Characterization of post-vaccination SARS-CoV-2 T cell subtypes in patients with different hematologic malignancies and treatments.

Background: To evaluate the benefits of SARS-CoV-2 vaccination in cancer patients it is relevant to understand the adaptive immune response elicited after vaccination. Patients affected by hematologic malignancies are frequently immune-compromised and show a decreased seroconversion rate compared to other cancer patients or controls. Therefore, vaccine-induced cellular immune responses in these patients might have an important protective role and need a detailed evaluation. Methods: Certain T cell subtypes (CD4, CD8, Tfh, γδT), including cell functionality as indicated by cytokine secretion (IFN, TNF) and expression of activation markers (CD69, CD154) were assessed via multi-parameter flow cytometry in hematologic malignancy patients (N=12) and healthy controls (N=12) after a second SARS-CoV-2 vaccine dose. The PBMC of post-vaccination samples were stimulated with a spike-peptide pool (S-Peptides) of SARS-CoV-2, with CD3/CD28, with a pool of peptides from the cytomegalovirus, Epstein-Barr virus and influenza A virus (CEF-Peptides) or left unstimulated. Furthermore, the concentration of spike-specific antibodies has been analyzed in patients. Results: Our results indicate that hematologic malignancy patients developed a robust cellular immune response to SARS-CoV-2 vaccination comparable to that of healthy controls, and for certain T cell subtypes even higher. The most reactive T cells to SARS-CoV-2 spike peptides belonged to the CD4 and Tfh cell compartment, being median (IQR), 3.39 (1.41-5.92) and 2.12 (0.55-4.14) as a percentage of IFN- and TNF-producing Tfh cells in patients. In this regard, the immunomodulatory treatment of patients before the vaccination period seems important as it was strongly associated with a higher percentage of activated CD4 and Tfh cells. SARS-CoV-2- and CEF-specific T cell responses significantly correlated with each other. Compared to lymphoma patients, myeloma patients had an increased percentage of SARS-CoV-2-specific Tfh cells. T-SNE analysis revealed higher frequencies of γδT cells in patients compared to controls, especially in myeloma patients. In general, after vaccination, SARS-CoV-2-specific T cells were also detectable in patients without seroconversion. Conclusion: Hematologic malignancy patients are capable of developing a SARS-CoV-2-specific CD4 and Tfh cellular immune response after vaccination, and certain immunomodulatory therapies in the period before vaccination might increase the antigen-specific immune response. A proper response to recall antigens (e.g., CEF-Peptides) reflects immune cellular functionality and might be predictive for generating a newly induced antigen-specific immune response as is expected after SARS-CoV-2 vaccination.

Customized EfficientNet for Histopathology Image Representation

In recent years, and amplified by the COVID-19 pandemic, the digitization of pathology has gained a considerable attention. Digital pathology provides crucial advantages compared to conventional light microscopy, including more efficient workflows, more accurate diagnosis and treatment planning, and easier collaboration. Despite promising progress, there are some critical challenges related to classifying images in digital pathology, such as huge input sizes (e.g., gigapixels) and expensive processing time. Most of the existing models for classification of histopathology images are very large and accordingly have many parameters to be learned/optimized. In addition, due to the large size of Whole Slide Images (WSIs), e.g., 100,000 × 100,000 pixels, models require enormous computational times to achieve reliable results. In order to address these challenges, we propose a more compact network which is customized to classify cancer subtypes with lower computation time and memory complexity. This model is based on EfficientNet topology, but it is tailored for classifying histopathology images. The utilized model is evaluated over three tumor types brain, lung, and kidney from The Cancer Genome Atlas (TCGA) public repository. Since the pre-trained EfficientNet works properly with the specific size of images, an effective approach is proposed to adjust the size of input images. The proposed model can be trained with a much smaller training set for applications such as image search that require robust and compact representations. The results show that the proposed model, compared to state-of-the-art models, i.e., KimiaNet, can classify cancer subtypes more accurately and provides superior results. In addition, the proposed model achieves memory and computational efficiency in the training phase and is a more compact deep topology compared to KimiaNet. © 2022 IEEE.

The expression of respiratory tract virus in pediatric glomerular disease: a retrospective study of 45 renal biopsy in China.

BACKGROUND: More attention has been put on the relationship between pediatric glomerular disease and respiratory tract virus infection. Children with glomerular illness, however, are uncommonly found to have biopsy-proven pathological evidence of viral infection. The purpose of this study is to determine whether and what kind of respiratory viruses are found in renal biopsy from glomerular disorders. METHODS: We used a multiplex PCR to identify a wide range of respiratory tract viruses in the renal biopsy samples (n = 45) from children with glomerular disorders and a specific PCR to verify their expression. RESULTS: These case series included 45 of 47 renal biopsy specimens, with 37.8% of male and 62.2% of female patients. Indications for a kidney biopsy were present in all of the individuals. In 80% of the samples, respiratory syncytial virus was discovered. Following that, the RSV subtypes in several pediatric renal disorders were found. There were 16 RSVA positives, 5 RSVB positives, and 15 RSVA/B positives, accounting for 44.4%, 13.9%, and 41.7%, respectively. Nephrotic syndrome samples made up 62.5% of RSVA positive specimens. The RSVA/B-positive was detected in all pathological histological types. CONCLUSIONS: Patients with glomerular disease exhibit respiratory tract viral expression in the renal tissues, especially respiratory syncytial virus. This research offers new information on the detection of respiratory tract viruses in renal tissue, which may facilitate the identification and treatment of pediatric glomerular diseases.

Outcome of COVID-19-Associated Acute Stroke: A Study from South India.

Background and Objective: Coronavirus 2019 (COVID-19) infection is prevalent worldwide. COVID-19 infection can lead to various neurological disorders including acute stroke. We investigated the functional outcome and its determinants among our patients with acute stroke associated with COVID-19 infection in the present setup. Materials and Methods: This study is a prospective study in which we recruited acute stroke patients with COVID-19 positivity. Data on duration of COVID-19 symptoms and type of acute stroke were recorded. All patients underwent stroke subtype workup and measurement of D-dimer, C-reactive protein (CRP), lactate-dehydrogenase (LDH), procalcitonin, interleukin-6, and ferritin levels. Poor functional outcome was defined by modified Rankin score (mRS) ≥3 at 90 days. Results: During the study period, 610 patients were admitted for acute stroke, of whom 110 (18%) tested positive for COVID-19 infection. Majority (72.7%) were men with a mean age of 56.5 years and mean duration of COVID-19 symptoms for 6.9 days. Acute ischemic and hemorrhagic strokes were observed in 85.5% and 14.5% patients, respectively. Poor outcome was observed in 52.7%, including in-hospital mortality in 24.5% patients. COVID-19 symptoms ≤5 days (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.20-2.99), CRP positivity (OR: 1.97, 95% CI: 1.41-4.87), elevated levels of D-dimer (OR: 2.11, 95% CI: 1.51-5.61), interleukin-6 (OR: 1.92, 95% CI: 1.04-4.74), and serum ferritin (OR: 2.4, 95% CI: 1.02-6.07), and cycle threshold (Ct) value ≤25 (OR: 8.8, 95% CI: 6.52-12.21) were independent predictors of poor outcome. Conclusion: Poor outcomes were relatively higher among acute stroke patients with concomitant COVID-19 infection. In the present study, we established the independent predictors of poor outcome to be onset of COVID-19 symptoms (<5 days) and elevated levels of CRP, D-dimer, interleukin-6, ferritin, and Ct value ≤25 in acute stroke.

Identifying tumor antigens and immuno-subtyping in colon adenocarcinoma to facilitate the development of mRNA vaccine.

The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1-IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune-hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)-related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA-based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.

Clustering Based Identification of SARS-CoV-2 Subtypes

With the availability of more than half a million SARS-CoV-2 sequences and counting, many approaches have recently appeared which aim to leverage this information towards understanding the genomic diversity and dynamics of this virus. Early approaches involved building transmission networks or phylogenetic trees, the latter for which scalability becomes more of an issue with each day, due to its high computational complexity. In this work, we propose an alternative approach based on clustering sequences to identify novel subtypes of SARS-CoV-2 using methods designed for haplotyping intra-host viral populations. We assess this approach using cluster entropy, a notion which very naturally captures the underlying process of viral mutation-the first time entropy was used in this context. Using our approach, we were able to identify the well-known B.1.1.7 subtype from the sequences of the EMBL-EBI (UK) database, and also show that the associated cluster is consistent with a measure of fitness. This demonstrates that our approach as a viable and scalable alternative to unveiling trends in the spread of SARS-CoV-2.

The Impact of COVID-19 Pandemic on Individuals With Pre-existing Obsessive-Compulsive Disorder in the State of Qatar: An Exploratory Cross-Sectional Study.

Background: Published evidence about the impact of the COVID-19 pandemic on Obsessive-Compulsive Disorder (OCD) is conflicting. Most studies suggest an increase in the severity of OCD in people with pre-existing OCD, whereas some do not. Aim: Given the conflicting evidence globally and lack of data from the Arab world, we aimed to explore the impact of the pandemic on obsessive-compulsive symptoms in adults with pre-existing OCD. Methods: A telephonic questionnaire-based cross-sectional study among adults with pre-existing OCD and specifically with fear of contamination and washing compulsions being major symptom dimensions of OCD. The severity of OCD during the pandemic was compared with their pre-pandemic scores. The severity of OCD was assessed using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Results: Those with the duration of diagnosis of OCD of<10 years showed a statistically significant increase in the mean YBOCS score of 5.54 from pre-pandemic to during pandemic, which was significant at p = 0.006. This significance was maintained across the Compulsive and Obsessive subsets of the scale. Conclusion: Adults with pre-existing OCD with fear of contamination reported a statistically significant increase in severity of obsessive-compulsive symptoms only if the duration of their OCD diagnosis was relatively shorter (<10 years). In the context of the conflicting evidence regarding the worsening of OCD symptoms due to the unique infection control measures of this pandemic, this study highlights the importance of the impact of the duration of the disorder and the subtype of the disorder. Such classification might help public health resources to be directed better at those most at risk and also help us understand the very nature of this disorder better.

Dramatic Decrease of Vitamin K2 Subtype Menaquinone-7 in COVID-19 Patients.

(1) Background: Vitamin K (VK) is a fat-soluble compound with a common chemical structure, a 2-methyl-1,4-naphthoquinone ring, and a variable aliphatic side-chain. VK is involved in the synthesis of blood-clotting proteins, bone stability, anti-oxidative, and immune inflammatory-modulatory functions. Vitamin K also activates protein S, which acts as an antioxidant and anti-inflammatory. The fact that cytokine overproduction, oxidative stress, and disturbed microcirculation by thrombogenicity play a central role in severe COVID-19 prompted us to analyze this vitamin. (2) Methods: We analyzed by a validated liquid-chromatography tandem mass-spectrometry method serum vitamin K1, MK4, MK7, and VK epoxide levels in 104 healthy controls, 77 patients with non-COVID-19 pneumonia, and 135 hospitalized COVID-19 patients with potentially fatal outcomes admitted to our University Hospital between April and November 2020. We included the quotient between VK and triglyceride (TG, nmol/mmol/L) values in the analyses with respect to the TG transporter function for all VK subtypes. Additionally, we assessed anthropometric, routine laboratory, and clinical data from the laboratory and hospital information systems. (3) Results: The COVID-19 patients had significantly lower MK7 levels than non-COVID-19 pneumonia patients and healthy controls. COVID-19 and non-COVID-19 pneumonia patients had significantly lower vitamin K1 and significantly higher MK4 compared to healthy controls, but did not differ significantly from each other. Between COVID-19 non-survivors (n = 30) and survivors (n = 105) no significant differences were seen in all vitamin K subtypes, despite the fact that non-survivors had higher peak concentrations of IL-6, CRP, d-dimer, and higher oxygen needs, respectively. (4) Conclusions: The present data identified significantly decreased vitamin K1, K2 (MK7), and increased MK4 levels in patients with COVID-19 compared to healthy controls. Vitamin K2 (MK7) was lowest in COVID-19 patients irrespective of potentially fatal courses, indicating consumption of this VK subtype by COVID-19 immanent effects, most probably inflammatory and oxidative stress factors.

COVID-19 Acute Respiratory Distress Syndrome: One Pathogen, Multiple Phenotypes.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome arising from multiple causes with a range of clinical severity. In recent years, the potential for prognostic and predictive enrichment of clinical trials has been increased with identification of more biologically homogeneous subgroups or phenotypes within ARDS. COVID-19 ARDS also exhibits significant clinical heterogeneity despite a single causative agent. In this review the authors summarize the existing literature on COVID-19 ARDS phenotypes, including physiologic, clinical, and biological subgroups as well as the implications for improving both prognostication and precision therapy.

Low expression of TMPRSS2-a SARS-CoV-2 internalization protease-associates with basal subtype of head and neck squamous cell carcinoma.

SARS-CoV-2 is a single-stranded RNA virus that has caused the ongoing COVID-19 pandemic. ACE2 and other genes utilized by SARS-CoV-2 to enter human cells have been shown to express in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. However, their expression pattern in different subtypes has not been investigated. Hence, in the current study, we have analyzed the expression of ACE2, TMPRSS2 and FURIN in 649 HNSCC patients from two independent cohorts. Our analysis showed significantly lower expression of TMPRSS2 while significantly increased expression of ACE2 and FURIN in HPV-negative HNSCC. Comparison of expression of these genes in the three subtypes of HNSCC patients (basal, classical and inflamed/mesenchymal) showed no significant difference in the expression of ACE2 among the three subtypes; however, the basal subtype showed significantly reduced expression of TMPRSS2 but significantly increased expression of FURIN. Comparison of expression of these genes between the HPV-negative patients of basal subtype vs all others confirmed significantly lower expression of TMPRSS2 in HPV-negative patients of basal subtype as compared to all others. Our study shows that the different subtypes of HNSCC patients have different expression patterns of genes utilized by the SARS-CoV-2 to enter human cells, and hence, their susceptibility to SARS-CoV-2 may also be different. As the expression of TMPRSS2 is significantly lower in the HNSCC patients of the basal subtype, we predict that these patients would be less susceptible to SARS-CoV-2 infection than the patients of other subtypes. However, these findings need to be further validated.

Identifying Potential Gene Defect Patterns Related to COVID-19 Based on Pharmacological and Bioinformatics Analysis for Lung Adenocarcinoma.

Background: Coronavirus disease 2019 (COVID-19) greatly affects cancer patients, especially those with lung cancer. This study aimed to identify potential drug targets for lung adenocarcinoma (LUAD) patients with COVID-19. Methods: LUAD samples were obtained from public databases. Differentially expressed genes (DEGs) related to COVID-19 were screened. Protein-protein interactions among COVID-19-related genes, the traditional Chinese medicine (TCM) and TCM target genes were analyzed by CytoScape. The correlation between tumor microenvironment and COVID-19 target genes were assessed by Pearson correlation analysis. Unsupervised consensus clustering was conducted to categorize molecular subtypes. Results: We filtered 26 COVID-19 target genes related to TCM for LUAD. Interleukin (IL)-17 signaling pathway and tumor necrosis factor (TNF) signaling pathway were significantly enriched in these 26 genes. A strong correlation was found between COVID-19 target genes and tumor microenvironment (TME), cell death. Importantly, interleukin-1beta (IL1B) was identified as a core gene in the protein-protein interactions (PPI) network. Based on the 26 target genes, two molecular subtypes showing distinct overall survival, TME and response to target therapy were developed. Conclusions: This study explored 26 COVID-19 target genes, which could serve as potential therapeutic drug targets for LUAD. IL1B was verified as a critical target for developing new molecular drugs. Furthermore, two novel molecular subtypes showed the potential to guide personalized therapies in clinical practice.

Guillain-Barré Syndrome;a Neurological Disease during Convalescence Period

Aims Coronavirus can attack the central and peripheral nervous systems in different ways and produce neurological manifestations. This study aimed to summarize the neurological manifestations and electrophysiological studies of COVID-19 patients during the recovery phase, suggesting Guillain-Barré syndrome. Patients & Methods This case report study was done in the Department of Physiology, College of Medicine at Al-Mustansiriya University, in cooperation with Al-Yarmouk Teaching Hospital in Baghdad. Patients during the convalescent period (1-3 months post-infection) of COVID-19 disease with neurological manifestations were included. Neurologists and neurosurgeons referred the patients for an electromyography and nerve conduction study to identify their illnesses. Findings Seven patients (4 females and 3 males) presented with clinical manifestations that highly suggested Guillain-Barré syndrome. The patients were presented with a rapidly progressive ascending weakness of both lower and upper limbs and diffuse, hypo-or-areflexia of the deep tendon reflexes. The sensory symptoms were distributed in both hands and feet, pain, paresthesia, and numbness. Electrophysiology studies confirmed five patients have acute inflammatory demyelinating polyradiculoneuropathy, one patient has acute motor axonal neuropathy, and one has acute motor and sensory axonal neuropathy subtypes. Conclusion Clinical manifestations of Guillain-Barré syndrome confirmed by electrophysiological studies are associated with COVID-19, which show similarity with GBS due to the post-viral infections with an autoimmune background. Therefore coronavirus infection is an etiological factor of Guillain-Barré syndrome. Copyright © 2021, the Authors ;Publishing Rights, ASPI

Changes in Influenza Activity and Circulating Subtypes During the COVID-19 Outbreak in China.

Background: Non-pharmaceutical interventions (NPIs) to mitigate COVID-19 can impact the circulation of influenza viruses. There is a need to describe the activity of influenza and its subtypes during the COVID-19 pandemic to aid in the development of influenza prevention and control measures in the next influenza season. Method: Data from pathogenic surveillance performed by the Chinese National Influenza Center from January 2016 to August 2021 were extracted and stratified by type and subtype for northern China and southern China. The distribution of influenza activity and circulating subtypes were described during the COVID-19 pandemic, and data from 2016 to 2019 were used for comparisons. Results: Influenza activity declined rapidly and then rose slowly during the COVID-19 pandemic in China. The distribution of influenza subtypes changed from A-dominant to B/Victoria-dominant after the COVID-19 outbreak. Discussion: Whether the B/Yamagata lineage has disappeared from China deserves more attention in future virologic monitoring programs. The influenza vaccination campaign in the 2021-2022 season is an important means by which to reduce the proportion of susceptible people and limit the damage that potentially greater and earlier circulation of the virus could cause.

Establishment and evaluation of a quadruple quantitative real-time PCR assay for simultaneous detection of human coronavirus subtypes.

BACKGROUND: The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and four seasonal human coronaviruses (HCoVs) (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) still circulate worldwide. The early clinical symptoms of SARS-CoV-2 and seasonal HCoV infections are similar, so rapid and accurate identification of the subtypes of HCoVs is crucial for early diagnosis, early treatment, prevention and control of these infections. However, current multiplex molecular diagnostic techniques for HCoV subtypes including SARS-CoV-2 are limited. METHODS: We designed primers and probes specific for the S and N genes of SARS-CoV-2, the N gene of severe acute respiratory syndrome coronavirus (SARS-CoV), and the ORF1ab gene of four seasonal HCoVs, as well as the human B2M gene product. We developed and optimized a quadruple quantitative real-time PCR assay (qq-PCR) for simultaneous detection of SARS-CoV-2, SARS-CoV and four seasonal HCoVs. This assay was further tested for specificity and sensitivity, and validated using 184 clinical samples. RESULTS: The limit of detection of the qq-PCR assay was in the range 2.5 × 101 to 6.5 × 101 copies/µL for each gene and no cross-reactivity with other common respiratory viruses was observed. The intra-assay and inter-assay coefficients of variation were 0.5-2%. The qq-PCR assay had a 91.9% sensitivity and 100.0% specificity for SARS-CoV-2 and a 95.7% sensitivity and 100% specificity for seasonal HCoVs, using the approved commercial kits as the reference. Compared to the commercial kits, total detection consistency was 98.4% (181/184) for SARS-CoV-2 and 98.6% (142/144) for seasonal HCoVs. CONCLUSION: With the advantages of sensitivity, specificity, rapid detection, cost-effectiveness, and convenience, this qq-PCR assay has potential for clinical use for rapid discrimination between SARS-CoV-2, SARS-CoV and seasonal HCoVs.

Interplay of Influenza A/B Subtypes and COVID-19

Influenza, or most commonly termed the flu, is a common respiratory illness caused by viral infection. The circulation of this virus is found year-round but is more common during the flu season: fall and winter. In the United States, the number of reported cases begins to rise in October, reaches a peak in December, and returns to normal in April. Even though there are four subtypes of the Influenza virus, the seasonal flu outbreaks in humans are caused by type A and B viruses. eVision utilizes influenza data provided by the United States Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO) to analyze influenza A and B cases throughout the flu season. During the 2019-20 flu season, the positive influenza cases reported in the US were between 36 and 56 million, which is the highest over the past six years. However, during the 2020-21 flu season which is the first complete flu season within the COVID-19 pandemic, the reported flu cases reduced drastically to 1,899;of which 713 were caused by influenza A viruses, and 1,186 by influenza B viruses. This indicates that the number of flu B cases was higher than that of flu A which was not normally the case prior to the COVID-19 pandemic. It was further observed that flu B reached its peak either at the same time or earlier than flu A which is also unusual compared to the flu trends prior to the onset of the COVID-19 pandemic. This peculiar trend is also noted during the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. This paper reports the findings on deviation in the Influenza type A and type B trends during the circulation of Coronavirus in the US and Canada and provides possible reasons for these changes. © 2021 IEEE.

Analyses of Long-Term Epidemic Trends and Evolution Characteristics of Haplotype Subtypes Reveal the Dynamic Selection on SARS-CoV-2.

The scale of SARS-CoV-2 infection and death is so enormous that further study of the molecular and evolutionary characteristics of SARS-CoV-2 will help us better understand and respond to SARS-CoV-2 outbreaks. The present study analyzed the epidemic and evolutionary characteristics of haplotype subtypes or regions based on 1.8 million high-quality SARS-CoV-2 genomic data. The estimated ratio of the rates of non-synonymous to synonymous changes (Ka/Ks) in North America and the United States were always more than 1.0, while the Ka/Ks in other continents and countries showed a sharp decline, then a slow increase to 1.0, and a dramatic increase over time. H1 (B.1) with the highest substitution rate has become the most dominant haplotype subtype since March 2020 and has evolved into multiple haplotype subtypes with smaller substitution rates. Many evolutionary characteristics of early SARS-CoV-2, such as H3 being the only early haplotype subtype that existed for the shortest time, the global prevalence of H1 and H1-5 (B.1.1) within a month after being detected, and many high divergent genome sequences early in February 2020, indicate the missing of early SARS-CoV-2 genomic data. SARS-CoV-2 experienced dynamic selection from December 2019 to August 2021 and has been under strong positive selection since May 2021. Its transmissibility and the ability of immune escape may be greatly enhanced over time. This will bring greater challenges to the control of the pandemic.

COVID-19: depression and eating consequences in the social distancing

The new coronavirus (Sars-Cov-2) imposed new challenges for the adoption and maintenance of a healthy diet that in the presence of mental disorders, such as depression, may play a deleterious role in the interaction between the needs imposed by the pandemic and the ability to adopt appropriate coping strategies, and the incorporation of protective measures, such as healthy lifestyle habits. The diagnosis of depression includes specific symptoms that can directly impact lifestyle habits, such as changes in weight, apetite and in the usual sleep pattern, besides that fatigue and decresead energy. Thus, this study aimed to present the relationship between depression and eating consequences. In the current context, the presence of depression impacts negatively the general health, the ability to self-care and the maintenance of healthy lifestyles, and can also amplify the difficulties of adapting to the demands imposed due to social distancing and the need to prevent spread and infection by Sars-Cov-2.

Identification of Tumor Antigens and Immune Subtypes for the Development of mRNA Vaccines and Individualized Immunotherapy in Soft Tissue Sarcoma.

Soft tissue sarcomas (STS) are a rare disease with high recurrence rates and poor prognosis. Missing therapy options together with the high heterogeneity of this tumor type gives impetus to the development of individualized treatment approaches. This study identifies potential tumor antigens for the development of mRNA tumor vaccines for STS and explores potential immune subtypes, stratifying patients for immunotherapy. RNA-sequencing data and clinical information were extracted from 189 STS samples from The Cancer Genome Atlas (TCGA) and microarray data were extracted from 103 STS samples from the Gene Expression Omnibus (GEO). Potential tumor antigens were identified using cBioportal, the Oncomine database, and prognostic analyses. Consensus clustering was used to define immune subtypes and immune gene modules, and graph learning-based dimensionality reduction analysis was used to depict the immune landscape. Finally, four potential tumor antigens were identified, each related to prognosis and antigen-presenting cell infiltration in STS: HLTF, ITGA10, PLCG1, and TTC3. Six immune subtypes and six gene modules were defined and validated in an independent cohort. The different immune subtypes have different molecular, cellular, and clinical characteristics. The immune landscape of STS reveals the immunity-related distribution of patients and intra-cluster heterogeneity of immune subtypes. This study provides a theoretical framework for STS mRNA vaccine development and the selection of patients for vaccination, and provides a reference for promoting individualized immunotherapy.

New Insights Into Pancreatic Cancer: Notes from a Virtual Meeting.

Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase in incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving the outcome of patients. On the 4th and 5th of February 2021, three German pancreatic cancer research centers, the Clinical Research Unit 5002 from Göttingen, the Collaborative Research Center 1321 from Munich, and Clinical Research Unit 325 from Marburg organized the 1st Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting in order to foster scientific exchange. This report summarizes current research and proceedings presented during that meeting.

Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients.

Background: The host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify. Methods: We performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses. Results: The immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%. Conclusions: The present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.