How resilient was trade to COVID-19?☆

We provide stylized facts on the short-run resilience of exports to the COVID-19 pandemic across product characteristics. Relying on global monthly product-level exports to the United States, Japan, and 27 European Union countries from January 2018 to December 2021, we show that products with a higher reliance on China or few countries as input suppliers saw stronger declines in exports as a result of the COVID-19 shock while those with more automated production processes saw exports increase. Our analysis also shows that product characteristics played different roles mediating export responses at different stages of the 2020-2021 COVID-19 crisis. We document rapid reductions in vulnerabilities for exports of unskilled-intensive production. Reliance on diversified inputs from abroad progressively contributed to resilience following an initial negative role when trade was severely disrupted globally.

A urine-based ELISA with recombinant non-glycosylated SARS-CoV-2 spike protein for detecting anti-SARS-CoV-2 spike antibodies.

Serological assays have been widely used to detect anti-SARS-CoV-2 antibodies, which are generated from previous exposure to the virus or after vaccination. The presence of anti-SARS-CoV-2 Nucleocapsid antibodies was recently reported in patients´ urine using an in-house urine-based ELISA-platform, allowing a non-invasive way to collect clinical samples and assess immune conversion. In the current study, we evaluated and validated another in-house urine-based ELISA for the detection of anti-SARS-CoV-2 Spike antibodies. Three partial recombinant SARS-CoV-2 Spike proteins comprising the Receptor Binding Domain, expressed in eukaryotic or prokaryotic systems, were tested in an ELISA platform against a panel of over 140 urine and paired serum samples collected from 106 patients confirmed positive for SARS-CoV-2 by qRT-PCR. The key findings from our study were that anti-SARS-CoV-2 Spike antibodies could be detected in urine samples and that the prokaryotic expression of the rSARS-CoV-2 Spike protein was not a barrier to obtain relatively high serology efficiency for the urine-based assay. Thus, use of a urine-based ELISA assay with partial rSARS-CoV-2 Spike proteins, expressed in a prokaryotic system, could be considered as a convenient tool for screening for the presence of anti-SARS-CoV-2 Spike antibodies, and overcome the difficulties arising from sample collection and the need for recombinant proteins produced with eukaryotic expression systems.

Heterogeneity of humoral response patterns in mildly symptomatic, non-hospitalized COVID-19 patients: A one-year longitudinal study.

The duration and protectiveness of antibodies against SARS-CoV-2 in infected subjects are still uncertain; nonetheless, anti-S-specific antibodies can contribute to protective immunity against new infections. It has been described that the level of antibodies produced in COVID-19 is related to the severity of symptoms, and the majority of the humoral response studies have been conducted in hospitalized patients who have been, then, followed over time. However, about 80% of SARS-CoV-2 infections in unvaccinated people are mild to asymptomatic, and this percentage reaches more than 95% in vaccinated individuals. Therefore, understanding the long-term dynamics of the antibody responses in this predominant part of the COVID-19-affected population is essential. In this study, we followed a cohort of individuals with mild COVID-19 who did not require hospitalization. We collected blood samples at sequential times after the SARS-CoV-2-positive qRT-PCR result. From 65 recruited patients, 50 had detectable antibodies at screening. Anti-SARS-CoV-2 IgM levels peaked around two weeks post-COVID-19 diagnostics, becoming undetectable after 65 days. IgG levels reached a peak in approximately one month and remained detectable for more than one year. In contrast to the levels of anti-SARS-CoV-2, antibody neutralization potency indexes persisted over time. In this study, humoral responses in mild COVID-19 patients persisted for more than one year. This is an important long-term follow-up study that includes responses from COVID-19 patients before and after vaccination, a scenery that has become increasingly difficult to evaluate due to the growing vaccination of the world human population.

Palliative Care in Breast Cancer During the COVID-19 Pandemic: A Scoping Review.

BACKGROUND: The COVID-19 pandemic has harmed the provision of palliative care (PC) services for women with breast cancer due to all the restrictions that came along with the virus. OBJECTIVE: To map the available evidence on the situation of PC in breast cancer during the COVID-19 pandemic. METHODS: A scoping review was carried out based on the methodology proposed by the Joanna Briggs Institute. The search was conducted in nine databases, one electronic repository, and one library, using controlled vocabularies. RESULTS: Twenty-nine articles and seven documents were included. The majority (11.4% each) were published in the United Kingdom, Italy, and the United States, 38.9% addressed palliative radiotherapy (RT), and 47.2% consisted of recommendations. From the content analysis, five categories were obtained focused on the recommendations on changes in palliative treatment guidelines and the response of PC teams to the evolving crisis. CONCLUSIONS: The evidence pointed to the management of general PC, palliative RT, palliative chemotherapy, management of metastatic breast cancer, and use of technologies in palliative care. No recommendations were found to manage frequent symptoms in PC, indicating the need to develop primary studies that investigate these aspects in detail in this vulnerable group. IMPLICATIONS: The results contained in this document can provide professionals working in this field of care with a global view of how other teams have dealt with the pandemic, thereby identifying the best guidelines to apply in their reality, taking into account the clinical and social situation of each patient.

Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern.

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

"Having a family is the new normal": Parenting in neoliberal academia during the COVID-19 pandemic.

The outbreak of the COVID-19 pandemic has made explicit the burden of care shouldered by academic mothers, in addition to juggling their scholarly commitments. Although discussions are abundant on the impact of caring responsibilities on the careers of women academics, neoliberal academia continues to minimize such struggles. Despite the disruptions to family routines caused by the health crisis, academic institutions have expected academic mothers and fathers to continue undertaking their professional responsibilities at the same level as before, disregarding their parenting demands. This paper contributes to the research on parenthood in academia by looking at how, throughout the pandemic, academic parents have negotiated the tensions between parenthood and academic demands, and by investigating the strategies they use to confront neoliberal culture of academic performativity, even amid the health crisis. The paper engages with the "space invaders" concept used by Puwar (2004) to analyze the "hypervisibility" of academic mothers' and fathers' "bodies out of place" during the pandemic, and to investigate their "renegade acts" against the uncaring attitudes of their institutions. Evidence is drawn from a qualitative study conducted during December 2020 and January 2021 among scholars affiliated to Portuguese academic institutions: 17 in-depth interviews conducted with women, and two mixed-gender focus groups. Our results research reveal how the experiences of academic mothers and fathers were not uniform during the pandemic. In addition, it shows how, despite their commitment to their academic responsibilities, these parents have crafted various resistance strategies to confront the institutional pressure to continue maintain their working routines, and instead positioning themselves as "more than just academics."

The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature.

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation.

SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the immune response triggered. We documented a variant-specific pattern of infection severity, inducing discrete lung and blood immune responses and differentially impacting primary lymphoid organs. Infections with variants alpha and delta promoted bone marrow (BM) emergency myelopoiesis, with blood and lung neutrophilia. The defects in the BM hematopoietic compartment extended to the thymus, with the infection by the alpha variant provoking a marked thymic atrophy. Importantly, the changes in the immune responses correlated with the severity of infection. Our study provides a comprehensive platform to investigate the modulation of disease by SARS-CoV-2 variants and underscores the impact of this infection on the function of primary lymphoid organs.

Monitoring the Establishment of VOC Gamma in Minas Gerais, Brazil: A Retrospective Epidemiological and Genomic Surveillance Study.

Since its first identification in Brazil, the variant of concern (VOC) Gamma has been associated with increased infection and transmission rates, hospitalizations, and deaths. Minas Gerais (MG), the second-largest populated Brazilian state with more than 20 million inhabitants, observed a peak of cases and deaths in March-April 2021. We conducted a surveillance study in 1240 COVID-19-positive samples from 305 municipalities distributed across MG's 28 Regional Health Units (RHU) between 1 March to 27 April 2021. The most common variant was the VOC Gamma (71.2%), followed by the variant of interest (VOI) zeta (12.4%) and VOC alpha (9.6%). Although the predominance of Gamma was found in most of the RHUs, clusters of Zeta and Alpha variants were observed. One Alpha-clustered RHU has a history of high human mobility from countries with Alpha predominance. Other less frequent lineages, such as P.4, P.5, and P.7, were also identified. With our genomic characterization approach, we estimated the introduction of Gamma on 7 January 2021, at RHU Belo Horizonte. Differences in mortality between the Zeta, Gamma and Alpha variants were not observed. We reinforce the importance of vaccination programs to prevent severe cases and deaths during transmission peaks.

COVID-19 pandemic decreased sleep quality of medical students.

Objective: Medical students are especially vulnerable to situations of poor sleep quality due to academic demands. The COVID-19 pandemic brought significant changes and high psychological stress, causing a great impact on this population. Here we aim to analyze the influence of the pandemic on the sleep quality of medical students. Methods: Cross-sectional, observational, and descriptive study with a quantitative approach carried out with students from medical universities in Rio Grande do Norte state (Brazil) through the online application of two questionnaires: Pittsburgh sleep quality index (PSQI-BR) and sociodemographic questionnaire (SQ). Results: A total of 142 medical students participated in this study: 103 women and 39 men. We observed a prevalence of low sleep quality in 78.16% of the sample and that the pandemic significantly affected the sleep quality among medical students (p<0.05). We also found an alteration in the sleep pattern in 83% of the participants, mainly due to anxiety symptoms (38%). Finally, we observed no statistically significant difference in sleep quality or sleep patterns between genders or college period (p>0.05). Discussion: This rate of poor sleep quality is higher than the prevalence of periods before the pandemic (58%). Concerns about COVID-19's negative impact on medical education, delayed training, and impact on the generation of medical jobs can directly aggravate the sleep quality. Conclusion: The COVID-19 pandemic negatively influenced the sleep quality of medical students, increasing the prevalence of poor sleep quality and promoting changes in the sleep pattern.

Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature.

Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups-healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.

Risk factors and survival in patients with COVID-19 in northeastern Brazil.

BACKGROUND: Knowledge about the epidemiology and risk factors surrounding COVID-19 contributes to developing better health strategies to combat the disease. OBJECTIVE: This study aimed to establish a survival analysis and identify the risk factors for patients with COVID-19 in an upper middle-income city in Brazil. METHODS: A retrospective cohort study was conducted with 280 hospitalized patients with COVID-19. The eCOVID platform provided data to monitor COVID-19 cases and help the communication between professionals. RESULTS: Age ≥ 65 years was associated with decreased survival (54.8%), and females had a lower survival rate than males (p = 0.01). Regarding risk factors, urea concentration (p<0.001), hospital length of stay (p = 0.002), oxygen concentration (p = 0.005), and age (p = 0.02) were associated with death. CONCLUSION: Age, hospital length of stay, high blood urea concentration, and low oxygen concentration were associated with death by COVID-19 in the studied population. These findings corroborate with studies conducted in research centers worldwide.

“Having a family is the new normal”: Parenting in neoliberal academia during the COVID‐19 pandemic

The outbreak of the COVID‐19 pandemic has made explicit the burden of care shouldered by academic mothers, in addition to juggling their scholarly commitments. Although discussions are abundant on the impact of caring responsibilities on the careers of women academics, neoliberal academia continues to minimize such struggles. Despite the disruptions to family routines caused by the health crisis, academic institutions have expected academic mothers and fathers to continue undertaking their professional responsibilities at the same level as before, disregarding their parenting demands. This paper contributes to the research on parenthood in academia by looking at how, throughout the pandemic, academic parents have negotiated the tensions between parenthood and academic demands, and by investigating the strategies they use to confront neoliberal culture of academic performativity, even amid the health crisis. The paper engages with the “space invaders” concept used by Puwar (2004) to analyze the “hypervisibility” of academic mothers' and fathers' “bodies out of place” during the pandemic, and to investigate their “renegade acts” against the uncaring attitudes of their institutions. Evidence is drawn from a qualitative study conducted during December 2020 and January 2021 among scholars affiliated to Portuguese academic institutions: 17 in‐depth interviews conducted with women, and two mixed‐gender focus groups. Our results research reveal how the experiences of academic mothers and fathers were not uniform during the pandemic. In addition, it shows how, despite their commitment to their academic responsibilities, these parents have crafted various resistance strategies to confront the institutional pressure to continue maintain their working routines, and instead positioning themselves as “more than just academics.”

Remote work do's and don'ts

The article talks about remote work during COVID-19 pandemic that is now a part of everyone's daily lives, and provides more flexibility to manage jobs and the needs of homelife, among other perks. Presents some tips that are helpful for employees to navigate this stay-at-home world including: trying to stick to a work schedule, to avoid overwork;organising day by creating a to-do list of daily tasks;and obtain a quality office chair with lumbar support.

DEVELOPMENT AND VALIDATION OF AN ENZYME-LINKED IMMUNOASSAY KIT FOR DIAGNOSIS AND SURVEILLANCE OF COVID-19.

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule.

The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.

Tracking the turnover of SARS-CoV-2 VOCs Gamma to Delta in a Brazilian state (Minas Gerais) with a high-vaccination status.

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein.

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.