms 1, 2, and 3, were 6% (n=9), 5.4% (n=27) and 3.3% (n=33) at 14 days, and 11.5% (n=17), 11.6% (n=58), and 8.5% (n=85) at 90 days, respectively, which were similar in pairwise comparisons. At 90 days, vaccination rates were similar across the two implementation rounds (3.9% vs. 3.6%) and were similar to the rate (3.3%) among patients who were not selected for intervention arms or implementation rounds (n=8,671). Conclusions: Digitally-enabled outreach that included SMS messaging outreach augmented with clinician recommendations did not improve COVID-19 vaccination rates. Trial Registration: This study is registered at ClinicalTrails.gov Identifier: NC-T04952376.