ABSTRACT
Objective: The current study aimed to describe the clinical characteristics of mild SARS-CoV-2 infected pregnant women with abnormal liver function (ALF), explore the association between ALF with maternal and fetal outcomes. Method(s): This retrospective analysis included 87 pregnant patients with mild SARS-CoV-2 infection admitted and treated from December 1, 2022, to 31, 2022 in the department of Obestircs at Beijing Obstetrics and Gynecology Hospital. We evaluated patients for demographic and clinical features, laboratory parameters and pregnancy complications. Result(s): 27 Patients in this cohort had clinical presentations of ALF. Compared with the control group, the peripheral blood platelet (PLT), D-dimer quantitative determination (D-Dimer), lactate dehydrogenase (LDH), total protein (TP), albumin (ALB), indirect bilirubin (DBIL), gamma- glutamyltranspeptidase (GGT) and total bile acid (TBA) showed significantly differences (p<0.05). 12 cases (44.44%) complicated with pregnancy induced hypertension (PIH), 14 cases (51.85%) complicated with intrahepatic cholestasis of pregnancy (ICP), 2 cases (7.4%) complicated with acute fatty liver during pregnancy (AFLP) and 5 cases (14.81%) complicated with postpartum hemorrhage in patients with abnormal LFT were significantly higher than those in the control group (p<0.05). Compared with the control group, the incidence of premature delivery (22.22%) and fetal distress (37.04%) in the experiment group were significantly higher (p<0.05), and the incidence of neonatal asphyxia was not significantly different (p>0.05). Conclusion(s): Pregnant women are generally susceptible to mild SARS-CoV-2 and may induce ALF. ALF is associated with increased risk of mother and infant. The maternal and infant outcomes of those who terminated pregnancy in time are acceptable. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating liver function and relevant indicators. The long-term outcomes in the future are worth to further study.Copyright © 2023
ABSTRACT
Objective To summarize and analyze the features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). Methods In this study,an analysis was performed for the liver function test results of the locally transmitted or imported pediatric patients with SARS - CoV - 2 infection during isolation who were admitted to Guangzhou Eighth People's Hospital,Guangzhou Medical University,since May 21,2021,and the clinical data and the constituent ratio of liver injury were compared between the pediatric patients infected with Delta variant and those infected with Omicron variant. The independent samples t - test or the Mann - Whitney U test was used for comparison of continuous data between two groups,and the chi - square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results A total of 85 pediatric patients infected with SARS - CoV - 2 were enrolled,among whom there were 32 (37. 6%)pediatric patients infected with Delta variant and 53 (62. 4%)pediatric patients infected with Omicron variant,and there were no significant differences between the two groups in age,sex, body height,body weight,and comorbidities (all P > 0. 05). There were no significant differences between the two groups in alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma - glutamyl transpeptidase,total bilirubin,albumin,and cholinesterase (all P > 0. 05),and the pediatric patients infected with Omicron variant had a significantly higher level of total bile acid (TBA)than those infected with Delta variant (Z = - 2. 336,P = 0. 020). However,the median values of TBA were within the normal range and the ratios of abnormal TBA were no significant difference between the two groups (P > 0. 05). Among the 85 pediatric patients,10 (11. 8%)had a mild increase in liver function parameters,among whom 7 had an increase in TBA,1 had an increase in ALT, 1 had increases in ALT and AST,and 1 had an increase in ALP. The analysis of liver injury in the pediatric patients infected with Delta variant or Omicron variant showed that there was no significant difference in the constituent ratio of liver injury caused by the two variants (6. 3% vs 15. 1%,chi2 = 0. 691,P = 0. 406). Conclusion Mild liver injury is observed in pediatric patients infected with Delta and Omicron variants of SARS - CoV - 2,but further studies are needed to evaluate the long - term influence of such infection on liver function.Copyright © 2022 Editorial Board of Jilin University
ABSTRACT
The coronavirus disease 2019 (COVID-19) has become a global pandemic. It is urgent to find treatments to control the infection and improve symptoms. Homologous modeling and clinical analyses suggest that histamine receptor antagonists have broad prospects in the treatment of COVID-19. This article introduces the research progress of histamine H1 receptor antagonist combined with azithromycin, histamine H2 receptor antagonist famotidine alone or combined with aspirin, and histamine H1 and H2 receptor antagonists used in combination in the treatment of COVID-19. Finally, the possible mechanism of histamine receptor antagonists in the treatment of COVID-19 was introduced and the application prospect of histamine receptor antagonists in the treatment of COVID-19 was analyzed.Copyright © 2022, Second Military Medical University Press. All rights reserved.
ABSTRACT
Wastewater surveillance has been widely used to track the prevalence of SARS-CoV-2 in communities. Although some studies have investigated the decay of SARS-CoV-2 RNA in wastewater, understanding about its fate during wastewater transport in real sewers is still limited. This study aims to assess the impact of sewer biofilms on the dynamics of SARS-CoV-2 RNA concentration in naturally contaminated real wastewater (raw influent wastewater without extra SARS-CoV-2 virus/gene seeding) using a simulated laboratory-scale sewer system. The results indicated that, with the sewer biofilms, a 90% concentration reduction of the SARS-CoV-2 RNA was observed within 2 h both in wastewater of gravity (GS, gravity-driven sewers) and rising main (RM, pressurized sewers) sewer reactors. In contrast, the 90% reduction time was 8–26 h in control reactors without biofilms. The concentration reduction of SARS-CoV-2 RNA in wastewater was significantly more in the presence of sewer biofilms. In addition, an accumulation of c.a. 260 and 110 genome copies/cm2 of the SARS-CoV-2 E gene was observed in the sewer biofilm samples from RM and GS reactors within 12 h, respectively. These results confirmed that the in-sewer concentration reduction of SARS-CoV-2 RNA in wastewater was likely caused by the partition to sewer biofilms. The need to investigate the in-sewer dynamic of SARS-CoV-2 RNA, such as the variation of RNA concentration in influent wastewater caused by biofilm attachment and detachment, was highlighted by the significantly enhanced reduction rate of SARS-CoV-2 RNA in wastewater of sewer biofilm reactors and the accumulation of SARS-CoV-2 RNA in sewer biofilms. Further research should be conducted to investigate the in-sewer transportation of SARS-CoV-2 and their RNA and evaluate the role of sewer biofilms in leading to underestimates of COVID-19 prevalence in communities.
ABSTRACT
Compound Qinlan Oral Liquid (,CQOL) is derived from Yinqiao San (), which is composed of Jinyinhua (Lonicerae Japonicae Flos), Huangqin (Scutellariae Radix), Lianqiao (Forsythiae Fructus) and Banlangen (Isatidis Radix). It is a common clinical herbal medicine for clearing heat and detoxification, and has antiviral effects. By reviewing the active ingredients of CQOL and the research progress on its anti-influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy, with view to providing a basis for the clinical use of CQOL in treatment of respiratory diseases caused by SARS-CoV-2.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.
ABSTRACT
Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.
ABSTRACT
OBJECTIVES: On March 11, 2020, the WHO classified COVID-19 as a global pandemic. Measures to quell the pandemic included limiting non-essential activities including clinic visits and procedures. It is unclear if individuals with OI had disruptions in their access to healthcare or medications, and if such disruptions affected patients' symptoms. METHOD(S): A REDCap survey was distributed through the OI Foundation on August 31. Surveys completed through September 11 by individuals with OI or their caregiver are included in this analysis. Participants were asked to compare their symptoms and access to healthcare during the first 4 months of the pandemic to the 4 months before the pandemic. RESULT(S): 85 surveys were completed, and 6 were partially completed. The median age of participants was 40 years;35% were children. 32% of participants self-identified as having severe OI. Although most reported no changes in bone pain or fractures, 46% reported they were less likely to seek emergency medical care to treat a fracture, while 33% reported they were more likely to treat fractures at home (Fig 1A). There were delays in accessing all services, with greatest delays accessing dentistry (74%) and aquatic therapy (84%) (Fig 1B). 36% of participants receiving bisphosphonate infusions had delayed infusions because of the pandemic (Fig 1C). Of note, 50% of planned surgeries were delayed. CONCLUSION(S): Although many individuals with OI and their caregivers reported delays in accessing bone-related services/clinics during this 4-month period, there was not a concomitant increase in reported symptoms. This may have related to shelter-in-place restrictions and decreased activity. Limitations of this study include small sample size and potential selection bias because responses were obtained only from OIF members. To address these limitations, we are distributing the survey through healthcare providers of individuals with OI across major regions of the US from a variety of practice types including endocrine, orthopedics and multidisciplinary clinics. Furthermore, as the COVID-19 pandemic continues, we hope that this survey will provide information to address what aspects of healthcare may be in greatest need, as well as the modality through which services may be met. (Figure Presented).
ABSTRACT
Submission content Introduction: An unusual case of a very young patient without previously known cardiac disease presenting with severe left ventricular failure, detected by a point of care echocardiogram. Main Body: A 34 year old previously well man was brought to hospital after seeing his general practitioner with one month of progressive shortness of breath on exertion. This began around the time the patient received his second covid-19 vaccination. He was sleeping in a chair as he was unable to lie flat. Abnormal observations led the GP to call an ambulance. In the emergency department, the patient required oxygen 5L/min to maintain SpO2 >94%, but he was not in respiratory distress at rest. Blood pressure was 92/53mmHg, mean 67mmHg. Point of care testing for COVID-19 was negative. He was alert, with warm peripheries. Lactate was 1.0mmol/L and he was producing more than 0.5ml/kg/hr of urine. There was no ankle swelling. ECG showed sinus tachycardia. He underwent CT pulmonary angiography which demonstrated no pulmonary embolus, but there was bilateral pulmonary edema. Troponin was 17ng/l, BNP was 2700pg/ml. Furosemide 40mg was given intravenously by the general medical team. Critical care outreach asked for an urgent intensivist review given the highly unusual diagnosis of pulmonary edema in a man of this age. An immediate FUSIC Heart scan identified a dilated left ventricle with end diastolic diameter 7cm and severe global systolic impairment. The right ventricle was not severely impaired, with TAPSE 18mm. There was no significant pericardial effusion. Multiple B lines and trace pulmonary effusions were identified at the lung bases. The patient was urgently discussed with the regional cardiac unit in case of further deterioration, basic images were shared via a cloud system. A potential diagnosis of vaccination-associated myocarditis was considered,1 but in view of the low troponin, the presentation was felt most likely to represent decompensated chronic dilated cardiomyopathy. The patient disclosed a family history of early cardiac death in males. Aggressive diuresis was commenced. The patient was admitted to a monitored bed given the potential risk of arrhythmia or further haemodynamic deterioration. Advice was given that in the event of worsening hypotension, fluids should not be administered but the cardiac centre should be contacted immediately. Formal echocardiography confirmed the POCUS findings, with ejection fraction <35%. He was initiated on ACE inhibitors and beta adrenergic blockade. His symptoms improved and he was able to return home and to work, and is currently undergoing further investigations to establish the etiology of his condition. Conclusion(s): Early echocardiography provided early evidence of a cardiac cause for the patient's presentation and highlighted the severity of the underlying pathology. This directed early aggressive diuresis and safety-netting by virtue of discussion with a tertiary cardiac centre whilst it was established whether this was an acute or decompensated chronic pathology. Ultrasound findings: PLAX, PSAX and A4Ch views demonstrating a severely dilated (7cm end diastolic diameter) left ventricle with global severe systolic impairment.
ABSTRACT
Aim: People with type 1 or type 2 diabetes have a higher hospital admission rate following Covid-19 infection. This study aims to determine the degree to which the results of a previous study in Greater Manchester (GM) could be replicated in national-level data for England. Method(s): We focussed on the univariable regression analysis, which shows the association between admission and Covid-19 infection in people with diabetes. Modelling was conducted using logistic regression on data from the Covid-IMPACT database. Odds ratios were compared descriptively with the previous study. Result(s): In people with type 2 diabetes, factors associated with an increased risk of hospitalisation similar to the previous study were: older age, male sex, higher social deprivation, higher body mass index (BMI), higher cholesterol, lower eGFR, taking an ACE-inhibitor/ ARB, not taking metformin, and having asthma or hypertension. Patients with COPD, and those taking aspirin or clopidogrel also had increased risk, but the national data showed a greater risk (GM COPD odds ratio 1.89 [1.63-2.19] vs national 2.34 [2.28-2.40] / aspirin 1.49 [1.34-1.66] vs 1.66 [1.63-1.70] / clopidogrel 1.71 [1.47-1.98] vs 1.99 [1.94-2.04]). Similar results were observed in patients with type 1 diabetes. However, due to the increase in sample size, many factors which were previously not statistically significant have become significant, such as in type 2 diabetes BMI, low HDL-cholesterol. Conclusion(s): We have successfully replicated the methods, results and conclusions of our previous study in relation to factors associated with increased risk of hospital admission in diabetes individuals. Regional databases are suitable for large cohort studies, and in this instance produced similar results to a national database, validating our previous findings.
ABSTRACT
The aim of the study is to describe a case of COVID-19 and myocardial infarction in an elderly patient. Material and methods. The analysis of medical documentation (outpatient card of the patient, medical history, postmortem report) was carried out. Studied macro- and micropreparations (staining with hematoxylin and eosin). Results. A 67-year-old patient, from 23.04.2020 to 26.04.2020, was hospitalized with a diagnosis of suspected coronavirus infection (COVID-19). On the background of the treatment, the patient's biological death occurred (26.04.2020). The sectional study revealed signs of bilateral total hemorrhagic pneumonia. The signs of acute transmural myocardial infarction of the anterior wall of the left ventricle were determined. Posthumously, SARS-CoV-2 RNA was detected in the lung tissue by nucleic acid amplification. In the described clinical case, a patient with concomitant cardiovascular diseases, such as arterial hypertension, coronary heart disease, developed complications against the background of COVID-19: hemorrhagic pneumonia and myocardial infarction with a fatal outcome.Copyright © Infectious Diseases: News, Opinions, Training.
ABSTRACT
Compared to other respiratory viruses, the proportion of hospitalizations due to SARS-CoV-2 among children is relatively low. While severe illness is not common among children and young individuals, a particular type of severe condition called multisystem inflammatory syndrome in children (MIS-C) has been reported. The aim of this prospective cohort study, which followed a group of individuals under the age of 19, was to examine the characteristics of patients who had contracted SARS-CoV-2, including their coexisting medical conditions, clinical symptoms, laboratory findings, and outcomes. The study also aimed to investigate the features of children who met the WHO case definition of MIS-C, as well as those who required intensive care. A total of 270 patients were included between March 2020 and December 2021. The eligible criteria were individuals between 0-18 with a confirmed SARS-CoV-2 infection at the Infectious Disease Hospital "Prof. Ivan Kirov"in Sofia, Bulgaria. Nearly 76% of the patients were <= 12 years old. In our study, at least one comorbidity was reported in 28.1% of the cases, with obesity being the most common one (8.9%). Less than 5% of children were transferred to an intensive care unit. We observed a statistically significant difference in the age groups, with children between 5 and 12 years old having a higher likelihood of requiring intensive care compared to other age groups. The median values of PaO2 and SatO2 were higher among patients admitted to the standard ward, while the values of granulocytes and C-reactive protein were higher among those transferred to the intensive care unit. Additionally, we identified 26 children who met the WHO case definition for MIS-C. Our study data supports the evidence of milder COVID-19 in children and young individuals as compared to adults. Older age groups were associated with higher incidence of both MIS-C and ICU admissions.Copyright © 2023 P. Velikov et al., published by Sciendo.
ABSTRACT
INTRODUCTION. The aetiology of Kawasaki disease (KD) remains unknown. Changes in infectious exposure during the COVID-19 pandemic owing to infection prevention measures may have affected the incidence of KD, supporting the pathogenic role of an infectious trigger. The purpose of this study was to evaluate the incidence, phenotype and outcome of KD before and during the COVID-19 pandemic in Denmark. METHODS. This was a retrospective cohort study based on patients diagnosed with KD at a Danish paediatric tertiary referral centre from 1 January 2008 to 1 September 2021. RESULTS. A total of 74 patients met the KD criteria of whom ten were observed during the COVID-19 pandemic in Denmark. Alof these patients were negative for SARS-CoV-2 DNA and antibodies. A high KD incidence was observed during the first six months of the pandemic, but no patients were diagnosed during the following 12 months. Clinical KD criteria were equally met in both groups. The fraction of intravenous immunoglobulin (IVIG) non-responders was higher in the pandemic group (60%) than in the in the pre-pandemic group (28.3%), although the rate of timely administered IVIG treatment was the same in both groups (>= 80%). Coronary artery dilation was observed in 21.9% in the pre-pandemic group compared with 0% in KD patients diagnosed during the pandemic. CONCLUSION. Changes in KD incidence and phenotype were seen during the COVID-19 pandemic. Patients diagnosed with KD during the pandemic had complete KD, higher liver transaminases and significant IVIG resistance but no coronary artery involvement.Copyright © 2023, Almindelige Danske Laegeforening. All rights reserved.
ABSTRACT
Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO , ALC-0315 in Comirnaty , SM-102 in Spikevax ). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic. Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.
ABSTRACT
Self-medication is a widespread public health concern. University students are likely to be more prone to it since self-medication rates increase with educational level. Studies have shown that self-medication rates vary among academics belonging to different faculties, and medical students have the highest self-medication rates. However, it is unknown whether this holds in a vulnerable situation, such as the COVID-19 pandemic. It is also unknown whether differences in technical knowledge of drugs influence self-medication rates among students. Thus, this study analyzes and compares prophylactic self-medication among graduate students of different faculties in the context of the COVID-19 pandemic. This cross-sectional observational study was conducted at a private university in southern Brazil. Students from the medicine, law, life sciences, and fine arts faculties were surveyed, and their responses were compared using a chi-square test. Among 396 respondents, 29.5% reported using preventive medication for COVID-19, and medical students were the least likely to do so. The self-medication rate was 13.6% among respondents, and self-medication did not differ significantly between students of different faculties. Of the students who self-medicated 63% reported having studied the medication before using them. Furthermore, the media did not induce drug use among 81.8% respondents. These results show that medical students used fewer preventive medications during the pandemic and refute the assertion that self-medication rates are higher among medical students. They also show that self-medication rates during the pandemic were significantly lower than those before the pandemic. These revelations show a new aspect of self-medication.Copyright © 2021 Muslim OT et al.
ABSTRACT
BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
BackgroundThe decrease in uric acid levels attracts more and more attention from clinicians every year [1]. In particular, a factor such as Covid-19 can cause a significant decrease in uric acid due to its increased excretion by the kidneys [2]. This retrospective study aimed to determine changes in the level of uric acid in different years, which allows us to assume the influence of different strains of Covid-19 on uric acid.ObjectivesTo analyze the relationship between uric acid levels through admission to the hospital and Covid-19 severity during 2020 and 2021 years.MethodsOur retrospective study includes 127 hospitalized patients with confirmed Covid-19 in 2021 and 63 patients in 2020 (only patients who didn't receive urate-lowering therapy). Most patients were over 45 years old (84,2% vs 90,5%), women and men almost equally. The severity of Covid-19 we determined by the type and presence of oxygen support ((1) without O2, (2) O2 by mask or nasal cannula, (3) continuous positive airway pressure, (4) positive bi-pressure in the airways or high-flow oxygen, (5) invasive ventilation). A chi-squared test and comparison of means were used.ResultsWe cannot establish the dependence of the uric acid level on the severity of the course of the Covid-19 disease, which is determined by the type of oxygen support in both 2020 and 2021. For example, in 2021, the difference between the least severe type (without O2) and the most severe (invasive ventilation) was almost the same (246.2 vs 277.12 µmol/L), as between O2 by mask or nasal cannula and positive bi-pressure in the airways or high-flow oxygen (257 vs 239.1 µmol/L). However, it was established that in 2020, higher indicators of the level of uric acid were observed for all types of oxygen support. For example, for patients who were without O2, it is higher by 72.95 µmol/L, which is statistically significant. In addition, we analyzed the dependence of the uric acid level on such indicators as the patient's age, the level of lymphocytes, C-reactive protein, and LDH at admission to the hospital. As a result of the analysis, it was found that the dependence is present for the LDH indicator (the lower the LDH, the higher the uric acid: chi-square at the level of 0.05), and for all other indicators, it was absent in 2021. In 2020, a positive relationship between CRP, LDH, and uric acid levels was also observed.ConclusionAlthough there is a trend towards lower uric acid levels in the background of Covid-19, it is not a marker of a severe disease course. The lower uric acid levels in 2021 are likely due to a feature of the strains circulating in 2021 that caused more significant renal excretion of uric acid.References[1]Hu F, Guo Y, Lin J, Zeng Y, Wang J, Li M, Cong L. Association of serum uric acid levels with COVID-19 severity. BMC Endocr Disord. 2021 May 8;21(1):97. DOI: 10.1186/s12902-021-00745-2. PMID: 33964922;PMCID: PMC8106517.[2]Dufour I, Werion A, Belkhir L, Wisniewska A, Perrot M, De Greef J, Schmit G, Yombi JC, Wittebole X, Laterre PF, Jadoul M, Gérard L, Morelle J;CUSL COVID-19 Research Group. Serum uric acid, disease severity, and outcomes in COVID-19. Crit Care. 2021 Jun 14;25(1):212. DOI: 10.1186/s13054-021-03616-3. PMID: 34127048;PMCID: PMC8201458.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
Objectives: Investigate the utilization of cycled antineoplastic therapies (where dosages vary per monthly supply) for various cancers among Medicare-eligible patients, and medical costs and outcomes associated with discontinuation gaps in monthly adherence. Method(s): This retrospective study used the MarketScan Supplemental and Coordination of Benefits Design databases from 2019-2020. Discontinuations were calculated for 2020 utilizing cycled medications (8 generic products) from 6 therapeutic categories, where discontinuation was defined as the first gap in medication supply during the last 6 months of the year at intervals of >=1.5*prior supply. Continuous enrollment was required, as were ICD oncology diagnosis codes for those at least 65 years of age. New to therapy/diagnosis was inferred from 2019 metric files. Patients were excluded if hospice care and inpatient transplant services were indicated. Models examined adherence level (discontinued or not) and 10 covariates (including COVID-19 indications), with interaction terms, for significant associations with medical costs (inpatient and outpatient), hospitalizations, and length of hospital stay (LOS). Result(s): Patients who met metric criteria (n=1,357;Mean age 73.9) had a discontinuation rate of 16.7%. A total of 64.0% were new to therapy/diagnosis and 5.2% were identified having COVID-19 in 2020. However, COVID-19 was not significantly correlated with a discontinuation. Hospitalization rate was at 30.3% with mean LOS=9.8. Models found significant discontinuation effects with increased total medical costs ($11,977, p<.03), odds of hospitalization (2.7, p<.0001), and LOS (5.4, p<.03). COVID-19 patients had significantly higher total medical costs ($18,145, p<.007), odds of hospitalization (6.3, p<.0001), and non-oncology LOS (4.6, p<.009). Significant covariate interactions are discussed in the poster. Conclusion(s): Medication adherence (fewer gaps in medication coverage) on cycled oral antineoplastics can lead to lower medical costs and fewer hospitalization events or LOS as compared to lower adherence levels. This was independent of COVID-19 indications that were associated with increased costs, hospitalization, and non-cancer LOS.Copyright © 2023
ABSTRACT
Over the past century, synthetic polymers have had a transformative impact on human life, replacing nature-derived materials in many areas. Yet, despite their many advantages, the structure and function of synthetic polymers still appear rudimentary compared to biological matter: cells use dynamic self-assembly to construct complex materials and operate sophisticated macromolecular devices. The field of DNA nanotechnology has demonstrated that synthetic DNA molecules can be programmed to undergo predictable self-assembly, offering unparalleled control over the formation and dynamic properties of artificial nanostructures. Intriguingly, the principles of DNA nanotechnology can be applied to the engineering of soft programmable materials, bringing the abilities of synthetic polymers closer to their biological counterparts. In this perspective, we discuss the unique features of DNA-functionalized polymer materials. We describe design principles that allow researchers to build complex supramolecular architectures with predictable and dynamically adjustable material properties. Finally, we highlight two key application areas where this biologically inspired material class offers particularly promising opportunities: (1) as dynamic matrices for 3D cell and organoid culture and (2) as smart materials for nucleic acid sequencing and pathogen detection.
ABSTRACT
BackgroundPatients suffering from systemic autoimmune rheumatic disease (SARD) display poor antibody development after two doses of mRNA vaccinations leaving these patients with only limited humoral protection against severe SARS-CoV-2 disease courses. Of key interest is the effect of conventional synthetic (csDMARD) and biological/ targeted drugs (b/tsDMARDs) disease modifying antirheumatic drugs on the time of protection.ObjectivesTo compare antibody titer development in patients with vasculitis and connective tissue disease (CTD) with healthy controls 6 months after two mRNA vaccinations and after third immunization. To analyze factors, that affect the velocity of titer decline, well as qualitative humoral response.MethodsPatients with SARD were enrolled and matched for gender and age with healthy control subjects (HC) and the humoral response after 6 months to two doses of mRNA vaccine BNT162b2 in terms of SARS-COV-2 antibody titer was assessed. In addition to binding antibody units (BAU) we also analyzed neutralizing antibodies. Patients receiving B-cell depleting therapy and those with prior SARS-CoV-2 infection (via detection of nucleocapsid antibodies) were excluded. Differences between two groups were calculated with Wilcoxon signed-rank test.ResultsA total of 53 patients with SARD (42 patients suffering from connective tissue disease and 11 with vasculitis respectively) and 73 HC were analysed. Interestingly only patients receiving a combination therapy of different csDMARDs/ b/tsDMARDs demonstrated diminished antibody titers 6 months after two doses of mRNA vaccine (p-value p-value<0,001), whereas patients receiving only csDMARD as monotherapy displayed comparable antibody levels to healthy controls. This effect was equalized after a third booster vaccination (p-value=0,13). Concerning disease entities, patients with vasculitis seemed to have lower BAU than HC (p-value<0,05) and patients suffering from CTD. After third vaccination both patient groups had lower antibody levels than HC (vasculitis: p-value <0,0001;CTD: p-value p-value<0,01). Lower antibody levels before third vaccination correlated with lower antibodies after third immunization.ConclusionPatients with autoimmune rheumatic diseases undergoing combination therapy may be more vulnerable to SARS-CoV-2 infection, due to reduced antibody levels 6 months following two doses of mRNA vaccine. Our data strongly recommends antibody measurements in patients receiving combination therapy and individualized earlier booster vaccination.Figure 1.Anti-SARS-Cov-2 S antibody titers. A: Antibody titers measured 6 months after two doses of mRNA vaccination in patients with connective tissue disease, vasculitis and healthy controls. B, Antibody levels according to disease entity. AB: antibody;BAU: binding antibody unit;CTD: connective tissue disease;HC: healthy control;mono: disease modifying anti-rheumatic drug monotherapy;combination: combination therapy of disease modifying anti-rheumatic drugs;RBD: receptor binding domain;[Figure omitted. See PDF]Table 1.Demographic parameters and therapy of study participants.SARD (n=53)HC (n=73)Age, mean (standard deviation)53.55 (±14.04)51.27 (±14.07)Female45 (84.9%)47 (64.4%)Connective tissue disease42 (79%)Vasculitis11 (21%)csDMARD or b/tsDMARD monotherapy22 (41%)csDMARD and/or b/tsDMARD combination therapy13 (25%)No therapy18 (34%)Methotrexate8 (15%)Mycophenolate mofetil10 (19%)Hydroxychloroquine17 (32%)Azathioprine8 (15%)Belimumab3 (6%)Tocilizumab3 (6%)Glucocorticoid dose 1. vaccination, mean (standard deviation)2.8 (±10.8)Glucocorticoid dose 2. vaccination, mean (standard deviation)2.6 (±10.7)SARD: Systemic autoimmune rheumatic disease, HC: Healthy controls, csDMARD: conventional synthetic disease modifying antirheumatic drugs and b/tsDMARD: biological/ targeted drugs disease modifying antirheumatic drugsREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsElisabeth Simader Speakers bureau: Lilly, Thomas Deimel: None declared, Felix Kartnig: None declared, Selma Tobudic: None declared, Helmuth Hasla her Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Thomas Maria Karonitsch: None declared, Daniel Mrak: None declared, Thomas Nothnagl: None declared, Thomas Perkmann: None declared, Helga Lechner-Radner: None declared, Judith Sautner: None declared, Florian Winkler: None declared, Heinz Burgmann Speakers bureau: speaker fees from Shionogi, Pfizer, MSD, Paid instructor for: advisory boards for Valneva, MSD, Gilead, Consultant of: consulting fees from MSD, Pfizer, Takeda, Gilead, Daniel Aletaha Speakers bureau: other from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: grants from Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Stefan Winkler: None declared, Stephan Blüml Speakers bureau: personal fees from Abbvie, personal fees from Novartis, Peter Mandl Speakers bureau: reports speaker fees from AbbVie, Janssen and Novartis, Grant/research support from: research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB.
ABSTRACT
Over the last few decades, the emergence and re-emergence of various pathogenic viruses have significantly impacted human health. The continuous rise in cases with increasing mortality rates has driven the chase for effective treatment options and early diagnosis to combat this global health issue. Currently, used laboratory techniques for virus detection require complex equipment, trained personnel, and, most importantly, are time-consuming. In times of outbreaks and epidemics like COVID-19 and Ebola, easy-to-use and point-of-care tests, especially for developing and underdeveloped countries, are indispensable. This chapter explicitly discusses the availability of the detection methods for various human viral pathogens with their shortcomings and recent advancements in biosensors. With the ongoing improvement in biosensors, these hold important avenues for rapid, sensitive, and scalable devices for viral diagnostic purposes. The effectiveness of previously known and current approaches/devices/methods that utilize different principles for detection has also been reviewed here, with the listing of all the available tests for various human pathogens. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.