Steroid use in measles: A retrospective cohort study during the 2017 outbreak in tertiary referral center, Rome and Latina, Italy.

INTRODUCTION: Since early January 2017, a new measles outbreak in Italy has been observed. The aim of the study was to compare features between adults and children measles cases and evaluate the effect of steroid treatment on the above parameters. METHODS: A retrospective multicenter, descriptive study was performed. We analyzed all patients admitted to the Department of Public Health and Infectious Diseases, Sapienza University, Rome and Latina, from January 2017 to December 2017 and discharged with diagnosis of measles. RESULTS: We identified 113 patients discharged with the diagnosis of measles infection cases of which 59 adults and 54 children (≤16 years). In adult population 32 patients (54 %) were males, with a median age of 30.5 years old and all unvaccinated (100 %). Keratoconjunctivitis 30 (50 %) was the most frequent complication. In pediatric population 27 (50 %) patients were males, with a median age of 3 years old. Information on measles vaccination status was available for only 21 (38.8 %) of cases. Keratoconjunctivitis 40 (74 %) was the most frequent complication. Analyzing the differences between adult and pediatric patients we found that children were significantly more likely to have keratoconjunctivitis and diarrhea as complications than adults in which the rate of thrombocytopenia and hepatitis was highest. Thirty-nine adult subjects (66 %) have been treated with systemic corticosteroids. CONCLUSIONS: Pediatric patients differ from adults in complications and liver involvement. Regarding steroids use, although there is no clear indication of steroid use during measles, there is no evidence of a worse outcome in our cases series.

Differential expression of Type I interferon and inflammatory genes in SARS-CoV-2-infected patients treated with monoclonal antibodies.

INTRODUCTION: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients. METHODS: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR. RESULTS: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-ß) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients. CONCLUSION: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients.

Hyperinflammatory syndrome in a paediatric patient with a recent diagnosis of HIV/AIDS infection: hemophagocytic lymphohistiocytosis or immune reconstitution syndrome?

INTRODUCTION: Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue destruction. It could either be due to a primary genetic defect or be triggered by secondary causes such as infections, autoimmune diseases, rheumatological diseases or post-transplant immunosuppression. We here report the case of a 4-year-old child with a recent AIDS diagnosis who developed a severe systemic inflammation. CASE REPORT: We here report the case of a 4-year-old child with a recent AIDS diagnosis who was admitted to the ER with acute respiratory failure due to Pneumocystis jiroveci infection and Aspergillosis; the following microbiological assessment also showed a CMV, HSV, EBV and HHV-7 coinfection. On the 51st day after she'd started antiretroviral therapy, 39th after she'd followed a course of Bactrim and Caspofungin for PJI and Ambisome for pulmonary Aspergillosis, she started presenting fever, unresponsive to broad-spectrum antibiotic therapy. She also presented worsening of her clinical conditions, with evidence at the laboratory assessments of progressive raise in inflammatory indexes, coagulopathy, trilinear cytopenia and hyperferritinemia. To perform the differential diagnosis between IRIS and HLH, HLA-DR on T cells was studied, turning out negative for IRIS. Therefore, in the suspicion of HLH, a bone marrow aspirate and biopsy were performed with evidence of trilinear cytopenia, prevalence of T-cells and macrophages with signs of phagocytosis. She was started on high-dose steroids and Anakinra for a total of 29 days, resulting in prompt apyrexia and progressive improvement of her clinical conditions and laboratory results. CONCLUSION: To the best of our knowledge there is poor literature available about the differential diagnosis of HLH and IRIS, therefore medical management in the concurrence of these two conditions needs to be further investigated, especially in a setting where immunological testing is not quickly available. The clinical differences between these pathologies are blurred and the bone marrow biopsy within marker for IRIS helped us to distinguish these two entities.

Assessment of Anxiety, Depression, Work-Related Stress, and Burnout in Health Care Workers (HCWs) Affected by COVID-19: Results of a Case-Control Study in Italy.

This study aims to investigate whether HCWs infected with COVID-19 may experience potential psychological consequences and a higher incidence of depression, anxiety, work-related stress, and burnout compared to non-infected HCWs. A case-control study with 774 participants was conducted comparing COVID-19-infected HCWs (cases) and non-infected HCWs (controls) from the Occupational Medicine Unit at the Teaching Hospital Policlinico Umberto I, who were administered the same questionnaire including Hospital Anxiety and Depression Scale, Copenhagen Burnout Inventory and Karasek's Job Content Questionnaire. No differences in the levels of burnout and decision latitude were found between the two groups. Cases showed higher level of anxiety and job demand compared to controls. In contrast, levels of depression in the case group were significantly lower compared to the control group. The results are indicating the need for workplace health promotion activities based on stress and burnout management and prevention. Multiple organizational and work-related interventions can lower the impact of mental health-related issues in the COVID-19 pandemics, including the improvement of workplace infrastructures, as well as the adoption of correct and shared anti-contagion measures, which must include regular personal protective equipment supply, and the adoption of training programs that deal with mental health-related issues.

Clinical characteristics and risk factors for mortality in COVID-19 patients during the first wave of the COVID-19 pandemic in Rome, Italy: a single-center retrospective study.

Background: Since the beginning of 2020, the SARS-CoV-2 pandemic has become a serious public health problem. Numerous studies have highlighted the main clinical features of COVID-19, mainly the huge heterogeneity of the clinical manifestations that can vary from asymptomatic infection to serious viral pneumonia with a high mortality rate. The aim of this study was to analyze retrospectively the clinical characteristics and assess the risk factors for mortality in an Italian cohort of patients with COVID-19. Methods: Retrospective analysis including patients with COVID-19 admitted to the Infectious Diseases wards of Azienda Ospedaliera Universitaria Policlinico "Umberto 1", Rome, from March 2020 to May 2020. The data were part of an electronic anonymous web-based database processed by SIMIT (Italian Society of Infectious and Tropical Diseases). Results: 258 patients were included in the analysis, and 34 (13.2%) died. The median age was 62 (IQR, 52-74), 106 (40%) were women, and 152 (60%) were males, 172 (66.7%) had at least one co-morbidity. The most common signs and symptoms were: fever [221 (85.6%)], cough [135 (52.3%)], and dyspnea [133 (51.5%)]. The PaO2/FiO2 ratio was often altered [352 (IQR, 308-424)]. Lymphopenia [lymphocyte counts, 875/µL (IQR, 640-1250)] and high levels of D-dimer [mg/dL, 874 (IQR, 484-1518)] were found. Non-survivors were older than survivors [median age, 74 (IQR, 67-85)] vs. 61 (QR, 51-72)], mostly men [25 (73.5%)] and more frequently with more than 2 comorbidities [21 (61.8%) vs. 94 (42.1%)]. In the multiple logistic regression model, the variables associated with in-hospital mortality were age [OR, 3.65 (95% CI, 1.22-10.89)], male gender [OR, 2.99 (95% CI, 1.18-7.54)], blood urea [OR, 2.76 (95% CI, 1.20-6.35)] and a low PaO2/FiO2 ratio [OR, 0.28 (95% CI, 0.12-0.62)]. Conclusion: The mortality rate in COVID-19 was 13,2%. The risk factors associated with in-hospital mortality were advanced age, male sex, increased blood urea, and the PaO2/FiO2 ratio reduction.

Liver Involvement in SARS-CoV-2 Vertically Infected Newborn: A Case Report.

Neonatal SARS-CoV-2 infection can occur antenatally, peripartum, or postnatally. In the newborn, clinical manifestations may vary including fever and respiratory, gastrointestinal and neurological symptoms. Most commonly, they are subclinical. We herein present a case of vertical transmission of SARS-CoV-2 presenting with liver injury, characterized by an increase in serum transaminases.

Consequences of Early Separation of Maternal-Newborn Dyad in Neonates Born to SARS-CoV-2 Positive Mothers: An Observational Study.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues its spread all over the world, data on perinatal management of the maternal-infant dyad are urgent. We performed an observational study to describe the effects of the early separation of the maternal-infant dyad, in case of maternal SARS-CoV-2 infection. We reported the medical records for 37 neonates born to 37 SARS-CoV-2 positive mothers in a setting of separation of the dyad after birth. Data on neonatal infection, clinical condition, and breastfeeding rate were recorded until the first month of life. No maternal deaths were recorded; 37.8% of women had at least one pregnancy-related complication. We reported a high adherence to recommended safety measures after discharged with 84.8% of the mothers using at least one personal protective device and 51.5% using all the protective devices. We reported one case of vertical transmission and no cases of horizontal transmission. However, the separation of the dyad had a negative impact on breastfeeding because only 23.5% of the newborns received exclusively human milk during the first month of life. Despite early separation of the dyad protecting the newborns from possible horizontal transmission of SARS-CoV-2, it negatively affects breastfeeding during the first months of life.

Increased sCD163 and sCD14 Plasmatic Levels and Depletion of Peripheral Blood Pro-Inflammatory Monocytes, Myeloid and Plasmacytoid Dendritic Cells in Patients With Severe COVID-19 Pneumonia.

Background: Emerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects). Methods: On admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups. Results: Compared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1-68.4] specificity 73.8% [CI: 58.9-84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492). Conclusions: The increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.

Assessment of Biventricular Function by Three-Dimensional Speckle Tracking Echocardiography in Adolescents and Young Adults with Human Immunodeficiency Virus Infection: A Pilot Study.

BACKGROUND: The purpose of the study was to assess biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in adolescents and young adults with human immunodeficiency virus (HIV) infection on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction. METHODS: Twenty-one patients aged 12-39 years with HIV, 21 normal controls of the same age and sex, and 21 patients with idiopathic nonischemic dilated cardiomyopathy (DCM) were studied with 3DSTE. All HIV patients were stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection, and were on highly active antiretroviral therapy with good immunological control. Standard echocardiographic measures of left ventricular (LV)-right ventricular (RV) function were assessed. 3D LV global longitudinal strain (GLS), circumferential strain, radial strain, and LV twist were calculated. Global area strain (GAS) was calculated by 3DSTE as percentage variation in surface area defined by the longitudinal and circumferential strain vectors. 3D RV global and free-wall longitudinal strain (FWLS) were obtained. RESULTS: LV GLS and GAS were lower in HIV patients compared to normal controls (p = 0.002, and p = 0.01, respectively). There were no significant differences in LV ejection fractions between the groups. There was a weak positive correlation between LV GLS and age (r = 0.215, p = 0.034) and a weak negative correlation between LV GLS and nadir-CD4 T-cells count (r = 0.198, p = 0.043). DCM patients had more marked and widespread reduction in LV GLS and GAS compared to controls (p < 0.001), whereas in HIV patients LV strain impairment (p < 0.05) was more localized in basal and apical regions. RV FWLS was significantly reduced in HIV patients when compared with the control group (p = 0.03). No patient had pulmonary systolic pressure higher than 35 mm Hg. CONCLUSIONS: 3DSTE may help to identify HIV patients at high cardiovascular risk allowing early detection of biventricular dysfunction in the presence of normal LV ejection fraction and in the absence of pulmonary hypertension. LV strain impairment in HIV patients is less prominent and widespread compared to DCM patients.

Aseptic meningitis induced by intravenous immunoglobulins in a child with acute Epstein-Barr virus infection and thrombocytopenia.

Drug-induced aseptic meningitis (DIAM) represents a diagnostic challenge since clinical and cerebrospinal fluid (CSF) findings may be indistinguishable from a bacterial meningitis. Intravenous immunoglobulin (IVIg) are commonly used in a variety of diseases, including inflammatory and autoimmune disorders. Although usually well-tolerated, various adverse effects have been reported. DIAM is a serious neurological side effect of IVIg therapy: albeit rare (0.067% of all IVIg infusions), the condition represents an important diagnostic challenge and should be considered by physicians. Here we report a case of an aseptic meningitis induced by IVIg therapy in a child with acute Epstein-Barr virus (EBV) infection and thrombocytopenia.

Intracranial tuberculous mass lesions treated with thalidomide in an immunocompetent child from a low tuberculosis endemic country: A case report.

RATIONALE: Tuberculous meningitis is a highly morbid, often fatal disease. PATIENT CONCERN: We describe a case of an Italian child. DIAGNOSES:: we diagnosed early a Tuberculous meningitis complicated by the occurrence of hydrocephalus, stroke, and paradoxical reaction with brain pseudo-abscesses. INTERVENTIONS: The child started readily a specific therapy associated with steroids and thalidomide was introduced few month later. OUTCOMES: the patient had a favorable outcome without neurologic sequelae. LESSONS: Despite the prompt specific anti-tubercular and adjuvant corticosteroid therapies, only the addition of thalidomide to the treatment allow to a favorable clinical outcome.

Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: a case report.

BACKGROUND: Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treatment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates. CASE PRESENTATION: This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify Mycobacterium tuberculosis were negative, while a non classical method based on intracellular cytokine flow cytometry response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by a nested polymerase chain reaction amplifying a 123 base pair fragment of the M. tuberculosis DNA. CONCLUSIONS: We diagnosed tuberculous meningitis at an early stage through an innovative immunological approach, supported by a nested polymerase chain reaction for detection of M. tuberculosis DNA. An early diagnosis is required in order to promptly initiate a therapy and to increase the patient's survival.

Blood Myeloid Dendritic Cells and slanDC in Antiretroviral Therapy- Suppressed HIV-Infected Patients.

Myeloid dendritic cells (mDCs) play a complex role in HIV infection regardless of viral replication. The aim of our study was to analyse mDCs in long term antiretroviral therapy (ART)- suppressed HIV-infected patients. We evaluated the numbers of mDCs and slanDC in the context of different degree of CD4+ T cell recovery, persistent T cell activation (as HLA-DR+/CD3+ expression) and monocyte-macrophage activation assessed in terms of circulating levels of both sCD14 and sCD163. We enrolled 72 aviremic patients under effective ART and 34 healthy donors (HD). Patients were divided into two groups on the bases of ΔCD4, indicating the difference between the value of CD4 at the time of sampling and CD4 nadir. Higher levels of mDCs and slanDC were found in patients with ΔCD4>200/mmc in comparison to HD. In those patients also an increased level of sCD14 was found, whereas sCD163 seemed to be at normal levels. An augmentation of activated CD4 T lymphocytes was found, although less pronounced in patients with ΔCD4<200/mmc. In conclusion, our findings showed an expansion of mDCs with a shift to inflammatory slanDC that could sustain both microbial translocation and HIV latency in CD4 T cells.

Extravirologic modulation of immune response by an NRTI-sparing antiretroviral regimen including darunavir and maraviroc.

Dual therapies, including protease inhibitor + maraviroc (MVC), may represent an alternative to traditional regimens for management of HIV infection. The aim of this in vitro study was to assess the effects of darunavir (DRV) alone or in combination with MVC on cell apoptosis and chemotaxis. A significant decrease of cell apoptosis was found after DRV treatment. The addition of MVC to DRV also had an in vitro down-regulating effect on cell migration. The combination of an NRTI-sparing regimen including DRV+ MVC may have a potential role in immune system modulation by the direct down regulation of apoptosis and chemotaxis.

Rate and determinants of treatment response to different antiretroviral combination strategies in subjects presenting at HIV-1 diagnosis with advanced disease.

BACKGROUND: The optimal therapeutic strategies for patients presenting with advanced disease at HIV-1 diagnosis are as yet incompletely defined. METHODS: All patients presenting at two outpatient clinics in 2000-2009 with an AIDS-defining clinical condition or a CD4+ T cell count < 200/µL at HIV-1 diagnosis were analyzed for the presence of combined immunovirological response, defined by the concomitant presence of an absolute number of CD4+ T cells > 200 cells/µL and a plasma HIV-1 RNA copy number < 50/mL after 12 months of HAART. RESULTS: Among 102 evaluable patients, first-line regimens were protease inhibitors [PI]-based in 78 cases (77%) and efavirenz-based in 24 cases (23%). The overall response rate was 65% (95% CI: 55-74), with no differences by gender, age, nationality, route of transmission, hepatitis virus coinfections, presence of AIDS-defining clinical events, baseline HIV-1 viral load, or type of regimen (response rates with PI-based and efavirenz-based therapy: 63% and 71%, respectively, p = 0.474). Response rate was significantly better with higher baseline CD4+ T cell counts (78% with CD4+ ≥ 100/µL, compared to 50% with CD4+ < 100/µL; odds ratio: 3.5; 95% CI: 1.49-8.23, p = 0.003). Median time on first-line antiretroviral therapy was 24 months (interquartile range: 12-48). Switch to a second line treatment occurred in 57% of patients, mainly for simplification (57%), and was significantly more common with PI-based regimens [adjusted hazard ratios (AHR) with respect to efavirenz-based regimens: 3.88 for unboosted PIs (95% CI: 1.40-10.7, p = 0.009) and 4.21 for ritonavir-boosted PI (95% CI 1.7-10.4, p = 0.002)] and in older subjects (≥ 50 years) (AHR: 1.83; 95% CI: 1.02-3.31, p = 0.044). Overall mortality was low (3% after a median follow up of 48 months). CONCLUSIONS: Our data indicate that a favorable immunovirological response is possible in the majority of naive patients presenting at HIV-1 diagnosis with AIDS or low CD4+ T cell counts, and confirm that starting HAART with a more compromised immune system may be associated with a delayed and sometimes partial immune recovery. Simpler regimens may be preferable in this particular population.

Influence of previous tuberculin skin test on serial IFN-γ release assays.

Tuberculin skin test (TST) and interferon-γ release assays (IGRAs) have been proposed for serial testing in tuberculosis. In the present study, we assessed the effect of TST on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) results by monitoring the evolution of responses during a follow-up period of 6 weeks. One hundred and two subjects were initially tested with QFT-GIT and subsequently with TST; then the QFT-GIT was performed serially 1, 2, 4, and 6 weeks after the TST. A subgroup of 40 subjects was also assessed by older version of the QuantiFERON-TB Gold (QFT-G) assay. The results showed no significant variation in IFN-γ response over time in the tested patients, although two TST-positive subjects showed evidence of possible boosting effect. In addition, a direct comparison between the QFT-G and QFT-GIT test showed no significant differences at any time point with excellent agreement between two tests. No significant differences were seen in IFN-γ responses between BCG-unvaccinated and BCG-vaccinated patients at each time point. In conclusion, our findings indicate that TST does not influence the outcome of subsequent IGRAs testing in individuals with negative TST results, but it can boost the IFN-γ response in subjects sensitized to TB antigens and not detected by IGRA.

Rapid identification of Bartonella henselae by real-time polymerase chain reaction in a patient with cat scratch disease.

We report a localized submandibular lymph node infection in a patient with cat scratch disease. Directly performing real-time polymerase chain reaction assay on the biopsy sample, Bartonella henselae DNA was simultaneously detected and identified.

Acute cerebellitis caused by herpes simplex virus type 1.

Cerebellar disorders due to herpes simplex virus (HSV) infection are rare and always associated with herpes simplex encephalitis. We report 2 cases of severe primary acute cerebellitis caused by HSV type 1 that were identified by nested polymerase chain reaction performed on cerebrospinal fluid samples.