ABSTRACT
Objectives: Aicardi-Goutières syndrome (AGS) is a rare neurological disease with cutaneous manifestations. We report a case of AGS with chilblain-like lesions and psychiatric symptoms, which are exceptionally presented in these patients. Moreover, the diagnostic process was challenging since skin lesions appeared during the COVID-19 pandemic, when chilblain-like lesions where commonly seen among pediatric and adolescent populations. Method: A 17-year-old man with personal history of pychomotor delay and limb spasticity, was seen at the emergency department with acral lesions worsened by exposure to cold, suggestive of perniosis. He presented one year later, during the first wave of the COVID-19 pandemic in Spain, with new chilblain-like lesions on his feet. Histological findings were consistent with trombotic vasculophaty. Coagulation workup and inmunological investigations were normal. Ten months later, the patient presented at the emergency department with hallucinations and catatonia, requiring hospitalization. Computed tomographic scan was performed showing intracranial calcifications. Results: Based on the developmental delay, spasticity, psychomotor retardation, cutaneous and radiological findings, AGS was suspected and confirmed with a genetic testing (biallelic pathogenic variants in SAMHD1). Discussion: AGS is considered a type I interferonopathie presenting with an early onset encephalopathy;however it has a broad clinical spectrum, with milder phenotypes of later onset, where the presenting symptom may be cutaneous rather than neurological. The genetic basis of AGS have highlighted the fundamental role of nucleic acid signalling in the induction of type I IFN and the range of phenotypes associated with mutations in these genes is much broader than previously realized. Skin manifestations represent the most prominent extraneurologic features, being chilblain-like lesions the most frequent. However, to our knowledge, there is only one previous report of AGS with psychiatric symptoms. The dermatologist must be aware of this syndrome, and consider it when assessing patients with chilblain-like lesions in the presence of neurological symptoms, even if they are mild.
ABSTRACT
Introduction & Objectives: The TMPRSS2 protein has been found to be involved as a critical host cell factor in severe acute respiratory syndrome caused by coronavirus 2(SARS-CoV-2). The production of this protein is regulated by the androgen receptor (AR), also in non-prostatic tissues, including the lung. There is the speculation that androgen deprivation therapy (ADT) may protect patients affected by prostate cancer (PC) from SARS-CoV-2 infection. Our goal is to analyze the severity of COVID-19 in PC patients and the possible influence of ADT on this infection. Materials & Methods: Retrospective study of patients treated for COVID-19 between March 15th and May 15th 2020 in our institution who had previous diagnosis of PC. Patients were divided into two: Those treated with ADT during the infection or the year before, and those who were not treat with ADT on that period. Differences between groups in demographic characteristics, parameters of PC disease, risk factors for SARS-CoV-2 pneumonia, the presence of severe COVID-19 and mortality rates were analyzed. Results: During the study period, a total of 1365 patients were treated in our center for COVID-19 documented with positive PCR. From a total of 1349 subjects registered in our PC database, 156 were on ADT treatment and 1193 were not. Out of the total, 61 (4.52%) PC patients suffered from COVID-19, 11 (18.0%) belonged to the ADT group and 50(82.0%) to the non-ADT group. The mean age of the series was 77.6 years (SD:7.7). The cumulative incidence recorded of COVID-19 in total PC patients was 4.5% (95%CI: 3.5-5.8). Demographic variables, comorbidities and risk factors for infection were quite homogeneous in both groups. Although a worse tendency was observed in the non-ADT group, no statistically significant differences were found in any of the variables analyzed. Regarding the influence of ADT on the course of the disease, no statistically significant differences were found neither in the exitus rate (27.3% vs. 34.0%;p 0.481), nor in the presence of severe COVID-19: need for intubation or ICU admission(0% vs 6.3%;p 0.561) and need for corticoid treatment, interferon beta or tocilizumab (60% vs. 34.7%;p 0.128). In the univariate analysis, treatment with ADT was not found to be a protective factor for worse clinical evolution (RR 1.11;95%CI 0.67-1.85;p=0.68) or exitus (RR 0.8;95%CI 0.28-2.27;p=0.68). We also found no statistically significant differences when multivariate analysis adjusted for clinically relevant comorbidities was performed. Conclusions: In our study, the use of ADT has not been shown to be a protective factor against serious COVID-19. In view of the results published to date, more research in this area is definitely needed to draw firm conclusions.
ABSTRACT
INTRODUCTION Immunocompromised patients have been excluded from initial trials evaluating SARS-CoV-2 mRNA vaccines and there is a critical need to warrant vaccine efficacy in hematopoietic stem cell transplant (HSCT) recipients. In this study, we evaluated antibody responses to 2 doses mRNA SARS-CoV-2 vaccine in allogeneic HSCT recipients. METHODS We retrospectively enrolled successive hematopoietic cell transplant recipients across France who completed the 2-dose SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273) between January 1 st and July 15 th 2021. All included patients had an available semi-quantitative antispike serologic testing after the second dose (from Roche, DiaSorin, Abbott or Siemens). We excluded patients with a prior COVID-19 confirmed by serology or PCR. For detectable antibody, we calculated the binding antibody units per milliliter (BAU/mL) according to the WHO International Standard by applying conversion factors given by the manufacturers (Kristiansen et al., The Lancet 2021). Antibody response was categorized as “weak” or “good” with a threshold of 264 BAU/mL which has been associated to an estimate of 80% of mRNA vaccine-induced protection against symptomatic COVID-19 in immunocompetent patients (Feng S. et al., medRxiv 2021). We built a multivariate logistic regression model to assess factors independently associated with the absence of antibody response after the second dose of mRNA vaccination. RESULTS Overall, 620 allogeneic HSCT recipients from 12 hospitals across France were included in the analysis (60% male with a median age of 59 years old [IQR 47-66]), most with a myeloid (69%) or lymphoid (26%) malignancies. Donors were matched unrelated for 51%, HLA-identical sibling for 31% and haplo-identical for 18%. Thirty-one percent of HSCT recipients underwent a myeloablative conditioning, while 69% received a reduced intensity conditioning. The two doses of vaccines were given one month apart and the median time between transplantation and the initiation of vaccination was 29 months [IQR 14-58]. At a median of 33 [IQR 27-50] days after dose 2, an antibody response was detectable in 496 patients (80% [95CI: 77 to 83%]). Median [IQR] antibody levels was 243 BAU/mL [29.4-1391]. We classified detectable antibody responses as “weak” in 189 patients (30% [95CI 27 to 34%]) and as “good” in 306 (49% [95CI: 45 to 53%]). In the multivariate analysis including 533 patients (420 with detectable antibodies), factors associated with the absence of humoral responses were a time-interval from HSCT < 12 months (ajusted Odds-Ratio (aOR) 2.8 [95CI 1.6 to 4.8]), absolute lymphocyte count <1G/L (aOR 3.0 [95CI 1.7 to 5.0]), systemic immunosuppressive treatments within 3 months of vaccination (aOR 4.5 [95CI 2.7 to 7.5]), together with the use of rituximab within 6 months (aOR 15.1 [95CI 4.3 to 52.7]). In a subsequent multivariate analysis conducted a subset of 227 patients (170 with detectable antibodies) with available gammaglobulinemia as well as B and T lymphocytes counts, factors remaining associated with the absence of antibody response were only low B-lymphocytes count (aOR 5.5 [95CI 2.4 to 12.3]) and time-interval from HSCT < 12 months (aOR 3.3 [95CI 1.5 to 7.2]). CONCLUSION After 2 dose mRNA vaccination, the majority of allogeneic HSCT recipients developed an antibody response although a significant proportion of these responses may be insufficient. Studies are still needed to investigate the effect of a third vaccine dose in patients with a null or weak humoral response. Disclosures: Loschi: Servier: Ended employment in the past 24 months, Honoraria;Novartis: Ended employment in the past 24 months, Honoraria;Gilead: Ended employment in the past 24 months, Honoraria;AbbVie: Ended employment in the past 24 months, Honoraria;CELGENE/BMS: Honoraria;MSD: Honoraria.