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Background/aims: Controlled DCD organ donation (cDCD) is a strategic target for the Italian transplantation network. Italian peculiarities in cDCD donation make published results questionable and raise concern over organ ischemic damage. Consequently, normothermic regional perfusion (NRP) has been strongly recommended in potential cDCD donors. In 2019 the randomized multicenter DONARE study was designed to describe ischemic-reperfusion and inflammatory biomarkers during NRP and to test the potential benefit of apheresis by an adsorbent filter (CytoSorb) included in the NRP circuit. The aim of this report is to describe the modulation of the clinical characteristics and of the NRP in the DONARE study enrolled cases. Method(s): The study protocol was defined by the DCD national working group and proposed to all the Italian DCD donation centers. The coordinating center (CNT) has monitored the evolving cDCD activity to preserve the study capacity of representing the Italian scenario. Samples have been blindly centralized to an independent laboratory for cytokines profiling. The outcomes of transplanted organs have been recorded in the national quality database. Result(s): From September 2020 to June 2022, 27 out of the 40 planned cases have been enrolled in six centers: 4 in 2020, 12 in 2021 and 11 within June 2022. Approval is still pending in other centers. Main causes of exclusion among potential cDCD donors were: age above 65 (in 2020), e-CPR prior- to-death, shortage in personnel and COVID-19 restrictions. The age limit for enrolment (<65yrs) was abolished by amendment due to the national trend: mean age of enrolled cases increased from 57+/-6 in 2020 to 67+/-6 years in 2022. Mean NRP duration decreased from 223,3+/-39,2 in 2020 to 168,9+/-42,6 minutes in 2022;serial samples (4/2 with/without Cytosorb, from T0 to T4) from different points of the NRP circuit have been completed throughout the procedure in all the cases. All the enrolled cases became utilized donors. No study-related adverse event has been reported. Conclusion(s): Coordination of multicenter studies in the rapidly evolving scenario of controlled DCD donation should take advantage of continuous monitoring of real-life procedures and auditing of adherence to operational recommendations. The interim evaluation confirms the feasibility and safety of the study.
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Introduction Patients with hematological malignancies, including multiple myeloma (MM), experience suboptimal responses to SARS-CoV-2 vaccination. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) are precursors to MM and exhibit altered immune cell composition and function. The SARS-CoV-2 pandemic and the subsequent population-wide vaccination represent an opportunity to study the real-life immune response to a common antigen. Here, we present updated results from the IMPACT study, a study we launched in November 2020 to characterize the effect of plasma cell premalignancy on response to SARS-CoV2 vaccination (vx). Methods We performed: (i) ELISA for SARS-CoV-2-specific antibodies on 1,887 peripheral blood (PB) samples (237 healthy donors (HD), and 550 MGUS, 947 SMM, and 153 MM patients) drawn preand post-vx;(ii) single-cell RNA, T cell receptor (TCR), and B cell receptor (BCR) sequencing (10x Genomics) on 224 PB samples (26 HD, and 20 MGUS, 48 SMM, and 24 MM patients) drawn preand post-vx;(iii) plasma cytokine profiling (Olink) on 106 PB samples (32 HD, and 38 MGUS and 36 SMM patients) drawn pre- and post-vx;and (iv) bulk TCR sequencing (Adaptive Biotechnologies) on 8 PB samples from 4 patients (2 MGUS, 2 SMM) drawn pre- and post-vx. Results Patients with MGUS and SMM achieved comparable antibody titers to HD two months post-vx. However, patient titers waned significantly faster, and 4 months post-vx we observed significantly lower titers in both MGUS (Wilcoxon rank-sum, p=0.030) and SMM (p=0.010). These results indicate impaired humoral immune response in patients with MGUS and SMM.At baseline, the TCR repertoire was significantly less diverse in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.039), while no significant difference was observed in the BCR repertoire (p=0.095). Interestingly, a significant increase in TCR repertoire diversity was observed post-vx in patients with SMM (paired t-test, p=0.014), indicating rare T cell clone recruitment in response to vaccination. In both HD and patients, recruited clones showed upregulation of genes associated with CD4+ naive and memory T cells, suggesting preservation of the T cell response in SMM, which was confirmed by bulk TCR-sequencing in 4 patients.Lastly, by cytokine profiling, we observed a defect in IL-1beta and IL-18 induction post-vx in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.047 and p=0.015, respectively), two key monocyte-derived mediators of acute inflammation, suggesting an altered innate immune response as well. Conclusion Taken together, our findings highlight that despite the absence of clinical manifestations, plasma cell premalignancy is associated with defects in both innate and adaptive immune responses. Therefore, patients with plasma cell premalignancy may require adjusted vaccination strategies for optimal immunization.
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Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.
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The COVID19 pandemic accelerated opportunities for innovation within the decentralization process of clinical trials with opportunities for implementation of patient-centric workflows for efficiency and cost-reduction. Decentralized sample collection, particularly whole blood using dried blood spots (DBS) provides the ideal mechanism for patient driven sample collection with ease of access to sample generation, drug level assessments and metabolomic prMegofiling, providing longitudinal real-time measure of drug specific pharmacodynamic readout for safety and efficacy. In this study, we report the development of a protocol for the capture and comprehensive profiling of metabolomics using dried blood spots from a cohort of 49 healthy volunteer donors. Using liquid chromatography combined with mass spectrometric (UPLC-MS/MS) methods an untargeted metabolomic approach resulted in the identification of >800 biochemicals of which a significant subset was found to be presented in corresponding matched plasma (from whole blood) samples. The biochemicals identified from the DBS samples included metabolites that were part of the lipid, amino acid, nucleotide, peptide, cofactors, carbohydrate and energy super pathways. A significant number of metabolites identified in the DBS samples were xenobiotics including those representing the biotransformation products of drugs. The overall metabolite profiles were analyzed for precision and accuracy of measure, variability in performance and dynamic range to establish benchmarks for evaluation. An additional cohort with a longitudinal sampling as part of the protocol provided the reproducibility of the analytic method for inter-day variability of metabolite performance over time. Although metabolomic profiles varied between individuals from a population perspective, there was minimal variation observed within individuals when samples were profiled longitudinally over several weeks. Thus, the protocols for DBS collection and the corresponding capture of a large set of metabolites with reproducible performance provides an opportunity for its implementation in oncological clinical trials as part of a de-centralized clinical trial solution.
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Aim: To determine the association between Covid-19 and diabetes mellitus. Study Design: Retrospective study. Place and Duration of Study: Department of Medicine & Respiratory Physiology, Independent Medical College Faisalabad from 1st July 2022 to 31st December 2022. Methodology: Fifty five patients received at outdoor patient department of Independent University Hospital with confirmed diagnosis for Covid-19 through naso-pharyngeal reverse transcription polymerase chain reaction (RT-PCR) and aged 13-65 years were included. The complete medical files of each confirmed Covid-19 case was completely studied in relevance to diabetes mellitus association and compared with normal matched controls that only visited the OPD against the suspicion of the disease and underwent complete biochemical profiling. The baseline levels of HbA1C and glucose monitoring in each patient and control was done and compared. Result(s): The mean age of the CoVid-19 cases was 39.5+/-5.3 years while of controls as 25.65+/-4.3 years. There was an obvious significant variance in the odds ratio of Covid-19 patients and those of controls in reference to diabetes mellitus. A significant increase was observed in Odds Ratio of Covid-19 cases within the age group of 51-65 years. The Elixhauser Comorbidity Index (ECI) categories also presented, ECI >5 to be higher in Covid-19 cases than controls. Conclusion(s): There is a higher risk of diabetes new onset in Covid-19 confirmed cases as compared to matched controls.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.
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Introduction: SARS-CoV-2 replicates primarily in the airways but generates a systemic immune response mediated by Type I interferons (IFN-I). Pernio is a rare skin manifestation of disorders characterized by excessive IFN-I signalling. Although pernio increased in incidence during the pandemic, the relationship to SARS-CoV-2 remains controversial. Because of the pivotal nature of interferons in COVID-19 outcomes, pernio offers a window to investigate the biology underlying host resiliency to SARS-CoV-2 infection. Method(s): To further assess COVID-associated pernio, we characterized clinical samples from affected patients across 4 waves of the pandemic and investigated mechanistic feasibility in a rodent model. Patients were followed longitudinally with banking of blood and tissue. Golden hamsters were mock-treated or intra-nasally infected with SARS-CoV-2 and harvested at 3-and 30-days post-infection. Result(s): In affected tissue, immunophenotyping utilizing multiplex immunohistochemistry profiled a robust IFN-1 signature characterized by plasmacytoid dendritic cell activation. Viral RNA was detectable in a subset of cases using in situ hybridization for the SARS-CoV-2 S gene transcript. Profiling of the systemic immune response did not reveal a durable type 1 interferon signature. Consistent with previous literature, antibody and T-cell specific responses to SARS-CoV-2 were not detected. Nasopharyngeal SARS-CoV-2 inoculation in hamsters resulted in rapid dissemination of viral RNA and the generation of an IFN-I response that were both detectable in the paws of infected animals. Conclusion(s): Our data support a durable local IFN signature, with direct evidence of viral SARS-CoV-2 RNA in acral skin and suggest that COVID-associated pernio results from an abortive, seronegative SARS-CoV-2 infection.
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The proceedings contain 92 papers. The topics discussed include: cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients;adult outcomes of childhood-onset idiopathic nephrotic syndrome: findings from a health insurance database;the genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies;translational profiling of developing podocytes during glomerulogenesis;MAGED2 is required under hypoxia for cAMP signaling by inhibiting MDM2-dependent endocytosis of G-Alpha-S;high throughput investigation of the metabolic flux of intact cortical kidney tubules;peritoneal membrane junction and solute transporter expression and function in health, CKD and PD;and Function and interaction of coronavirus ion channel proteins.
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Intro: With the relentless waves of coronavirus disease 2019(COVID-19), there is a need for widespread community adoption of infection prevention(IP) measures including hand hygiene, use of face masks, and staying at home when unwell. Understanding the profile of individuals who do not consistently practice IP can help target public health education. Method(s): We conducted a nationally-representative population survey from November 2020 to January 2021. Households were randomly selected from a proportionately stratified national census. The household member with the most recent birthday was invited to complete the survey. Three questions on a 5-point Likert-scale(never-rarely-occasionally-often-always) assessed IP behaviours(hand hygiene, face mask use when having a cough/cold, staying at home when having a cold/flu) before and during the pandemic. A multivariable logistic regression model was constructed to assess factors associated with the non- or inconsistent("never-rarely-occasionally") adoption of any of the three IP behaviours during the pandemic. Finding(s): Mean age of 2004 respondents was 44.5(SD 15.0) years, with 52% females and 65% being highly educated (diploma/degree holders). Although 12% reported consistently("often-always") adopting all 3 IP behaviours pre-pandemic, the majority(n=1752, 87%) reported doing so during the pandemic. After adjusting for age, educational level, and presence of chronic illness, males(AOR 1.71 [95%CI 1.30, 2.25], Chinese(AOR 1.48 [1.07, 2.05]), low-adopters of healthy lifestyle(AOR 1.59 [1.03, 2.45]) and those who did not or inconsistently adopted IP behaviours pre-pandemic(AOR 8.92 [3.28, 24.27]) were more likely not to or inconsistently adopt the 3 IP behaviours during the pandemic. Discussion(s): During the ongoing pandemic, educational messages and information channels on IP measures could be more targeted at males and Chinese. Additionally, the promotion of healthy lifestyle and consistent adoption of IP behaviours during non-pandemic times is critical for consistent adoption of IP behaviours during pandemics. Conclusion(s): Males, Chinese, and low-adopters of healthy lifestyle and IP behaviours pre-pandemic do not consistently practice IP during the pandemic.Copyright © 2023
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Background: The continued emergence of severe acute respiratory syndrome coronaviruses (SARS-CoVs) and recent explosion of the SARS-CoV-2 pandemic highlights the need for broad and potent antibody recognition and understanding the contexts in which they may develop. Antibodies with cross reactivity across SARS lineages may be of particular value in preparing for future outbreaks of new sarbecoviruses. Method(s): We isolated monoclonal antibodies (mAbs) from an individual 60-days post-vaccination, 30-days post Delta-infection. Reconstructed antibodies were screened for binding to a panel of prefusion-stabilized Spike trimers from SARS-CoV-2 and other beta-coronaviruses using enzyme-linked immunosorbent assay (ELISA). Neutralization potency and breadth was assessed using a spike-pseudotyped lentivirus neutralization assay. Additionally, epitope and escape mutant profiling was conducted by deep mutational scanning (DMS) to identify mutations that affect antibody binding. Lastly, binding breadth was further evaluated using a yeast display library of RBDs from SARS-CoV-2 variants and related sarbecoviruses. Result(s): We identified several SARS-CoV-2-specific mAbs that neutralized SARS-CoV-2 variants of concern (VOCs) and SARS-CoV-1. Notably, two of these mAbs (C68.61 and C68.185) neutralized SARS-CoV-1 with an IC50 = 307 and 139 ng/mL (respectively) that is similar to or better than the potency of S309 (IC50 = 206 ng/mL) and CR3022 (IC50 = 981 ng/mL), which are mAbs isolated from individuals with SARS-CoV-1 infections. C68.61 also neutralized all Omicron VOCs tested and retained neutralization activity against currently circulating variants BQ1.1 (IC50=790 ng/ml) and XBB (IC50=590 ng/ml). Key C68.61 mAbescape mutations identified by DMS in the Omicron BA.2 background yeast display library included sites K462, E465, R466, and I468, which are conserved sites across all VOCs and SARS-CoV-1. The isolated mAbs displayed crossreactive binding to RBDs from diverse SARS-CoV-1-related CoVs and African and European sarbecovirus isolates as well as SARS-CoV-2 VOCs. Conclusion(s): Here we describe mAbs from a SARS-CoV-2-infected individual that bound and neutralized both SARS-CoV-2 and SARS-CoV-1, including one that showed breadth across recent VOCs. Given their breadth, these SARS-CoV-2 cross-reactive mAbs may be robust to viral escape and thus could contribute to therapeutic efforts. In addition, these mAbs displayed broad cross-reactive activity across sarbecoviruses and may be beneficial against future spillover events.
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Background: At least 10% of SARS-CoV-2 infected patients suffer from persistent symptoms for >12 weeks, known as post-COVID-19 condition (PCC) or Long Covid. Reported symptomatology is diverse with >200 physical and neurological debilitating symptoms. Here, we analyzed pro-inflammatory cytokine levels as a potential mechanism underlying persistent symptomatology. Method(s): Clinical data and samples used belong to the KING cohort extension, which includes clinically well characterized PCC (N=358, 59 persistent symptoms evaluated), COVID-19 recovered and uninfected subjects. We used Gower distances to calculate symptom's similarity between PCC and Ward's hierarchical clustering method to identify different symptom patterns among PCC patients. Cytokine levels of randomly selected PCC, recovered and uninfected subjects (N=193) were measured on plasma samples collected >6 months after acute infection using the 30-Plex Panel for Luminex. Mann- Whitney t-test was used to compare PCC vs recovered groups and Kruskal-Wallis t-test for >2 groups comparisons (PCC vs recovered vs Uninfected and within PCC clusters). FDR correction was applied for statistical significance (p-adj). Result(s): Hierarchical clustering identified 5 different PCC clusters according to their symptomatology, where PCC3 and PCC5 clusters showed higher prevalence of women ( >80%) and more persistent symptoms, while acute COVID-19 was mild in >80% of the patients. We selected 91 PCC (belonging to each cluster), 57 recovered and 45 uninfected subjects for cytokine profiling (Table 1). 13 soluble markers were significantly elevated (IL-1beta, Eotaxin, MIP-1beta, MCP-1, IL-15, IL-5, HGF, IFN-alpha, IL-1RA, IL-7, MIG, IL-4 and IL-8) in PCC and recovered groups compared to uninfected subjects (all p-adj< 0.04). In addition, PCC subjects tended towards higher levels of IL-1RA compared to recovered group (padj= 0.071). Within PCC clusters, FGF-basic and RANTES were elevated while IL-2 and MIG were decreased in PCC3 and PCC5 compared to the other PCC clusters (all p-adj< 0.04). TNF-alpha, IP-10, G-CSF and MIP-1alpha were decreased in PCC3 and PCC5 not reaching statistical significance (all p-adj=0.07). Conclusion(s): Some cytokines remained altered in all SARS-CoV-2 infected subjects independently of persistent symptoms after 6 months from acute infection. Differences between PCC and recovered individuals are limited after correction. Importantly, PCC cytokine profiles showed differences between clusters, which suggests different PCC subsyndromes with distinct etiology. Subjects Characteristics (Table Presented).
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Background: Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and -cross neutralization capacity of maternal/ cord antibody responses to COVID-19 vaccination during pregnancy can inform neonatal immunity. Method(s): Here we characterized binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants by enzyme-linked immunosorbent assay Results: Our results reveal that current vaccination induced significantly higher (p=0.003) RBD-specific binding IgG titers in cord blood compared to maternal blood for both Wuhan and Omicron BA1 strain. Interestingly, binding IgG antibody levels for the Omicron BA1 strain were significantly lower (P< 0.0001) when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, BA4/5 specific neutralizing antibody levels were significantly lower (P< 0.0001) compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not at all detected in both maternal and cord blood. Conclusion(s): Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for Wuhan and Delta variants but not for Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for boosters as new variants emerge.
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Outbreaks of chilblains, a hallmark sign of type I interferonopathies, have been reported during the COVID-19 pandemic. These cases occurred mostly in patients who were asymptomatic and showed negative results from PCR and serology tests for SARS-CoV-2. We hypothesized that chilblain patients are predisposed to mount a robust innate immunity against the virus, which clinically manifests as chilblains and promotes early viral clearance, thereby preventing pulmonary disease and precluding adaptive responses. By profiling skin lesions in the early stage following chilblain onset, we uncover a transient IRF7-dependent type I interferon (IFN) signature that is driven by the acral infiltration of systemically activated plasmacytoid dendritic cells (pDCs). Patients' peripheral blood mononuclear cells (PBMCs) demonstrate increased production of IFNalpha when exposed to SARS-CoV-2 and influenza A, but not herpes simplex virus 1 (HSV-1), indicating a heightened ability to detect RNA -but not DNA- viruses. Further investigations revealed enhanced responsiveness of pDCs in chilblain patients to the RNA sensor TLR7, but not the DNA sensor TLR9. Collectively, our study establishes a two-step model for the immunopathology of SARS-CoV-2-related chilblains: enhanced TLR7 immunity in pDCs, likely triggered by SARS-CoV-2 exposure at the mucosal site, leads to prompt viral clearance, which explains the lack of infection markers in most cases. Subsequently, systemic spread of activated pDCs and infiltration of the toes in response to mechanical stress or acral coldness, may result in IFN-mediated tissue damage with development of chilblains.Copyright © 2023
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Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 in-fection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Method(s): High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum tri-plex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and di-hydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Result(s): A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were-7.86,-10.29 and-7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion(s): Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.Copyright © 2021 Bentham Science Publishers.
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Introduction: Acute Kidney Injury is common among COVID-19 patients and is associated with adverse outcomes. This study aims to determine AKI's prevalence and short-term outcomes among admitted COVID-19 patients, as this is not well understood in East Africa. Method(s): We reviewed medical records of all laboratory confirmed COVID-19 patients hospitalized in a private facility in Nairobi between 1st January and 31st December 2021. Data on patient baseline characteristics, clinical course during admission and short-term outcomes were extracted. Patients with confirmed renal failure at admission, chronic dialysis before admission or patients with less than 2 serum creatinine levels measurements available were excluded. AKI was defined according to the KDIGO criteria using serum creatinine levels. Descriptive statistics of means, medians, inter-quartile range and standard deviation as well as the use of frequency/proportion/percentages for categorical variables were used for profiling participants' socio-demographics and clinical parameters. Means for patients with AKI and those without AKI were compared using the Mann-Whitney U test and the Kruskal-Wallis test for continuous variables, Chi-square test was used for categorical variables. Univariate and logistical regression analysis was used to determine the association between AKI severity and various risk factors. Result(s): The majority of the 365 included patients were male (61.4%) aged >= 50 years. AKI developed in 74 (20.3%) patients with 52.7%, 18.9% and 28.4% in stages 1, 2 and 3 respectively. Of these 13.5% needed renal replacement therapy. AKI was common in critically ill patients (43.2%) with the majority being in stages 2 and 3. It was further associated with respiratory failure as 36.0% of mechanically ventilated patients developed AKI compared to 17.8% of non-ventilated patients. Among the AKI patients, 24.3% died and 75.7% were discharged. Of the survivors, the majority (56.8%) achieved full renal recovery at discharge. The AKI risk factors were older age (OR 1.046 p<0.001), male sex (OR 2.490 p 0.002), multiple comorbidities (OR 3.694 p 0.001), hypertension (OR 2.598 p 0.001), diabetes mellitus (OR 2.586 p<0.001) and pre-existing CKD (OR 10.550 p<0.001). Conclusion(s): AKI in COVID-19 is common and results in full renal recovery in most patients. Its severity increases in critically ill patients and is significantly associated with respiratory failure and mortality. No conflict of interestCopyright © 2023
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Introduction: The molecular mechanisms linked to the pathology of severe COVID-19 and its outcomes are poorly described. Aim(s): To analyze the proteomic profile of bronchial aspirates (BAS) samples from critically ill COVID-19 patients in order to identify factors associated with the disease and its prognosis. Method(s): Multicenter study including 74 critically ill non-COVID-19 and COVID-19 patients. BAS was obtained by bronchoaspiration after invasive mechanical ventilation (IMV) initiation. Proximity extension assay (PEA) technology was used for proteomic profiling. Random forest (RF) statistical models were used to predict the variable importance. Result(s): After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-alpha showed differences between COVID-19 and non-COVID-19 patients. Reduced levels of ENTPD2 and PTN were observed in non-survivors, even after adjustment. AGR2, NQO2, IL-1alpha, OSM and TRAIL, were the top five strongest predictors for ICU mortality and were used to build a prediction model. PTN (HR=4.00) ENTPD2 (HR=2.14) and the prediction model (HR=6.25) were associated with higher risk of death. In survivors, FCRL1, NTF4 and THOP1 correlated with lung function (DLCO levels) 3-months after hospital discharge. Similar findings were observed for Flt3L and THOP1 and radiological features (TSS). The proteins identified are expressed in immune and non-immune lung cells. A poor control of viral infectivity and an inappropriate reparative response seems to be linked to the disease and fatal outcomes, respectively. Conclusion(s): In critically ill COVID-19 patients, specific proteomic profiles are associated with the pathology, mortality and lung sequelae.
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Background: Around 80% of patients who developed COVID-19-driven ARDS present lung ailment. There is a lack of knowledge of the mechanisms that mediate the pulmonary outcomes. Aim(s): To characterize the factors linked to diffusion impairment in survivors of severe COVID-19. Method(s): Prospective cohort study including 87 COVID-19-induced ARDS survivors. A complete pulmonary evaluation was performed 3 months after hospital discharge. 364 proteins were quantified using the proximity extension assay (PEA). Partial least square-discriminant analysis (PLS-DA) and random forest (RF) were used for multivariable analyses. Result(s): Moderate to severe diffusion impairment (DLCO<60% predicted) was observed in the 30% of the cohort. 15 proteins were differentially detected [false discovery rate (FDR)<0.05] in the univariate analysis. Pleiotrophin showed the highest differences (fold change=2.22 and FDR=0.001). In continuous analysis, proteins were inversely and independently associated with DLCO, and in some cases showed a robust dose-response relationship. PLS-DA and RF identified proteomic profiles related to the severity of diffusion capacity. Clusters identified were enriched in mediators of cell proliferation and differentiation, tissue remodeling, angiogenesis, coagulation, inflammation, immune response and fibrosis. Proteins are expressed in immune and non-immune lung cells. Conclusion(s): In survivors of COVID-19-driven ARDS, lung dysfunction is linked to plasma factors involved in injury and repair mechanisms. The host proteomic profile provides a novel understanding of post-acute sequelae and may be source of therapeutic strategies and biomarkers.
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Background: The key impact of SARS-CoV-2 is its ability to cause a life-threatening infection in the lung. Aim(s): Using spatially resolved multiplex imaging the present study decodes the immunopathological complexity of severe COVID-19. Method(s): Autopsy lung tissue from 18 COVID-19 patients was used to map immune and structural cells in acute/exudative, intermediate and advanced diffuse alveolar damage (DAD) through multiplex immunohistochemistry and spatial statistical analyses. Cytokine profiling, viral, bacteria and fungi detection and transcriptome analyses were also performed. Result(s): All cases displayed concomitant patterns of DAD. The spatially resolved multiplex data revealed intricate patchworks of mm -size microenvironments representing distinct immunological niches. In-depth analysis of DAD areas revealed that the temporal/spatial DAD progression is associated with expansion of adaptive immune cells, macrophages, CD8 T cells, fibroblasts, angiogenesis and lymphangiogenesis. Viral load correlated positively with acute DAD and negatively with disease/hospital length. Cytokines correlated mainly with macrophages and CD8 T cells. Pro-coagulation and acute repair markers were enriched in acute DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Conclusion(s): Our unraveling of the spatio-temporal immunopathology in COVID-19 cases exposes the heterogeneous dynamics of acute viral infection and subsequent responses that occur side-by-side in the lungs. This complex disease feature has important implications for disease management and development of novel immunemodulatory treatments.
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Background Understanding the underlying mechanisms of post-COVID sequelae (Long COVID) is urgently needed to guide interventions. Aim To compare the inflammation profiles of four recovery clusters post-hospitalisation. Methods Post-Hospitalisation COVID-19 (PHOSP-COVID) is a prospective, multi-centre study across UK. Four recovery clusters previously identified using clinical data (symptoms, mental health, cognitive impairment, and physical function) at 5 months post-discharge were used based on severity of on-going health impairments: very severe, severe, moderate (cognitive), and mild. Inflammatory profiling performed from plasma samples using the Olink Explore 384 inflammation panel. Multinomial logistic regression for each protein was undertaken comparing the mild cluster with each of the remaining clusters with FDR of 0.1 to adjust p values. Results 626 participants (clusters: very severe n=111, severe n=173, moderate/cognitive n=73 and mild n=269). Proteomic results from 296 proteins were included. After adjustment for age, BMI, and comorbidity count, 13 proteins were significantly elevated in the very severe cluster, and 2 proteins in the moderate/cognitive cluster, compared to the mild cluster (Figure 1). Conclusion Inflammatory mediators consistent with persistent lung and systemic inflammation were associated with the severity of ongoing health impairments highlighting potential therapeutic pathways to be tested.
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The proceedings contain 40 papers. The topics discussed include: respiratory hypersensitivity profiling among farmers with pesticide exposure: field- based, cross-sectional study;requirements of prescription safety eye wear;Covid-19 and comorbidities: deleterious impact on infected patients;knowledge regarding heat stress and practice of personal protective equipment use among healthcare workers during the Covid 19 pandemic;arrhythmia burden in Covid-19 patients from industrial workforce evaluated by remote patient monitoring technology;a qualitative perspective of construction site migrant workers' plight during covid-19 lockdown in Bhavnagar (Western India);elimination of volatile organic compound VOCs exposure at chemical testing laboratory: through effective OHIH assessment;and perceived morbidity, its risks and catastrophic health expenditure among construction workers: a cross sectional observation from Ahmedabad.
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The proceedings contain 25 papers. The topics discussed include: altitude effect on melanoma epidemiology in the Veneto region: a pilot study;novel predisposition genes double a decreasing CDKN2A mutation rate: five years of (tele)- counselling and gene panel testing for hereditary melanoma within the Italian melanoma intergroup;genetic profiling of atypical deep penetrating NEVI (DPN);ultra-high frequency ultrasound monitoring of melanomas arising in congenital melanocytic nevi: a case series;a segmentation algorithm for skin melanoma regression;impact of the COVID-19 pandemic on primitive melanoma diagnoses at the IDI-IRCCS of Rome;a novel-algorithm combining static and dynamic features to identify melanoma in digital dermoscopy monitoring;and non-sentinel lymph node detection meanwhile sentinel lymph node biopsy in not-complete lymph node dissection era: a new technique for better staging and treating melanoma patients.