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Background: Long-term data on COVID-19 vaccine safety, immunogenicity, and acceptance in adults with CHD are lacking. Methods: This is a prospective study including adults with CHD patients undergoing COVID-19 vaccination from January 2021 to June 2022. Data on adverse events, antispike IgG titre, previous or subsequent COVID-19 infection, booster doses, and patients’ attitude towards vaccination were collected. Results: Four hundred and ninety CHD patients (36 ± 13 years, 53% male, 94% with moderate/complex defects) were prospectively included: 433 (88%) received a Pfizer–BioNTech mRNA vaccine, 31 (6%) Moderna mRNA vaccine, 23 (5%) AstraZeneca–Oxford ChAdOx1 nCov-19 vaccine, and 3 (0.6%) Janssen Vaccine; 310 (63%) received a booster dose. Median follow-up after vaccination was 1.53 [1.41–1.58] years. No major adverse event was reported. Eighty-two fully vaccinated patients contracted COVID-19 during follow-up after a median of 5.4 [4.3–6.5] months from the last dose. One patient with Ebstein’s disease died from severe COVID-19. Symptoms’ duration in patients who tested positive after vaccination was significantly shorter than in the group tested positive before vaccination (5.5 [3–8] versus 9 [2.2–15] days, p = 0.04). Median antispike IgG titre measured in 280 individuals (57%) at a median of 1.4 [0.7–3.3] months from the last dose was 2381 [901–8307] BAU/ml. Sixty patients (12%) also showed positive antinucleocapsid antibodies, demonstrating previous SARS-COV2 exposure. Twenty-nine percent appeared to have concerns regarding vaccine safety and 42% reported fearing potential effects of the vaccine on their cardiac disease before discussing with their CHD cardiologist. Conclusion: COVID-19 vaccines appear safe in the mid-term follow-up in adults with CHD with satisfactory immunogenicity and reduction of symptoms’ duration in case of infection.

Background real-world data on COVID-19 vaccine safety, immunogenicity and acceptance in adults with congenital heart disease (ACHD) are lacking. Methods ACHD patients who were offered COVID-19 vaccination from January to June 2021 were included. Data on adverse events, on patients’ attitude towards vaccination and antispike IgG titre were retrospectively collected. A group of healthy individuals with similar age and sex undergoing vaccination was included for comparison. Results 208 patients followed in a single ACHD tertiary centre (33.3 [26–45]years,54%male) received COVID-19 vaccine, 65% vaccinated at our institution: 199 (96%)received Pfizer–BioNTech BNT162b2 vaccine, 4 (2%)Moderna-1273 and 5 (2%)AstraZeneca–ChAdOx1. Median follow-up after vaccination was 79 [57–96]days. No major adverse event was reported and there was no difference in the in adverse events incidence between ACHD patients and the control group. One patient was diagnosed with acute pericarditis. There were two unrelated deaths during follow-up. Three (1.5%)vaccinated patients tested positive for COVID-19. Antispike IgG titre, available in 159 (76%)patients, was 1334 [600–3401]BAU/ml, not significantly different from the control group (p = 0.2). One patient with Fontan failure was seronegative. Advanced physiological stage was related to lower antibody response, independently from previous viral exposure (p, Graphical abstract Image 1

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

È stato proposto di aggiungere un "quarto 90" agli obiettivi di diagnosi e cura per le persone affette da infezione da HIV, per garantire che il 90% delle persone con soppressione della carica virale abbia anche una buona qualità di vita. Questo nuovo obiettivo amplierebbe il paradigma del continuum dell’assistenza, oltre l'endpoint già esistente della soppressione virale, utilizzando gli strumenti disponibili per rilevare la condizione di disagio correlata ad un’infezione cronica. Appare necessario prendere in considerazione le comorbidità e la qualità della vita auto-percepita per la valutazione della qualità della vita nelle persone con HIV, realizzando un nuovo approccio a questo argomento ancora non ben approfondito. Lo scopo dello studio è stato quello di valutare negli adulti positivi HIV stabilmente viro-soppressi il grado di aderenza e di compliance alla terapia, la qualità della vita auto-percepita e la presenza di comorbidità, al fine di identificare eventuali eventi sentinella precoci, che influenzano l'aderenza del paziente, e pianificare approcci personalizzati al fine di migliorare l'aderenza per quei pazienti con un rischio di ridotta compliance terapeutica. Nel complesso, la qualità della vita auto-percepita nel nostro studio era buona. Più precisamente, il 70% degli intervistati ha posto il proprio stato di benessere nel punteggio compreso tra 70 e 100 e il 20% tra 40 e 50. Solo tre pazienti si sono dichiarati insoddisfatti della propria condizione psicofisica, identificandola con punteggi compresi tra 30 e 40 in due casi e tra 10 e 20 in un caso. La maggior parte dei pazienti ha riportato anche una condizione di benessere ed equilibrio più che accettabile, con un'incidenza di sintomi molto bassa (soprattutto stanchezza), che non ha influenzato le normali attività della vita quotidiana. I risultati del nostro studio, anche se non significativi per l'adozione di un approccio psicoterapeutico di massa, hanno comunque consentito l'avvio precoce di un percorso psicoterapeutico personalizzato per migliorare l'aderenza e gestire la depressione. In conclusione, la valutazione soggettiva della qualità della vita, della depressione e di altri eventi sentinella può diventare una variabile molto importante per l'implementazione dei programmi di assistenza medica, al fine di migliorare l'aderenza ai percorsi di terapia e prevenzione e di ottenere un soddisfacente livello di interazione con l’operatore sanitario. Pertanto, si ritiene essenziale includere questo tipo di valutazione nella pratica clinica di routine. Il questionario a risposta multipla è uno strumento pratico, semplice ed affidabile per rilevare precocemente eventuali barriere all'aderenza terapeutica al fine di prevenire il fallimento virologico e salvare future opzioni terapeutiche.

BackgroundThe inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing.Study descriptionIn this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease.ConclusionsThis observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.

In recent months, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. COVID-19 patients show mild, moderate or severe symptoms with the latter ones requiring access to specialized intensive care. SARS-CoV-2 infections, pathogenesis and progression have not been clearly elucidated yet, thus forcing the development of many complementary approaches to identify candidate cellular pathways involved in disease progression. Host lipids play a critical role in the virus life, being the double-membrane vesicles a key factor in coronavirus replication. Moreover, lipid biogenesis pathways affect receptor-mediated virus entry at the endosomal cell surface and modulate virus propagation. In this study, targeted lipidomic analysis coupled with proinflammatory cytokines and alarmins measurement were carried out in serum of COVID-19 patients characterized by different severity degree. Serum IL-26, a cytokine involved in IL-17 pathway, TSLP and adiponectin were measured and correlated to lipid COVID-19 patient profiles. These results could be important for the classification of the COVID-19 disease and the identification of therapeutic targets.

Background The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and the trend in biochemical parameters and clinical events during and after DAA regimen. Methods We performed a multicentre retrospective cohort study, enrolling all 243 HIV–HCV-coinfected adult patients treated with DAAs between January 2015 and December 2018 in one of the nine participating Infectious Disease Centers in southern Italy, eight in Campania and one in Apulia. Results Of the 243 patients enrolled, 233 (95.9%) obtained an SVR at 12 weeks (SVR12). Of the 10 patients with non-SVR, 7 were tested for NS3, NS5A and NS5B resistance-associated substitutions (RASs) by sequencing analysis and 6 showed at least 1 major RAS in 1 HCV region (all in NS5A, 2 in NS5B and 1 in NS3). Comparing the 233 patients achieving SVR and the 10 non-achievers, no variable was independently associated with non-SVR. During and after DAA regimen, no modification in the biochemical parameters and clinical events was observed; however, the serum cholesterol and low-density lipoprotein (LDL) levels showed an increase (from 159 ±41.3 mg/dl at baseline to 174 ±44.5 mg/dl at week 12 after stopping treatment, PConclusions The treatment with DAAs led to a high SVR12 rate in HIV–HCV-coinfected subjects, irrespective of epidemiological, clinical or virological characteristics. However, the DAA regimen was associated with an increase in total- and LDL-cholesterol, to be taken into account in the management of HIV infection

Background Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? Discussion Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. Conclusions Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

Integrase strand transfer inhibitors are a new class of antiretroviral agents recently licensed for the treatment of both naive and experienced HIV-infected patients. They inhibit the catalytic activity of the HIV-encoded enzyme integrase and prevent the integration of the HIV genome into the host cell genome, so slowing the propagation of the infection. Integrase strand transfer inhibitors cause a rapid drop in viral load, exhibit very low drug interactions (except elvitegravir/cobicistat), and have low pill burden and convenient dosing frequency. Drugs in this class have been compared to others in antiretroviral-naive patients with efavirenz and with protease inhibitors. Final results of the STARTMRK trial highlighted the better virologic and immunologic performance of raltegravir over efavirenz/emtricitabine/tenofovir disoproxil co-formulation. Raltegravir was also superior to atazanavir/ritonavir and darunavir/ritonavir in the ACTG 5257 study for the combined virologic/tolerability endpoint. Elvitegravir/cobicistat/emtricitabine/tenofovir was non-inferior to efavirenz/emtricitabine/tenofovir and to atazanavir/ritonavir plus emtricitabine/tenofovir in terms of confirmed virologic response in the GS-US-236-0102 and GS-US-236-0103 studies, respectively. Finally, dolutegravir showed non-inferiority compared to raltegravir in the SPRING-2 study and was superior to efavirenz and darunavir/ritonavir in the SINGLE and FLAMINGO trials, respectively. The aim of this review is to analyze the data on efficacy and safety of integrase strand transfer inhibitors in antiretroviral-naive HIV patients and discuss the strengths and weaknesses of drugs within this class.