Feasibility and outcomes of psychotherapeutic group therapy for patients with fatigue and emotional and cognitive disturbances secondary to COVID-19 disease.

About 10 % of all symptomatic COVID-19 patients suffer from long-lasting health complaints. Fatigue, cognitive and emotional disorders are the most frequent neuropsychiatric symptoms. Evidence-based therapies for these post-covid impairments are still lacking. Here, we examined the feasibility of a newly developed group-therapy program for patients with fatigue, emotional and cognitive disorders following COVID-19. 24 patients with ICD-10 diagnosis of F06.8 and U0.09 participated in the group therapy on average 13 month after their acute COVID-19 infection. Before and after the group therapy they underwent a comprehensive clinical and neuropsychological assessment. The group therapy was held online and consisted of 8 weekly sessions with psychotherapeutic and psychoeducational elements regarding fatigue and pacing, mindfulness, psychiatric disorders, cognition as well as physical activity after COVID-19. Participation in the group was high with an average of 7.25 of 8 visited sessions. Mean overall group satisfaction was 7.78 out of 10 points. Patients improved in their self-reported fatigue, daily living skills, depression and subjective cognitive abilities as well as in their objective performance in neuropsychological tests of attention during the study time. The newly developed group therapy program for patients with fatigue and emotional and cognitive disorders following an infection with SARS-CoV-2 was well accepted and evaluated and is feasible in an online setting. Copyright © 2023. Thieme. All rights reserved.

Comparing psychological distress in Australians before and during the COVID-19 pandemic

Objective: To determine if psychological distress has increased during the COVID-19 pandemic, and to identify predictors of distress. Method: Kessler Psychological Distress Scale (K10) scores from nationally representative Australian samples before (n = 955) and during (n = 1173) the pandemic were compared. The pandemic sample also completed additional COVID-19 attitudinal scales. Results: The pandemic sample reported significantly higher distress than the pre-pandemic sample, especially among Melbourne residents, women, and younger and older Australians. Stress attributed to COVID-19, feeling the pandemic management is out of control, and an unwillingness to vaccinate were also predictive of psychological distress. Conclusions: Women, youth, and Melbourne residents were most vulnerable to the negative effects of COVID-19 on wellbeing, while feelings related to a loss of control, stress about the virus, and vaccine hesitancy may have also contributed to psychological distress. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Third Places: An Option for Reconfiguring Work-Community Relationships?

This text addresses one of the terms applied to describe spaces of experimentation, namely third place. This concept refers to new places that connect the functions of working, living, and socializing. These three functions had been separated by capitalism under a Fordist mode of regulation. However, since the 2000s, various space-based initiatives have reunited them. In this context, third places represent reference points for community life that favor broader and more creative exchanges at the local level and thus help to maintain sociability, especially in the post-COVID-19 era. Third places offer the opportunity to rethink the link between the workplace and mobility, to review spatial planning practices, and to re-examine the relationship between the local and the global. © 2022, University of Alberta Library. All rights reserved.

Third places: an option for reconfiguration work-community relations?

This text addresses one of the terms applied to describe spaces of experimentation, namely third place. This concept refers to new places that connect the functions of working, living, and socializing. These three functions had been separated by capitalism under a Fordist mode of regulation. However, since the 2000s, various space-based initiatives have reunited them. In this context, third places represent reference points for community life that favor broader and more creative exchanges at the local level and thus help to maintain sociability, especially in the post-COVID-19 era. Third places offer the opportunity to rethink the link between the workplace and mobility, to review spatial planning practices, and to re-examine the relationship between the local and the global.

Tiki Torch Fuel Injury in a Toddler Requiring Extracorporeal Life Support

INTRODUCTION: Injury from hydrocarbon inhalation, such as with tiki torch fuel, can range from asymptomatic requiring only observation to fatal due to severe acute respiratory distress syndrome. Treatment is largely supportive. DESCRIPTION: A 12-month-old male was found by a family member drenched in tiki torch fluid with suspected hydrocarbon inhalation. On presentation to the Emergency Department, he was lethargic but with a clear respiratory exam. Within an hour, he developed tachypnea and hypoxemia requiring endotracheal intubation. Chest radiography revealed interval increase in bilateral heterogeneous airspace opacities. He was also found to be parainfluenza 3 positive. Despite optimization of sedation and paralysis, administration of corticosteroids and bronchodilators, and increasing respiratory support, he had worsening hypoxemia and hypercarbia. On hospital day 2, he had an oxygenation index of 60 and a P/F ratio of 40, so he underwent cannulation with veno-arterial extracorporeal membrane oxygenation (ECMO). In addition to diuretics and chest physiotherapy, due to persistent fevers, elevated inflammatory markers, and severity of illness, he received antibiotics for 7 days. Over the next 3 days, he improved and was subsequently decannulated from ECMO. Sixteen days after initial injury, he was extubated and weaned from supplemental oxygen three days later. He has not had any respiratory complications in the 12 months since injury. However, he did require rehospitalization due to thrombotic stroke suspected to be secondary to recent COVID-19 infection, history of ECMO and family history of thromboembolic events. DISCUSSION: Although most children with injuries related to hydrocarbon ingestion and aspirations can be observed and discharged, some injuries can lead to significantly worse symptoms including pulmonary edema, bronchoconstriction, hypoxemia and worsening respiratory distress which may require invasive support or ultimately be fatal. Presentations can evolve rapidly over 6-8 hours and peak at 48 hours due to the disturbance of surfactant and consequences of inflammation. While bronchodilators may provide benefit, steroids and surfactant therapy is controversial. Therapy is largely supportive. Most children can be expected to have a full recovery.

Glomerular Annexin A3 and Cathepsin C Staining in COVID-19-Associated and HIV-Associated Nephropathy (HIVAN)-Associated Collapsing Glomerulopathy

Background: Prior studies demonstrated glomerular tuft staining for annexin A3 (Anxa3), a marker of parietal epithelial cells (PECs), and cathepsin C (Ctsc), a master regulatory protease, distinguishing primary collapsing glomerulopathy (CG) from other glomerular diseases. We hypothesized these staining patterns would differentiate COVID-19 associated CG (COVID-19+/CG+) from COVID-19(+) without CG (COVID-19+/CG-). Method(s): Biopsy sections used were from patients with COVID-19 infections and a pathologist-based tissue diagnoses including CG (COVID-19+/CG+;n=4) or lacking CG diagnosis (COVID-19+/CG-;n=6) were stained for Anxa3 and Ctsc using published protocols. HIVAN-associated CG (n=4) biopsies were used as a secondary CG control. Historical controls data for non-CG biospies (PMID:32561683). Glomerular staining was tabulated as for PEC staining, phenotypic characteristics of normal and activated (enlarged nuclei, hypertrophic/enlarged cuboidal shape cells, vacuolization) PECs, and for glomerular tuft to Bowman's capsule adhesions or cellular PEC bridges. Globally scarred glomerulii were omitted from analysis. Serial section staining was used to demonstrate Anxa3 and Ctsc co-localization. Differences in the mean (i) number of glomeruli staining OR (ii) glomerular tuft area stained for Anxa3 and Ctsc per biopsy were compared by one-tailed t-test assuming an increase in staining in CG over non-glomerular disease. A p-value <0.05 was used for statistical significance. Result(s): All COVID-19+/CG+ and HIVAN patients with CG demonstrated extensive Anxa3 and Ctsc glomerular tuft staining. The frequency of glomerular tuft Anxa3 and Ctsc staining and percent glomerular area was significantly (p<0.05) increased in biopsies with COVID-19+/CG+, compared to COVID-19+/CG- (log2FC 2.8-2.9). No statistical difference in frequency or area stained for Anxa3 and Ctsc was observed between COVID-19+/CG+ and HIVAN-associated CG. Conclusion(s): Anxa3 and Ctsc glomerular tuft expression is increased significantly in COVID-19 and HIVAN patients with CG, mirroring our findings in primary CG. These data support the hypotheses that (a) migration of activated PECs into the glomerular tuft is a prevalent event in both primary CG and virus-associated secondary CG, and (b) glomerular Anxa3 or Ctsc may be theragnostic biomarkers of CG.

TGF-β SIGNALING PATHWAY SHAPES ADAPTIVE IMMUNITY in EARLY SARS-CoV-2 INFECTION

Background: SARS-CoV-2 induces cytokine response dysregulation and immune dysfunction. What remains unclear is how cytokine signaling shapes immune responses during early SARS-CoV-2 infection when adaptive immunity is developing. Our goal is to identify immune pathways that shape the early development of adaptive immune responses in COVID-19 patients. We performed paired single-cell transcriptomic and epigenomic profiling at two time-points of early SARS-CoV-2 infection to determine immune signatures of acute infection and epigenetic drivers that underpin immune response dynamics. Methods: PBMC samples were collected from four moderate to severe COVID-19 patients at two early time-points (n = 3 for Week 1 and n = 3 for Week 2 after symptom onset, including 2 participants having paired blood sampling at both time points) and from two healthy controls (n = 2). Using paired scRNA-Seq and scATAC-Seq, we captured transcriptomic and epigenomic profiles in the same single cells to identify chromatin accessibility changes as a potential mechanism for the surge and decline of immune responses elicited during acute SARS-CoV-2 infection. Using bioinformatic approaches, we identified heterogeneous immune cell populations, modeled cell differentiation trajectories, determined dysregulated immune pathways through gene set enrichment analysis, and connected chromatin co-accessible landscapes. Results: We captured transcriptomic and epigenomic profiles of 43,726 single cells and identified paired transcriptional and epigenetic landscapes in six major immune cell types: CD4+ T cells, CD8+ T cells, B cells, dendritic cells, monocytes, and NK cells. We found that early SARS-CoV-2 infection induced a surge in IL-2, IL-6, IFN-α, IFN-γ, TNF-α, and NF-κB responses at Week 1 that declined at Week 2 in adaptive immune cells (CD4+ T, CD8+ T, and B cells). In contrast, TGF-β responses surged early at Week 1 and continued to increase at Week 2 in these cells. In B cells and plasmablasts, we found early surges of IGHA1 (encoding IgA heavy chain) and SOX4 (an essential transcription factor for B cell development) expressions that correlated with expression of SMAD-dependent TGF-β signaling pathway. Further, we found a notable increase in chromatin accessibility at the SMAD binding regulatory element 150 kb upstream of SOX4 in B cells of infected patients. Conclusion: Our data suggest a significant increase in TGF-β activity that instructs dynamic B cell-associated protective immunity during early SARS-CoV-2 infection.

Cancer patients display diminished viral RNA clearance and altered T cell responses during SARS-CoV-2 infection

Cancer patients display immunomodulation related to malignancy and anti-cancer therapies, but how these factors impact COVID-19 remains unknown. To investigate immune responses in cancer patients with COVID-19, we undertook a prospective case-control study, enrolling hospitalized solid tumor patients with acute COVID-19, as well as age-, gender-, and comorbidity-matched COVID-19 patients without cancer as controls. Using biospecimens collected during hospitalization, we performed virologic measurements as well as in-depth immunophenotyping of cellular, antibody and cytokine responses. We enrolled 17 cancer patients (cases) admitted to Yale-New Haven Hospital between March 15 and June 30, 2020 with COVID-19, as well as 17 matched non-cancer patients (controls) admitted with COVID-19. No significant differences were observed between cases and controls based on patient characteristics (age, gender, race, co-morbidities, smoking history, days from symptom onset to COVID-19 diagnosis) or outcomes (COVID-19 severity, length of hospital stay, rate of intubation or mortality). The most common primary tumor sites were lung (4/17) and gastrointestinal (4/17);all cases had received cancer-directed therapy within 6 months of COVID-19 diagnosis, with 13/17 receiving treatment less than 1 month prior to hospitalization. Three of 17 cases had received immune checkpoint inhibitor therapies. Despite having similar SARS-CoV-2 viral RNA loads at the time of COVID-19 diagnosis when compared with controls, cancer cases had increased viral RNA abundance during hospitalization, suggesting slower clearance. Antibody responses against SARS-CoV-2 were preserved in cancer cases, with cases displaying similar levels of IgM and IgG antibodies directed against SARS-CoV-2 epitopes compared to controls. Cytokine profiling revealed higher plasma levels of CCL3, IL1A and CXCL12 in cancer cases compared to controls. Using flow cytometric immunophenotyping, we found that innate immune and non-T cell adaptive immune parameters were similar between cases and controls hospitalized with COVID-19. However, among cancer cases on conventional therapies, T cell lymphopenia was more profound, and these cases demonstrated higher levels of CD8+ exhausted (CD8+CD45RA-PD1+TIM3+ ), CD8+GranzymeB+ and CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ activated T cells when compared with controls;interestingly, these differences were not observed in patients who had received immune checkpoint inhibition. Thus, we found reduced viral RNA clearance and specific alterations in T cell and cytokine responses in cancer patients hospitalized with COVID-19 compared with matched controls with COVID-19. This dysregulated T cell response in cancer patients, which may reflect immune modulation due to chronic antigen stimulation as well as cancer therapies, may lead to altered virologic and clinical outcomes in this population.

Metabolic Syndrome Is Associated With Worse Outcomes in SARS-CoV-2 Positive Emergency Department Patients

Study Objective: Increased body mass index (BMI) and metabolic syndrome (MetS) have been associated with adverse outcomes in numerous diseases. However, the role of BMI and MetS in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remains unclear. We sought to examine the associations of increased BMI and MetS on several clinical outcomes in all ED patients tested for SARS-CoV-2 and then in the subset of COVID positive patients only. Methods: The REgistry of potential COVID-19 in emERgency care (RECOVER) is an observational study of SARS-CoV-2 tested patients from 155 US EDs. Inclusion criteria were a nucleic acid test at index visit. Body mass was categorized per CDC designations ie, BMI 18.5 to <25 kg/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2 and ≥40 kg/m2. The presence of metabolic syndrome was defined as having 3 or more defining characteristics per the electronic medical record at the time of index visit;these included an elevated BMI (≥30 kg/m2), hyperlipidemia, hypertension, and diabetes. We used multivariable logistic regression to test for associations of several variables (including BMI, MetS, age, sex, race, ethnicity, and smoking) on the following clinical outcomes, first comparing SARS-CoV-2 positive and SARS-CoV-2 negative patients (N=27, 051) and then in the COVID+ subset (N=14, 056): hospital admission, intensive care unit (ICU) care, intubation, 30-day mortality and 30-day new or recurrent venous thromboembolism (VTE). Results: We report that BMI ≥ 30 kg/m2 was associated with SARS-CoV-2 test positivity (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.08-1.20). Analysis of BMI ≥ 40 kg/m2 revealed a stronger association with test positivity (OR 1.24, 95% CI 1.14-1.35). By contrast, MetS was not associated with testing positive (OR 0.95, 95% CI 0.89-1.01) in the overall cohort. In COVID+ patients, BMI ≥ 40 kg/m2 was associated with ICU care (adjusted odds ratio [aOR] 1.97;95% CI 1.65-2.35), intubation (aOR 2.69;95% CI 2.22-3.26) and mortality (aOR 1.50;95% CI 1.22-1.84). MetS was associated with worsened clinical outcomes: hospital admission (aOR 2.11;95% CI 1.89-2.37), ICU care (aOR 1.58;95% CI 1.40-1.78), intubation (aOR 1.46;95% CI 1.28-1.66), mortality (aOR 1.29;95% CI 1.13-1.48) and VTE (aOR 1.51;95% CI 1.07-2.13). Conclusions: In this large nationwide sample of ED patients undergoing SARS-CoV-2 testing, we report that BMI ≥ 30 kg/m2, BMI ≥ 40 kg/m2 and not MetS was associated with SARS-CoV-2 test positivity. Multivariable analysis in COVID positive patients only revealed significant associations of BMI ≥ 40 kg/m2 with three outcomes (ICU care, intubation and mortality) and of MetS with five outcomes (hospital admission, ICU care, intubation, mortality and VTE).

Susceptibility of mature human myocardial cell types to sars-cov-2

Background: SARS-CoV-2 is a highly transmissible and virulent respiratory pathogen responsible for the global coronavirus disease 2019 (COVID-19) pandemic. A significant number of patients infected with SARS-CoV-2 show signs of myocardial injury ranging from asymptomatic troponemia to acute congestive heart failure and cardiogenic shock. The precise mechanisms underlying myocardial injury in this cohort are unclear, and it is difficult to distinguish weather new onset cardiac dysfunction is representative of active myocardial infection or a consequence of systemic illness. To address this gap in knowledge we constructed a model to assess replicative potential of SARS-CoV2 in primary cell lines derived from adult and pediatric myocardium including cardiomyocytes, fibroblasts, and endothelial cells and corroborated our in vitro findings with a pathologic analysis of myocardial tissue obtained from patients infected with SARS-CoV-2. Methods: Samples of atrial myocardium obtained from patients undergoing cardiac surgery were enzymatically digested and purified into cardiomyocyte, fibroblast, and endothelial cell populations. Susceptibility to infection with SARS-CoV-2 was then assessed in primary human myocardial cell types and compared against induced cardiomyocytes derived from human pluripotential stem cells. Infectivity was quantitatively assessed using qPCR against genomic and subgenomic viral RNA and normalized to GAPDH. Postmortem heart and lung FFPE tissue from de-identified patients who died from SARS CoV-2 infection were obtained and analyze by immunofluorescence for viral spike and nucleocapsid protein or stained with hematoxylin and eosin for histological evaluation. Results: Primary cardiomyocytes obtained from adult (n=7) and pediatric (n=7) atrial myocardium could not support active replication SARS-CoV-2 virus and there was no evidence of viral replication in pathologic myocardial specimens obtained from COVID infected patients (n=7). Collectively our data indicate that primary cardiac cell types are unable to support the level of viral replication observed in iPSCM (p=0.0007) suggesting that induced pluripotential stem cells may not adequately model the response of mature myocardium to SARS-CoV-2.

Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. Although effective vaccines are currently being deployed, the adaptive immune determinants that promote viral clearance and confer protection remain poorly defined. Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contribute to viral clearance in the setting of primary infection. Furthermore, we find that either convalescent mice or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351. In addition, we find that this protection is largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection.

Data-driven Simulation and Optimization for Covid-19 Exit Strategies

The rapid spread of the Coronavirus SARS-2 is a major challenge that led almost all governments worldwide to take drastic measures to respond to the tragedy. Chief among those measures is the massive lockdown of entire countries and cities, which beyond its global economic impact has created some deep social and psychological tensions within populations. While the adopted mitigation measures (including the lockdown) have generally proven useful, policymakers are now facing a critical question: how and when to lift the mitigation measures? A carefully-planned exit strategy is indeed necessary to recover from the pandemic without risking a new outbreak. Classically, exit strategies rely on mathematical modeling to predict the effect of public health interventions. Such models are unfortunately known to be sensitive to some key parameters, which are usually set based on rules-of-thumb. In this paper, we propose to augment epidemiological forecasting with actual data-driven models that will learn to fine-tune predictions for different contexts (e.g., per country). We have therefore built a pandemic simulation and forecasting toolkit that combines a deep learning estimation of the epidemiological parameters of the disease in order to predict the cases and deaths, and a genetic algorithm component searching for optimal trade-offs/policies between constraints and objectives set by decision-makers. Replaying pandemic evolution in various countries, we experimentally show that our approach yields predictions with much lower error rates than pure epidemiological models in 75% of the cases and achieves a 95% R2 score when the learning is transferred and tested on unseen countries. When used for forecasting, this approach provides actionable insights into the impact of individual measures and strategies. © 2020 Owner/Author.