Clinical Findings and Outcomes from 1306 Patients with Covid-19 Pneumonia in an Intermediate Respiratory Care Unit: A Prospective, Observational Study

Background: An intermediate respiratory care unit (IRCU) may be a valuable tool for optimizing patient care, allowing to implement standardized algorithm management to decrease clinical failure and mortality. We aimed to describe the practice of noninvasive respiratory strategies (NRS) in a novel facility fully dedicated to COVID-19 and to establish outcomes of these patients Methods: Prospective, observational study performed at one hospital in Spain. We included consecutive patients admitted to IRCU due to COVID-19 requiring NRS between December 2020 and September 2021. Data collected included mode and usage of NRS, endotracheal intubation and mortality to day 30. A multivariable Cox proportional hazards method was used to assess risk factors associated with clinical failure and mortality Findings: 1306 patients with COVID-19 were included. Of them, 64.6% were men and mean age was 54.7 years. During IRCU stay, 345 patients presented a clinical failure, (89.6% intubated;14.5% died). Cox model showed a higher clinical failure in IRCU when time between symptoms onset and hospitalization < 10 days (HR 1.59;95% CI 1.24-2.03;p<0.001) and PaO2/FiO2 <100 (HR 1.59;95% CI 1.27-1.98;p<0.001). Conversely, these variables were not associated with an increased mortality to day 30 Interpretation: IRCU may be a useful option for the multidisciplinary management of COVID-19 patients requiring NRS;thus, reducing ICU overcharge. Men gender, gas-exchange and blood chemistry at admission are associated with worse clinical outcomes, while older age, gas-exchange and blood chemistry are associated with 30-day mortality.

Predominant SARS-CoV-2 variant impacts accuracy when screening for infection using exhaled breath vapor.

BACKGROUND: New technologies with novel and ambitious approaches are being developed to diagnose or screen for SARS-CoV-2, including breath tests. The US FDA approved the first breath test for COVID-19 under emergency use authorization in April 2022. Most breath-based assays measure volatile metabolites exhaled by persons to identify a host response to infection. We hypothesized that the breathprint of COVID-19 fluctuated after Omicron became the primary variant of transmission over the Delta variant. METHODS: We collected breath samples from 142 persons with and without a confirmed COVID-19 infection during the Delta and Omicron waves. Breath samples were analyzed by gas chromatography-mass spectrometry. RESULTS: Here we show that based on 63 exhaled compounds, a general COVID-19 model had an accuracy of 0.73 ± 0.06, which improved to 0.82 ± 0.12 when modeling only the Delta wave, and 0.84 ± 0.06 for the Omicron wave. The specificity improved for the Delta and Omicron models (0.79 ± 0.21 and 0.74 ± 0.12, respectively) relative to the general model (0.61 ± 0.13). CONCLUSIONS: We report that the volatile signature of COVID-19 in breath differs between the Delta-predominant and Omicron-predominant variant waves, and accuracies improve when samples from these waves are modeled separately rather than as one universal approach. Our findings have important implications for groups developing breath-based assays for COVID-19 and other respiratory pathogens, as the host response to infection may significantly differ depending on variants or subtypes.

In recent decades, scientists have found we exhale thousands of compounds that reveal much about our health, including whether we are sick with COVID-19. Our team asked whether the breath profile of someone infected with the Delta variant of COVID-19 would match the breath profile caused by the Omicron variant­a version of the virus that is more transmissible. We analyzed breath samples from 142 people, some sick with either the Delta or Omicron variant of COVID-19, and others who were negative for COVID-19. Our results indicate that the Delta variant altered the contents of our breath in a different way than the Omicron variant, and breath-based tests improved when optimized to detect only one of the variants. These findings might impact the design of future breath-based tests for COVID-19.

University students' perceptions of shifting between online and offline learning: lessons from Kerala, India

Purpose: The study explores the perspectives of college students on the pedagogical shift as well as frequent transitions between online and offline learning modes during the COVID-19 pandemic in Kerala, the most literate state in India. Design/methodology/approach: A descriptive cross-sectional study was conducted among 1,366 college students in Kerala during December 2021. A pre-tested questionnaire was sent using Google Forms to students of arts and science colleges. The authors analyzed quantitative data using descriptive statistics and qualitative data using thematic content analysis. Findings: The reported advantages of online learning were increased technical skill, flexibility in study time, effectiveness in bridging the gap of the missed academic period and provision of attending more educational webinars. Students expressed concerns of increased workload, difficulty in concentration due to family circumstances, academic incompetency, uncleared doubts and addiction to mobile phones and social media during the online classes. The main advantages reported for switching to an offline learning mode were enhanced social interaction, effective learning, better concentration and reduced stress. The reported challenges of offline classes were fear of getting the disease, concern of maintaining social distancing and difficulty in wearing masks during the classes. The shift in offline to online learning and vice versa was perceived as a difficult process for the students as it took a considerable time for them to adjust to the switching process of learning. Originality/value: Students' concerns regarding transition between different learning modes provide important information to educators to better understand and support the needs of students during the pandemic situations. © 2022, Madhavan Maya*, V.M. Anjana* and G.K. Mini.

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.

Whose Concerns? It's Time to Adjust the Lens of Research on Police-Involved Overdose Response

(p. 1326) creatively use body-worn camera footage- a previously unused data source-to support the following findings of previous research: (1) police can administer naloxone during an overdose, (2) combativeness toward first responders by overdose survivors is rare, (3) drug exposure is nota risk to police officers, and (4) arrests do occur at the scene of overdose emergencies as the result of police presence.1,2 Although we recognize this article's contribution to the growing literature on law enforcement involvement in overdose response, we would caution policymakers about using the findings of this study to bolster (or worse, solely rely on) the role of police in overdose response. White et al. document that arrest- of both overdose victims and other bystanders-does indeed occur. [...]their conclusion that concerns about police-administered naloxone are "overstated" is dismissive of the most problematic and disruptive concern examined in the study. The disproportionate risk of violence at the hands of police is a powerful deterrent to inviting law enforcement interaction (specifically by calling 911)-one that cannot be resolved by the limited protections provided by most 911 Good Samaritan laws.10 Furthermore, druginduced homicide investigations not only directly undermine the protective mechanisms of 911 Good Samaritan laws5 but are also disproportionately used against non-White persons-and almost exclusively in response to the preventable overdose deaths of White persons.11 Disproportionate policing, police violence, and incarceration of Black and Indigenous persons affect these groups' access to overdose prevention interventions, broadly, and to naloxone, specifically, especially in cases when the nearest available naloxone rests in the hands of police. Black and Indigenous people have the highest fatal overdose rates and are least served by resource allocations that further support police involvement in overdose response. [...]methodologically sound and Black and Indigenous PWUD-informed research indicates otherwise, policymakers and resource allocation decision-makers should consider any life-saving gains via police-involved overdose response to be disproportionately unavailable and inaccessible to Black and Indigenous people.

Complicaciones neurológicas en pacientes críticos por SARS-CoV-2 Neurological complications in critical patients with COVID-19

Introducción Nos proponemos analizar las complicaciones neurológicas de los pacientes con infección grave por SARS-CoV-2 que han requerido ingreso en unidad de cuidados intensivos (UCI). Pacientes y métodos Estudio descriptivo retrospectivo, observacional, de pacientes consecutivos ingresados en UCI por infección respiratoria grave por SARS-CoV-2 desde el 1 de abril hasta el 1 de junio de 2020. Resultados Registramos 30 pacientes con síntomas neurológicos, 21 hombres (72,40%), edad media: 57,41 años ± 11,61 desviación estándar (DE). Estancia media en UCI: 18,83 ± 14,33 DE. A nivel sindrómico: 28 pacientes (93,33%) con síndrome confusional agudo, 15 (50%) con patología neuromuscular, 5 (16,66%) con cefalea, 4 (13,33%) con patología cerebrovascular y 4 (13,33%) con encefalopatías/encefalitis. Punción lumbar normal en 6 pacientes (20%). La RMN craneal o TAC craneal mostró alteraciones en 20 casos (66,6%). Se realizó EEG en todos los pacientes (100%), alterado en 8 pacientes (26,66%). En 5 de los 15 pacientes con miopatía clínica se ha podido confirmar con ENMG. Hemos encontrado relación entre la mayor edad y los días de ingreso en UCI (p = 0,002;IC 95%: 4,032-6,022;OR: 3,594). Conclusiones La infección grave por COVID-19 afecta mayoritariamente a hombres, similar a lo descrito en otras series. La mitad de nuestros pacientes presenta una miopatía aguda, y casi la totalidad de los pacientes salen de la UCI con síndromes confusionales agudos que evolucionan a una resolución completa, sin correlacionarse con los resultados del EEG o de pruebas de neuroimagen. La mayor edad se asocia con un mayor número de días de estancia en UCI.

Real-world impact of vaccination on coronavirus disease 2019 (COVID-19) incidence in healthcare personnel at an academic medical center.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination effectiveness in healthcare personnel (HCP) has been established. However, questions remain regarding its performance in high-risk healthcare occupations and work locations. We describe the effect of a COVID-19 HCP vaccination campaign on SARS-CoV-2 infection by timing of vaccination, job type, and work location. METHODS: We conducted a retrospective review of COVID-19 vaccination acceptance, incidence of postvaccination COVID-19, hospitalization, and mortality among 16,156 faculty, students, and staff at a large academic medical center. Data were collected 8 weeks prior to the start of phase 1a vaccination of frontline employees and ended 11 weeks after campaign onset. RESULTS: The COVID-19 incidence rate among HCP at our institution decreased from 3.2% during the 8 weeks prior to the start of vaccinations to 0.38% by 4 weeks after campaign initiation. COVID-19 risk was reduced among individuals who received a single vaccination (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.40-0.68; P < .0001) and was further reduced with 2 doses of vaccine (HR, 0.17; 95% CI, 0.09-0.32; P < .0001). By 2 weeks after the second dose, the observed case positivity rate was 0.04%. Among phase 1a HCP, we observed a lower risk of COVID-19 among physicians and a trend toward higher risk for respiratory therapists independent of vaccination status. Rates of infection were similar in a subgroup of nurses when examined by work location. CONCLUSIONS: Our findings show the real-world effectiveness of COVID-19 vaccination in HCP. Despite these encouraging results, unvaccinated HCP remain at an elevated risk of infection, highlighting the need for targeted outreach to combat vaccine hesitancy.

RE-SIGNIFY the DOMESTIC SPACE in TIMES of CONFINEMENT from the APPLICATION of ETHNOGRAPHIC TOOLS and PERSONAL CENTERED DESIGN

The Covid-19 crisis has been described as the “greatest challenge that humankind has faced since the 2nd World War,” having an impact on health, society, and the global economy. Houses and domestic spaces are key sites through which COVID-19 is experienced, thus, an interdisciplinary approach is needed. The goal of this research project is to forge an analytical approach while experimenting with micro-ethnography and auto-ethnography tools to analyse how we inhabit the domestic spaces in complex situations of confinement imposition in order to arrive at an outward reflection from within. The project reflects on an innovative social experiment that opens up new paths of design provoking to help us rethink the domestic space. This paper has the objective to compile, compare and explain the processes and results around the characterization of the domestic space, centring on the person in times of confinement through an ethnographic approach. © PDE 2021.

Managing expansions in medical students' clinical placements caused by curricular transformation: perspectives from four medical schools.

Many challenges could occur that result in the need to handle an increase in the number of medical student clinical placements, such as curricular transformations or viral pandemics, such as COVID 19. Here, we describe four different institutions' approaches to addressing the impact of curricular transformation on clerkships using an implementation science lens. Specifically, we explore four different approaches to managing the 'bulge' as classes overlap in clerkships Curriculum leaders at four medical schools report on managing the bulge of core clinical placements resulting from reducing the duration of the foundational sciences curriculum and calendar shifts for the respective clerkship curriculum. These changes, which occurred between 2014 and 2018, led to more students being enrolled in core clinical rotations at the same time than occurred previously. Schools provided respective metrics used to evaluate the effectiveness of their bulge management technique. These data typically included number of students affected in each phase of their curricular transformation, performance on standardized examinations, and student and faculty feedback. Not all data were available from all schools, as some schools are still working through their 'bulge' or are affected by COVID-19. There is much to be learned about managing curricular transformations. Working on such endeavors in a learning collaborative such as the AMA Accelerating Change in Medical Education Initiative provided support and insights about how to survive, thrive and identifying lessons learned during curricular transformation.

SARS-CoV-2 infection generates tissue-localized immunological memory in humans.

Adaptive immune responses to SARS-CoV-2 infection have been extensively characterized in blood; however, most functions of protective immunity must be accomplished in tissues. Here, we report from examination of SARS-CoV-2 seropositive organ donors (ages 10 to 74) that CD4+ T, CD8+ T, and B cell memory generated in response to infection is present in the bone marrow, spleen, lung, and multiple lymph nodes (LNs) for up to 6 months after infection. Lungs and lung-associated LNs were the most prevalent sites for SARS-CoV-2­specific memory T and B cells with significant correlations between circulating and tissue-resident memory T and B cells in all sites. We further identified SARS-CoV-2­specific germinal centers in the lung-associated LNs up to 6 months after infection. SARS-CoV-2­specific follicular helper T cells were also abundant in lung-associated LNs and lungs. Together, the results indicate local tissue coordination of cellular and humoral immune memory against SARS-CoV-2 for site-specific protection against future infectious challenges.

The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.

Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host-microbe interaction. The use of stem cells-that have self-renewal capacity to proliferate and differentiate into specialized cell types-for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications.

Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19.

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract.

Lasting memories of SARS-CoV-2 infection.

Maintaining virus-specific adaptive immunity is critical for ongoing protection against SARS-CoV-2 infection. In this issue, Breton et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202515) identify polyfunctional SARS-CoV-2-specific T cell responses in the peripheral blood of individuals who recovered from COVID-19 that were present at 1 mo and persisted until 6 mo after infection.

Risk of adverse coronavirus disease 2019 outcomes for people living with HIV.

OBJECTIVE: To assess whether people living with HIV (PLWH) are at increased risk of coronavirus disease 2019 (COVID-19) mortality or adverse outcomes, and whether antiretroviral therapy (ART) influences this risk. DESIGN: Rapid review with meta-analysis and narrative synthesis. METHODS: We searched databases including Embase, Medline, medRxiv and Google Scholar up to 26 August 2020 for studies describing COVID-19 outcomes in PLWH and conducted a meta-analysis of higher quality studies. RESULTS: We identified 1908 studies and included 19 in the review. In a meta-analysis of five studies, PLWH had a higher risk of COVID-19 mortality [hazard ratio 1.95, 95% confidence interval (CI): 1.62-2.34] compared with people without HIV. Risk of death remained elevated for PLWH in a subgroup analysis of hospitalized cohorts (hazard ratio 1.60, 95% CI: 1.12-2.27) and studies of PLWH across all settings (hazard ratio 2.08, 95% CI: 1.69-2.56). Eight other studies assessed the association between HIV and COVID-19 outcomes, but provided inconclusive, lower quality evidence due to potential confounding and selection bias. There were insufficient data on the effect of CD4+ T-cell count and HIV viral load on COVID-19 outcomes. Eleven studies reported COVID-19 outcomes by ART-regimen. In the two largest studies, tenofovir disoproxil fumarate-based regimens were associated with a lower risk of adverse COVID-19 outcomes, although these analyses are susceptible to confounding by co-morbidities. CONCLUSION: Emerging evidence suggests a moderately increased risk of COVID-19 mortality among PLWH. Further investigation into the relationship between COVID-19 outcomes and CD4+ T-cell count, HIV viral load, ART and the use of tenofovir disoproxil fumarate is warranted.

Analysis of respiratory and systemic immune responses in COVID-19 reveals mechanisms of disease pathogenesis.

Immune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4 + T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163 + and immature phenotypes. Extensive accumulation of CD163 + monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.