Design and preclinical evaluation of a universal SARS-CoV-2 mRNA vaccine.

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated lipid nanoparticle (LNP) formulated mRNA vaccines that induce only T cell responses or both T cell and neutralizing antibody responses by using two mRNAs. One mRNA encodes SARS-CoV-2 Omicron Spike protein in prefusion conformation for induction of neutralizing antibodies. The other mRNA encodes over one hundred T cell epitopes (multi-T cell epitope or MTE) derived from non-Spike but conserved regions of the SARS-CoV-2. We show immunization with MTE mRNA alone protected mice from lethal challenge with the SARS-CoV-2 Delta variant or a mouse-adapted virus MA30. Immunization with both mRNAs induced the best protection with the lowest viral titer in the lung. These results demonstrate that induction of T cell responses, in the absence of preexisting antibodies, is sufficient to confer protection against severe disease, and that a vaccine containing mRNAs encoding both the Spike and MTE could be further developed as a universal SARS-CoV-2 vaccine.

Multi-center Integrating Radiomics, Structured Reports, and Machine Learning Algorithms for Assisted Classification of COVID-19 in Lung Computed Tomography

Purpose To evaluate the classification performance of structured report features, radiomics, and machine learning (ML) models to differentiate between Coronavirus Disease 2019 (COVID-19) and other types of pneumonia using chest computed tomography (CT) scans. Methods Sixty-four COVID-19 subjects and 64 subjects with non-COVID-19 pneumonia were selected. The data was split into two independent cohorts: one for the structured report, radiomic feature selection and model building (n = 73), and another for model validation (n = 55). Physicians performed readings with and without machine learning support. The model's sensitivity and specificity were calculated, and inter-rater reliability was assessed using Cohen's Kappa agreement coefficient. Results Physicians performed with mean sensitivity and specificity of 83.4 and 64.3%, respectively. When assisted with machine learning, the mean sensitivity and specificity increased to 87.1 and 91.1%, respectively. In addition, machine learning improved the inter-rater reliability from moderate to substantial. Conclusion Integrating structured reports and radiomics promises assisted classification of COVID-19 in CT chest scans.

Multi-center Integrating Radiomics, Structured Reports, and Machine Learning Algorithms for Assisted Classification of COVID-19 in Lung Computed Tomography.

Purpose: To evaluate the classification performance of structured report features, radiomics, and machine learning (ML) models to differentiate between Coronavirus Disease 2019 (COVID-19) and other types of pneumonia using chest computed tomography (CT) scans. Methods: Sixty-four COVID-19 subjects and 64 subjects with non-COVID-19 pneumonia were selected. The data was split into two independent cohorts: one for the structured report, radiomic feature selection and model building (n = 73), and another for model validation (n = 55). Physicians performed readings with and without machine learning support. The model's sensitivity and specificity were calculated, and inter-rater reliability was assessed using Cohen's Kappa agreement coefficient. Results: Physicians performed with mean sensitivity and specificity of 83.4 and 64.3%, respectively. When assisted with machine learning, the mean sensitivity and specificity increased to 87.1 and 91.1%, respectively. In addition, machine learning improved the inter-rater reliability from moderate to substantial. Conclusion: Integrating structured reports and radiomics promises assisted classification of COVID-19 in CT chest scans.

The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals.

Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants. SIGNIFICANCE: This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873.

Anxiety, insomnia, and depression during COVID-19 lockdown in elite individual and team sport athletes.

PURPOSE: Pandemic-induced lockdowns disrupted sport training and competition. We aimed to identify the impact on the mental health of high-level athletes and clarify whether the effects differ for team-based and individual athletes. METHODS: This cross-sectional survey, stratified by sex and sport type, collected demographic data and mental health measurements from 274 Brazilian high-performance athletes (142 from team sports and 132 from individual sports) involved with the Brazilian Olympic Committee program for the Tokyo Olympics 2021. Depression, disturbed sleep, and anxiety were assessed by the 9-Item Patient Health Questionnaire, 7-Item Insomnia Severity Index, and 7-Item Generalized Anxiety Disorder scale respectively. Responses were analyzed dichotomously according to published threshold values, characterizing the relative frequency distribution of prevalence (PCRS) or non-prevalence of clinically relevant symptoms (NPCRS). RESULTS: Out of all participants, 47 [17.1%], Z(274) = 15.38, p = .001, 32 [11.7%], Z(274) = 17.94, p = .001, and 49 [17.9%], Z(274) = 15.04, p = .001 had PCRS of anxiety, insomnia, and depression, respectively. There were no significant differences in the PCRS among genders. Compared with individual sport athletes, team sport athletes were more likely to report PCRS of insomnia (12 [37.5%] vs 20 [62.5%], Z(274) = -2.00, p = .046), and depression (18 [36.7%] vs 31 [63.3%], Z(274) = -2.63, p = .009) but not for anxiety. CONCLUSION: Athletes reported high levels of mental health problems during the lockdown. Team sport athletes reported worse symptoms of insomnia and depression than individual sport athletes, possibly due to the impact of unaccustomed social isolation and lack of social team activity. Therefore, it becomes relevant to consider psychological support to team sport athletes who for some reason, such as a pandemic, enduring crisis even injury rehabilitation needs to be isolated.

Anthropometric Measurements and Laboratory Investigations in Children and Youth With Type 1 Diabetes Before and During the COVID-19 Pandemic.

OBJECTIVES: Our aim in this study was to compare rates of anthropometric, blood pressure (BP) and glycated hemoglobin (A1C) measurements and laboratory screening for hypothyroidism, nephropathy and dyslipidemia in children and youth with type 1 diabetes (T1D), 1 year before and after the onset of COVID-19. METHODS: Clinical data were analyzed from a voluntary registry of children and youth with T1D followed at the BC Children's Hospital between March 2019 and 2021. Logistic and Poisson mixed-effect models were used. RESULTS: Four hundred forty patients, with median (interquartile range) age and time since diagnosis 12.7 (9.5 to 15.4) and 4.7 (2.6 to 7.9) years, respectively, were included. Clinic visits were all in-person before March 2020, and 99% via telemedicine afterward. The number of visits per patient was 2 (2 to 3), with a 6% increase during the pandemic (relative risk [RR], 1.06; 95% confidence interval [CI], 1.01 to 1.10). There was a substantial decrease in height, weight and BP measurements (RR, 0.32; 95% CI, 0.28 to 0.36; RR, 0.34, 95% CI, 0.31 to 0.38; RR, 0.005, 95% CI, 0.002 to 0.014, respectively); only 49% of patients had anthropometric and 1% BP data during the pandemic year, compared with >97% before the pandemic. A1C measurements dropped from 3 (2 to 4) to 1 (1 to 2) per patient per year (RR, 0.53; 95% CI, 0.48 to 0.57). Rates of screening investigations were suboptimal before the pandemic, and these rates continued to decline. CONCLUSIONS: Shifting to telemedicine allowed ongoing care during the pandemic, but the frequency of anthropometric, BP and A1C measurements decreased dramatically. A combined telemedicine/in-person model may be needed to ensure adequate care for this population.

Seropositive Wild Boars Suggesting the Occurrence of a Wild Cycle of Trichinella spp. in Brazil.

Trichinella is a zoonotic nematode traditionally detected worldwide in both domestic and wild animals. In South America, along with the occurrence of this parasite in domestic pigs and wild boars, there are reports of infection in wild carnivores. Brazil is considered free of the domestic cycle of Trichinella, but there is unpublished serological evidence of infection in wild boars, which changed the Brazilian status in OIE regarding the disease after an official communication. We investigated Trichinella spp. infection in wild boars and wild carnivores in the Southeastern region of Brazil. A total of 136 samples were tested, 121 from wild boars and 15 from wild carnivores. Artificial enzymatic digestion (AED) tests were performed on muscle samples from 37 wild boars and 15 wild carnivores, and 115 serum samples from wild boars were tested by iELISA. Seven serum samples from wild boars tested positive (7/115 = 6.1%, 95% CI 3.0-12.0), but no larvae were found in the AED. There was no significant difference between sex, age, and location of the samples. The serological results suggest that a wild cycle of Trichinella spp. may occur in Brazil, but further analyses should be performed to confirm the presence of the parasite.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.

Pockets of Resilience – the Digital Responses of Youth Collectives in Contemporary Art Museums During Lockdown

When museums across the world closed due to the COVID-19 pandemic and staff struggled to rethink their new roles in a challenging and unprecedented context, youth collectives – long-term programs for teens and young adults, aged 15–24 – reinvented themselves. The focus of my research is the digital projects developed during lockdown by youth collectives in three metropolitan contemporary art museums. These include MOCA Teens, the MCA Youth Committee and Duchamp & Sons, based, respectively, at LA MOCA (U.S.A.), MCA Australia, and Whitechapel Gallery (U.K.). They adjusted quickly to the new digital pace and devised creative communication and mediation strategies that allowed their collaborative work to continue online. For this research, I combined the analysis of the digital content they produced – websites, social media and podcasts – with interviews I did with the museum educators leading each program. The success of these projects is grounded on a shared trust between museums, educators, and participants. [ FROM AUTHOR] Copyright of Journal of Museum Education is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Usability of Virtual Visits for the Routine Clinical Care of Trans Youth during the COVID-19 Pandemic: Youth and Caregiver Perspectives.

We evaluated families' perspectives on the usability of virtual visits for routine gender care for trans youth during the COVID-19 pandemic. An online survey, which included a validated telehealth usability questionnaire, was sent to families who had a virtual Gender Clinic visit between March and August 2020. A total of 87 participants completed the survey (28 trans youth, 59 caregivers). Overall, usability was rated highly, with mean scores between "quite a bit" and "completely" in all categories (usefulness, ease of use, interface and interaction quality, reliability, and satisfaction). Caregivers reported higher usability scores compared to trans youth [mean (SD) 3.43 (0.80) vs. 3.12 (0.93), p = 0.01]. All families felt that virtual visits provided for their healthcare needs. A total of 100% of youth and caregivers described virtual appointments as safer or as safe as in-person visits. A total of 94% of participants would like virtual visits after the pandemic; families would choose a mean of two virtual and one yearly in-person visit with a multidisciplinary team. Overall, virtual gender visits for trans youth had impressive usability. Participants perceived virtual visits to be safe. For the future, a combination of virtual and in-person multidisciplinary visits is the most desired model.

Has the COVID-19 Pandemic Accelerated the Future of Work or Changed Its Course? Implications for Research and Practice.

The COVID-19 pandemic is a unique transboundary crisis which has disrupted people's way of life more dramatically than any event in generations. Given the ambiguity surrounding the end of the COVID-19 pandemic and its enduring negative effects, it is important to understand how this has affected important future of work trends. The aim of the current paper is to assess the impact of the COVID-19 pandemic on commonly discussed future of work trends relevant to occupational safety and health priority areas. These topics include work arrangements, compensation and benefits, and the organization of work. For each topic, we assess trends leading up to the COVID-19 pandemic, discuss the impact of the pandemic on these trends, and conclude with implications for research and practice. Overall, the pandemic appears to have both accelerated and disrupted various trends associated with future of work topic areas. These effects are discussed in terms of implications for both policymakers and organizations.

Circulating acetylated polyamines correlate with Covid-19 severity in cancer patients.

Cancer patients are particularly susceptible to the development of severe Covid-19, prompting us to investigate the serum metabolome of 204 cancer patients enrolled in the ONCOVID trial. We previously described that the immunosuppressive tryptophan/kynurenine metabolite anthranilic acid correlates with poor prognosis in non-cancer patients. In cancer patients, we observed an elevation of anthranilic acid at baseline (without Covid-19 diagnosis) and no further increase with mild or severe Covid-19. We found that, in cancer patients, Covid-19 severity was associated with the depletion of two bacterial metabolites, indole-3-proprionate and 3-phenylproprionate, that both positively correlated with the levels of several inflammatory cytokines. Most importantly, we observed that the levels of acetylated polyamines (in particular N1-acetylspermidine, N1,N8-diacetylspermidine and N1,N12-diacetylspermine), alone or in aggregate, were elevated in severe Covid-19 cancer patients requiring hospitalization as compared to uninfected cancer patients or cancer patients with mild Covid-19. N1-acetylspermidine and N1,N8-diacetylspermidine were also increased in patients exhibiting prolonged viral shedding (>40 days). An abundant literature indicates that such acetylated polyamines increase in the serum from patients with cancer, cardiovascular disease or neurodegeneration, associated with poor prognosis. Our present work supports the contention that acetylated polyamines are associated with severe Covid-19, both in the general population and in patients with malignant disease. Severe Covid-19 is characterized by a specific metabolomic signature suggestive of the overactivation of spermine/spermidine N1-acetyl transferase-1 (SAT1), which catalyzes the first step of polyamine catabolism.

Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

Nursing and "being with" in a world with COVID-19: an existentialist look.

OBJECTIVE: To reflect on nursing from an existentialist perspective, in which "being-with" has been shown to be the best type of care in a world with Covid-19. METHOD: Reflective theoretical study on nursing in the context of a pandemic using an existentialist philosophical theoretical framework. RESULTS: Nursing is now perceived by society as a profession whose practices are beyond the clinical conditions that affect individuals who live with this pandemic, as taking care of others is not only performing technical actions, but means, fundamentally, taking sensitive ones, like "being-with" in a present and authentic way. FINAL CONSIDERATIONS: The pandemic has caused changes in the way human beings relate to the world, leading to reflections on values ​​due to the restrictions imposed by it. In this scenario, nurses becomes visible, being the protagonists in the different care spaces, since the focus of its practice is existential care, which is established through relationships in encounters between beings, thus making "being-with" possible.

Combination treatments with hydroxychloroquine and azithromycin are compatible with the therapeutic induction of anticancer immune responses.

Amid controversial reports that COVID-19 can be treated with a combination of the antimalarial drug hydroxychloroquine (HCQ) and the antibiotic azithromycin (AZI), a clinical trial (ONCOCOVID, NCT04341207) was launched at Gustave Roussy Cancer Campus to investigate the utility of this combination therapy in cancer patients. In this preclinical study, we investigated whether the combination of HCQ+AZI would be compatible with the therapeutic induction of anticancer immune responses. For this, we used doses of HCQ and AZI that affect whole-body physiology (as indicated by a partial blockade in cardiac and hepatic autophagic flux for HCQ and a reduction in body weight for AZI), showing that their combined administration did not interfere with tumor growth control induced by the immunogenic cell death inducer oxaliplatin. Moreover, the HCQ+AZI combination did not affect the capacity of a curative regimen (cisplatin + crizotinib + PD-1 blockade) to eradicate established orthotopic lung cancers in mice. In conclusion, it appears that HCQ+AZI does not interfere with the therapeutic induction of therapeutic anticancer immune responses.

Perspectives on the COVID-19 pandemic impact on cardio-oncology: results from the COVID-19 International Collaborative Network survey.

BACKGROUND: Re-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated. OBJECTIVES: To assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers' opinions on healthcare policies among oncology and cardiology practitioners. METHODS: An electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology, American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty. RESULTS: One thousand four hundred fifteen providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p = 0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p = < 0.001). Academic physicians (74.5%) felt better supplied with personal protective equipment (PPE) vs non-academic (74.5% vs 67.2%; p = 0.018). Telemedicine was less common in Europe 81% (74/91), and Latin America 64% (101/158), than the United States, 88% (950/1097) (p = < 0.001). 95% of all groups supported more active leadership from medical professional societies. CONCLUSIONS: These results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.

Access to healthcare and prevalence of anxiety and depression in persons with epilepsy during the COVID-19 pandemic: A multicountry online survey.

OBJECTIVE: The objective of this study was to assess access to healthcare and to estimate the prevalence of depression and anxiety among persons with epilepsy (PWE) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a multicountry online survey among PWE. Persons with epilepsy were invited to participate through various social media channels. The Hospital Anxiety and Depression Scale (HADS) and 9-item Patient Health Questionnaire (PHQ-9) scale were used to score anxiety and depression. Logistic regression modeling was used to investigate factors associated with anxiety and depression. RESULTS: Three hundred ninety-nine PWE were included (mean age: 38.22 ±â€¯12.09 years), the majority were female (80.2%) and living in high-income countries (83.2%). Two hundred three PWE reported symptoms of a cold since January 2020. Nine (25%) of the 36 PWE tested for COVID were positive. A total of 72 PWE (19.6%) reported problems to obtain antiseizure medication (ASM), which in 25% of cases was directly COVID-related. Of the 399 PWE, 201 (50.4%) screened positive for anxiety according to the HADS; 159 (39.8%) and 187 (46.9%) PWE screened positive for depression based on the HADS and PHQ-9 scale, respectively. Female gender and financial problems were associated with both depression and anxiety. A planned follow-up consultation with the treating physician was associated with a lower risk of depression, whereas difficulties to access ASM treatment increased the odds of depression. In 65/137 (47.4%) PWE with a planned follow-up visit with the treating physician, this consultation was canceled. CONCLUSIONS: Innovative approaches are needed to ensure continuity in access to ASM treatment. Healthcare workers should ensure continued follow-up, either through inperson or telehealth appointments, to timely identify symptoms of anxiety and depression and act accordingly.