Is there an association between peri-diagnostic vaccination and clinical outcomes in COVID-19 patients?

Background: Peri-diagnostic vaccination contemporaneous with SARS-CoV-2 infection might boost antiviral immunity and improve patient outcomes. We investigated, among previously unvaccinated patients, whether vaccination (with the Pfizer, Moderna, or J&J vaccines) during the week before or after a positive COVID-19 test was associated with altered 30-day patient outcomes. Methods: Using a deidentified longitudinal EHR repository, we selected all previously unvaccinated adults who initially tested positive for SARS-CoV-2 between December 11, 2020 (the date of vaccine emergency use approval) and December 19, 2021. We assessed whether vaccination between days -7 and +7 of a positive test affected outcomes. The primary measure was progression to a more severe disease outcome within 30 days of diagnosis using the following hierarchy: hospitalization, intensive care, or death. Results: Among 60,031 hospitalized patients, 543 (0.91%) were initially vaccinated at the time of diagnosis and 59,488 (99.09%) remained unvaccinated during the period of interest. Among 316,337 nonhospitalized patients, 2,844 (0.90%) were initially vaccinated and 313,493 (99.1%) remained unvaccinated. In both analyses, individuals receiving vaccines were older, more often located in the northeast, more commonly insured by Medicare, and more burdened by comorbidities. Among previously unvaccinated patients, there was no association between receiving an initial vaccine dose between days -7 and +7 of diagnosis and progression to more severe disease within 30 days compared to patients who did not receive vaccines. Conclusions: Immunization during acute SARS-CoV-2 infection does not appear associated with clinical progression during the acute infectious period.

Risk Factors for SARS-CoV-2 Infection and Severe Outcomes Among People With Human Immunodeficiency Virus: Cohort Study.

Background: Studies on COVID-19 in people with HIV (PWH) have had limitations. Further investigations on risk factors and outcomes of SARS-CoV-2 infection among PWH are needed. Methods: This retrospective cohort study leveraged the national OPTUM COVID-19 data set to investigate factors associated with SARS-CoV-2 positivity among PWH and risk factors for severe outcomes, including hospitalization, intensive care unit stays, and death. A subset analysis was conducted to examine HIV-specific variables. Multiple variable logistic regression was used to adjust for covariates. Results: Of 43 173 PWH included in this study, 6472 had a positive SARS-CoV-2 result based on a polymerase chain reaction test or antigen test. For PWH with SARS-CoV-2 positivity, higher odds were found for those who were younger (18-49 years), Hispanic White, African American, from the US South, uninsured, and a noncurrent smoker and had a higher body mass index and higher Charlson Comorbidity Index. For PWH with severe outcomes, higher odds were identified for those who were SARS-CoV-2 positive, older, from the US South, receiving Medicaid/Medicare or uninsured, a current smoker, and underweight and had a higher Charlson Comorbidity Index. In a subset analysis including PWH with HIV care variables (n = 5098), those with unsuppressed HIV viral load, a low CD4 count, and no antiretroviral therapy had higher odds of severe outcomes. Conclusions: This large US study found significant ethnic, racial, and geographic differences in SARS-CoV-2 infection among PWH. Chronic comorbidities, older age, lower body mass index, and smoking were associated with severe outcomes among PWH during the COVID-19 pandemic. SARS-CoV-2 infection was associated with severe outcomes, but once we adjusted for HIV care variables, SARS-CoV-2 was no longer significant; however, low CD4 count, high viral load, and lack of antiretroviral therapy had higher odds of severe outcomes.

Incidence and Risk Factors for Severe Outcomes in Pediatric Patients With COVID-19.

OBJECTIVES: Throughout the pandemic, children with COVID-19 have experienced hospitalization, ICU admission, invasive respiratory support, and death. Using a multisite, national dataset, we investigate risk factors associated with these outcomes in children with COVID-19. METHODS: Our data source (Optum deidentified COVID-19 Electronic Health Record Dataset) included children aged 0 to 18 years testing positive for COVID-19 between January 1, 2020, and January 20, 2022. Using ordinal logistic regression, we identified factors associated with an ordinal outcome scale: nonhospitalization, hospitalization, or a severe composite outcome (ICU, intensive respiratory support, death). To contrast hospitalization for COVID-19 and incidental positivity on hospitalization, we secondarily identified patient factors associated with hospitalizations with a primary diagnosis of COVID-19. RESULTS: In 165 437 children with COVID-19, 3087 (1.8%) were hospitalized without complication, 2954 (1.8%) experienced ICU admission and/or intensive respiratory support, and 31 (0.02%) died. We grouped patients by age: 0 to 4 years old (35 088), and 5 to 11 years old (75 574), 12 to 18 years old (54 775). Factors positively associated with worse outcomes were preexisting comorbidities and residency in the Southern United States. In 0- to 4-year-old children, there was a nonlinear association between age and worse outcomes, with worse outcomes in 0- to 2-year-old children. In 5- to 18-year-old patients, vaccination was protective. Findings were similar in our secondary analysis of hospitalizations with a primary diagnosis of COVID-19, though region effects were no longer observed. CONCLUSIONS: Among children with COVID-19, preexisting comorbidities and residency in the Southern United States were positively associated with worse outcomes, whereas vaccination was negatively associated. Our study population was highly insured; future studies should evaluate underinsured populations to confirm generalizability.

Pseudorandomized Testing of a Discharge Medication Alert to Reduce Free-Text Prescribing.

BACKGROUND: Pseudorandomized testing can be applied to perform rigorous yet practical evaluations of clinical decision support tools. We apply this methodology to an interruptive alert aimed at reducing free-text prescriptions. Using free-text instead of structured computerized provider order entry elements can cause medication errors and inequity in care by bypassing medication-based clinical decision support tools and hindering automated translation of prescription instructions. OBJECTIVE: The objective of this study is to evaluate the effectiveness of an interruptive alert at reducing free-text prescriptions via pseudorandomized testing using native electronic health records (EHR) functionality. METHODS: Two versions of an EHR alert triggered when a provider attempted to sign a discharge free-text prescription. The visible version displayed an interruptive alert to the user, and a silent version triggered in the background, serving as a control. Providers were assigned to the visible and silent arms based on even/odd EHR provider IDs. The proportion of encounters with a free-text prescription was calculated across the groups. Alert trigger rates were compared in process control charts. Free-text prescriptions were analyzed to identify prescribing patterns. RESULTS: Over the 28-week study period, 143 providers triggered 695 alerts (345 visible and 350 silent). The proportions of encounters with free-text prescriptions were 83% (266/320) and 90% (273/303) in the intervention and control groups, respectively (p = 0.01). For the active alert, median time to action was 31 seconds. Alert trigger rates between groups were similar over time. Ibuprofen, oxycodone, steroid tapers, and oncology-related prescriptions accounted for most free-text prescriptions. A majority of these prescriptions originated from user preference lists. CONCLUSION: An interruptive alert was associated with a modest reduction in free-text prescriptions. Furthermore, the majority of these prescriptions could have been reproduced using structured order entry fields. Targeting user preference lists shows promise for future intervention.

Engineered synaptic tools reveal localized cAMP signaling in synapse assembly.

The physiological mechanisms driving synapse formation are elusive. Although numerous signals are known to regulate synapses, it remains unclear which signaling mechanisms organize initial synapse assembly. Here, we describe new tools, referred to as "SynTAMs" for synaptic targeting molecules, that enable localized perturbations of cAMP signaling in developing postsynaptic specializations. We show that locally restricted suppression of postsynaptic cAMP levels or of cAMP-dependent protein-kinase activity severely impairs excitatory synapse formation without affecting neuronal maturation, dendritic arborization, or inhibitory synapse formation. In vivo, suppression of postsynaptic cAMP signaling in CA1 neurons prevented formation of both Schaffer-collateral and entorhinal-CA1/temporoammonic-path synapses, suggesting a general principle. Retrograde trans-synaptic rabies virus tracing revealed that postsynaptic cAMP signaling is required for continuous replacement of synapses throughout life. Given that postsynaptic latrophilin adhesion-GPCRs drive synapse formation and produce cAMP, we suggest that spatially restricted postsynaptic cAMP signals organize assembly of postsynaptic specializations during synapse formation.

Thiol-epoxy/maleimide ternary networks as softening substrates for flexible electronics.

Softening microelectrode arrays, or flexible bioelectronic systems which can dynamically change modulus under the application of an external stimulus such as heat or electromagnetic radiation, have been of significant interest in the literature within the previous decade. Through their ability to actively soften in vivo, these devices have shown the capacity to attenuate the neuronal damage associated with insertion of rigid microelectrode arrays into soft tissue. Thiol-click substrates specifically have shown particularly impressive results for fabricating devices requiring small-scale, high-performance electronics for neural recording. However, previous attempts to engineer increasingly lower-modulus substrates for these devices have failed due to the fundamental chemistries' (the thioether linkage) flexibility. This failure has led to substrates without sufficient mechanical rigidity for penetrating soft tissue at physiological temperatures, or sufficient softening capacity to reduce the mechanical mismatch between soft tissue and implantable device. In this work, a ternary thiol-epoxy/maleimide network is investigated as a potential substrate materials space in which the degree of softening can be modulated without sacrificing the mechanical rigidity at physiological temperatures. Using these networks as platforms for the microfabrication of electrode arrays, example implantable intracortical microelectrode arrays are fabricated on both thiol-epoxy and thiol-epoxy/maleimide networks to demonstrate the insertion capacity of microelectrode arrays on the ternary polymer networks.