Extracorporeal Membrane Oxygenation in Immunocompromised Patients With Acute Respiratory Distress Syndrome—A Retrospective Cohort Study

Objective: Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO.Methods: This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease.Results: This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%).Conclusions: Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.

Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?

Background The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. Method This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. Results A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. Conclusion The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.

A Multicentre, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase (MIRROR): 12-Month Efficacy, Safety, Immunogenicity, and Pharmacokinetic Findings of an Open-label Study

Background: Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase+methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here.Methods: Uncontrolled gout patients (serum urate [SU]≥6 mg/dL and SU≥6 mg/dL despite urate-lowering therapy [ULT], ULT intolerance, or functionally-limiting tophi) were included. Patients with immunocompromised status, G6PD deficiency, severe kidney disease, or methotrexate contraindication were excluded. Oral methotrexate (15 mg/week) and folic acid (1 mg/day) were administered 4-weeks before and during pegloticase therapy. Twelve-month responder rate (SU<6 mg/dL for ≥80% during Month 12), 52-week change from baseline in SU, and extended safety were examined. Efficacy analyses were performed for patients receiving ≥1 pegloticase infusion. PK/anti-drug antibodies (ADAs) were examined and related to efficacy/safety findings. Results: Fourteen patients were included (all male, 49.3 ± 8.7 years, 13.8 ± 7.4 year gout history, pre-therapy SU: 9.2 ± 2.5 mg/dL). Three patients were non-responders and discontinued study treatment before 24-weeks, one patient exited the study per-protocol at 24-weeks (enrolled prior to treatment extension amendment), and 10 remained in study through Week 52. Of the 10, 8 completed 52-weeks of pegloticase+methotrexate and were 12-month responders. The remaining two discontinued pegloticase+methotrexate at Week 24 (met treatment goals) and stayed in study under observation (allopurinol prescribed at physicians’ discretion); one remained a responder at 12-months. At 52-weeks, change from baseline in SU was -8.2 ± 4.1 mg/dL (SU: 1.1 ± 2.4 mg/dL, n=10). Gout flares were common early in treatment but progressively decreased while on therapy (Weeks 1-12: 13/14 [92.9%], Weeks 36-52: 2/8 [25.0%]). One patient recovered from sepsis (serious AE). Two non-responders developed high ADA titres; fewer patients had trough concentrations (Cmin) below quantitation limit (BQL) and median Cmin was higher (1.03 mg/mL vs. BQL) than in pegloticase monotherapy trials.Conclusions: Methotrexate+pegloticase co-therapy was well-tolerated over 12-months, with sustained SU lowering, progressive gout flare reduction, and no new safety concerns. Antibody/PK findings suggest methotrexate attenuates ADA formation, coincident with higher treatment response rates.Trial registration: ClinicalTrials.gov: NCT03635957, registered 17 August 2018, https://clinicaltrials.gov/ct2/show/NCT03635957

S100A8 and S100A9, biomarkers of SARS-Cov-2-infected patients, suppress HIV replication in primary macrophages

S100A8 and S100A9 are members of the Alarmin family; these proteins are abundantly expressed in neutrophils and form a heterodimer complex. Recently, both proteins were identified as novel biomarkers of SARS-CoV-2 infection and were shown to play key roles in inducing an aggressive inflammatory response by mediating the release of large amounts of pro-inflammatory cytokines, called the cytokine storm. Although co-infection with SARS-CoV-2 in people living with HIV-1 may result in an immunocompromised status, the role of the S100A8/A9 complex in HIV-1 replication in primary T cells and macrophages is still unclear. Here, we evaluated the roles of the proteins in HIV replication to elucidate their functions. We found that the complex had no impact on virus replication in both cell types; however, the subunits of S100A8 and S100A9 inhibits HIV in macrophages. These findings provide important insights into the regulation of HIV viral loads during SARS-CoV-2 co-infection.

Humoral response after SARS-CoV-2 mRNA vaccines in dialysis patients: Integrating anti-SARS-CoV-2 Spike-Protein-RBD antibody monitoring to manage dialysis centers in pandemic times

Dialysis patients are both the most likely to benefit from vaccine protection against SARS-CoV-2 and at the highest risk of not developing an immune response. Data from the medical field are thus mandatory. We report our experience with a BNT162b2-mRNA vaccine in a retrospective analysis of 241 dialysis patients including 193 who underwent anti-Spike-Protein-Receptor-Binding-Domain (RBD) IgG analysis. We show that a pro-active vaccine campaign is effective in convincing most patients to be vaccinated (95%) and frequently elicits a specific antibody response (94.3% after two doses and 98.4% after three doses). Only immunocompromised Status is associated with lack of seroconversion (OR 7.6 [1.5–38.2], p = 0.02). We also identify factors associated with low response (last quartile; IgG<500AU/mL): immunocompromised status, age, absence of RAAS inhibitors, low lymphocytes count, high C Reactive Protein; and with high response (high quartile; IgG>7000AU/mL): age; previous SARS-CoV-2 infection and active Cancer. From this experience, we propose a strategy integrating anti-spike IgG monitoring to guide revaccination and dialysis center management in pandemic times.

COVID-19-related outcomes in immunocompromised patients: A nationwide study in Korea

Background Given the rapid increased in confirmed coronavirus disease 2019 (COVID-19) and related mortality, it is important to identify vulnerable patients. Immunocompromised status is considered a risk factor for developing severe COVID-19. We aimed to determine whether immunocompromised patients with COVID-19 have an increased risk of mortality. Method The groups’ baseline characteristics were balanced using a propensity score-based inverse probability of treatment weighting approach. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for the risks of in-hospital mortality and other outcomes according to immunocompromised status using a multivariable logistic regression model. We identified immunocompromised status based on a diagnosis of malignancy or HIV/AIDS, having undergone organ transplantation within 3 years, prescriptions for corticosteroids or oral immunosuppressants for ≥30 days, and at least one prescription for non-oral immunosuppressants during the last year. Results The 6,435 COVID-19 patients (≥18 years) included 871 immunocompromised (13.5%) and 5,564 non-immunocompromised (86.5%). Immunocompromised COVID-19 patients were older (60.1±16.4 years vs. 47.1±18.7 years, absolute standardized mean difference: 0.738). The immunocompromised group had more comorbidities, a higher Charlson comorbidity index, and a higher in-hospital mortality rate (9.6% vs. 2.3%; p < .001). The immunocompromised group still had a significantly higher in-hospital mortality rate after inverse probability of treatment weighting (6.4% vs. 2.0%, p < .001). Multivariable analysis adjusted for baseline imbalances revealed that immunocompromised status was independently associated with a higher risk of mortality among COVID-19 patients (adjusted odds ratio [aOR]: 2.09, 95% CI: 1.62–2.68, p < .001). Conclusions Immunocompromised status among COVID-19 patients was associated with a significantly increased risk of mortality.

SARS-CoV-2 infection in a child with Fanconi anemia and determined immunosuppressed status

Introduction. SARS-CoV-2 virus infection affects all age groups. In children, the infection mainly causes asymptomatic or mildly symptomatic forms of the disease, regardless of their immune status. Case presentation. We describe the case of a 7-year-old male child, known to have Fanconi anemia, scheduled for bone marrow transplantation. The patient comes from a family outbreak of COVID-19, which is why he was tested for SARS-CoV-2 infection. He is asymptomatic at the time of admission to our clinic. The clinical examination performed at the time of admission shows a patient in good general condition, afebrile, with pale skin and mucous membranes, without respiratory changes. Paraclinically, severe neutropenia, severe normochromic normocytic anemia and severe thrombocytopenia are detected, for which transfusions of erythrocyte mass and platelet mass are performed. Due to the immunocompromised status, antibiotic therapy is instituted. If necessary, symptomatic treatment is administered. The evolution is favorable, and the SARS-CoV-2 RT-PCR control test is negative on the eighth day of hospitalization. Conclusions. Immunocompromised status is not a major risk factor for severe COVID-19 in children.

Psychological Distress Among Cancer Patients During COVID-19 Pandemic in the World: A Systematic Review

Aim: Patients with malignancies, experience high rates of psychological distress. Fear of Corona-infection combined with the interruptions in some treatment programs might affect the psychological health of cancer patients. This review study was conducted to investigate the psychological distress among cancer patients during COVID-19 pandemic to offer system-adapted individual solutions.Materials and methods: To identify the psychological distress of cancer patients, a comprehensive search was carried out in PubMed, Web of Science, and Scopus. English language and original articles were included in this study. Articles that addressed any psychological distress among cancer patients during COVID-19 pandemic were included.Results: At first 1,410 articles, were included in the study. After removing duplicate articles and reviewing the title and abstract, 55 articles were selected for the review. The findings of this study revealed COVID-19 greatly affects psychological health of cancer patients. Fear of COVID-19, fear of disease progression, disruption of oncology services, cancer stage, and immunocompromised status were the most common causes of psychological distress in oncology patients which can influence patients' decisions about treatment.Conclusion: The COVID-19 related anxiety is an expected reaction to the current situation. Although psychological distress affects many people, it can confuse cancer patients to the point that they refuse to continue treatment for the fear of infection and worsening of their condition. Since the end of this pandemic is unknown, this action can endanger the health and prognosis of this group of patients, so it seems that using psychological interventions and intensive counseling in the current situation is one of the main priorities for cancer patients.

Non-relapse mortality among patients diagnosed with chronic GVHD: An updated analysis from The Chronic GVHD Consortium

Chronic graft-versus-host disease (GVHD) is the leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. To better understand patients at highest risk for non-relapse mortality (NRM), we analyzed patient, transplant, and chronic GVHD-related variables, risk factors, and causes of non-relapse deaths in an updated cohort of 937 subjects enrolled on two prospective, longitudinal observational studies through the Chronic GVHD Consortium. The median follow-up of survivors was 4 years (0.1 months - 12.5 years). Relapse accounted for 25% of the 333 deaths. The cumulative incidence of NRM was 22% at 5 years and increased over time with a projected 40% (95%CI, 30-50) at 12 years. Centers reported that chronic GVHD (37.8%) was the commonest cause of NRM and was associated with organ failure, infection, or additional cause not otherwise specified. The next most frequent causes without mention of chronic GVHD were infection (17%) and respiratory failure (10%). In multivariate analysis, an increased risk for NRM was significantly associated with the use of reduced intensity conditioning, higher total bilirubin, NIH skin score 2-3, NIH lung score 1-3, worse modified HAP adjusted activity score, and decreased distance on walk test. In conclusion, chronic GVHD NRM does not plateau but increases over time and is most commonly attributed to GVHD or infection, presumably associated with immunocompromised status. Severe skin and lung chronic GVHD remain challenging manifestations associated with increased NRM, for which novel therapeutic options are needed that do not predispose patients to infections.

Varicella Pneumonia in an Adult with Immunocompromised Status: Case Report

Varicella is an acute infectious disease caused by the varicella zoster virus. It mainly occurs in infants and preschool children, the morbidity is only 2% in adults. Adult chickenpox is a self-limited disease, which is easier to control the development of rashes to some certain extent, shorten the course of the disease, reduce or avoid long-term complications. We present the case of a 23-year-old man with varicella. He had a two-day fever and four-hour erythematous rashes. The rashes spread around the face, two arms, and trunk. No special finding was in laboratory examination but low immunity. Computed tomography of the chest revealed obvious pneumonia manifestation of two lungs. Varicella pneumonia was considered and antiviral therapy, as well as Chinese patent drug of inhibiting lung-energy and dispersing heat, were applied. Fourteen days later, he was fully recovered. Varicella pneumonia was one of the severe forms, especially in hypoimmunity patients while low immunity may be its main cause. All patients with varicella should detect immunity-related laboratory tests included in lymphocyte subsets, which was important to help their recovery and cut costs.