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Introduction: TBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case Presentation: A 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient's irreversible neurological status. The patient was disconnected from ECMO and expired. Discussion(s): Though we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.Copyright © 2023 Elsevier Inc.
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Objective: To determine the effect of thymic response to COVID-19 pneumonia on imaging and its impact on disease severity and outcome. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging (AFIRI), Rawalpindi Pakistan, from Mar to Jul 2020. Methodology: A total of 1620 COVID-19 patients above the age of 18, of either gender, were included in the study. Their findings on High-Resolution CT (HRCT) chest were recorded and graded according to the CT severity score (CTSS) out of a total of 40;less than or equal to 19 was taken as mild while >20 scores were considered as severe disease. The thymic response was assessed by imaging appearance on CT and was graded from 0-3 as follows: fatty, predominantly fatty, mixed density (fat and soft density), and soft density. Fatty replacement implied thymic involution, while soft density depicted a reactivation of thymic tissue after a disease process depictive adequate thymic response. Results: A significant difference in thymic response was observed in patients of different age groups (p<0.001), with the younger age group demonstrating thymic reactivation/ response in the majority (170/244, 69.7%). CT severity score and mortality were significantly higher in older patients demonstrating poor thymic response to COVID pneumonia. Conclusion: Response of the thymus to acute viral infection by Sars COVID-19 is impaired as age progresses;this accounts for greater disease severity, morbidity and mortality in older patients.
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INTRODUCTION: In our study, we aimed to investigate whether the COVID-19 infection itself or the vaccination against it affect the differentiation of T cells in the thymus, and whether the reduction in T cell counts observed in the blood of COVID-19-infected individuals is also observed at the tissue level in the thymus. METHOD: Data from a total of 55 thymectomy patients were processed to create three groups: 1) the pre-COVID-19 (PC) group included 22 patients, 12 women and 10 men, who underwent thymectomy between 2008 and 2013; 2) in the no-COVID-19 (NC) group (patients without verified infection or vaccination), 20 patients, 11 women and 9 men, underwent thymectomy in 2020-2021; 3) the vaccinated or infected COVID-19 (VIC) group included 13 patients, 4 women and 9 men, who underwent thymectomy also in 2020-2021. The pathological samples were immunohistochemically tested for CD4, CD8, CD25 and FOXP3 to verify the helper, cytotoxic and regulatory T cells. RESULTS: The VIC group had significantly lower values for CD4, compared to the PC and NC groups. The FOXP3 value was significantly lower in the VIC and NC groups compared to the PC group. No significant differences were found for CD8 and CD25 between the groups studied. DISCUSSION: The COVID-19 infection or vaccination affects the T cell composition of the thymus. Decreased expression of CD4 has been demonstrated in the VIC group, which confirms a decrease in the T cell counts that also occurs in the thymus. The low FOXP3 levels observed in the NC group during the COVID-19 era, compared to the PC group, may be indicative of a high rate of asymptomatic coronavirus infections and a worsening of immunetolerance. CONCLUSION: First in the world, we have verified that the helper T cell composition of the thymus in COVID-19 infection era is reduced, and in the asymptomatic patients the immune function is decreased as well. Orv Hetil. 2022; 163(52): 2062-2066.
Subject(s)
COVID-19 , Pandemics , T-Lymphocytes , Thymus Gland , Female , Humans , Male , COVID-19/immunology , COVID-19/prevention & control , Forkhead Transcription Factors/metabolism , Thymus Gland/immunology , Lymphocyte Count , T-Lymphocytes/immunology , VaccinationABSTRACT
Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.
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Background: Radiological changes in children with lung damage caused by SARS-CoV-2 can be diagnosed by radiology exams with the identification of interstitial inflammation characterized of viral pneumonia. Aim(s): Evaluation of pulmonary radiological manifestations in children with COVID-19 infection. Method(s): Expected research evaluated pulmonary radiological changes among 315 children with SARS-CoV-2 infection, with moderate and severe form, from the age of 2 days till 18 years. Age distribution of hospitalized children with clinical signs of COVID-19 infection:<28 days-36 children(11,4%:95%CI8,2-15,6),28 days-1year-72 children(22,9%:95%CI18,4-28),1-3years-65 children(20,6%:95%CI16,4-25,6),4-7 years-66 children(21%:95%CI16,7-26),7-18years-76 children(24,1%:95%CI19,6-29,3). Result(s): Chest X-ray in children with SARS-CoV-2 infection found interstitial changes of the ground glass"type among 161 children(52.8%:95%CI 47-58.5) Condensation opacities in 51 children(16.7%:95%CI12.8-21.5)confirmed pneumonia of bacterial etiology associated with COVID-19 infection. Bronchitis was confirmed in 62 cases among hospitalized children(20.3%:95% CI16-25.4),and obstructive bronchitis characterized by imaging of hyperinflation- among 25 children(12.6%:95%CI8,3-18). Young children and infants had a thymus hyperplasia in 21.6%:95%CI17.2- 26.8 cases. At the acute stage of COVID-19 infection signs of fibrosis, atelectasis, traction bronchiectasis were detected in unique cases(0.3%:95%CI0-2.1). Conclusion(s): Lung damage caused by COVID-19 infection in children is generally characterized by changes with interstitial inflammation that are confirmed by Chest X-ray.
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This study aimed to review zinc's effectiveness as an antivirus in treating herpes simplex virus infection. The authors use international journals published from 2000-2022, and use search engines such as Google Scholar, PubMed, and Science Direct with the keywords "zinc and herpes simplex virus". The herpes simplex virus that often causes symptoms in humans are HSV type 1 and type 2. The lesions appear as vesicles which then rupture into ulcers. Zinc is one of the most abundant nutrients or metals in the human body besides iron. Studies about the effects of zinc on HSV have shown that it has the function of inhibiting the viral life cycle. HSV attaches to the host cells to replicate and synthesize new viral proteins. Zinc can inhibit this process by depositing on the surface of the virion and inactivating the enzymatic function which is required for the attachment to the host cell, disrupting the surface glycoprotein of the viral membrane so it could not adhere and carry out the next life cycle, it can also inhibit the function of DNA polymerase that works for viral replication in the host cell. This article showed that zinc has effectiveness as an antivirus against the herpes simplex virus, therefore, patients infected with HSV can be treated with zinc as an alternative to an antivirus drug.Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.
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SARS-CoV2 infection induces a complex interaction between virus and host immune system, activating multiple inflammatory pathways and leading to hyperinflammation, diffuse alveolar damage (DAD), ARDS, and multiorgan failure. We aimed to correlate the quantification of viral load, inflammatory cells and cytokines in lung tissue of fatal COVID-19. We assessed inflammatory cells by multiplex immunohistochemistry, cytokines by Luminex xMAP Assay and viral load by real time PCR in autopsy lung tissue of 18 COVID-19 patients. Correlations were considered statistically significant if p<0.05. Macrophages correlated with IL-1beta (r=0.54), IL-10 (r=0.5), IFN-alpha2 (r=0.72), IFN-gamma (r=0.6), CCL20 (r=0.5), TGF-beta1 (r=0.6), TGF-beta2 (r=0.6). CD4+T cells correlated with CCL20 (r=0.6), MDC/CCL2 (r=0.53), CCL17 (r=0.5), IP-10 (r=0.6), CXCL9 (r=0.6). CD8+T cells correlated with IL-1beta (r=0.54), IL-4 (r=0.63), IL-6 (r=0.7), IL-8 (r=0.63), IL-10 (r=0.6), TNF-alpha (r=0.6), IFN-gamma (r=0.74), CCL20 (r=0.7), TGF-beta1 (r=0.7), TGF-beta2 (r=0.56), TGF-beta3 (r=0.54), MDC/CCL2 (r=0.7), CCL17 (r=0.64). Langerin dendritic cells (DC) correlated with symptom onset to death interval (r=0.6), hospitalization length (r=0.65), mechanical ventilation (MV) length (r=0.6), ICU stay (r=0.6), exudative DAD (r=-0.5), viral load (r=-0.6). Myeloid DC correlated with symptom onset to death interval (r=0.8), hospitalization length (r=0.8), MV length (r=0.8), ICU stay (r=0.8), exudative DAD (r=-0.5), viral load (r=-0.7). Viral load correlated with symptom onset to death interval (r=-0.7), hospitalization length (r=-0.8), MV length (r=-0.7), ICU stay (r=-0.8), exudative DAD (r=0.6). There is a complex temporal inflammatory modulation in severe COVID-19.
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Introduction and Aims: Thymoma is a rare but the commonest primary malignancy of the anterior mediastinum(35%), with an annual incidence around 3 per million population (Girard et al. Annals of Oncology 2015;26:v40-55).Standard first line imaging is CT thorax with contrast. During the Covid-19 era more CTs were performed. Weevaluated whether this affected the diagnosis and management of thymomas in a UK district general hospital. Method(s): We included CT scan reports from 1 January 2019 to 31 December 2021 with the terms 'thymoma','thymic' and 'thymus' (n=171). Non-diagnoses and existing diagnoses of thymomas were excluded. Data wascollected on patient demographics, presenting symptoms, scan circumstances, size of mass, further investigationsand staging. Result(s): We identified 21 potential diagnoses of thymoma, ages ranging from 14 to 89 years. Half were male and71% Caucasian. Commonest presenting symptoms were shortness of breath and cough (33%). 3 scans wereperformed as part of Covid management. 7 patients underwent a biopsy, of whom 4 had histology-confirmedthymoma (Table 1). Discussion(s): Results highlight that despite frequent mentions of mediastinal abnormalities in CT reports, few are investigated. Only 57% of those biopsied were diagnosed with thymoma, likely representing underdiagnosis. In addition, the increased number of CTs performed during the Covid pandemic did not result in more diagnoses of thymoma.
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The outbreak of COVID-19 occurred in January 2020, the epidemic is still rampant around the world. The Shanghai Expert Consensus on Comprehensive Treatment and Management of Corona Virus Disease 2019 was issued in early March 2020, which provided the guidance of the standardized treatment and rational medication for COVID-19. The administration of " four agents (glucocorticoids, heparin, high-dose vitamin C, Interferon-kappa) and one peptide (thymic peptide)" recommended by the consensus is the key to successfully block and treat critical illness.Copyright © 2021 Chinese Medical Association
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As the leading central immune organ, the thymus is where T cells differentiate and mature, and plays an essential regulatory role in the adaptive immune response. Tuft cells, as chemosensory cells, were first found in rat tracheal epithelial, later gradually confirmed to exist in various mucosal and non-mucosal tissues. Although tuft cells are epithelial-derived, because of their wide heterogeneity, they show functions similar to cholinergic and immune cells in addition to chemosensory ability. As newly discovered non-mucosal tuft cells, thymic tuft cells have been demonstrated to be involved in and play vital roles in immune responses such as antigen presentation, immune tolerance, and type 2 immunity. In addition to their unique functions in the thymus, thymic tuft cells have the characteristics of peripheral tuft cells, so they may also participate in the process of tumorigenesis and virus infection. Here, we review tuft cells' characteristics, distribution, and potential functions. More importantly, the potential role of thymic tuft cells in immune response, tumorigenesis, and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection was summarized and discussed.
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BACKGROUND: Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. METHODS: This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19. RESULTS: During hospitalization, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/mL. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017-0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID-19 using the net reclassification (1.16, 95% CI: 0.82-1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09-0.26, p < .001) improvement. CONCLUSION: CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.
Subject(s)
COVID-19 , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Chemokines , Cholecalciferol , COVID-19/diagnosis , COVID-19/therapy , Lactate Dehydrogenases , Ligands , Renal Dialysis/adverse effects , Retrospective Studies , SARS-CoV-2ABSTRACT
OBJECTIVE: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. METHOD: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. RESULT: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. CONCLUSION: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.
Subject(s)
COVID-19 , Fatty Liver , Humans , COVID-19/diagnostic imaging , COVID-19/epidemiology , Retrospective Studies , Thymus Gland/diagnostic imaging , Disease ProgressionABSTRACT
Case 1 was an 81-year-old man undergoing treatment for the nummular eczema of the lower leg. The day after being administered the first dose of a COVID-19 vaccine, the patient developed generalized pruritus, multiple serous papules, and erythema on the trunk, upper extremities, and palms, as well as worsening of pre-existing eczema on the lower legs. The serum TARC level of the patient was 1,383 pg/mL. After taking oral antihistamines and topical steroids for two weeks, the erythema faded, papules crusted, and serum TARC level normalized. Case 2 was a 22-year-old woman who had been treated with topical steroids for contact dermatitis by poultices on the ankles. On the same day as she received the second dose of COVID-19 vaccine, erythema with pruritus on the dorsum of the feet appeared and gradually expanded to papules and edematous erythema on the face, extremities, and trunk. The serum TARC level of the patient was 2,090 pg/mL. After taking 15 mg/day oral prednisolone and topical steroids for 10 days, overall erythema became hyperpigmented, and the erythema on the dorsum of the hands and fingers persisted for approximately 2 weeks and then became pigmented. Serum TARC level normalized after the skin rash reformed. Case 3 was a 74-year-old woman with a history of asthma. She received SBT/ABPC therapy for acute cholangitis for one week. Ten days after treatment, she received the first COVID-19 vaccination dose. Two days after vaccination, the patient became aware of pruritus on the extremities ipsilateral to the vaccination site, and small erythematous patches appeared all over the body in a disseminated pattern. Her serum TARC level was 3,862 pg/mL. After taking oral antihistamines and topical steroids for 3 weeks, the erythema completely faded, and the serum TARC level normalized. The DLST showed positive by SBT/ABPC, but the result of drug challenge test was negative. There have been no previous case reports of rash with a high TARC level after vaccination. In the future, it is necessary to accumulate patients with a high TARC level by vaccination and analyze the clinical and pathological trends including immunological mechanisms. Copyright © 2022 Osaka University Medical School. All rights reserved.
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Background/Purpose: The 2019 outbreak of coronavirus disease COVID-19 causes immune system disruption. Recent studies reported that the decrease or depletion of regulatory T cell (Treg) may be responsible for overstimulation of the immune system and lung damage in patients with severe COVID-19. This study aims to find the molecular mechanisms and genetic biomarkers associated with Tregs in COVID-19, providing new ideas for the treatment of COVID-19. Method(s): RNA sequencing data of peripheral blood mononuclear cells (PBMC) from 252 COVID-19 infected patients and 69 healthy controls (HC) were obtained from the GEO database. The Tregs composition of COVID-19 samples was quantified using the CIBERSORT deconvolution method. The differential genes (DEGs) were identified by the limma R package. Gene co-expression network analysis (WGCNA) was used to identify the gene. Differentially expressed Tregs-related genes (DETregRGs) were obtained by intersecting DEGs with the highly related modular genes obtained in the previous step. The potential biological functions and pathways of DETregRGs were then explored. Protein-protein interaction (PPI) networks were subsequently constructed to identify hub genes. In addition, the prediction of small molecule drugs for the potential treatment of COVID-19 was made using the CMap database. Result(s): After the weighted gene co-expression network analysis (WGCNA), the turquoise module was highly correlated with Treg expression and a total of 134 DEGs was identified as DETregRGs. These genes were mainly involved in GO biological processes, such as the inflammatory response, and T cell differentiation of thymus. Then, 11 hub genes (including RPS12, RPL21, RPS3A, CD8B, CD3D, TRAT1, RPS6, CD3E, CD28, RPL3, and CD4) were ranked based on Molecular Complex Detection (MCODE) analysis. The TregRG score of COVID-19 patients showed significantly lower than HC, calculated by the 'singscore' algorithms. After the signature query of the CMap database, the KU-0063794, an mTOR inhibitor ranked second in the negative enrichment score, may restore immune system dysregulation caused by increased Th17 differentiation and decreased Treg differentiation during SARS-CoV- 2 infection. Conclusion(s): Our study examined in detail the molecular mechanisms underlying the inadequacy of Tregs in patients with COVID-19 infection. mTOR inhibitors may improve COVID-19 symptoms by expanding Tregs which may be one of the potential therapeutic methods that need further investigation. (Figure Presented).
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BACKGROUND: Lymphopenia, particularly when restricted to the T-cell compartment, has been described as one of the major clinical hallmarks in patients with coronavirus disease 2019 (COVID-19) and proposed as an indicator of disease severity. Although several mechanisms fostering COVID-19-related lymphopenia have been described, including cell apoptosis and tissue homing, the underlying causes of the decline in T-cell count and function are still not completely understood. OBJECTIVE: Given that viral infections can directly target thymic microenvironment and impair the process of T-cell generation, we sought to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on thymic function. METHODS: We performed molecular quantification of T-cell receptor excision circles and κ-deleting recombination excision circles to assess, respectively, T- and B-cell neogenesis in SARS-CoV-2-infected patients. We developed a system for in vitro culture of primary human thymic epithelial cells (TECs) to mechanistically investigate the impact of SARS-CoV-2 on TEC function. RESULTS: We showed that patients with COVID-19 had reduced thymic function that was inversely associated with the severity of the disease. We found that angiotensin-converting enzyme 2, through which SARS-CoV-2 enters the host cells, was expressed by thymic epithelium, and in particular by medullary TECs. We also demonstrated that SARS-CoV-2 can target TECs and downregulate critical genes and pathways associated with epithelial cell adhesion and survival. CONCLUSIONS: Our data demonstrate that the human thymus is a target of SARS-CoV-2 and thymic function is altered following infection. These findings expand our current knowledge of the effects of SARS-CoV-2 infection on T-cell homeostasis and suggest that monitoring thymic activity may be a useful marker to predict disease severity and progression.
Subject(s)
COVID-19 , Lymphopenia , Humans , COVID-19/metabolism , SARS-CoV-2 , Thymus Gland , Lymphopenia/genetics , Patient AcuityABSTRACT
Background: COVID-19 is still instigating significant social and economic chaos worldwide; however, there is no approved antiviral drug yet. Here, we used in silico analysis to screen potential SARS-CoV-2 main protease (Mpro) inhibitors extracted from the essential oil of Thymus schimperi which could contribute to the discovery of potent anti-SARS-CoV-2 phytochemicals. Methods: The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of compounds were determined through SwissADME and ProToxII servers. AutoDock tools were used for molecular docking analysis studies, while Chimera, DS studio, and LigPlot were used for post-docking studies. Molecular dynamic simulations were performed for 200 ns under constant pressure. Results: All compounds exhibited a bioavailability score of ≥0.55 entailing that at least 55% of the drugs can be absorbed unchanged. Only five (9%), nine (16%) and two (3.6%) of the compounds showed active hepatotoxicity, carcinogenicity, and immunotoxicity, respectively. Except for flourazophore P, which showed a little mutagenicity, all other compounds did not show mutagenic properties. On the other hand, only pinene beta was found to have a little cytotoxicity. Five compounds demonstrated effective binding to the catalytic dyad of the SARS-CoV-2 Mpro substrate binding pocket, while two of them (geranylisobutanoate and 3-octane) are found to be the best hits that formed hydrogen bonds with Glu166 and Ser144 of SARS-CoV-2 Mpro. Conclusion: Based on our in silico analysis, top hits from Thymus schimperi may serve as potential anti-SARS-CoV-2 compounds. Further in vitro and in vivo studies are recommended to characterize these compounds for clinical applications.
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Introduction: A worldwide pandemic infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a deadly disease called COVID-19. Interaction of the virus and the Angiotensin converting-enzyme 2 (ACE2) receptor leads to an inflammatory-induced tissue damage. Thymus vulgaris L. (TvL) is a plant with a long history in traditional medicine that has antimicrobial, antiseptic, and antiviral properties. Thymol and Carvacrol are two important biological components in Thyme that have anti-inflammatory, antioxidant, and immunomodulatory properties. This study is a molecular review on the potential effects of TvL and its active compounds on SARS-COV2 infection. Method: This is a narrative review in which using PubMed, Scopus, ISI, Cochrane, ScienceDirect, Google scholar, and Arxiv preprint databases, the molecular mechanisms of therapeutic and protective effects of TvL and its active compounds have been discussed regarding the molecular pathogenesis in COVID-19. Results: Thyme could suppress TNF-alpha, IL-6, and other inflammatory cytokines. It also enhances the anti-inflammatory cytokines like TGF-beta and IL-10. Thyme extract acts also as an inhibitor of cytokines IL-1-beta and IL-8, at both mRNA and protein levels. Thymol may also control the progression of neuro-inflammation toward neurological disease by reducing some factors. Thyme and its active ingredients, especially Thymol and Carvacrol, have also positive effects on the renin-angiotensin system (RAS) and intestinal microbiota. Conclusions: Accordingly, TvL and its bioactive components may prevent COVID-19 complications and has a potential protective role against the deleterious consequences of the disease.
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BACKGROUND: Multisystem inflammatory syndrome (MIS-C) is the most important complication of COVID-19 in the pediatric population. Unfortunately, this problem is an unpredictable situation in patients with COVID-19. We aimed to evaluate the effects of MIS-C on thymus dimensions in pediatric patients. METHODS: We retrospectively analyzed the files of 368 pediatric patients aged 2-18 years, who were diagnosed with COVID-19. Computer Tomography (CT) images of 22 patients diagnosed with COVID-19 and 10 patients diagnosed with MIS-C were evaluated in detail by two board-certified radiologists. Eighteen age and sexmatched patients who applied to the emergency department of our hospital for any reason and had a CT scan for any reason were selected as the control group. The data of both groups were statistically compared. RESULTS: Considering the differences between the groups in terms of laboratory data, monocytes, hemoglobin, and platelet were significantly lower in the MIS-C group than the other groups. Procalcitonin, C- reactive protein, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and proBNP levels were statistically significantly higher in the MIS-C group compared to the other groups Regarding the differences in thymus dimensions, thymus AP diameter, transverse diameter, length, thickness, and volume were significantly higher in the MIS-C group than in the other groups There was a significant positive correlation between the transverse diameter of the thymus and CRP, procalcitonin, pro-brain natriuretic peptide (proBNP), and NLR levels. CONCLUSIONS: Our study shows that thymus dimensions and acute phase reactants are higher in pediatric patients in the MIS-C group. Also, thymus transverse diameter, thymus thickness, and PLR values pose a risk for the development of MIS-C. More research is needed on the role of the thymus gland in the pathogenesis and diagnosis of MIS-C.
Subject(s)
COVID-19 , Procalcitonin , Humans , Child , Retrospective Studies , Thymus Gland/diagnostic imaging , C-Reactive ProteinABSTRACT
Despite the social distancing and hygiene rules prescribed by the WHO, the novel Corona-virus is still on the way of a significant rapid rise in deaths. Therefore, identification of chemotherapeutic drugs against Corona Viral Infection all around the world is still requires. Some medicinal plants have a valuable therapeutic effect when mixt with honey, the obtained formulations are preliminary use in Cameroon against viral infection particularly respiratory infections. In this work, we looked for the potential anti-SARS-CoV-2 molecule throw execution of in silico computational studies of six Cameroonian plants intervening in the treatment respiratory infections in apiphytotherapy. AutoDock Vina was used for docking studies against SARS-CoV-2 main protease (Mpro) and spike (SP) proteins. We further conducted of pharmacokinetics properties and the safety profile of compounds with the top score in order to identify the best drug candidates. Totally 100 compounds were screened, of these, eighteen showed high binding affinity against SARS-CoV-2 Mpro and SP. The results suggest the effectiveness of compounds 10 and 17 obtained from Citrus Sinensis as potent drugs against SARS-CoV-2 as they tightly bind to its Mpro and SP with low binding energies. The stability of the two compounds complexed with Mpro and SP was validated through MD simulation. The availability of potent protein inhibitors and diverse of compounds from Cameroon flora scaffolds indicate the feasibility of developing potent Mpro and SP proteins inhibitors as antivirals for COVID-19. Based on further in vivo and in vitro experiments and clinical trials, some of these phytoconstituents could be proposed for effective inhibition of the replication of the SARS-CoV-2.
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SESSION TITLE: Amazing Chest Imaging Findings SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Thoracic Castleman disease is challenging to diagnose and can mimic various lymphoproliferative disorders. Herein we present a case of unicentric thoracic castleman disease co-existing with thymoma, mimicking a thymoma drop metastasis. CASE PRESENTATION: A 50-year-old previously healthy Caucasian female presented to the emergency room with COVID-19 related respiratory symptoms. CTA was consistent with COVID-19 pneumonia and incidentally showed a 4.2 x 3.1 cm mass in the right anterosuperior mediastinum abutting the ascending aorta and superior right atrium, and a 3.3 x 2.1 cm mass in right posterior costophrenic sulcus abutting the right 11th rib raising suspicion for thymoma with a "drop metastases.” CT abdomen/pelvis was unrevealing. For proper staging, US guided biopsy of chest wall mass was performed which showed reactive lymphoid tissue. CT guided biopsy of the mediastinal mass revealed a thymoma. Due to ongoing concern for pleural metastases and possible sampling error with prior biopsy of the costophrenic lesion, she underwent surgical resection of the anterior mediastinal mass and chest wall lesion including part of 11th rib. The chest wall lesion was noted to be extrapleural. Surgical biopsy confirmed WHO grade B1 Thymoma and the chest wall lesion showed hyaline vascular Castleman disease. DISCUSSION: Pleural "Drop” metastasis from a thymoma or thymic carcinoma should be considered in patients with an anterior mediastinal mass and pleural based lesions. Imaging shows one or more pleural nodules or masses, which can be smooth, nodular, or diffuse. [1]. In our case, a basilar, discrete, nodular mass was suspicious for a drop metastasis. At the time of surgery, the lesion was noted to be extrapleural. Unicentric Castleman disease is a benign lymphoproliferative disorder which presents as a homogeneous, well-marginated, highly vascularized enhancing mass commonly involving the mediastinum. These lesions can mimic thymoma, lymphoma, sarcoma, hemangiopericytoma, and neural crest derived neoplasms. Pleural Castleman disease can arise from visceral and parietal pleura with extension into the chest wall or lung fissures and can cause pleural effusion. Intercostal disease can resemble other chest wall masses and cause rib erosions [2]. Chest-wall localization is a rare manifestation of Castleman disease often diagnosed due to non-specific thoracic symptoms such as dyspnea, cough, chest-wall pain or generalized malaise.[3] Complete excision of the lesion is generally curative with cure rate of 95-100%, with recurrence reported with partially resected lesions. CONCLUSIONS: Castleman disease located in the chest wall can present diagnostic and management challenges particularly when present in the context of other lesion with metastatic potential. Reference #1: 1.Benveniste, M.F.K., Rosado-de-Christenson, M.L., Sabloff, B.S., Moran, C.A., Swisher, S.G. and Marom, E.M. (2011). Role of Imaging in the Diagnosis, Staging, and Treatment of Thymoma. RadioGraphics, 31(7), pp.1847–1861. Reference #2: 2.Ko, S.-F., Hsieh, M.-J., Ng, S.-H., Lin, J.-W., Wan, Y.-L., Lee, T.-Y., Chen, W.-J. and Chen, M.-C. (2004). Imaging Spectrum of Castleman's Disease. American Journal of Roentgenology, 182(3), pp.769–775 Reference #3: 3. Rena, O., Casadio, C. and Maggi, G. (2001). Castleman's disease: unusual intrathoracic localization. European Journal of Cardio-Thoracic Surgery, 19(4), pp.519–521. DISCLOSURES: No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Alina Wasim