Reduction In Lymphocyte Count Research Articles

Application of clinical and CT imaging features in the evaluation of disease progression in patients with COVID-19

BackgroundThe Corona Virus Disease 2019(COVID-19) pandemic has strained healthcare systems worldwide, necessitating the early prediction of patients requiring critical care. This study aimed to analyze the laboratory examination indicators, CT features, and prognostic risk factors in COVID-19 patients.MethodsA retrospective study was conducted on 90 COVID-19 patients at the First Affiliated Hospital of Gannan Medical University between December 17, 2022, and March 17, 2023. Clinical data, laboratory examination results, and computed tomography (CT) imaging data were collected. Logistic multivariate regression analysis was performed to identify independent risk factors, and the predictive ability of each risk factor was assessed using the area under the receiver operating characteristic (ROC) curve.ResultsMultivariate logistic regression analysis revealed that comorbid diabetes (odds ratio [OR] = 526.875, 95%CI = 1.384-1960.84, P = 0.053), lymphocyte count reduction (OR = 8.773, 95%CI = 1.432–53.584, P = 0.064), elevated D-dimer level (OR = 362.426, 95%CI = 1.228-984.995, P = 0.023), and involvement of five lung lobes (OR = 0.926, 95%CI = 0.026–0.686, P = 0.025) were risk factors for progression to severe COVID-19. ROC curve analysis showed the highest predictive value for 5 lung lobes (AUC = 0.782). Oxygen saturation was positively correlated with normally aerated lung volume and the proportion of normally aerated lung volume (P < 0.05).ConclusionsThe study demonstrated that comorbid diabetes, lymphocyte count reduction, elevated D-dimer levels, and involvement of the five lung lobes are significant risk factors for severe COVID-19. In CT lung volume quantification, normal aerated lung volume and the proportion of normal aerated lung volume correlated with blood oxygen saturation.

#3974 EFFECTIVE PREDICTION OF NEED FOR CHRONIC DIALYSIS IN CHILDREN, BASED ON RANDOM FORREST ALGORITHMS USING BLOOD CELL COUNT-DRIVEN PARAMETERS

Abstract Background and Aims Persistent, low-grade inflammation is a significant component of chronic kidney disease (CKD) that plays a pivotal role in its pathophysiology, progression, complications, and all-cause mortality. Previous studies have searched for simple, cost-effective, and universally available markers useful in the systemic inflammation assessment in CKD patients. In the adult population, an increase in neutrophil count, correlated with a reduction in lymphocyte count, indicates the rate of progression to dialysis and predicts mortality in hemodialysis and peritoneal dialysis patients. Due to modulating role of platelets within the inflammatory pathways, a mean platelet volume (MPV) and platelet-to-lymphocyte ratio have also been proposed as markers of inflammation. The systemic immune inflammation index (SII) is a newly defined ratio combining neutrophil, lymphocyte, and platelet counts. It is proposed as a prognostic indicator comprehensively reflecting patients' inflammatory and immune status. Recently, elevated SII has shown a predictive value for mortality risk among CKD adult patients. SII has not been evaluated in the pediatric CKD population so far. Thus, the study aimed to analyze complete blood cell count (CBC) driven parameters, including SII, in children with CKD and to assess their potential usefulness in the prediction of the need for chronic replacement therapy with the use of artificial intelligence tools. Method The study group consisted of 27 predialysis children with CKD stages 4-5 (stage 4 - 11 patients, stage 15 - 16 children) and 40 patients on chronic dialysis (HD - 21 children, APD - 19 patients). The patients’ age ranged from 5 to 18 years, children under 5 were excluded due to the different CBC profile regarding neutrophil – lymphocyte proportions. The evaluated CBC parameters were: hemoglobin, hematocrit, leukocyte, neutrophil, monocyte, lymphocyte, platelet counts and MPV. Kidney function, standard biochemical parameters, CRP and SII were also analyzed. This database was used for further analysis. The recursively selected subsets of input variables constituted the input of random forrest classifier (RFC). Each variant has been optimized, taking into account various features (accuracy, AUROC, precision, recall, MCC), then the best model was saved. The aim was to narrow the set of input parameters so that high predictive power is secured, whereas overfitting or overcomplicating could be avoided. Moreover, the GINI importance was measured in order to define the parameter with the largest share in the prediction. Results The best Random Forest Classifier contained neutrophil count, MPV, and SII as input variables, and achieved the following values: AUROC 0.9286, accuracy 93.75%, precision 0.9437, recall 0.9375 and MCC 0.87. The statistics for each class were as follows: precision 0.90, recall 1.00 and f1-score 0.95 for children with CKD 4-5 on conservative treatment; precision 1.0, recall 0.86, and f1-score 0.92 for patients on chronic dialysis. The values of mean GINI importance measured for 40 random splits of the base for MPV, neutrophil count and SII, were 0.28, 0.32 and 0.39, respectively. Conclusion RFC built up with the input variables of neutrophil count, MPV, and SII, was the best predictor of progression into pediatric end stage kidney disease requiring chronic dialysis. SII turned out the most important parameter in the created model, having the largest share in the prediction of need for renal replacement therapy.

Hematological Changes in Patients with Severe COVID-19: Systematic Review and Meta-Analysis

Aims: To produce a systematic review with meta-analysis on the hematological manifestations of COVID-19, comparing the changes among the clinical severity groups.&#x0D; Study Design: We conducted a systematic review with meta-analyses.&#x0D; Methodology: A systematic review was carried out based on the PRISMA 2020 protocol in Medline/Pubmed, Embase, LILACS and SciElo databases. A standardized mean difference was calculated to assess the differences between the groups, with a confidence interval of 95%. Heterogeneity was calculated using the Chi-square test and the I2 test. Significant heterogeneity was defined as p&lt;0.10 or I2&gt;50%.&#x0D; Results: The systematic review search identified a total of 2682 articles, and at the end of the screening, 55 were selected for review and 16 for meta-analysis. The selected articles enrolled 13,289 participants, 10,312 with a mild to moderate clinical condition and 3977 with a severe to critical clinical condition. When comparing the severe disease group with the mild disease group, it was found that the mean values of leukocytes, neutrophils, C-reactive protein (CRP), ferritin, fibrinogen, and prothrombin time (PT) were significantly higher, and the lymphocyte count was significantly lower in the severe group.&#x0D; Conclusions: Individuals with severe COVID-19 had reduced lymphocyte count and elevated leukocytes, neutrophils, CRP, ferritin, fibrinogen, and PT.

Jatropha tanjorensis Euphorbiaceae Ethanolic Leaves Extract Reverses Phenylhydrazine Induced Haematological Alterations in Albino Wistar Rats

Introduction: Phenylhydrazine has been used in many studies to evaluate its modulatory effects in various biochemical parameters in whole blood and red blood cell lysate. Jatropha tanjorensis Euphorbiaceae have high antioxidants properties; its leaves phytochemical analysis shows the presence of flavonoids, tanins, terpenoids, saponis. This study investigated the ameliorative effects of Jatropha tanjorensis Euphorbiaceae on phenylhydrazine induced haematological alterations in albino Wistar rats. &#x0D; Materials and Methods: Wistar rats of both sexes (180-200g) were divided into 4 groups (n=5). Group 1 received rat chow; Group 2 received (200 mg/kg) of J. tanjorensis orally. Group 3 received phenylhydrazine only (10 mg/kg). Group 4 received phenylhydrazine (10 mg/kg) + J. tanjorensis (250 mg/kg). All animals were allowed free access to clean drinking water and normal rat chow ad libitum for 35 days. After which animals were sacrificed and blood samples collected for biochemical analysis.&#x0D; Results: Results obtained showed that phenylhydrazine induced normochromic anemia with significant increase in white blood cell count, and neutrophil counts, eosinophils (insignificant) count with a significant reduction in lymphocyte count. However, J. tanjorensis extract reversed the adverse haematological changes induced by phenylhydrazine.&#x0D; Conclusion: In conclusion, Jatropha tanjorensis Euphorbiaceae demonstrated antioxidant, anti-inflammatory, and anti-thrombotic effects and reversed the haematological alterations brought upon by phenylhydrazine administration.

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Nomogram Based on Preoperative Absolute Lymphocyte Count to Predict Local Recurrence in Patients with Non-Small Cell Lung Cancer After Microwave Ablation.

This study aims to investigate the prognostic value of preoperative absolute lymphocyte count (preALC) for non-small cell lung cancer (NSCLC) after microwave ablation (MWA) and build a combined nomograph with clinical features to predict the local recurrence. A total of 118 NSCLC patients who underwent microwave ablation were enrolled in this study. The median local recurrence-free survival (LRFS) was 35.5 months. Independent prognostic factors obtained by multivariate analysis were included in the prediction model. The prognostic value of the model was assessed by the area under the time-dependent receiver operating characteristic curve (T-AUC). Histological subtype and preALC were independent risk factors for local relapse-free survival. According to the time-dependent receiver operating characteristic curve (T-ROC), the optimal cut-off value of preALC was 1.965×109/L, the sensitivity was 0.837, and the specificity was 0.594. The area under the T-ROC curve (AUC) of preALC was 0.703. To establish a nomogram to predict the local recurrence rate of NSCLC after MWA based on the prognostic factors revealed by Cox regression. Preoperative lymphocyte count reduction is associated with poor prognosis of NSCLC. The nomogram model combined with preALC can provide a good individualized prediction of local recurrence after microwave ablation.

P748 Pharmacokinetics, relative bioavailability, and dose proportionality of a tablet formulation of the sphingosine 1-phosphate-1 receptor modulator VTX002 (formerly OPL-002)

Abstract Background VTX002 is an oral selective sphingosine 1-phosphate-1 receptor (S1P1R) modulator in clinical development for treatment of ulcerative colitis (UC). Single and multiple doses of a spray-dried dispersion (SDD) oral suspension of VTX002 were well-tolerated up to 45 mg in a phase 1 study in healthy participants and were accompanied by dose proportional reductions in lymphocyte counts, an expected pharmacodynamic outcome of treatment.1 A separate phase 1 study compared the pharmacokinetics (PK) and pharmacodynamics of the SDD oral suspension and a tablet formulation of VTX002. Methods Healthy adult participants (N=12) were randomised (4 per dose group) in an open-label 3-way crossover study to receive single oral doses of 5 mg or 20 mg VTX002 tablets, or 20 mg VTX002 SDD suspension followed by at least a 1-week washout between each dose as shown in Fig. 1. Study assessments included: VTX002 plasma concentrations, PK parameters, change from baseline in absolute lymphocyte count (ALC), and adverse events (AE). Results A total of 10 participants completed the study. Mean plasma VTX002 concentrations were greatest with a single oral dose of 20 mg VTX002 SDD suspension (Fig. 2). The geometric mean peak (Cmax) and total (AUCinf) exposure to VTX002 were lower with the 5 mg (dose normalized to 20 mg tablet) and 20 mg VTX002 tablets compared to the 20 mg VTX002 SDD suspension (Table 1). Geometric mean ratios for the tablet and SDD formulations of VTX002 are shown in Table 2. Maximum percent (SD) reduction in ALC from baseline was greatest for the 20 mg VTX002 SDD suspension and was observed at 6 hours post-dose both for the SDD suspension and the 20 mg VTX002 tablet (59.9% [11.0%] and 51.6% [9.4%], respectively). The maximum percent reduction in ALC from baseline for the 5 mg VTX002 tablet was 22.4% (9.2%) which occurred 2 hours post-dose. A total of 23 AEs were reported; of which 19 were considered mild, and 4 were moderate. Conclusion All doses and formulations of VTX002 were well-tolerated and associated with ALC reductions. Data from this relative bioavailability study was used to convert the results from the prior phase 1 multiple ascending dose study performed with VTX002 SDD suspension to AUC equivalent tablet doses and enable tablet dose selection for phase 2. A phase 2 study of VTX002 tablets for treatment of UC is underway (ClinicalTrials.gov Identifier:NCT05156125). 1Luo A, et al. 2020 Gastroenterology. 2020;158(6):S1188.

Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma

IntroductionThis phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody.MethodsRO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model.ResultsOverall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%).ConclusionsRO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma.Trial RegistrationClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www.clinicaltrials.gov/ct2/show/NCT04434469.

Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors.

Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC). While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown. A multicenter, retrospective-prospective Italian study. We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables. We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively). Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i.

Sepsis Due to Bacterial Infection: An Analysis based on Ratio Count of Neutrophil – Lymphocyte

Sepsis due to bacterial infection is a serious medical emergency and requires prompt and proper handling. Various parameters such as white blood cells count, CRP, and PCT level are used as a marker of sepsis due to bacterial infection. Sepsis is a condition of systemic inflammation with infection. Physiological response to systemic inflammation involves an increased level of neutrophils and a reduction of lymphocyte count; therefore, combining both parameters seems logical, and NLCR could be a simple and even better marker in predicting sepsis. This research aimed to determine the sensitivity and specificity of the NLCR test in patients with sepsis due to bacterial infection. This research was conducted by observing 70 sepsis patients aged 14-70 years at a private hospital in Bekasi and UKI general hospital in July-September 2015 through medical records. This research was an observational study with a cross-sectional design. The result of this research showed ROC curve for NLCR test with sensitivity 97.8 % , specificity 84.0 % , and cut off ≥ 6,4 (AUC: 0,94, p-value &lt;0,05). In conclusion, the NLCR is an ideal and efficient marker to diagnose sepsis due to bacterial infection with good sensitivity and specificity tests.&#x0D; Keywords: Sepsis, NLCR, Sensitivity, Specificity.

Lymphocytopenia delays recovery in COVID-19 infected patients.

Objective: To observe the effect of reduced lymphocyte count on the recovery of Covid 19 infected patients. Study Design: Observational study. Setting: Rawal Institute of Health Sciences Islamabad, Pakistan Institute of Medical Sciences, Islamabad. Period: March 2021 till June 2021. Material &amp; Methods: Sample Size: One hundred adult humans suffering from COVID-19 infection. Hundred adult patients with positive PCR test for corona virus were selected. Adult patients belonging to both genders with reduced lymphocyte count and no immunological and blood disorder were included and those below the age of 18 years with any disorder related to immune system or blood were excluded. Adult patients were divided in two groups A and B with 50 patients in each group. Lymphocyte count of all the patients was noted from the record in the laboratory of Rawal institute of health sciences and Pakistan institute of Medical sciences Islamabad. Group A were those whose lymphocyte count was close to reference range and group B were those whose lymphocyte count was very low. Follow up of all the patients was done. Reduction and disappearance of symptoms like fever and cough were considered as recovery symptoms. Statistical Analysis: Data was entered using SPSS version 25. Data was checked for normality by using shapirowilk test. The comparison in the days of recovery with the lymphocyte count showed a significant difference of P value of 0.00. Results: Group A patients had mean lymphocyte count 0.87 x 109 / L and Group B had mean lymphocyte count of 0.45 x 109 / L. The average recovery time for corona virus infected patients with marked reduction in lymphocyte count is 19 days and those with mild reduction in lymphocyte count the average recovery time is 12 days. Conclusion: Patients suffering from COVID-19 infection with less lymphocytopenia showed early recovery and disappearance of symptoms as compared to those with more lymphocytopenia.

Dose-dependent reduction of lymphocyte count and heart rate after multiple administration of LC51-0255, a novel sphingosine-1-phosphate receptor 1 modulator, in healthy subjects.

Aim: Sphingosine-1-phosphate receptor mediates the egress of lymphocytes from lymphoid organs, and its inhibition results in a decreased number of circulating lymphocytes. The aim of the current study was to investigate the safety and pharmacodynamic and pharmacokinetic characteristics of a novel sphingosine-1-phosphate receptor modulator, LC51-0255. Methods: A phase 1 randomized, double-blind, placebo-controlled, multiple dosing, dose-escalation study was conducted on healthy Korean male subjects. Results: After single and daily administration of LC51-0255 for 21 days, a dose-dependent decrease in lymphocyte count and heart rate was observed through 0.25–2 mg dose range of LC51-0255. The mean elimination half-life of LC51-0255 was 76–95 h. LC51-0255 was accumulated with a mean accumulation ratio of 5.17–6.64. During the study, LC51-0255 was generally well tolerated. The most common treatment-emergent adverse event was bradycardia. No clinically significant event of arrhythmia, including AV block, was observed. No clinically significant difference in blood pressure was observed between the dose groups. In other safety assessments, no clinically significant abnormalities were observed, except for bradycardia. Conclusion: Daily administration of LC51-0255 in the range of 0.25–2 mg resulted in a dose-dependent reduction of lymphocyte counts and heart rate. LC51-0255 is generally safe and well tolerated in healthy volunteers.

Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step?

Background: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). Methods: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low- and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. Results: Sixty-three patients were male, and the median age was 83 (3–205) months. Fifty-nine patients (59.6%) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or >1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). Conclusions: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.

Radiological evidence in clinical prevalence of hematological changes in multidrug resistant pulmonary tuberculosis

Background: Globally, tuberculosis is the leading cause of death. India accounts for the highest proportion of drug resistant tuberculosis among all other countries. Objectives: This study investigated the changes in hematological parameters with respect to radiological evidences in multidrug resistant tuberculosis patients. Materials and Methods: The study enrolled a total of 273 patients with the confirmative diagnosis of multidrug resistant tuberculosis. The radiological evidences were classified into mild, moderate and severe lung involvement. Results: The chest radiographs illustrated tracheal deviation (74), loss of lung volume (35), pleural effusion (25), lobar collapse and fibrotic manifestations. The defensive leucocytes, phagocytic neutrophils, anucleated platelet cells and platelet volume observed an increase with severe lung grading (p&lt;0.0001). Reduced lymphocyte count, mean platelet size observed with the intense lung involvement. Prevalence of normocytic, normochromic anemia, anisocytosis was prominent in these patients. The erythrocyte sedimentation rate observed no significant changes in the categorized radiological grades of lung. Radiological grading reported a weak positive correlation with the hematological parameters. Conclusion: The study noticed the changes in the complete blood count parameters with radiological signs and recommend monitoring of these investigations in determining the progression of the lung involvement in the multidrug resistant pulmonary tuberculosis patients.

Single-center experience on progressive multifocal leukoencephalopathy (PML) cases, neuroimaging relevance, and management at West Virginia University (WVU).

Progressive multifocal leukoencephalopathy (PML) is an increasingly common and rapidly fatal demyelinating infection of central nervous system caused by the highly prevalent John Cunningham (JC)virus in immunocompromised individuals belonging to all age groups and genders. Human immunodeficiency virus (HIV) is the most common predisposing factor among other immunodeficient conditions leading to reactivation and multiple neurological symptoms. It has varied findings on magnetic resonance imaging (MRI) and diagnosis is confirmed by positive JC virus in cerebrospinal fluid (CSF). We report 12 confirmed cases of PML from a single academic center. We comprehensively described clinical presentations, risk factors, CSF and neuroimaging findings, treatment and outcome for these cases of PML, a rare disease. The cases were almost equivalently distributed among young and old age groups and both genders. Positive JC virus on CSF was present in the majority of cases along with mild to severe reduction in lymphocyte counts. Significant MRI changes were present in all cases ranging from T2 hypertense signals to white matter lesions in various regions. Treatment with the reversion of immune-modulators, optimization of antiviral therapy (ART), plasmapheresis (PLEX), IVIG, Mirtazapine, oral steroids, and others was started as soon as the diagnosis was made in the majority of the cases. However, PML is a rapidly fatal illness and hence, survival was only seen in 4 cases in our study. The objective of this article is to highlight the importance of early diagnosis of PML with CSF findings and neuroimaging, early reversion of immunosuppressive medications, and careful monitoring and treatment of HIV cases with goals to reduce mortality, long-term morbidity, and deficits.

P237 New-onset systemic lupus erythematosus following COVID-19 vaccination: a report of two cases

Abstract Background/Aims There is a growing number of reports of new-onset autoimmune disease or complications of underlying autoimmune disorders following COVID-19 infection and vaccination. Methods We describe two cases of systemic lupus erythematosus (SLE) that developed de novo in two female patients shortly after receiving their COVID-19 vaccinations. Results The first case is a 29-year-old female with no prior medical history. One week following her COVID-19 Pfizer/BioNTech vaccination, she developed widespread pruritus, fatigue, myalgia, arthralgia, fever and night sweats. Blood tests showed pancytopenia and she was referred for an urgent haematology opinion due to lymphoma. Positron Emission Tomography/computed tomography (PET/CT) demonstrated widespread lymphadenopathy. Bone and lymph node biopsy showed reactive changes only. Her symptoms progressed with polyarticular inflammatory arthritis, oral ulceration, Raynaud’s, pleuritic chest pain, palmar purpuric rash, and a widespread tender urticarial rash. Further investigations showed low complement C3/C4, anti-double stranded DNA antibody titre (dsDNA) &amp;gt;200 IU/mL, positive Anti-Ro antibody, positive Anti-La antibody, weakly positive anti-RNP antibody and an Anti-C1q antibody &amp;gt;400 units/ml with a urine protein/creatinine ratio (PCR) of 39 mg/mmol. A diagnosis of SLE with urticarial vasculitis was made and she commenced Hydroxychloroquine in addition to weaning prednisolone (60mg). A skin biopsy confirmed lupus vasculitis. Despite high dose prednisolone, urine PCR increased over 2 weeks from 39 to 84 mg/mmol. Renal biopsy demonstrated class 3 lupus nephritis. She was pulsed with 500mg IV methyl prednisolone over 3 days and commenced mycophenolate 1g BD. Within weeks she was in clinical remission. The second case is a 70-year-old female with a past medical history of diverticulosis, uterine fibroids and small hand joint osteoarthritis. She presented with a sudden onset, 6-week history of bilateral symmetrical small and large joint synovitis that developed 8 days following the first dose of the COVID-19 Oxford-AstraZeneca vaccine. Her investigations showed reduced lymphocyte counts (0.9 109/L), raised CRP 26 mg/L and ESR 32 mm/hr. Antinuclear antibodies were weakly positive with a homogenous pattern. DsDNA titre was raised at 175 IU/mL and C4 reduced at 0.14 g/L. There was no proteinuria or any evidence of major internal organ involvement. She was started on a short reducing course of oral prednisolone given the severity of her presenting clinical features. Her symptoms improved, with no recurrence on stopping steroids but she has continued elevation in DsDNA; a conservative management approach is being adopted. Conclusion Both cases met the EULAR/ACR and SLICC classification criteria for SLE. There was a clear temporal association between the onset of SLE symptoms and COVID-19 vaccination. Our cases raise the possible association/causation of SLE following COVID-19 vaccination. Potential mechanisms include immune responses elicited by the COVID-19 vaccination, triggering autoimmunity in genetically predisposed individuals. Further research and data from registries are required. Disclosure J. Beynon: None. M. Alsharkawy: None. L. Sammut: None. J. Ledingham: None.

Estimation of Thrombocytopenia in Patients of COVID-19 in a Tertiary Care Centre as a Prognostic marker

Introduction: Severe COVID-19 can lead to critical illness, with Acute Respiratory Distress (ARDS) and Multi-organ Failure (MOF) as its primary complications, eventually followed by intravascular coagulopathy. Haematological changes are common in patients with COVID-19, which include reduced lymphocyte count and platelet count but normal white blood cell count and prolonged activated partial thromboplastin time. Using a simple test like platelet count for assessing the risk of mortality and early identification of severe cases will help in preventing the life threatening complications in patients of COVID-19. Aims and Objectives: To study trends of thrombocytopenia in patients of COVID-19 and to study the correlation between thrombocytopenia and severity of cases of COVID-19. Materials and Methods: The study was carried out in Central Clinical Laboratory in a tertiary care centre. A total of 138 random subjects who were admitted in the COVID ICU were included after they satisfied the eligibility criteria. The CBCs were analyzed on the Beckmann Coulter automated cell count analyzer with EDTA samples obtained from peripheral venipuncture of the patients. Platelet trends over the three samples were studied. Results: An average of all three platelets counts for the patients revealed an overall decreasing trend in cases of non survivors, whereas an overall upward trend was noted in the survivors. A total of 79 patients showed thrombocytopenia (platelet count less than 1.5 lakhs/mm3), during at least one of the tests.46 (33.33%) of these patients succumbed, whereas 33 (23.9%) patients survived. Decreasing trends or overall decreasing trends (Increasing then decreasing) were observed in larger number of non survivors as compared to survivors. Also increasing or overall increasing trends (decreasing then increasing) were common in the survivors. Discussion: Hematological changes are common in SARS patients. For thrombocytopenia, the possible mechanisms of SARS-CoV associated thrombocytopenia may include, 1. Direct infection of megakaryocytes and platelets potentially, inducing cell apoptosis and growth inhibition and/or 2. Immune damage of megakaryocyte progenitor cells or platelets; In addition, the lung damage in SARS patients may also play a role in inducing thrombocytopenia. Conclusion: In this study, we found that platelet count may be a simple, economic, rapid and commonly available laboratory parameter that could straightforwardly discriminate between COVID patients with and without severe disease, while the study of serial platelets counts as trends could help identifying those with a serious risk of mortality.

Фенотипічні особливості імунокомпетентних клітин у I-II триместрах вагітності в жінок із безплідністю в анамнезі

It is impossible to solve the socio-economic problem of increasing the birth rate in Ukraine without determining the mechanisms of pregnancy disorders, among which immune ones occupy an important place, and developing individualized scientifically based therapy schemes. Purpose - to determine the characteristics of levels of immunocompetent blood cells based on the CD phenotype in women with a history of infertility at different stages of pregnancy. Materials and methods. With a FACSCan cell cytofloorimeter (Becton Dickinson, USA) and a test of Becton Dickinson systems (USA) determined using monoclonal antibodies (MCAs) to differentiated lymphocyte antigens, and activation markers (HLA-DR, CD25, CD69) or having inhibitory properties (CD158a) relative levels of immunocompetent cells 436 non-pregnant (reference group n) and 514 pregnant women with a history of infertility at different dates of the I and II trimesters of pregnancy (groups a-e). Results. Against the background of reduced lymphocyte count and increased blood granulocytes in pregnant women, a significantly high relative level of T-L and T-cytotoxic subpopulations were found with their activation (CD3+CD8+HLA-DR+- and CD3+CD8+Cd In this gestation period there is also an increase as the number of T-helpers (CD3+CD4+-L), and their activation with expression on the membranes of HLA-DR- and CD25-molecules. In the first 10 weeks of pregnancy, a decrease in the expression of inhibitory molecules CD158a (KIR2DL1) on NK T CD3+CD4+CD56+-cl and the relative level of B-lymphocytes (CD19+), as well as their subpopulations B-1a (CD19+CD5+) from 8 to 28 weeks was noted. Conclusions. The peculiarities of the levels of peripheral blood immune system cells according to their CD phenotypes make it possible to observe the dynamics of the most important of them (CD3+CD8+HLA-DR+-, CD3+CD8+CD56+-, CD. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: CD-phenotype, immunocompetent cells, pregnant women, history of infertility, flow cytometry.

Upregulated Proteasome Subunits in COVID-19 Patients: A Link with Hypoxemia, Lymphopenia and Inflammation.

Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and β core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expression.

Short-term treatment with Atorvastatin selectively decreases Lymphocyte count

Statins are a chemically related group used as lipid-lowering agents, studies confirmed that statins have additional pleiotropic, cholesterol independent, effects mediated by inhibition of isoprenoid synthesis with subsequent inhibition of the downstream signaling molecules like Rho, Rac, and Ras. However, different statin members might have a distinctive effect on the immune system; thereby having different peripheral and cardiovascular actions, such extra-hepatic effects impose the preferences of one statin over another. The present study aimed to identify the role of the short-term utilization of atorvastatin on leukocyte concentration as a representative in vivo marker for immunomodulation. Two widely used statin agents were included in the study- the lipophilic (atorvastatin) versus the hydrophilic (rosuvastatin) for comparison. Blood samples were withdrawn from the two statin groups, before and after therapy, and an automated differential white blood cell count was performed to determine the difference between the studied samples. The results showed that short-term use of atorvastatin, but not rosuvastatin, was associated with a selective reduction of lymphocyte count (p&lt;0.0001). The study concluded that lymphocyte levels were reduced significantly after short-term use of atorvastatin; an effect which might need to be considered in certain immunological disease associated with cardiac ones.