Psychopathological Symptoms and Mentalizing Capabilities in Adolescents with Anorexia Nervosa before and during Covid-19 Pandemic

Introduction: The COVID 19 pandemic, associated with confinement and social isolation, seems to have impacted the course of many mental disorders in children and adolescents. Specifically, it has created a global context likely to increase eating disorders' (Eds') risk and symptoms and to decrease factors that protect against EDs. Previous studies have highlighted a link between mentalizing deficits and clinical problems. This study aims to compare Covid-Period vs. NON-Covid Period adolescent patients affected by Anorexia Nervosa (AN) considering their psychopathological symptoms and their mentalizing capabilities. Method(s): 206 female adolescents (aged between 12 and 17 years) affected by AN were recruited from the Service for Eating Disorders at S. Gerardo Hospital in Monza. Exclusion criteria were the presence of intellectual disabilities and neurological disorders. The first group of 94 subjects was recruited between September 2018 and February 2020 (NON-Covid Period), and the second group of 112 individuals was recruited between August 2020 and May 2022 (Covid Period). The following instruments were administrated: EDI-3 (Eating Disorders Inventory-3) was used to provide a standardized clinical evaluation of symptomatology associated with eating disorders;SCL-90R (Symptom Checklist 90- Revised) was used to assess psychological problems and psychopathological symptoms;Reflective Functioning Questionnaire (RFQ) was used to assess mentalizing skills, considering that Reflective functioning (RF) is the operationalization of the mental processes underlying the capacity to mentalize. Result(s): A preliminary analysis of data showed worse values in primary and composites scales of EDI-3, higher levels of general psychopathological suffering (SCL-90 composite scales) and more marked levels of hypo-mentalization (RFQ-u) in the Covid-Period subjects: the differences were statistically significant. Conclusion(s): Although these results are still preliminary, it is possible to hypothesize a correlation between marked levels of hypo-mentalization and higher rates of psychopathological suffering and a worse clinical pattern of Anorexia Nervosa. It is also possible to hypothesize that a preventive intervention to strengthen the reflexive functions may result protective factor against the onset of more severe clinical manifestations and comorbidities;mentalizing abilities could be an important target for therapeutic interventions. Further research should be conducted on larger samples and with a new assessment after treatment interventions.

Immunogenicity and Clinical Efficacy of Two Doses of Mrna-Based Covid-19 Vaccines for Patients with Solid Tumors on Active Anti-Cancer Treatment

Background: Real world studies on the immunogenicity of BNT162b2 and mRNA-1273 in patients (pts) with cancer showed a reduced seroconversion. The aim of the study is to evaluate the immunogenicity and clinical efficacy of two doses of mRNA vaccines in cancer pts, during or after active treatment. Patients and Methods: This is a single institution, prospective, observational study, conducted at Luigi Sacco Hospital in Milan, IT. Seric antibody levels were measured in solid cancer pts and in healthy controls before the 1st dose (T0) and 30 days after the 2nd one (T1) by a fluorescence bead-based assay. Seroconversion (SR) was defined as anti-S and anti-RBD > 700 MFI (Median Fluorescence Intensity). Previous exposure was defined as anti-N >700 MFI (E-group: exposed;nonE-group: non exposed). Clinical efficacy was defined as the percentage of subjects who did not develop COVID-19 six months after the second dose. Result(s): 195 cancer pts: median age 64.1 y (Q1-Q3 53.8- 72.0);female 138 (70.8%);E-group (12.6%);active therapy 144 (86.7%);advanced stage of disease 131 (67.2%);breast cancer 100 (51.3%);chemotherapy 65 (33.3%), targeted therapy 69 (35.4%);multiple comorbidities 44 (22.6%);prophylaxis with G-CSF 15 (7.7%). 20 healthy subjects were enrolled as controls: median age 28.5 y (Q1-Q3 25.0-42.0), female 11 (55.0%). SR in nonEgroup was lower than in healthy controls (66.7% vs 95.0%, p=0.0085). Conversely, SR in E-group was comparable to healthy controls (93.3%, p=0.0020). In cancer pts, multiple comorbidities (p=0.0274) and the use of G-CSF (p=0.0151) negatively correlated with SR;mRNA-1273 induced a higher SR (p<0.0001). Clinical efficacy in pts was 97.4%. 7 pts were diagnosed for SARS-CoV-2 infection and confirmed by a RNA test. 5 pts developed COVID-19: 3 of them did not seroconvert at T1. COVID-19 disease was mild and managed at home. Only 1 hospitalization was recorded, but no ventilation or no intensive care admission was required. Conclusion(s): In our study, cancer pts with a previous SARS-CoV-2 infection showed a higher SR, similar to the one observed in healthy people. Besides, the presence of comorbidities and the use of G-CSF negatively affected the SR, while mRNA-1273 induced a higher SR. Interestingly, no COVID-19 serious complication or death were observed in all subgroups. Finally, as the third dose is the actual standard, identification of persistent non-responder pts is critical in order to select who could benefit of new treatments as monoclonal antibodies.

Immunogenicity after the third dose of mRNA-based COVID-19 vaccines in patients with solid tumors

Background: Despite of the administration of multiple doses of vaccines (vax), cancer patients (pts) are a group at high risk of COVID-19 complications. The aim of this study is to evaluate the factors associated with the humoral response to the 3rd dose (D) of mRNA-based vax in cancer pts during or after active treatment. Patients and Methods: Single institution, prospective study conducted at the L. Sacco Hospital, Milan, between 5/2021-4/2022. 30 days after the 2nd and 30 days after the 3rdD of BNT162b2 or mRNA-1273 (selected based on local pharmacy availability), seric levels of 3 antibodies (Ab) were measured in solid tumors pts during or after the active treatment, by a fluorescence bead-based assay. Anti-S and anti-RBD IgG to determine the humoral response to vax, anti-N IgG to identify a previous exposure to SARS-Cov-2. Primary objective: to assess the seroconversion (SC) rate and the Ab titres after 3rdD. Secondary Objectives: to detect any relation between the 3rdD response and pre-defined pts variables;to evaluate the humoral response to 3rdD in pts not responding to the 2ndD. Result(s): 99 of 110 pts were evaluated: 67.7% female, median age 63 ys, 49.5% breast cancer, 67.7% advanced stage. Active treatment: 40.4% biologic agent, 23% chemotherapy (alone or combination), 11.1% hormone. 3rdD vax type: 74.8% BNT162b2, 25.2% mRNA-1273. SC after 3rdD was obtained in 99% of pts. The use of GCSF was associated with a lower amount of anti-RBD IgG (p=0.03). A 6 vs 5 months interval between 2nd and 3rdD was correlated with higher anti-S IgG level (p<0.001). The heterologous vax regimen was associated with higher rate of anti-S IgG (p=0.04), especially the sequence mRNA- 1273 x 2 -> BNT162b2 (p=0.001). No significant correlation at the multivariate analyses was found between Ab levels and the other variables tested (age, BMI, cancer type, tumor stage, use of steroids, previous exposure to SARS-CoV-2, anti-cancer therapy, neutropenic potential of the therapy). 21/22 pts not responding to the 2ndD obtained SC after 3rdD. Conclusion(s): 3rdD of anti-COVID-19 vax is effective in cancer pts with solid tumors undergoing or after recent treatment. In this group the 3rdD oversteps all the negative influence of the factors related to the 2ndD vax failure, achieving the same response of the healthy population and demonstrating efficacy in not previously responders, too. The better performance of the heterologous vax regimen could be due to an exposition to a wider range of epitopes.

Colchicine anti-inflammatory therapy for non-intensive care unit hospitalized COVID-19 patients: results from a pilot open-label, randomized controlled clinical trial.

Systemic inflammation is a hallmark of severe coronavirus disease-19 (COVID-19). Anti-inflammatory therapy is considered crucial to modulate the hyperinflammatory response (cytokine storm) in hospitalized COVID-19 patients. There is currently no specific, conclusively proven, cost-efficient, and worldwide available anti-inflammatory therapy available to treat COVID-19 patients with cytokine storm. The present study aimed to investigate the treatment benefit of oral colchicine for hospitalized COVID-19 patients with suspected cytokine storm. Colchicine is an approved drug and possesses multiple anti-inflammatory mechanisms. This was a pilot, open-label randomized controlled clinical trial comparing standard of care (SOC) plus oral colchicine (colchicine arm) vs. SOC alone (control arm) in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. Colchicine treatment was initiated within first 48 hours of admission delivered at 1.5 mg loading dose, followed by 0.5 mg b.i.d. for next 6 days and 0.5 mg q.d. for the second week. A total of 96 patients were randomly allocated to the colchicine (n=48) and control groups (n=48). Both colchicine and control group patients experienced similar clinical outcomes by day 14 of hospitalization. Treatment outcome by day 14 in colchicine vs control arm: recovered and discharged alive: 36 (75.0%) vs. 37 (77.1%), remain admitted after 14-days: 4 (8.3%) vs. 5 (10.4%), ICU transferred: 4 (8.3%) vs. 3 (6.3%), and mortality: 4 (8.3%) vs. 3 (6.3%). The speed of improvement of COVID-19 acute symptoms including shortness of breath, fever, cough, the need of supplementary oxygen, and oxygen saturation level, was almost identical in the two groups. Length of hospitalization was on average 1.5 day shorter in the colchicine group. There was no evidence for a difference between the two groups in the follow-up serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, interleukin-6 (IL-6), high-sensitivity troponin T (hs-TnT) and N-terminal pro b-type natriuretic peptide (NT pro-BNP). According to the results of our study, oral colchicine does not appear to show clinical benefits in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. It is possible that the anti-inflammatory pathways of colchicine are not crucially involved in the pathogenesis of COVID-19.

Influenza and pneumococcal vaccines in cancer patients on active therapy: A prospective study

Background: Due to immunosuppression, influenza virus and S. pneumoniae infections in cancer patients (pts) are responsible of a 4 times higher morbidity and mortality rates. Inadequate data are available about efficacy, safety, timing and immunogenicity of influenza (I) and pneumococcal (P) vaccine (vax) in pts undergoing active oncologic treatment. Nevertheless, the main Oncology societies recommend I and P vax in cancer pts and their family members (FMs). Materials and Methods: This is a single institution prospective study conducted at L. Sacco Hospital (Milan) between Sept 20 and Apr 21. The aim was to evaluate efficacy and safety of vax. Pts with diagnosis of tumor, age>18ys, in active antineoplastic treatment and FMs age>18ys were included. Each pt received I+P vax on the same day of therapy. Pts were compared with a control group of FMs, with age- and gender-adjusted logistic regression. Monthly monitoring was scheduled to register any Adverse Events (AEs) after injection (local and systemic AEs), episode of Influenza Like Illness (ILI), pneumococcal infection, access to Emergency department (ED) or Hospital admission (HA) and delay of treatment (DT). Results: 194 pts (63y median age, 67.5% female) and 140 FMs (59y median age, 49% female) were enrolled. CANCER: 92% solid and 8% hematological malignancy, 69% metastatic stage. TREATMENTS: 54% =1 previous line of therapy;38% chemotherapy, 31% target, 17% chemo+target, 14% hormone therapy. VAX: 47% pts and 72% FMs received I-vax for first time. I+P-vax were administered in 100% pts and 49% FMs. LOCAL AEs: I-vax: 34% pts and 19.6% FMs (p=0.01), P-vax: 35.7% pts and 20.7% FMs (p=0.11). The most common was pain in site of injection. SISTEMIC AEs: 19.6% pts and 8.5% FMs (p=0.11);the most frequent was fatigue. EFFICACY: ILI were recorded in 8.8% pts (3 had a HA and 1 a DT) and 3.6% FMs (p=0.04). No PI was recorded. Type of therapy, previous treatment and the use of steroid don't significantly impact on vax safety and efficacy. Conclusions: Despite the atypical season, I+P vax are safe and effective in cancer pts. The limited number of ILI events observed could be referred to vax but also to COVID-19 risk prevention and mitigation measures. No differences in efficacy and safety were observed between the 2 groups, except for local I-vax AEs. Moreover, the vax administration in the Oncology department, a wide vaccination coverage was achieved (>70% of cancer pts), reducing the pressure on territorial healthcare system.

DYNAMITE: A phylogenetic tool for identification of dynamic transmission epicenters

Molecular data analysis is invaluable in understanding the overall behavior of a rapidly spreading virus population when epidemiological surveillance is problematic. It is also particularly beneficial in describing subgroups within the population, often identified as clades within a phylogenetic tree, that represent individuals connected via direct transmission or transmission via differing risk factors in viral spread. However, transmission patterns or viral dynamics within these smaller groups should not be expected to exhibit homogeneous behavior over time. As such, standard phylogenetic approaches that identify clusters based on summary statistics (e.g., median genetic distance over the clade) would not be expected to capture dynamic clusters of transmission. For this purpose, we have developed DYNAMITE (DYNAMic Identification of Transmission Epicenters), a cluster identification algorithm based on a branchwise (rather than traditional cladewise) search for cluster criteria, allowing partial clades to be recognized as chains of transmission linked individuals. Using simulated viral outbreaks with varying cluster types and dynamics, as well as a SARS-CoV-2 South African dataset including the variant of concern B.1.351, we show that DYNAMITE is consistently more sensitive than existing tools in detecting both static and dynamic transmission clusters of epidemiological relevance. DYNAMITE has been implemented in R and released as open source at: github.com/ProsperiLab/DYNAMITE.

Safety and efficacy of influenza and pneumococcal vaccines in cancer patients on active therapy: A prospective study

Background: Influenza virus and S. pneumoniae infections in cancer patients (pts) are responsible of a higher morbidity and mortality rates. Limited data are available about safety, efficacy, immunogenicity and timing of influenza (I) and pneumococcal (P) vaccine (vax) in pts receiving active treatment. However, I and P vax in cancer pts and their family members (FMs) are reccomended. Methods: This is a single institution prospective study conducted at L. Sacco Hospital (Milan, Italy) between Sept 20 and Apr 21. The aim was to assess efficacy and safety of vax. Cancer pts, age>18yo, in active antineoplastic treatment and FMs age>18yo were included. Each pt received I+P vax on the same day of therapy. Any local and systemic Adverse Event (AE), episode of Influenza Like Illness (ILI), pneumococcal infection (PI), access to Emergency Department (ED) or Hospital admission (HA) and delay of therapy (DoT) were recorded. The frequency of AEs, ILI episodes and PI among pts and age- and gender- matching FMs were compared. Results: 194 pts (63y median age, 67.5% female) and 140 FMs (59y median age, 49% female) were enrolled. CANCER: 92% solid and 8% hematological malignancy, 69% metastatic stage. TREATMENTS: 54% ≥1 previous line of therapy;38% chemotherapy, 31% target, 17% chemo+target, 14% hormone therapy. VAX: I-vax received for first time in 47% pts and 72% FMs. 100% pts and 49% FMs received I+P-vax. LOCAL AEs: I-vax: 34% pts and 19.6% FMs (p=0.01). P-vax: 35.7% pts and 20.7% FMs (p=0.11). The most common was pain in site of injection. SISTEMIC AEs: 19.6% pts and 8.5% FMs (p=0.11);the most frequent was fatigue. EFFICACY: ILI were recorded in 8.8% pts (3 had a HA and 1 a DoT) and 3.6% FMs (p=0.04). No PI was recorded. In a logistic regression analysis type of therapy, previous treatment and the use of steroid don’t significantly impact on vax safety and efficacy. Conclusions: Few ILI events were observed due to vax and probably to all measures adopted to prevent SARS-CoV-2 virus spread. Except for local I-vax AEs, no differences were observed in efficacy and safety between the 2 groups. During the observation time, >70% of cancer pts in active treatment received I and P vax, so the vaccination coverage was achieved, reducing the pressure on territorial healthcare system. Clinical trial identification: Trial protocol n. 2020/ST/433 release by Local Ethic Committee. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: N.M. La Verde: Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Speaker’s Bureau: Gentili;Financial Interests, Institutional, Funding: EISA. D. Dalu: Financial Interests, Personal, Invited Speaker: Gentili;Financial Interests, Personal, Other: MSD. A. Riva: Financial Interests, Personal, Other: MSD,;Financial Interests, Personal, Other: ViiV;Financial Interests, Personal, Other: Gilead;Financial Interests, Personal, Other: Janseen;Financial Interests, Personal, Other: Cilag. S. Antinori: Financial Interests, Personal, Other: Pfizer;Financial Interests, Personal, Other: Merck. M. Galli: Financial Interests, Personal, Other: ViiV;Financial Interests, Personal, Other: BMS;Financial Interests, Personal, Other: MSD;Financial Interests, Personal, Other: AbbVie;Financial Interests, Personal, Other: Gilead;Financial Interests, Personal, Other: Janssen;Financial Interests, Personal, Other: Roche. All other authors have declared no conflicts of interest.

Impact of the covid-19 pandemic in the MR availability for iron overloaded patients

Background: The T2∗ magnetic resonance imaging (MRI) technique for the noninvasive quantification of iron overload has significantly improved the survival of patients with hemoglobinopathies by tailoring the chelation therapy. In Italy, the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) Network, a collaborative project among MRI and hematological centers, has assured high-quality quantification of iron in vital organs such as heart, liver, and pancreas. The COVID-19 pandemic has disrupted healthcare services around the world, also leading to postpone or delete deferable diagnostic evaluations. Aims: We evaluated the impact of the COVID-19 pandemic on MRI services for iron overload quantification in Italy. Methods: The activity of the MRI centers of the E-MIOT Network in the year 2020 was compared to the activity in the same months of 2019. A specific survey was filled out by the MRI operators to evaluate if the availability of MRI slots for patients with hemoglobinothies was reduced and the reasons. Results: In comparison with the year 2019, in 2020 there was a significant reduction in the number of T2∗ MRIs performed (350 vs 656;P<0.0001). The comparison month by month between the two years highlighted a marked decline (86.9%) in the four-month period March-June 2020, a reduction in the gap between the two years in the three-month period July-September, and a new decline (41.4%) in the three-month period October-December (Figure 1A). No patient with hemoglobinopathy could undergo an MRI scan during the Italian lockdown (9 March-10 May 2020). Figure 1B shows the percentage of decline (year 2020 vs 2019) in the number of T2∗MRI scans for each MRI center. If no decline or an increase were present, the vertical axis was set at 0. All centers experienced a significant drop in the number of the T2∗ MRIs in the fourmonth period March-June (from 75 to 100%). In the three-month period July-September only the centers of Pisa and Taranto dropped the number of T2∗ MRIs due to the rescheduling of the other MRI appointments deleted during the lockdown. In the three-month period October- December a reduction of the T2∗ MRI scans was experienced by all centers, except for Campobasso. In the centers of Ferrara and Lamezia Terme the reduction was the consequence of the general reduction in the number of the total MRIs scheduled per day for the sanitation procedures. In the other centers, the availability for T2∗ MRI scans was unchanged in comparison to 2019, but the patients refused the MRI follow up for fear of getting sick of COVID. Summary/Conclusion: The COVID-19 pandemic is having a strong negative impact on the quantification of iron overload by MRI, which may seriously worsen the prognosis of patients with hemoglobinopathies. Strategies to ensure proved lifesaving MRI exam and to reassure patients about the health safety of the hospitals are recommended.

Impact of the COVID-19 pandemic in the MR availability for iron overloaded patients

Background: The T2∗ magnetic resonance imaging (MRI) technique for the noninvasive quantification of iron overload has significantly improved the survival of patients with hemoglobinopathies by tailoring the chelation therapy. In Italy, the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) Network, a collaborative project among MRI and hematological centers, has assured high-quality quantification of iron in vital organs such as heart, liver, and pancreas. The COVID-19 pandemic has disrupted healthcare services around the world, also leading to postpone or delete deferable diagnostic evaluations. Aim: We evaluated the impact of the COVID-19 pandemic on MRI services for iron overload quantification in Italy. Methods: The activity of the MRI centers of the E-MIOT Network in the year 2020 was compared to the activity in the same months of 2019. A specific survey was filled out by the MRI operators to evaluate if the availability of MRI slots for patients with hemoglobinothies was reduced and the reasons. Results: In comparison with the year 2019, in 2020 there was a significant reduction in the number of T2∗ MRIs performed (350 vs 656;P < 0.0001). The comparison month by month between the two years highlighted a marked decline (86.9%) in the four-month period March-June 2020, a reduction in the gap between the two years in the three-month period July-September, and a new decline (41.4%) in the three-month period October-December (Figure 1). No patient with hemoglobinopathy could undergo an MRI scan during the Italian lockdown (9 March-10 May 2020). Figure 2 shows the percentage of decline (year 2020 vs 2019) in the number of T2∗MRI scans for each MRI center. If no decline or an increase were present, the vertical axis was set at 0. All centers experienced a significant drop in the number of the T2∗ MRIs in the fourmonth period March-June (from 75 to 100%). In the three-month period July-September only the centers of Pisa and Taranto dropped the number of T2∗ MRIs due to the rescheduling of the other MRI appointments deleted during the lockdown. In the three-month period October-December a reduction of the T2∗ MRI scans was experienced by all centers, except for Campobasso. In the centers of Ferrara and Lamezia Terme the reduction was the consequence of the general reduction in the number of the total MRIs scheduled per day for the sanitation procedures. In the other centers, the availability for T2∗ MRI scans was unchanged in comparison to 2019, but the patients refused the MRI follow up for fear of getting sick of COVID. Conclusion: The COVID-19 pandemic is having a strong negative impact on the quantification of iron overload by MRI, which may seriously worsen the prognosis of patients with hemoglobinopathies. Strategies to ensure proved lifesaving MRI exam and to reassure patients about the health safety of the hospitals are recommended.

Clinical Features and Outcomes of Patients With Human Immunodeficiency Virus With COVID-19

Little is known about the clinical outcomes of patients with human immunodeficiency virus infected with SARS-CoV-2. We describe 47 patients referred to our hospital between 21 February and 16 April 2020 with proven/probable COVID-19, 45 (96%) of whom fully recovered and 2 who died. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.