LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1 [1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt's assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15 (Table 1). The overall UPA safety profile remained unchanged (Figure 1) [1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a (n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/ 48.263.1/54.1*/ 35.787.9/74.4/ 47.861.1/46.6/ 28.786.2/65.2/ 39.8Minimal disease activity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/ 43.458.1/46.7/3 7.678.6/63.5/ 50.954.0/40.8/ 30.379.6/59.9/ 44.6Resolution of enthesitis by Leeds Enthesitis Indexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds Dactylitis Indexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire- Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt's assessment of pain (numeric rating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease Activity Indexf-3.09-3.27-3.16-3.54-2.81-2.71Modified total Sharp/van der Heijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104);data are presented by originally randomized group. bPts with psoriasis affecting ≥3% of body surface area at BL. cPts with LEI >0 at BL;resolution LEI=0. dPts with LDI >0 at BL;resolution LDI=0. eData shown as MMRM (least squares mean) and AO (mean). fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria;ADA, adalimumab;AO, as observed;BL, baseline;MMRM, mixed effect model repeated measurement;NRI, non-responder imputation;PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index;pt, patient;UPA15/30, upadacitinib 15/30 mg once daily;wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB;and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.

Regulatory CD4+ and CD8+ T cells are negatively correlated with CD4+ /CD8+ T cell ratios in patients acutely infected with SARS-CoV-2.

Regulatory T cell can protect against severe forms of coronaviral infections attributable to host inflammatory responses. But its role in the pathogenesis of COVID-19 is still unclear. In this study, frequencies of total and multiple subsets of lymphocytes in peripheral blood of COVID-19 patients and discharged individuals were analyzed using a multicolor flow cytometry assay. Plasma concentration of IL-10 was measured using a microsphere-based immunoassay kit. Comparing to healthy controls, the frequencies of total lymphocytes and T cells decreased significantly in both acutely infected COVID-19 patients and discharged individuals. The frequencies of total lymphocytes correlated negatively with the frequencies of CD3- CD56+ NK cells. The frequencies of regulatory CD8+ CD25+ T cells correlated with CD4+ /CD8+ T cell ratios positively, while the frequencies of regulatory CD4+ CD25+ CD127- T cells correlated negatively with CD4+ /CD8+ T cell ratios. Ratios of CD4+ /CD8+ T cells increased significantly in patients beyond age of 45 years. And accordingly, the frequencies of regulatory CD8+ CD25+ T cells were also found significantly increased in these patients. Collectively, the results suggest that regulatory CD4+ and CD8+ T cells may play distinct roles in the pathogenesis of COVID-19. Moreover, the data indicate that NK cells might contribute to the COVID-19 associated lymphopenia.

Serositis and lymphopenia are common features of systemic lupus erythematosus following SARS-CoV-2 infection: A case report and literature review.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect a number of human systems, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. These symptoms persist long after the acute infection has healed and is called "long COVID". Interestingly, there have been a series of reports that SARS-CoV-2 infections trigger the development of various autoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory arthritis, myositis, vasculitis. Here, we report a novel case of SLE characterized by persistent pleural effusion and lymphopenia following SARS-CoV-2 infection. This is the first case in the Western Pacific region to our knowledge. Furthermore, we reviewed 10 similar cases including our case. By looking at the characteristics of each case, we found that serositis and lymphopenia are common features of SLE following SARS-CoV-2 infection. Our finding suggests that patients with prolonged pleural effusion and/or lymphopenia after COVID-19 should be checked for autoantibodies.

Differentially Expressed Inflammatory Cell Death-Related Genes and the Serum Levels of IL-6 are Determinants for Severity of Coronaviruses Diseases-2019 (COVID-19).

Background: Inflammatory cell death, PANoptosis, has been suggested to orchestrate the lymphocyte decrement among coronavirus disease-2019 (COVID-19) patients. The main aim of this study was to examine the differences in the expression of key genes related to inflammatory cell death and their correlation with lymphopenia in the mild and severe types of COVID-19 patients. Materials and Methods: Eighty-eight patients (36 to 60 years old) with mild (n = 44) and severe (n = 44) types of COVID-19 were enrolled. The expression of key genes related to apoptosis (FAS-associated death domain protein, FADD), pyroptosis (ASC (apoptosis-associated speck-like protein containing caspase activation and recruitment domains (CARD)), the adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli), and necroptosis (mixed lineage kinase domain-like, MLKL) genes were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay, and compared between the groups. The serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay (ELISA) assay. Results: A major increase in the expression of FADD, ASC, and MLKL-related genes in the severe type of patients was compared to the mild type of patients. The serum levels of IL-6 similarly indicated a significant increase in the severe type of the patients. A significant negative correlation was detected between the three genes' expression and the levels of IL-6 with the lymphocyte counts in both types of COVID-19 patients. Conclusion: Overall, the main regulated cell-death pathways are likely to be involved in lymphopenia in COVID-19 patients, and the expression levels of these genes could potentially predict the patients' outcome.

T Lymphocyte Subset Counts and Interferon-Gamma Production in Adults and Children with COVID-19: A Narrative Review.

Adults and children exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with minimal to mild symptoms, especially in the pediatric age. However, some children present with a severe hyperinflammatory post-infectious complication named multisystem inflammatory syndrome in children (MIS-C), mainly affecting previously healthy subjects. Understanding these differences is still an ongoing challenge, that can lead to new therapeutic strategies and avoid unfavorable outcomes. In this review, we discuss the different roles of T lymphocyte subsets and interferon-γ (IFN-γ) in the immune responses of adults and children. Lymphopenia can influence these responses and represent a good predictor for the outcome, as reported by most authors. The increased IFN-γ response exhibited by children could be the starting point for the activation of a broad response that leads to MIS-C, with a significantly higher risk than in adults, although a single IFN signature has not been identified. Multicenter studies with large cohorts in both age groups are still needed to study SARS-CoV-2 pathogenesis with new tools and to understand how is possible to better modulate immune responses.

Hematological Profile in COVID-19 Infection Among Patients in a Tertiary Care Hospital in Tamil Nadu, South India.

Introduction A wide range of hematological abnormalities has been observed in SARS-CoV-2 infection which is directly related to the disease progression, clinical severity, and mortality among affected individuals. The objective of this study was to evaluate the abnormalities in hematological parameters among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients in a tertiary care hospital in south India. Methods This was a cross-sectional study carried out in the pathology department of Karpaga Vinayaga Institute of Medical Sciences and Research Centre, Chengalpattu, Tamil Nadu, India from 1st May 2021 to 30th June 2021. The hematological reports including complete blood count (CBC), neutrophil-lymphocyte ratio (NLR), serum ferritin, serum C-reactive protein (CRP), serum lactate dehydrogenase (LDH), and D-dimer levels of all the blood samples from COVID-19 positive patients were retrieved from the laboratory records. The Leishman-stained peripheral smear findings were also tabulated and analyzed. Results Out of 65 patients, 38 (58.5 %) were males and 27 (41.5%) were females with a majority (78.4%) of them being more than 40 years of age. The salient hematological abnormalities were leukopenia (21.5%), elevated NLR (43%), and thrombocytopenia (6.2%). Peripheral smear showed schistocytes (15.4%), neutrophils with ring nuclei (84.6%), and toxic granules (81.5%). A statistically significant association between elevated NLR and serum CRP was seen among male patients. The association between the presence of schistocytes with serum LDH and D-dimer levels was statistically insignificant. Conclusions The significant hematological abnormalities in patients with COVID-19 infection were elevated NLR, lymphopenia, thrombocytopenia, and elevated D-dimer levels. Careful evaluation of the hematological parameters will help in categorizing the high-risk cases and thereby initiating early intervention and appropriate intensive care management. This will bring down the morbidity and mortality among COVID-19 patients.

Cellular Therapy Applications for COVID-19

COVID-19 is caused by infection with the novel coronavirus SARS-CoV2, which in turn precipitates severe acute respiratory distress syndrome (ARDS) due to being associated with a cytokine release syndrome (CRS). Inflammatory endothelialitis is also implicated in disease pathophysiology. Cell-based therapy (CBT) is undergoing testing in numerous mechanistic and pivotal clinical trials due to its known immunomodulatory properties. Culture-expanded mesenchymal stem cells (CD105+ cells) may be safely administered as an allograft and can suppress exuberant immune responses, improve endothelial function, and boost T- and B-cell responses. Early-stage open-label trials have reported potential clinical responses, and pivotal trials have been rapidly initiated. Coupled with the known safety profile, CBT may emerge as a valuable addition to the therapeutic armamentarium for SARS-CoV2. © Springer Nature Switzerland AG 2009, 2022, Corrected Publication 2022.

Restrospective study of hemogram profile in effusive feline infectious peritonitis

Feline Infectious Peritonitis (FIP) is highly mortality disease in cats. The reliable and fast diagnosis is crucial to the best prognosis. The aim of this study to evaluate the hemogram profile in cats infected with effusive FIP. Twenty cats had been diagnosed effusive FIP at Animal Clinic Department of Internal Medicine, Faculty Veterinary Medicine, Universitas Gadjah Mada were used in the study. The diagnosis were based on clinical examination, ultrasound, x-ray, rivalta test, and rapid test. The hemogram profile were analyzed include routine hematology and serum biochemistry. Hemogram profile in effusive FIP showed the decreased hematocrit, hyperproteinemia, and leukocytosis with an average 22.9+or-7.4%;9.0+or-2.2 g/dL;22425+or-4116 cells/mm3 respectively. Erythrocyte, hemoglobin and fibrinogen levels were still in the normal range. The results of differential leukocytes revealed that 90% cats had neutrophilia and 75% lymphopenia with an average 20066+or-3337 cells/mm3 and 1861+or-1818 cells/mm3 respectively. The blood chemistry profile showed 60% of cats experienced increase in SGPT and SGOT with an average 138.4+or-72.3 IU/L and 101+or-60.5 IU/L respectively. Hyperglobulinemia was found in 90% samples with an average 6.7+or-0.8 g/dL. All cats have a low albumin:globulin ratio with an average 0.3+or-0.1. The hemogram profile of effusive FIP were: leukocytosis, neutrophilia, lymphopenia, hyperglobulinemia, and decreased albumin-globulin ratio..

Relationship Between Viral Load and Laboratory Values and Radiological Findings in Patients with COVID-19

Introduction: This study investigates the relationship between the viral load calculated from oropharyngeal/nasopharyngeal swabs at diagnosis and the laboratory parameters and radiological findings in patients with Coronavirus disease-2019 (COVID-19).Materials and Methods: Sixty-seven patients who were positive for severe acute respiratory syndrome-coronavirus-2 via quantitative reverse transcription-polymerase chain reaction (qPCR) from their oropharyngeal/nasopharyngeal swabs and admitted to Malatya Turgut Ozal University Hospital were included in the study. Demographic data, laboratory parameters, and the severity of thorax computed tomography findings were recorded. The relationship between the viral load and these data was compared.Results: The mean age of the patients was 63.4 +/- 9.8 years, mean body mass index (BMI) was 28.6 +/- 5.4 kg/m2, and mean cycle threshold (Ct) values were 21.4 +/- 5.2 cycles. No correlation was found between Ct value and gender, age, and BMI. There was a significant relationship between radiological severity and Ct value, age, and gender. There was a significant correlation between the Ct value and C-reactive protein, leukocyte, neutrophil, lymphocyte, neutrophil-lymphocyte ratio, ferritin, albumin, and calcium levels. In contrast, no significant correlation was found betweenConclusion: The viral load amount shown by PCR during the early period predicts the condition of the patient's lung in the advanced immunological phase. The Ct value can be an independent factor for evaluating the patient's radiological and biochemical status.

Infections and causative microorganisms in patients with ANCA-associated vasculitis

Purpose: The aim of this study was to detect infections requiring hospitalization in patients with ANCA-associated vasculitis (AAV).Materials and Methods: This is a single-center, retrospective study conducted in Turkish patients with AAV. Infection episodes requiring hospitalization, reproducing pathogens, laboratory findings, immunosuppressive treatments given for the treatment of vasculitis, and the relationship with the infection were evaluated.Results: Seventy-four patients diagnosed with AAV were included in the study. Hospitalization due to infection was observed in 36 of the patients. The coexistence of diabetes mellitus (DM) was found to be significantly higher in the infected patient group. Cyclophosphamide (CYC) treatment found to increase risk of infection. More than 80% of the infected patient group presented with renal involvement (80.6%). A total of 68 infectious episodes were seen in 36 patients. The most common involvement of infection was the respiratory tract with a rate of 70.6%. Gram-negative bacteria were the most common pathogen, especially Pseudomonas aeruginosa. With the effect of the pandemic, SARS-CoV-2 has come to the fore among viral infections. Aspergillosis was the most frequently detected among fungal infections. Besides, aspergillosis was the cause of 85.7% (6 episodes) of fungal infections. Lymphopenia was observed in 76.5% of the infection episodes. 57.4% of infections developed in the first year of the induction therapy. The most frequently used immunosuppressive therapy for the treatment of vasculitis in infectious episodes was CYC (41.2%).Conclusion: Managing infections during the vasculitis treatment is crucially important. Lymphopenia, kidney involvement, DM and immunosuppressive therapy are factors that increase the risk of infection. Clinicians should take preventive measure especially for respiratory tract infections and gram-negative bacteria as pathogens.

A Pilot Trial of Thymalfasin (Thymosin-alpha-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection

Background. Thymosin-alpha-1 (T alpha 1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. Methods. Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of T alpha 1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. Results. A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25] ) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4(+) T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to T alpha 1. Conclusions. T alpha 1 increases CD4(+) T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19.

Lymphocytes count, acute phase protein and renal function in COVID-19 patients as disease severity predictors

Coronavirus disease 2019 is an infection caused by severe acute respiratory syndrome coronavirus-2. The clinical spectrum of this illness ranges from asymptomatic infection to acute respiratory distress syndrome (ARDS), circulatory shock, multiorgan failure, and ultimately death. The aims of this study are to assess of lymphocyte count, to study of acute phase proteins inflammatory biomarker which include ferritin, lactate dehydrogenase, and D-dimer, and to study of renal function markers which include blood urea nitrogen and serum creatinine. The data accumulated throughout this selective case control study which were extended from September 1st, 2020, to December 1st, 2020. A total of 176 human serum samples were collected, and subdivided into four groups moderate, sever, critical and control, each group comprised of 44 individuals. Results: The data was analyzed using the SPSS-20 statistical package that was available (Statistical Packages for Social Sciences-version 20). The results showed a highly significant decrease in the mean of Lymphocyte in Covid-19 patients when compared to the control group, p.value = 0.000. But Lymphocyte showed no significant differences among moderate, severe, and critical groups p.value = 0.580, p.value = 192, p.value = 456 respectively, where all of them had low lymphocyte count. The means of lactate dehydrogenase, ferritin, and D-dimer a showed a highly significant increase in Covid-19 patients when compared to the control group, p.value = 0.000, p.value = 0.000, p.value = 0.000 respectively. The results showed a highly significant increase in BUN in COVID-19 patient when compared with control group, p.value = 0.001, but the creatinine doesn't show any significant differences in COVID-19 patient when compared with control group, p.value = 0.405. Lactate dehydrogenase showed highly significant increase in critical group when compared with moderate group, p.value = 0.004, and showed significant differences in severe group when compared with moderate group, p.value = 0.031, but did not show significant differences between severe and critical groups, p.value = 0.690. Ferritin and D-dimer showed highly significant increase in critical group when compared with moderate group, p.value = 0.009, p.value = 0.000 respectively, and severe group, p.value = 0.002, p.value = 0.000 respectively. While, showed no nay significant differences between severe and moderate groups, p.value = 0.579, p.value = 0.075 respectively. Urea showed highly significant increase in critical group when compared with sever group and moderate group, p.value = 0.000. Creatinine showed significant increase in critical group when compared with sever group and moderate group, p.value = 0.031, p.value = 0.034 respectively. Both urea and creatinine showed no significant differences between severe and moderate groups p.value = 0.747, p.value = 0.958 respectively. Conclusions: In COVID- 19 patients, lymphopenia is a prognostic factor, increase levels of acute phase protein lactate dehydrogenase, D-dimer, and ferritin associated with disease severity, and the blood urea nitrogen and serum creatinine among critical group were associated with disease severity. © 2023 Author(s).

Diabetes as one of the long-term COVID-19 complications: from the potential reason of more diabetic patients' susceptibility to COVID-19 to the possible caution of future global diabetes tsunami.

According to recent researches, people with diabetes mellitus (type 1 and 2) have a higher incidence of coronavirus disease 2019 (COVID-19), which is caused by a SARS-CoV-2 infection. In this regard, COVID-19 may make diabetic patients more sensitive to hyperglycemia by modifying the immunological and inflammatory responses and increasing reactive oxygen species (ROS) predisposing the patients to severe COVID-19 and potentially lethal results. Actually, in addition to COVID-19, diabetic patients have been demonstrated to have abnormally high levels of inflammatory cytokines, increased virus entrance, and decreased immune response. On the other hand, during the severe stage of COVID-19, the SARS-CoV-2-infected patients have lymphopenia and inflammatory cytokine storms that cause damage to several body organs such as ß cells of the pancreas which may make them as future diabetic candidates. In this line, the nuclear factor kappa B (NF-κB) pathway, which is activated by a number of mediators, plays a substantial part in cytokine storms through various pathways. In this pathway, some polymorphisms also make the individuals more competent to diabetes via infection with SARS-CoV-2. On the other hand, during hospitalization of SARS-CoV-2-infected patients, the use of some drugs may unintentionally lead to diabetes in the future via increasing inflammation and stress oxidative. Thus, in this review, we will first explain why diabetic patients are more susceptible to COVID-19. Second, we will warn about a future global diabetes tsunami via the SARS-CoV-2 as one of its long-term complications.

Regulation of lymphocyte apoptosis in intensive care patients with COVID-19

Severity of a new coronavirus infection (COVID-19) caused by the SARS-COV-2 virus is largely due to abnormal immune condi-tion in these patients. Lymphopenia is observed in 85% of patients with severe COVID-19 that may be associated with enhanced apoptosis of lymphocytes. Objective. To analyze apoptotic death of lymphocytes and changes in proteins regulating apoptosis in patients with severe COVID-19. Material and methods. We analyzed 93 ICU patients. All patients were divided into three groups depending on severity and outcomes of disease: group 1 consisted of 53 patients with favorable course and outcomes of disease, group 2 included 26 patients with unfavorable course and favorable outcomes of disease, group 3 included 14 patients with unfavorable course and outcomes of disease. Blood sampling for analysis of apoptosis markers was carried out in 5-12 and 14-18 days after clinical manifestation of disease. Quantitative parameters of lymphocyte apoptosis were evaluated using flow cytometry. Regulatory proteins of apop-tosis (phosphorylated AKT, JNK, BAD, BCL-2, p-53, active caspase 8 and 9) were determined on the Luminex platform. We also assessed concentration of leukocytes, relative and absolute lymphocyte count, concentration of C-reactive protein (CRP), procal-citonin and lactate dehydrogenase. Results. Study groups significantly differed in NEWS score (p=0.001), SOFA score (p=0.001), CRP level (p=0.001), severity of lymph-openia (p=0.001) and level of CD14+HLA-DR+ monocytes (p=0.001). Quantitative parameters of lymphocyte apoptosis did not cor-relate with lymphopenia. The highest rates of lymphocyte apoptosis were observed in patients with favorable course and outcomes of disease. There was no correlation between concentration of lymphocytes in venous blood and level of proteins regulating apoptosis. Conclusion. Patients with severe COVID-19 are characterized by abnormal induction of lymphocyte apoptosis through external and internal activation pathways in response to viral aggression. In deceased patients, pro-apoptotic factors prevailed while activity of anti-apoptotic factors was decreased. © 2023, Media Sphera Publishing Group. All rights reserved.

Laboratory and clinical findings in hospitalized pregnant women with Covid-19 based on disease outcome during the outbreak of Delta variant in Ardabil (summer and autumn 2021).

Introduction: Due to the high risk of Covid-19 disease, especially delta variant in pregnant women, as well as the novelty of this epidemic in the world and the lack of similar studies in Iran and the region, it seems necessary to perform a study on mortality rate and laboratory and clinical findings of the disease in pregnant women. Therefore, this study was performed aimed to determine the laboratory and clinical findings in hospitalized pregnant women with Covid -19 based on disease outcome during the outbreak of Delta variant (summer and autumn 2021) in Ardabil province. Method(s): In this cross-sectional and descriptive study, all pregnant women with Covid-19 admitted to the hospitals of Ardabil province in summer and autumn 2021 at the time of delta outbreak were included. Finally, 187 infected pregnant mothers were studied. Demographic information, clinical signs and laboratory findings were studied in all mothers. Data were analyzed by SPSS (version 24) and Fisher Exact test and Pearson Correlation. P<0.05 was considered statistically significant. Result(s): Of the 187 infected pregnant women, 8 mothers died. Comorbidity was observed in 41 pregnant women. The most common clinical finding was shortness of breath (Dyspnea) and cough, and the most common laboratory finding was lymphopenia. Comparing the cured and dead mothers according to laboratory findings using Fisher's exact test showed that the difference between ALT (p <0.05), lactate dehydrogenase (p <0.001), AST (p <0.001), BS (P <0.05), creatinine (p <0.05) and total bilirubin (p<0.05) were statistically significant between the two groups. Conclusion(s): Infection to delta variant of Covid-19 disease resulted in 187 hospitalizations and 8 deaths of pregnant mothers in Ardabil province. Shortness of breath (Dyspnea) and cough were the most common clinical findings and lymphopenia was the most common laboratory finding.Copyright © 2022, Mashhad University of Medical Sciences. All rights reserved.

Laboratory and clinical findings in hospitalized pregnant women with Covid-19 based on disease outcome during the outbreak of Delta variant in Ardabil (summer and autumn 2021).

Introduction: Due to the high risk of Covid-19 disease, especially delta variant in pregnant women, as well as the novelty of this epidemic in the world and the lack of similar studies in Iran and the region, it seems necessary to perform a study on mortality rate and laboratory and clinical findings of the disease in pregnant women. Therefore, this study was performed aimed to determine the laboratory and clinical findings in hospitalized pregnant women with Covid -19 based on disease outcome during the outbreak of Delta variant (summer and autumn 2021) in Ardabil province. Method(s): In this cross-sectional and descriptive study, all pregnant women with Covid-19 admitted to the hospitals of Ardabil province in summer and autumn 2021 at the time of delta outbreak were included. Finally, 187 infected pregnant mothers were studied. Demographic information, clinical signs and laboratory findings were studied in all mothers. Data were analyzed by SPSS (version 24) and Fisher Exact test and Pearson Correlation. P<0.05 was considered statistically significant. Result(s): Of the 187 infected pregnant women, 8 mothers died. Comorbidity was observed in 41 pregnant women. The most common clinical finding was shortness of breath (Dyspnea) and cough, and the most common laboratory finding was lymphopenia. Comparing the cured and dead mothers according to laboratory findings using Fisher's exact test showed that the difference between ALT (p <0.05), lactate dehydrogenase (p <0.001), AST (p <0.001), BS (P <0.05), creatinine (p <0.05) and total bilirubin (p<0.05) were statistically significant between the two groups. Conclusion(s): Infection to delta variant of Covid-19 disease resulted in 187 hospitalizations and 8 deaths of pregnant mothers in Ardabil province. Shortness of breath (Dyspnea) and cough were the most common clinical findings and lymphopenia was the most common laboratory finding.Copyright © 2022, Mashhad University of Medical Sciences. All rights reserved.

Herpes Zoster Duplex Unilateralis as a manifestation of severe lymphopenia in COVID-19

SARS-CoV2 (severe acute respiratory syndrome coronavirus-2), a novel coronavirus was first reported in December of 2019 from Wuhan, China as an aetiological agent causing a new infectious respiratory disease (coronavirus disease 2019- COVID-19). The main clinical manifestations of COVID-19 are fever, cough, fatigue, dyspnoea and muscle aches. Herpes zoster is characterized by several groups of painful vesicles on an erythematous base with a distribution in a unilateral dermatome involving the skin and/or mucosa. Herpes zoster is caused by varicella zoster virus which remains dormant in the sensory root ganglion contained by the immune system particularly CD lymphocytes. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Brucellosis relapse seven years after first infection in a COVID-19 patient: A case report

Coronavirus disease 2019 (COVID-19) emerged in China and then has spread worldwide. It has been seen in Turkey since March. Brucellosis is a zoonotic disease which is observed in Turkey endemically. Here, we report the firstcase of Brucellosis relapse in a COVID-19 patient. A 39-year-old female had cough, dispnea, fatigue and backpain and miyalgia for one week was admitted. She had leucopenia and lymphopenia in whole blood count. She had a contact history with her COVID-19 positive sister. COVID-19 polymerase chain reaction (PCR) test resulted positive. She received hydroxychloroquine treatment for five days. Her COVID-19 PCR became negative and laboratory improved. Her miyalgia, back pain and fatigue got worse. When her medical history was elaborated, she had a brucellosis history seven years ago. She was completely treated and her Brucella serology tests were negative in 2015. She stated that she didn't consume any unpasteurized milk product recently. Rose-Bengal and Coombs agglutination tests were positive (1:320 titers). She was initialized on treatment and symptoms started to resolve after 15 days of treatment. Severe COVID-19 patients show lymphopenia, particularly reduction of T-cells. Cell mediated immunity is crucial against brucellosis. During pandemic, endemic infections like brucellosis can be observed in patients due to lymphopenia. Further immunological studies are needed.Copyright © 2022, Kuwait Medical Association. All rights reserved.