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Introduction/Aim: Rates of hospitalisation and death from COVID-19 in lung transplant (LTx) recipients vary internationally. We aimed to assess risk factors for this in an Australian cohort. Method(s): We performed a retrospective cohort study of all LTx recipients between January 2020 and September 2022. LTx recipients with COVID-19 were included. Baseline characteristics and treatments were recorded. Multivariate logistic regression was performed to identify risk factors associated with hospitalisation and death. Result(s): 128/387 (33%) recipients tested positive to SARS-CoV-2 during the study period, 97.6% during the Omicron waves with 40(31.3%) requiring hospitalisation and 10 (7.8%) died. The median (IQR) recipient age was 50.6 (22-77). The cohort was of Caucasian ethnicity 105 (82%), 48% were female with high vaccination rates (98.4%). Chronic lung allograft dysfunction (CLAD) was present in 48 (37.5%). 103 (80.5%) of patients received early SARS-CoV-2 treatment with either Sotrovimab 84(65%), Molnupirivir 50(39%) or combination 31(24%). 25 patients (19.5%) received no early treatment. All hospitalised patients received Remdesivir and Dexamethasone as per local treatment protocols. Regarding risk of hospitalisation, multivariate analysis showed that recipient age (1-unit change OR 1.04 95% CI 1.01-1.07 p = 0.019) was associated with an increased risk, whereas Molnupiravir was protective (OR 0.32 95% CI 0.13-0.80 p = 0.02). In univariable analysis, increasing age (1-unit change, OR 1.07 95% CI 1.02-1.129 p = 0.01) and severe disease (OR 9.95 95% CI 2.58-38.32 p =< 0.001) were associated with an increased risk of death. Male gender, non-Caucasian ethnicity, CLAD, CKD stage 3-5 were correlated with death with weak association. Conclusion(s): Recipient age is a significant risk factor for both hospitalisation and death, and older patients with COVID-19 should be monitored closely during COVID-19 illness. Molnupirivir is protective against hospitalisation, with Sotrovimab having a weak association. Further analysis of the protective effect of pre-exposure prophylaxis with emerging therapies such as Evusheld would be helpful to fully evaluate the currently available early disease therapies in Australia.
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Background: Reliable biomarkers of COVID-19 severity and outcomes are critically needed for clinical and research applications. We evaluated associations between anti-Spike IgG and SARS-COV-2 nucleocapsid antigen (N Ag) in plasma with clinical outcomes in outpatients with COVID-19. Method(s): We used data from 229 non-hospitalized, US-based adults with COVID-19 who enrolled between January and July 2021 into the placebo arm of the ACTIV-2/A5401 platform trial within 10 days of symptom onset. Pretreatment (day 0) plasma was analyzed by the quantitative Simoa SARS-CoV-2 IgG antibody (anti-Spike) assay (lower limit of quantification [LLoQ] 0.77ug/ mL), and the quantitative Simoa SARS-CoV-2 N Protein Advantage (Quanterix) measuring N Ag (LLoQ 3pg/mL). In addition to analyses for < LLoQ vs >=LLoQ anti-Spike and N Ag, we categorized participants into five N Ag groups (< 3 pg/ml;3-< 100 pg/ml;100-< 1,000 pg/ml;1,000-< 2,500 pg/ml;>=2,500 pg/ ml). Associations between SARS-CoV-2 anti-Spike and N Ag levels and clinical outcomes (all-cause hospitalization/death through day 28 and time to symptom improvement or resolution for two consecutive days from day 0 status) were estimated using log-binomial and Cox regression models, respectively. Result(s): At day 0, 40% had anti-Spike levels >=LLoQ and 64% of participants had plasma N Ag levels >=LLoQ. Participants with anti-Spike levels < LLoQ compared to those who had quantifiable anti-Spike at day 0, had an increased risk of hospitalization/death (16% vs 2%, RR [95% confidence interval (CI)]: 7.3 [1.8, 30.1]), and a significantly longer time to symptom improvement (median [Q1, Q3] 14 days [8, >27] vs 9 days [4, 16], hazard ratio [HR]: 0.6 [95%: CI: 0.4, 0.8], p< 0.001). Participants with higher N Ag levels at day 0 had an increased risk of hospitalization or death, ranging from 1% for < 3 pg/ml to 70% for >=2500 pg/ml (Figure). Compared to individuals who had N Ag levels < LLoQ at day 0, those in the highest category of N Ag levels (>=2500 pg/mL) experienced a significantly longer time to symptom improvement (median [Q1, Q3]: 25 days [13, >27] vs 10 days [5, 20];HR: 0.4 [95% CI: 0.2, 0.7];p=0.04). Conclusion(s): At study entry, the absence of Spike antibodies and higher levels of plasma SARS-CoV-2 N Ag predicted hospitalizations and death in untreated outpatients with COVID-19. These parameters may serve as informative biomarkers for risk stratification in the evaluation of outpatients with COVID-19. (Figure Presented).
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Background: The pathophysiology of viral-infections is highly complex and involves host immunocompetence, host genetics, and gene-environment interactions. We hypothesized that polymorphic variants in host genes, blood group and previous vaccination status against H1N1 may affect the clinical course of covid-19 infection. Method(s): A total of 202 subjects who were RT-PCR negative after Covid-19 infection were recruited. We investigated association between Covid-19 infection (Severity and recovery period) and multiple factors including ABO and Rh blood groups, H1N1 vaccination, polymorphism in Viral susceptibility genes (ACE2 G8790A), and polymorphism in host response genes (ACE I/D rs4646994, IL6- 174G/C, GSTT1/GSTM1 I/D and GSTP1 Ile 105 Val). Result(s): B-ve and O-ve ABO and Rh blood groups had significantly higher Covid-19 recovery period applied on one-vs.-all in a nonparametric t-test (p<0.05). Subjects who had vaccinated themselves against H1N1 presented with a lower recovery-period (p<0.05). Both variables (blood group and H1N1 vaccination) were not however associated with Covid-19 severity. Out of the studied polymorphisms, ACE2 G8790A and GSTT1/GSTM1 were significantly associated with covid-19 infection. Our results indicated that G/G genotype of ACE2 G8790A (OR 3.52, P 0.007) and GSTT1/ GSTM1 null (M1 - / - OR = 3.98, P = 0.0004;T1 - / - OR 3.84, P = 0.004) and double null (M1 - / - /T1 - / - OR = 9.66, P = 0.001) are likely to be associated with an increased risk for severe-critical outcomes in individuals with COVID-19. Other polymorphisms analyzed in this study were found to have no significant association with Covid-19 outcome. Conclusion(s): This study suggests that outcome of Covid-19 infection is affected by both clinical and genetic factors. Thus it seems plausible to utilize these factors as prediction and susceptibility markers in the prognosis of COVID-19, which may help to personalize the treatment.
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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current global pandemic of the COVID-19, which has persisted partly through the emergence of new variants. A non-infectious, convenient, and reproducible in vitro system is needed to assess drug susceptibility of new variants of concern and potential drug resistance mutations. Method(s): The SARS-CoV-2 replicon protocol was adapted and optimized based on {Zhang 2021}. The replicon RNA was produced by in vitro transcription of full-length replicon DNA assembled by ligation of plasmid fragments encoding for the SARS-CoV-2 non-structural proteins (Nsps), nucleoprotein and gaussia luciferase reporter protein. Wild-type and mutant replicon RNAs were transfected into Huh7-1CN cells by electroporation and treated with remdesivir (RDV). To determine EC50 values, luciferase activity was determined at 48 hours post transfection. A recombinant SARS-CoV-2 virus rescue system {Xie 2020} was used to generate matching Nsp mutants for comparison with the replicon system. Result(s): The selected substitutions reflective of Omicron BA.5 sub-lineage BF.7 variant: the triple mutants (Nsp12 (P323L) +Nsp13 (R392C) + Nsp14 (I42V), and a single Nsp12 L247F mutant as well as several specific Nsp12 mutations identified by in vitro resistance selection with RDV or RDV parent nucleoside analog GS-441524 were cloned into the replicon and tested for susceptibility to RDV. RDV inhibited the SARS-CoV-2 wild-type replicon with a mean EC50 value of 14.7 +/- 3.5 nM (N=9). The Nsp12 P323L substitution, a common polymorphism in all major variants of concern including Omicron, was fully susceptible to RDV with a 0.6-fold change in EC50 from the wild-type. The Omicron BF.7 triple mutants and L247F were also fully susceptible to RDV with 0.5- and 0.4-fold changes, respectively. Nsp12 substitutions F480L, V557L, V792I, S759A+V792I, and C799F resulting from in vitro resistance selections with RDV showed minimal to moderate levels of reduced susceptibility to RDV (1.8 to 18.3-fold change) (Table 1). The RDV EC50 fold changes correlated between the noninfectious replicon and recombinant infection virus system (Table 1). Conclusion(s): The replicon system is a convenient and reproducible model to test the susceptibility of SARS-CoV-2 mutant variants to RDV and potentially other antivirals. The common Nsp12 polymorphisms in all variants including the highly transmissible Omicron variant were fully susceptible to RDV.
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Introduction/Aim: As the causative agent of COVID-19, SARS-CoV-2 remains a global cause for concern. Compared to other highly pathogenic coronaviruses (SARS-CoV and MERS-CoV), SARS-CoV-2 exhibits stronger transmissibility but less lethality, indicating that SARS-CoV-2 displays unique characteristics, despite the partial genomic proximity. Thus, we aim to employ RNA sequencing to define transcriptional differences in epithelial responses following infection with SARS-CoV-2 compared to pathogenic SARS-CoV and MERS-CoV, and low pathogenic HCoV-229E. Method(s): Primary human bronchial epithelial cells (PBEC) were differentiated for 6 weeks at the air-liquid interface (ALI) before parallel infection by the 4 different coronaviruses (n = 4). After infection following apical application of coronaviruses at low dose (MOI 0.1), cells were harvested for bulk RNA sequencing. Gene were considered significant with a fold change (FC) > 2 and false discovery rate of FDR < 0.05. Inhibitor experiments were conducted on CALU-3 cells using DIM-C-pPhOH 10 muM (NR4A1 antagonist), Sp600125 10 muM (JNK inhibitor), T-5224 10 muM (AP-1 transcription factor inhibitor) and Cytosporone B (CsB 5 muM;NR4A1 agonist) preincubated for 1 h with these compounds and subsequently infected with SARS-CoV-2 or MERS-CoV (MOI of 1). Samples were collect 24 h later for PCR. Result(s): PCR and RNA-Seq demonstrated that all tested coronaviruses efficiently infected ALI-PBEC and replicated over 72 h (p < 0.05). RNA sequencing analysis revealed that infection with SARS-CoV, MERS-CoV and HCoV-229E resulted in largely similar transcriptional responses by the epithelial cells. However, whereas infection with these viruses was accompanied by an increased expression of genes associated with JNK/AP-1 signalling, including FOS, FOSB and NR4A1 (FC > 1, FDR < 0.05), no such increase was observed following SARS-CoV-2 infection. Further, we found that an NR4A1 antagonist reduced viral replication of MERS and SARs-CoV-2 100-fold in Calu-3 cells. Conclusion(s): In conclusion, these data suggest that SARS-CoV-2-infected ALI-PBEC exhibit a unique transcriptional response compared to other coronaviruses, which might relate to the pathogenicity of the virus.
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The Hermanos Ameijeiras Hospital (HAH) in Havana is the only center performing allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients in Cuba. Because transplants from unrelated donors are not possible due to political restrictions and economic embargo, in 2016 HAH and University of Illinois at Chicago (UIC) started a collaboration to support the training of a physician, annual educational programs and exchange of guidelines and protocols to perform haploidentical transplants. The first haploidentical transplant was performed at HAH in 2016. Because of limited resources, disease risk stratification is based on morphologic assessment, as cytogenetic is tested on an irregular basis. Peripheral blood stem cells (PBSC) were infused based on total nucleated cell count (TNC) due to lack of reagents for flow cytometry. Posttransplant chimerism and CMV monitoring cannot be performed. Transplant activity was stopped in 2020 due to high expenses allocated for COVID19 pandemic in Cuba. From 2016 to 2020, 16 haploidentical HSCT in 15 patients (9 males/ 6 females) were completed at HAH. The median age of patients was 34 years (range:21-54). Diagnoses included: acute leukemia, n=12, myelodysplastic syndrome, n=1, Hodgkin disease, n=1, and severe aplastic anemia, n=1. At the time of transplant, 11 patients were in morphologic remission and 5 had active disease. Conditioning regimens utilized were myeloablative (Flu/Bu) in 10 cases and at reduced intensity (Flu/Cy/ TBI200 +/- ATG) in 6 cases, and GVHD prophylaxis was standard PTCy on D3 and 4, CsA and mycophenolate. The donors were mother (n=10), father (n=1), child (1), or sibling (n=3) and the median age was 48 years (range: 26-68). All patients received fresh stem cells from PBSC(n=13) or bone marrow (n=3). Median cell dose infused was 5.5x108 TNC/kg (range: 2.2-8). All patients but 1 engrafted and median time to neutrophil and platelet engraftment was 17 days (range:12-28) and 16 days (range:11-30), respectively. Acute graft-versus-host disease (GVHD) grade 2-3 occurred in 50% of patients and chronic GVHD in 2 out of 8 that were evaluable. Day 100 and 2-year overall survival rates were 73% and 40%, respectively. With a medium follow-up of 18.8 months (range: 0.3-64), 5 of 15 patients (30%) are alive and complete remission. Causes of death in the remaining 10 patients included relapse of original disease, n= 4;bacterial infection, n=2;brain hemorrhage, n=1;VOD, n=1;graft failure, n=1;and multi-organ failure, n=1. Despite significant difficulties, HAH implemented a haploidentical transplant program for adult patients in Cuba. Among future steps, improving access to molecular testing and using younger donors will be pursued to improve on the results. The partnership between HAH and UIC has been instrumental in building clinical and research capacity and continues to support HAH in its mission to provide care to patients in Cuba.(Figure Presented)Copyright © 2023 American Society for Transplantation and Cellular Therapy
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Background: Immunocompromised hosts with prolonged SARS-CoV-2 infections have been associated with the emergence of novel mutations, especially in the Spike protein, a key target for vaccines and therapeutics. Here, we conducted a case-control study to measure the genetic diversity of SARSCoV- 2 and to search for immunocompromised-specific minority variants. Method(s): SARS-CoV-2-positive patients with lung/cardiac/kidney transplant, HIV-positive, or treated with high doses of corticosteroids for auto-immune diseases were considered as immunocompromised hosts. SARS-CoV-2-positive healthcare workers with no auto-immune disease were used as controls. Samples were analyzed by RT-qPCR at Pitie-Salpetriere and Bichat Claude-Bernard university hospitals (Paris, France). Samples with Cycle threshold < 30 were selected for SARSCoV- 2 whole-genome sequencing using Oxford Nanopore protocol. Raw sequence data were mapped onto the Wuhan-Hu-1 reference genome, and consensus sequences were produced to determine the lineage. Only sequences covering at least 95% at >=50X depth of the Spike gene were investigated. In-house algorithms were developed to identify all majority and minority mutations in Spike. We defined a minority variant when it was present in >=6% and < 50% of the reads;and a majority variant when it was present in >50%. Result(s): We sequenced SARS-CoV-2 genome from 478 COVID-19- positive immunocompromised patients and 234 controls. More minority non-synonymous mutations in Spike were detected in viruses from immunocompromised hosts, compared to viral genomes from controls, in both Delta (p=0.001) and Omicron (p< 0.001) lineages, but not in Alpha (p=0.66) (Figure 1). Interestingly, among the 52 patients infected with the Delta variant, we concomitantly detected at low frequencies the mutations H655Y, N764K, D796Y, in three patients (associated with different auto-immune disease), that are part of Omicron variants signature mutations. Similarly, some patients (n=7) infected by Omicron BA.1 lineage had R346T at low-frequency, later fixed in Omicron BA.4.6 and BQ.1.1 lineages. None of these mutations were observed in the viral genomes from controls. Conclusion(s): Here, we report a higher genetic diversity in Spike gene among SARS-CoV-2 sequences from immunocompromised hosts for Delta and Omicron lineages. These results suggest that immunocompromised patients are more likely to allow viral genetic diversification and are associated with a risk of emergence of novel SARS-CoV-2 variants. (Figure Presented).
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Attention Deficit Hyperactivity Disorder (ADHD) is characterized by oppositional, defiant, disobedient, disruptive and also aggressive behavior. Many genes are involved in its onset, particularly dopaminergic pathway genes. Moreover, genetic predisposition to aggression appears affected by the polymorphic genetic variants of the serotoninergic system, among which, functional polymorphisms in monoamine oxidase A (MAOA). The risk of contracting coronavirus infection may arouse in some people severe emotional distress characterized by symptoms of fatigue, guilt, and aggression. A survey on the psychological impact of COVID-19 pandemic in Italian families of children with neurodevelopmental disorders such as ADHD showed how children have been particularly affected by the emergency. The aim of this study was to determine whether polymorphisms at the MAOA gene are associated with increased or reduced susceptibility to develop ADHD. Therefore, the variants rs6323, rs587777457 and rs1137070 of the MAOA gene were evaluated by SBT in 35 children (mean age 10.257 range 6-16) with ADHD and 27 healthy individuals. Our analysis allowed us to identify the G/G genotype of the variant rs6323 (Arg297Arg) was significantly associated with an increased risk of ADHD (p = 0.015). Allele G indicates higher levels of the enzyme, while the T allele indicates lower levels of enzyme production. When compared in patients, the G allele was associated with higher anger (p-value = 0.01) and might cause aggressive behavior in males. Our study shows that defining a genetic profile of ADHD can provide important information on the etiopathogenesis of the disease and help identify the best therapeutic option for patients with this disorder.
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During the first and second waves of coronavirus-19 disease, Sardinia had one of the lowest hospitalization and related mortality rates in Europe. However, in contrast with this evidence, the Sardinia population showed a very high frequency of the Neanderthal risk locus variant rs35044562, considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 patients who had tested positive for SARS-CoV-2 and 314 healthy Sardinian controls (Italy). Patients were divided according to WHO classification: 120 patients asymptomatic, 90 pauci-symptomatic, 108 with a moderate disease course and 40 severely ill. The allele frequencies of Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness were calculated in patients and controls. The Thalassemia variant (rs11549407), the HLA haplotypes, the KIR genes, as well as KIRs and their HLA class I ligand combinations were also investigated. The rs35044562 and rs1156361 Neanderthal variants revealed a distribution in Hardy-Weinberg equilibrium (HWE) both in SARS-CoV-2 patients and the control population (X2HWE = 0.82, p = 0.37 and X2HWE = 0.13, p = 0.72, respectively). Our findings reported an increased risk for severe disease in Sardinian patients carrying the rs35044562 high-risk variant [OR 5.32 (95% CI 2.53-12.01), p<0.0001]. Conversely, the protective effect of the HLA-A*02:01~B*18:01~DRB1*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 - 41.0), p<0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.
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BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer- BioNTech), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ & CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017;OR 2.80, 95% CI 1.05-7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2 while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95% CI 0.05-0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058;OR 0.42, 95% CI 0.15-1.16), B*52:01:01 (p = 0.031;OR 0.38, 95% CI 0.14-1.03), DQA1*03:02:01 (p = 0.028;OR 0.39, 95% CI 0.15-1.00) and DPB1*02:01:02 (p = 0.024;OR 0.45, 95% CI 0.21-0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.
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Background/Purpose: Pediatric Acute Lymphoblastic Leukemia (ALL) affects ~4000 young Americans each year. Steroids are essential to curative ALL treatment yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. However, incidence and predisposing risk factors are not well understood. This review aims to describe the current literature on neuropsychiatric side effects of steroids in Pediatric ALL. Method(s): A precise search in PubMed and Embase was cultivated using controlled vocabulary terms (MeSH, Emtree) and keywords for the following concepts: pediatrics, steroids, side effects, cancer, and neurobehavioral manifestations. Keywords and controlled vocabulary for each subject were arranged logically and combined with other concepts by Boolean Logic, using the Boolean operator AND, resulting in 642 precise results exploring neurobehavioral side effects of steroids in children with cancer. Results (2010 to date of search) were imported into Covidence systematic review software, and reviewed by SB and AM. Result(s): Twenty-three articles met inclusion criteria. There is marked variability in research methodology and no standard measurement of neuropsychiatric symptoms. Commonly reported symptoms include mood swings, irritability, depression, anxiety, aggression, insomnia, mania, and psychosis with prevalence between 5% and 75%. Heterogeneous research methodology and descriptions of psychiatric symptoms make it difficult to determine risk factors, though dexamethasone, family psychiatric history, and younger age are consistently associated with greater risk of behavioral dysregulation. Genetic predisposition (Bcl1 polymorphism, SNPs in GR gene) may increase susceptibility to developing depression during treatment. Data suggest variable efficacy of antipsychotics, benzodiazepines, hydrocortisone, and potassium-chloride. Conclusions and Implications: Existing data about neuropsychiatric side effects of steroids in pediatric ALL is extremely heterogeneous, creating challenges for standardized assessment and treatment. The burden of these symptoms necessitates further research to identify and treat vulnerable patients. Standard measurement of these symptoms could be a first step in eventually alleviating this source of distress.
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We found a higher incidence of myocarditis in young males who had received Pfizer-BioNTech BNT162b2 vaccinations as compared with historical controls and unvaccinated individuals. The analyses focused on risk following the first and second vaccine in adults and adolescents, as well as risk in adults following the third (booster) vaccine. Males, mainly aged 12-30 years, were found to be at higher risk. However, the question remains what causes lead one specific young male, but not another, to develop post-vaccination myocarditis. The HLA molecule is known to play an important role in infectious and auto-inflammatory diseases. We hypothesized that differences in HLA alleles could lead to either protection or susceptibility to vaccination-induced myocarditis. On this basis, HLA typing was performed using next-generation sequencing technology for the HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci, in 21 wellcharacterized patients who developed myocarditis after the second Pfizer BNT162b2 vaccination. The HLA genotypes were compared with high-resolution HLA data of 272 healthy controls from the Hadassah Bone Marrow registry samples, who are representative of HLA frequencies in the Israeli population. Our findings demonstrated that in HLA class II, DRB1*14:01 (19.04% vs. 5.3%, Pcorr = 0.028, OR = 4.17), HLA-DQB1*05:03 (19.04% vs. 6.06%, Pcorr = 0.034, OR = 3.64) and DRB1*15:03 (7.14% vs. 0.0%, Pcorr = 0.003, OR = 41.76) were significantly associated with disease susceptibility. We further discovered susceptibility motifs in the HLA-DR peptidebinding grooves: His60 (Pcorr0.01, OR = 3.52) and Arg70 (Pcorr = 0.0047, OR = 3.43). Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves may have changed the binding affinity of different peptides derived from the Pfizer-BioNTech BNT162b2 vaccination, and induced myocarditis.
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The proceedings contain 115 papers. The topics discussed include: prevention and health promotion regarding sexual transmitted infections among university students in Germany;sexual risk behavior and condom use among Arab men tourists in Pattaya, Thailand;prevalence of individuals with risk for severe COVID-19 in whom ritonavir-containing therapies are contraindicated or may lead to interactions with concomitant medications;therapy adjustment using proviral DNA information among multi-class resistant HIV-1 infected and ART-experienced patients;are we on track to reach the WHO elimination goals for viral hepatitis among HIV+-individuals? updates on HBV prevalence and incidence, 1996-2019;telehealth or in-person HIV care? care continuity drove the decision process during the COVID-19 pandemic. results from a qualitative study in South Carolina;high burden of human papilloma virus infection in people living with HIV;and safety and effectiveness outcomes from the CARISEL study: Phase 3b hybrid-3 implementation study integrating CAB+RPV LA Into European clinical settings.
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The proceedings contain 255 papers. The topics discussed include: molecular pathology of mitochondrial disorders;defining causal genes at MHC in SLE - implications for myositis and other diseases that share MHC risk;role of mitochondria in skeletal muscle dysfunction in myositis;selective T cell depletion for inclusion body myositis: why and how;inclusion body myositis in 2022: from physiopathogenesis to clinical trials;autoantibodies and complement in experimental IMNM: from pathogenesis to therapy?;reliability of immunoassays for myositis autoantibodies;when JM patients lose their 'J': transition challenges in myositis car;fatigue and well-being of children with chronic inflammatory disease;physical fitness in long-term JDM;Eular Covid and COVAX registries' update: focus on myositis;and outcomes, biomarkers, and novel treatments for the skin in dermatomyositis.
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Background: The SARS-COV- 2 vaccination campaign has massively mobilized the allergists' community to screen patients deemed at risk for the SARS-COV- 2 vaccines. To describe data regarding the management of medical calls regarding the allergic risk for the SARS-COV- 2 vaccination, amongst French allergists. Method(s): A questionnaire-based survey was launched on the AdviceMedica platform (a platform of medical advice exchange between peers) between July and October 2021 (including two reminders). Result(s): Fifty-four allergists answered the survey. Three quarters of the responders were full-time allergists. Overall, 42% and 35% had an exclusive hospital or private practice, respectively. Allergists were mostly contacted by telephone (96.3%) and e-mail (79.6%), by general practitioners (92.6%) or physicians practicing in vaccination centers (88.8%) (median of vaccine related medical calls: 10 per week (Q25-Q75: 7-20, range (2-300). Allergists favored in-person visits rather than teleconsultations (85.2% vs. 61.1%). Allergy testing was prescribed for suspicions of allergy to polyethylene glycol (84.4%) or other vaccines and non-identified drugs (64.4%). Half of the responders (29, 53.7%) could perform vaccination and four (13.7%) declared reactions during vaccination. The responders used several tools in taking their clinical decision: exchanges with peers from the AdviceMedica platform (40.4%), advice from tertiary university hospital allergy units (25%), recommendations of the French Society of Allergy (17.3%). The three most frequent drawbacks that the allergists encountered were: having a hard time adding supplementary patient visits within optimal delays (three quarters of the responders), the reluctance expressed by the physicians requiring the advice and by the patients (two thirds) and the fact that the learnt society recommendations were deemed not to cover many on-field situations (one third). The major benefits from screening were estimated to be the lack of allergy contraindication to vaccination (88.7%) and the increased visibility of the allergist's role (69.8%). Conclusion(s): This survey put numbers on the management of screening patients deemed at risk for the SARS-COV- 2 vaccination amongst French allergists. Peer exchange was the most frequent tool in taking a clinical decision.
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Background: Myocarditis (MC) is an inflammatory condition of the myocardium often caused by a virus and can lead to hospitalization, heart failure, or death. Although rare, data suggest an increased incidence associated with the COVID-19 virus. However, the risk for COVID-19-induced MC remains poorly understood and debated. We sought to evaluate the prevalence of pandemic MC-related inpatient encounters during 2020 through a descriptive approach and compare it to the pre-pandemic era. Given that the first COVID-19 vaccine doses were administered on December 14, 2020, a significant increase in MC prevalence could be attributable to COVID-19 exposure. Method(s): Data were obtained from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). The database provides all-payers administrative claims data on the patient level. Using ICD-10-CM codes, a cohort of patients who had their first inpatient encounter with MC was identified and divided into pre-pandemic (January- October 2019) and pandemic (January-October 2020) groups and classified by age, gender, and month of hospitalization. We described these patients' demographics, calculated the prevalence ratio (PR) and 95% CI of MC-related encounters during the pandemic, and compared it with the same period in the pre-pandemic period. A p-value <0.05 was deemed significant. Result(s): The median age, length of stay in previous hospitalizations, mean gender and Elixhauser Comorbidity Index were similar between groups. The prevalence of MC was 22/100,000 cases in 2019 and 25/100,000 in 2020. The overall PR of hospitalization due to MC was 13% higher in 2020 than it was in 2019 (PR=1.13, p<0.0001), with a significantly higher risk in age groups 5-9 (PR=1.41 p=0.02), 60-64 (PR=1.24 p<0.0001), 65-69 (PR=1.14 p=0.01), 70-74 (PR=1.28 P<0.0001), and 80-85 (PR=1.36 p<0.0001). The risk was significantly higher in March (PR=1.27 p<0.0001), July (PR=1.41 p<0.0001, and September (PR=1.52 p<0.0001) in 2020. In 2020, the risk of MC in males with respect to females decreased by 3% compared to 2019. Discussion(s): Our results suggest a temporal correlation between increased prevalence of inpatient encounters for MC since COVID-19's inception. The risk was significantly higher in older adults and during months with a higher COVID-19 incidence. These findings do not demonstrate causation between the COVID-19 virus and MC and are limited by the typical biases associated with retrospective studies. Conclusion(s): Although MC is a less common hospitalization condition, our data supports a significantly increased prevalence of MC-related encounters during the initial year of the COVID-19 pandemic. We found risk variations according to age, gender, and month.Copyright © 2022
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Background: Genetic risk factors may be related to the infectivity and severity of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) and host transmembrane serine protease (TMPRSS2) have key role in viral cell entrance and priming. Methods: This case-control study on 147 healthy controls and 299 COVID-19 patients identified potential determinants and risk factors, including gene polymorphism involved in the severity (mild, moderate, severe) of COVID-19 disease defined by CORAD radiological criteria. Results: The ACE2 s2285666 and TMPRSS2 rs12329760 SNPs were significantly linked with COVID-19 disease severity, as were certain co-morbidities (hypertension, heart disease) and laboratory parameters. Both SNPs were amongst the highest predictors of disease severity: TMPRSS2 rs12329760 CT + TT [odds ratio (95% CI) 17.6 (5.1-61.10), ACE2 rs2285666 CT + TT 9.9 (3.2-30.9), both p < 0.001]. There was an increase in the expression of genotype frequencies of ACE2 rs2285666 and TMPRSS2 rs1232976 (TT), (CT + TT), and (T) allele in severe COVID-19 group compared to control and mild groups. Disease severity was also linked to elevated CRP, ferritin and D-dimer, and lower lymphocytes and platelet count (all p < 0.001). Conclusion: ACE2 rs2285666 and TMPRSS2 rs12329760 SNPs, in addition to lymphocyte count, CRP, D-dimers, ferritin, and hypertension, are predictors of COVID-19 disease severity.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Serine Endopeptidases , Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Case-Control Studies , Ferritins , Humans , Hypertension , Polymorphism, Single Nucleotide , SARS-CoV-2 , Serine Endopeptidases/geneticsABSTRACT
Background: Contraceptives are an important component of women's reproductive health care, as they not only reduce the number of unwanted pregnancies, but also improve reproductive function. However, oral contraceptives are known to increase the risk of venous thromboembolism. This risk is increased by infection with the COVID-19 virus that predisposes patients to both venous and arterial thrombosis as a result of excessive inflammation, platelet activation, aggravated endothelial dysfunction, and congestive events. If these patients have hereditary thrombophilia, the risk of venous thromboembolism becomes fatal. Case report: The paper describes a clinical case of a patient with total portal vein thrombosis, who have been taking oral contraceptives for a long time and recovering from the novel coronavirus infection. Studying the blood coagulation system and folate cycle genes, by using PCR, has revealed a gene mutation in the plasminogen activator inhibitor (serpine). The authors demonstrate the data of spiral computed tomography of the abdominal organs, as well as changes in laboratory parameters. Conclusion(s): A balanced approach is required when prescribing combined oral contraceptives during the COVID-19 pandemic, especially in women with prothrombotic mutations.Copyright © A group of authors, 2023.
ABSTRACT
The Acute Respiratory Syndrome caused by the new coronavirus described in Wuhan, China in 2019 is a viral, respiratory multifactorial infectious disease, which presents different stages depending on genetic and environmental factors that influence severity. As December 19, 2022, 653,192,573 COVID-19 cases worldwide and over six million deaths;330,795 occurred in Mexico, were reported. Our aim was to analyze the contribution of HLA in Mexican patients infected with COVID-19, categorized in different clinical subgroups. A total of 114 COVID-19 patients and 164 healthy controls, all of them Mexican Mestizos from the highlands, were included in the study;RNA columns were used for extraction, and real-time PCR method was performed for the virus identification. DNA was isolated with the Maxwell16 system and 11 HLA loci were typed using NGS (CareDx, Immucor, and One Lambda). The subjects included: 22 asymptomatic, 86 symptomatic and 109 who were previously vaccinated. We compared controls versus positive patients;versus symptomatic;vaccinated negative versus vaccinated positive;controls versus asymptomatic;asymptomatic versus symptomatic individuals. The significant high risk alleles were A*29:02 (OR = 3.95), B*45:01 (OR = 6.92), C*03:04 (OR = 2.24). DPB1*03:01(OR = 3.17) is a susceptibility marker in vaccinated and unvaccinated patients. The latter is prevalent in Hispanics, Russia, Finland, Spain and the United Kingdom. DQA1*02:01 (p = 0.009, OR = 1.96;DQB1*02:02 (p = 0.009, OR = 2.13) was a susceptibility marker in infected patients who were vaccinated. This is prevalent in Argentina, Brazil, Algeria, Australia, Canada, and China, while high-risk B*45:01 and C*03:04 are prevalent in India, Israel, Eastern Europe, and Mediterranean countries. Protective alleles where DRB1*04:01, A*02:01, DQB1*03:01 and DPB1*02:01. These data are relevant to prioritize vaccination, according to the HLA profile in Mexicans, therefore these data are relevant for the epidemiology of COVID-19.
ABSTRACT
COVID-19 has aspects on its pathogenesis that still need elucidating and an analysis of clinical and immunogenetic factors in each cohort of patients is paramount to understanding how genetic variability can explain the multiple clinical spectra seen in patients infected with SARS-CoV-2. The aim of this study was to correlate the KIR polymorphism/HLA class I ligand interactions from patients and healthy subjects with either the susceptibility or severity to COVID-19. Genotyping of HLA-A, -B, -C and KIR genes were carried out from 459 symptomatic as well as 667 non-infected Spanish Caucasian individuals using Lifecodes HLA-SSO and KIR-SSO kits (ImmucorTM, USA) and analyzed in the Luminex in this uni-centre case-control study performed at the University Hospital of Salamanca, Spain. Comparative KIR gene analysis showed that KIR2DS4 was significantly more representative in healthy versus infected individuals. When comparing subgroups of infected patients, KIR2DS3 had a higher frequency in those who progressed to a more severity disease and yet with higher mortality rate. Three functional combinations were significant on univariate analysis: KIR2DL2/C1, KIR2DS2/C1, and KIR2DS3/C1. However, in the multivariate analysis, only the KIR2DL2/C1 interaction remained significant (OR = 15.2 (95% CI 1.5-147), p = 0.0189). Compared with the solo-clinical characteristics predictive model, that included well-known comorbidity variables such as hypertension, age, sex, diabetes, C-reactive protein, dyslipidemia, smoking, ferritin, and fibrinogen, the clinical-and-KIR-based model showed a better ability to discriminate between severe and nonsevere patients with higher sensitivity and specificity. Our results support a fundamental role of KIR/ligand interaction in the clinical course of COVID-19. Since the KIR2DL2 gene has a high frequency in Spain (60%), the analysis of the KIR2DL2/C1 in symptomatic patients who require hospitalization could be helpful to better determine their prognosis.