Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study.

Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either "early" (within 14 d of intubation) or "late" (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, -16 to -8; p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, -23 to -9 d; p < 0.001) and 22 days (95% CI, -31 to -12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0; 95% CI, 1.8-5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study

OBJECTIVES: Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either “early” (within 14 d of intubation) or “late” (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, –16 to –8;p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, –23 to –9 d;p < 0.001) and 22 days (95% CI, –31 to –12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0;95% CI, 1.8–5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Low-dose IL-2 reduces IL-21+ T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients (preprint)

Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here, we examined the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) using high-resolution, single-cell multiomics and flow cytometry. We confirmed that iLD-IL-2 selectively expands thymic-derived FOXP3 + HELIOS + Tregs and CD56 br NK cells, and showed that treatment reduced the frequency of IL-21-producing CD4 + T cells and of two subsets of innate-like CD8 + T cells, mucosal-associated invariant T cells and V γ9 V δ2 T cells. The cellular changes induced by LD-IL-2 were associated with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. The anti-inflammatory nature of this gene expression signature was supported by the observation that the same genes were also modulated in COVID-19 patients, but in the opposite direction. These findings warrant continued investigations of the potential clinical benefits of iLD-IL-2 in immunotherapy and further understanding of the development of long-term sequelae in convalescent COVID-19 patients.

Immunodominant NP105-113-B*0702 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease (preprint)

NP 105-113 -B*07:02 specific CD8 + T-cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP 105-113 -B*07:02 specific T-cell clones and single cell sequencing were performed concurrently, with functional avidity and anti-viral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with TCR usage, transcriptome signature, and disease severity (acute N=77, convalescent N=52). We demonstrated a beneficial association of NP 105-113 -B*07:02 specific T-cells in COVID-19 disease progression, linked with expansion of T-cell precursors, high functional avidity and anti-viral effector function. Broad immune memory pools were narrowed post-infection but NP 105-113 -B*07:02 specific T-cells were maintained 6 months after infection with preserved anti-viral efficacy to the SARS-CoV-2 Victoria strain, as well as new Alpha, Beta and Gamma variants. Our data shows that NP 105-113 -B*07:02 specific T-cell responses associate with mild disease and high anti-viral efficacy, pointing to inclusion for future vaccine design.

COVID-19 Remote Consultation Services and Population in Health Inequity-Concentrating Territories: A Scoping Review.

Background: This review aimed to map initiatives for measuring the satisfaction of vulnerable populations with teleconsultation services offered by public and private health care providers in their territories, during the coronavirus disease (COVID-19) pandemic. Systematic studies on the opinions of people most affected by health inequities are limited. Therefore, we included evaluations of teleconsultation-based services offered to socioeconomically disadvantaged and clinically vulnerable populations globally, with a focus on surveillance, treatment, and prevention of COVID-19. Materials and Methods: This review includes analytical and descriptive observational studies primarily from MEDLINE, EMBASE, SCOPUS, and Web of Science databases, published after the World Health Organization received the first warnings about COVID-19 from Chinese authorities in December, 2019, until December 2020. The search strategy combined aspects of COVID-19, telemedicine, patient satisfaction, and key concepts of vulnerable populations. Results: We selected 33 studies for full-text reading and 10 for critical appraisal. Two categories emerged from the qualitative analysis: telehealth evaluation and services during COVID-19, and opinions of vulnerable populations. Television and social networks play a crucial role in providing information. Although teleconsultations are practical and cost effective for patients, the majority preferred receiving in-person treatment in primary care clinics. Conclusions: Listening to the opinions of vulnerable groups and their caregivers is critical both before and during adoption of COVID-19 control measures. Health managers need to monitor the health of and delivery of services to socioeconomically and clinically vulnerable people closely, to improve services, and provide care from a human rights perspective.

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity (preprint)

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

Standardization of elective tracheostomies at the Central Institute of the Hospital das Clínicas in São Paulo during the COVID-19 pandemic

ABSTRACT The COVID-19 Pandemic has resulted in a high number of hospital admissions and some of those patients need ventilatory support in intensive care units. The viral pneumonia secondary to Sars-cov-2 infection may lead to acute respiratory distress syndrome (ARDS) and longer mechanical ventilation needs, resulting in a higher demand for tracheostomies. Due to the high aerosolization potential of such procedure, and the associated risks of staff and envoirenment contamination, it is necesseray to develop a specific standardization of the of the whole process involving tracheostomies. This manuscript aims to demonstrate the main steps of the standardization created by a tracheostomy team in a tertiary hospital dedicated to providing care for patients with COVID-19. RESUMO A pandemia da COVID-19 tem gerado um número elevado de internações hospitalares e muitos pacientes são admitidos nas unidades de terapia intensiva para suporte ventilatório invasivo. A pneumonia viral provocada pelo Sars-cov-2 pode resultar na síndrome da disfunção respiratória aguda (SDRA) e em um tempo prolongado de ventilação mecânica, gerando uma demanda maior de traqueostomias. Diante do alto potencial de aerossolização desse procedimento, com risco de contaminação da equipe e do ambiente, é necessário criar uma padronização específica de todo o processo que envolve essa cirurgia. Este artigo visa demonstrar as principais etapas dessa padronização desenvolvida por um equipe dedicada à realização de traqueostomias em um hospital terciário dedicado ao atendimento de pacientes com suspeita ou confirmação de COVID-19.

Effect of the COVID-19 Pandemic on the Activity of Physicians Working in the Areas of Head and Neck Surgery and Otorhinolaryngology

Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, &#8764;40 days after the 1st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

Effect of the COVID-19 Pandemic on the Activity of Physicians Working in the Areas of Head and Neck Surgery and Otorhinolaryngology.

Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1 st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

Standardization of elective tracheostomies at the Central Institute of the Hospital das Clínicas in São Paulo during the COVID-19 pandemic.

The COVID-19 Pandemic has resulted in a high number of hospital admissions and some of those patients need ventilatory support in intensive care units. The viral pneumonia secondary to Sars-cov-2 infection may lead to acute respiratory distress syndrome (ARDS) and longer mechanical ventilation needs, resulting in a higher demand for tracheostomies. Due to the high aerosolization potential of such procedure, and the associated risks of staff and envoirenment contamination, it is necesseray to develop a specific standardization of the of the whole process involving tracheostomies. This manuscript aims to demonstrate the main steps of the standardization created by a tracheostomy team in a tertiary hospital dedicated to providing care for patients with COVID-19.

Clinical practice guidelines and recommendations in the context of the COVID-19 pandemic: systematic review and critical appraisal (preprint)

Background: The number of published clinical practice guidelines and recommendations related to SARS-CoV-2 infections causing COVID-19 has rapidly increased. However, insufficient consideration of appropriate methodologies in the guideline development could lead to misleading information, uncertainty among professionals, and potentially harmful actions for patients. Purpose: Rapid systematic review of clinical practice guidelines and recommendations in the context of COVID-19 to explore if basic methodological standards of guideline development have been met. Data sources: MEDLINE [PubMed], CINAHL [Ebsco], Trip and manual search; from Feb 1st 2020 until April 27th 2020. Study selection: All types of healthcare workers providing any kind of healthcare to any patient population in any setting. Data extraction: At least two reviewers independently extracted guideline characteristics, conducted critical appraisal according to The Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II) and classified the guidelines using the Association of the Scientific Medical Societies (AWMF) Guidance Manual and Rules for Guideline Development. We plan six-month updates (living review). Data synthesis: There were 1342 titles screened and 188 guidelines included. The highest average AGREE II domain score was 89% for scope and purpose, the lowest for rigor of development (25%). Only eight guidelines (4%) were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality, S3 according to AWMF). Patients were only included in the development of one guideline. A process for regular updates was described in 27 guidelines (14%). Limitations: Methodological focus only. Conclusions: Despite clear scope, most publications fell short of basic methodological standards of guideline development. Future research should monitor the evolving methodological quality of the guidelines and their updates over time. Registration/Publication: The protocol was published at www.researchgate.net, DOI: 10.13140/RG.2.2.21293.51689. Preliminary results are publicly available on medRxiv. Funding Source: This study was partly funded by the COVID-19 Rapid Response Funding Scheme of the Wiener Wissenschafts-, Forschungs- und Technologiefonds (WWTF)/Vienna Science and Technology Fund (project number COV20-028). The funding institution had no influence on the results of this work.