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Objectives: Cytomegalovirus (CMV) reactivation is a significant cause of morbidity and mortality in critically ill patients. Existing or newly developed immunosuppression appears to be the main factor for reactivation. COVID-19 patients with acute respiratory distress syndrome can be affected by a variety of conditions that cause immunosuppression. Clarifying CMV reactivation and notably its predictive features became important during the epidemic. Method(s): This is a retrospective, observational, and cohort study. All COVID-19 patients admitted to the ICU between March 11, 2020 and March 11, 2021 were analyzed. All of the information was gathered from the hospital's electronic records. CMV reactivation was defined as CMV DNA >=1000 copies/ml in tracheal samples. The patient population was analyzed in two groups, namely, patients with CMV reactivation and patients without reactivation. Result(s): During the study period, 99 of all COVID-19 ARDS patients fulfilled the inclusion criteria, and CMV reactivation was detected in 55 (55.6%) of them. Age, BMI, APACHE-II score, hypertension, chronic respiratory disease, the usage of interleukin blockers, the duration of steroid usage, procalcitonin (PCT), and CD-8 T-cell levels differed significantly from the patients without CMV reactivation. Furthermore, the reactivation group had longer ICU stays, longer durations of mechanical ventilation, and higher mortality. Conclusion(s): CMV can be reactivated in critically ill COVID-19 ARDS patients, which appears to correlate with worse outcomes. Obesity, the usage of IL-blockers and steroids >12 days, high PCT, and low CD-8 T-cell levels appear to be risk factors. Critically ill COVID-19 patients should be closely monitored with regard to immunosuppression and CMV status.Copyright © 2022 by The Cardiovascular Thoracic Anaesthesia and Intensive Care.
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SARS-CoV-2 pandemic is now a global medical and social problem. Little is known about its impact on some vulnerable subgroups, such as immunocompromised patients. Therefore, there is still a strong interest in exploring the impact of SARS- CoV-2 infection among HIV-positive individuals worldwide. Aim of the study: to analyze immunological aspects of the deceased, patients with HIV/COVID-19 coinfection. Materials and. methods. We provided retrospective analysis of 258 patient's electronic medical records. All patients were admitted, to the Infectious diseases hospital N2 with HIV/COVID-19 coinfection and died in May 2020 - February 2022. Standard, immunological parameters were analyzed, like CD4+, CD8+ counts and. immunoregulatory index for different patient's subgroups. Statistical data processing was provided by SPSS 17 version (allowable error E=5%). Results and. discussion. The study demonstrated. CD4+ and CD8+ reduction in HIV-infected with COVID-19. Late HIV-presenters didn't display such phenomenon probably because of immune system, exhaustion. COVID-19 itself in some cases could, lead, to immunodeficiency worsening due to depletion of T cell populations in HIV-patients on effective antiretroviral therapy. Conclusion. Comprehension, of different immunological characteristics in HIV/COVID-19 coinfected patients could, improve therapeutic approaches for this challenging cohort.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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INTRODUCTION: While myopericarditis due to Coxsackie virus-B has been widely reported, multi-organ involvement is rare. We report a unique case of Coxsackie B myopericarditis, which presented with rash, atypical pneumonia, hepatitis, and sepsis. DESCRIPTION: A previously healthy 32-year-old man presented to the emergency department in January 2022 endorsing shortness of breath, high-grade fever (39.2degreeC), non-pruritic rash on extremities, vomiting, and diarrhea. He had tachypnea (24/min), hypoxia (SpO2 93% on air), and mild lymphadenopathy in the neck. Initial evaluation was pertinent for leukocytosis (17.8 thousand/muL) with neutrophil predominance (89.4%), elevated inflammatory markers (D-dimer [4390 ng/mL], procalcitonin [1.79 ng/ mL], CRP [180.7 mg/L], lactate [3.19 mmol/L]), and transamnitis (AST: 160 U/L, ALT: 116 U/L);SARS-CoV-2 and blood cultures were negative. Chest imaging showed bibasilar consolidation, perihilar ground-glass nodules, and pericardial effusion;ultrasound showed acute hepatitis. He was empirically started on ceftriaxone and azithromycin. However, absence of clinical improvement, persistence of high-grade fever, and leukocytosis with low absolute CD3, CD4, and CD8 counts (286 cells/UL, 199 cells/UL and 71 cells/UL, respectively) suggested atypical infection;vancomycin and doxycycline were added. Further infection and autoimmune workup was negative. He developed atrial fibrillation and an echocardiogram was remarkable for ejection fraction of 50-55%, moderate pericardial effusion circumferential to the heart, and minimal collapse of the right atrium. On subsequent testing, Coxsackie virus B type 3 IgM was positive (1:320, reference 1:10). All antibiotics were discontinued, and the patient was managed with diltiazem, colchicine, ibuprofen, and supportive care;anticoagulation was not initiated. After a remarkable improvement in symptoms and rash, he was discharged home. Follow-up imaging showed resolution of bibasilar consolidations and pericardial effusion. DISCUSSION: The likely mechanism of Coxsackie virus B-induced damage to myocytes (and possibly multiorgan involvement) is immune-mediated and direct viral cytotoxicity. Our patient's atypical pneumonia responded well to colchicine and ibuprofen. A high index of suspicion is warranted.
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Background. Covid-19 infection is associated with a lack of immune resilience that may be magnified using immunomodulators to suppress the cytokine storm, facilitating the emergence of opportunistic infections. We describe five cases of cryptococcal infection complications among Covid-19 hospitalized patients. Methods. This was a retrospective cohort study based on chart review performed at the Audie Murphy Veteran Affairs Hospital from 8/2020 to 8/2021;a level 1A facility with 232 beds and an active bone marrow transplantation program. We included patients aged >= 18 with a diagnosis of Covid-19 and subsequent Cryptococcal infection based on cultures or antigen testing. Results. Our patients were all male with ages ranging between 64 to 80 years. Three had underlying type II diabetes, hypertension, and two had end-stage renal disease. Only one had underlying immunosuppression with hydroxychloroquine for rheumatoid arthritis and one had underlying cirrhosis. Four patients had disseminated disease/fungemia while one had localized pulmonary disease. All the cases had low CD4 counts (158-300) and low CD8 counts (92-290). Two of the fungemia cases were diagnosed by blood culture and the other two by serum cryptococcus antigen test. All the patients had received corticosteroids with or without remdesivir, while one received additional tocilizumab, one baricitinib and one convalescent plasma infusion. Four cases of fungemia received liposomal amphotericin B and three of them received additional flucytosine. The patient with cryptococcal pulmonary disease received only fluconazole. Four patients expired at 28 days after diagnosis, only one recovered and is still alive at 1-year follow up. Table 1. Case details. ESRD: end stage renal disease;DM-2: diabetes mellitus type ;HTN: hypertension;A-fib: Atrial Fibrillation;HFpEF: heart failure with preserved ejection fraction;PVD: peripheral vascular disease;RA: rheumatoid arthritis;PTSD: post traumatic stress disorder;BPH: benign prostatic hyperplasia;CAD: coronary artery disease;HLD: hyperlipidemia;CVA: cerebrovascular accident. Conclusion. Cryptococcus infection has been described among patients with Covid-19 during the pandemic. This may be due to immunosuppression caused by the Covid-19 infection and its related-treatments. Most of our patients presented with disseminated cryptococcus infection complicating covid-19 with resulting high mortality rates. Low CD4/CD8 counts and corticosteroid use were documented in all cases. Further studies are needed to better characterize at-risk patients for cryptococcal infection that may benefit from cryptococcal prophylaxis.
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Background and aims: Cladribine is a nucleoside analogue, approved for the treatment of active multiple sclerosis (MS). Looking at clinical trial results, during cladribine treatment, there is a marked and long-lasting CD19 B-cell depletion and a modest T-cell depletion. Immunoglobulin (Ig) levels were never explored. In our real-world study, we evaluated changes in lymphocytes, neutrophils and immunoglobulins over the first 12 months of cladribine treatment. Methods: This observational retrospective study has been conducted on prospectively collected data from 2018 to 2021. Clinical and laboratory data at baseline and after 2, 6 and 12 months were included. Results: Using baseline as reference, total lymphocyte count was lower after 2, 6, and 12 months. Neutrophils were lower after 2 and 6 months, but not after 12 months. We observed no changes in IgG, IgM and IgA over 12 months. CD19 B-cell count was lower after 2 and 6 months, but not after 12 months. CD8 T-cell count was lower after 2 and 6 months, but not after 12 months. CD4 T-cell count was lower after 2, and 6 months, but not after 12 months. Conclusion: We observed a significant decrease in total lymphocyte count from 2 months after cladribine treatment start until the end of year 1. After 12 months, we observed complete reconstitution of CD19 B-lymphocytes. Immunoglobulins remained stable over year-1 cladribine treatment that is also in line with observed normal antibody production to COVID-19 infection and vaccination in patients treated with cladribine.
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Introduction: Covid-19 is an infectious disease with systemic involvement, which causes intense changes in the blood system, such as neutrophilia and lymphopenia, as well as changes in coagulation function and the concentration of acute phase proteins. Infected patients require laboratory follow-up to assist in clinical and therapeutic management. It is important to define efficient parameters to predict the clinical course of the disease, especially when the overall symptoms are becoming worse, in an attempt to anticipate therapeutic measures and to ensure the most appropriate assistance. Purpose: To correlate neutrophil and lymphocyte counts and their subtypes with the severity and outcome of patients with Covid-19. Materials and methods: Patients hospitalized for severe Covid-19, of both genders and without evidence of bacterial pneumonia, seen at the CHC-UFPR between April and June 2020, were included. Lymphocyte subpopulation analysis was performed by multiparametric flow cytometry (MFC) on whole blood sample using antibodies against CD45, CD3, CD4, CD8 and CD19. A BD FACSCanto™ II cytometer and Infinicyt™ 2.0 analysis software were used. ROC curve and other statistical relationships were performed with IBM SPSS™ v. 25 software. Results: Patients were divided as moderate (not intubated, n = 41) and severe (intubated, n = 35). From the median total leukocyte, neutrophil and lymphocyte counts and their subsets, we define the cutoff values with the highest correlation with hospital discharge. Patients with lymphocyte counts higher than 489/μL, CD4 counts higher than 326 and CD8 counts higher than 121 had a greater chance of evolving with a better prognosis (p < 0.001). Patients who had neutrophil-to-lymphocyte ratio (NLR) higher than 15.2 showed greater correlation with worse prognosis. Patients with lymphopenia below cutoff values are 40 to 55% more likely to be intubated and 50 to 63% to progress to death. Patients with NLR higher than 15.2 have 53.1% more chances of being intubated and 78.1% of evolving to death. Discussion: Laboratory evaluation is essential in the follow-up of patients with Covid-19. In addition to routinely used biochemical markers, cellular analysis can provide valuable information about the clinic and its progression. Lymphopenia and neutrophilia are common parameters in patients with severe disease, so NLR analysis presents itself as an objective scale for stratification of infected patients with a high correlation with possible outcomes. Associated with this, assessment of the immune profile with low levels of T-cells and especially low levels of positive CD4 cells has been associated with worse prognosis in patients with severe Covid-19. Conclusion: We conclude that analysis of the neutrophil/lymphocyte ratio routinely obtained from the complete blood count may provide relevant prognostic information for patients with Covid-19. In addition, flow cytometry analysis of CD4 and CD8 T-lymphocytes can complement the screening of patients with Covid-19 by providing information on the immune profile of the disease.
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Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in poor outcome in patients with hematologic malignancies. Moreover, the efficacy of anti-SARS-CoV-2 mRNA vaccines appears lower in immunocompromised patients, including recipients of allogeneic stem cell transplantation (Allo-HSCT). In this population, data are scarce regarding factors predicting the response to mRNA vaccines. Methods This retrospective study aimed to decipher which factors, including immune status at time of vaccine and recipient/donor blood groups, might influence the antibody response after two injections (V1 and V2) of BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of allografted patients with no previous symptomatic nor asymptomatic COVID-19 infection. Possible previous asymptomatic COVID-19 infection was investigated in pre-V1 samples by testing for anti-nucleocapsid (N) antibodies (anti-SARS-CoV-2 immunoassay, Roche Elecsys®, Rotkreuz, Switzerland). Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested post-V2 (Roche Elecsys®). As recommended by the manufacturer, titers ≥0.8 U/mL were considered positive, the highest value being >250 U/mL. Blood samples were also collected before V1 and at distance from V2 to evaluate, by flow cytometry, total lymphocyte (Ly) counts and quantitative Ly subsets (CD3, CD4 and CD8 T cells, B and NK cells). Statistical analyses were performed on R (version 4.0.3). Patient characteristics were compared by using the Χ² test for discrete variables and the Wilcoxon test for continuous variables. Generalized linear models were used to conduct multivariate analyses. Results Samples were available from 117 Allo-HSCT patients who had been vaccinated between January 20 and April 17, 2021. Patient characteristics are provided in Table 1. The average interval from Allo-HSCT day 0 (D0) to V1 (D0-V1) was 654 (IQR: 372-1367) days (d). S-antibody response rate post-V2 was 82.9% for the entire cohort. Non-humoral responders (NHR) post-V2 (n = 20) had a lower D0-V1 interval (median 271 vs 914 d, p <10 -5) and a lower pre-V1 median total Ly count (0.62 vs 1.61x10 9/L, p < 10 -4). Lymphocyte subsets possibly predictive of antibody response were then investigated. NHR were associated with lower median CD3 (0.39 vs 0.97 x10 9/L, p = 0.01), CD4 (0.13 vs 0.35 x10 9/L, p=<10 -3), and B-cell (0.00 vs 0.28 G/L, p <10 -6) counts. NK and T CD8 counts were not statistically different between NHR and HR (respectively p=0.14 and p=0.06). No influence either was observed when considering the age of donors (p=0.39) or recipients (p=0.55), underlying disease (p=1), Allo-HSCT conditioning (p=0.11), blood groups (donor, p=0.55;receiver, p=0.39) or a previous history of graft versus host disease (GVHD;83.1 vs 83.6%, p=1). Conversely, ongoing immunosuppressive (IS)/chemotherapy treatment and a haploidentical source of graft were associated with lower responses to vaccination (respectively 62.5 vs 90.5%, p<10 -3, and 69.4 vs 88.6% for patients with matched donors, p=0.02). In multivariate analysis (Fig.1) also including D0-V1 interval, donor source, current IS/chemotherapy treatment and TCD4 Ly count, only B cell aplasia remained statistically associated with lack of antibody response after two vaccine injections (OR 0.01, 95%CI [0.00 - 0.10], p <10 -3). The possible modification in terms of lymphocyte counts between pre-V1 and post-V2 times has been also investigated showing that only CD4 lymphocytes counts improved significantly (0.31 vs 0.34 x10 9/L, p=0.01) between this interval. Conclusion B cell aplasia appears as a major predictor of anti SARS-CoV-2 mRNA vaccine failure after Allo-HSCT. It may be suggested from this result that a close immune monitoring should be proposed after allotransplant to propose the vaccine at the most appropriate time, meaning after of B cell detection, regardless of the delay from Allo-SCT or the presence of an IS/chemotherapy treatment. The possibility for these patients to have mounted a cellular response should also be considered, which was not investigated here. [Formula presented] Disclosures: Moreau: Celgene BMS: Honoraria;Sanofi: Honoraria;Abbvie: Honoraria;Oncopeptides: Honoraria;Amgen: Honoraria;Janssen: Honoraria.