Approach to COVID-19 in older adults and indications for improving the outcomes.

Background: COVID-19 continues to present challenges in the care of older adults with frailty and/or comorbidities and very old patients, who can be hospitalized with severe COVID-19 despite full vaccination. Frailty is a heterogeneous syndrome characterized by an increased aging-related vulnerability due to a reduced physiological reserve and function of systemic organs, and is associated with an impairment of activities of daily living. Frail older adults remain at elevated risk of mortality from COVID-19 compared to older adults without frailty, and some pre-existing risk factors such as malnutrition, prolonged bed rest, and the association with comorbidities can aggravate the SARS-CoV-2 infection. Furthermore, the severity of COVID-19 can impact on long-term functioning of older patients surviving from the infection. Persistent symptoms are another emerging problem of the post-vaccination phase of pandemic, as most patients suffer from chronic symptoms which can become debilitating and affect the daily routine. Aim of this review: In this complex relationship, the evaluation of COVID-19 in vulnerable categories is still a matter of high interest and personalized care plans based on a comprehensive geriatric assessment, tailored interventions; specific therapeutic algorithms among older adults are thus recommended in order to improve the outcomes.

Real-life safety of Emtricitabine/Tenofovir Alafenamide/Bictegravir.

INTRODUCTION: Integrase strand transfer inhibitors (INSTI) are one of the most prescribed drug classes for the treatment of HIV infection worldwide. Emtricitabine/Tenofovir Alafenamide/ Bictegravir (FTC/TAF/BIC) has been evaluated in randomized clinical trials; few studies have verified tolerability and safety in clinical practice. Our aim was to investigate the metabolic and hepatic safety in a real-life setting of FTC/TAF/BIC. MATERIALS AND METHODS: Consecutive people living with HIV infection (PLWH) enrolled in the SCOLTA project, switching to or initiating their first antiretroviral treatment with FTC/TAF/BIC were included. PLWH with HBV co-infection were excluded. Metabolic and hepatic variables were collected at T0 and T1, were defined as baseline and 6-month follow-up respectively, and their modifications were analysed using the paired t-test and the analysis of variance. RESULTS: Five hundred and thirty-nine PLWH with at least one follow-up visit were included in the analysis. Mean age was 48 years (±12.1), 74% were male, 16.1% were naïve to antiretrovirals (ART). At T1, ART-experienced PLWH showed a significant reduction of total cholesterol (TC) and triglycerides, and a slight increase in blood glucose (BG) and ALT. On the contrary, in ART-naïve PLWH blood lipids significantly increased, although with an unaffected TC/high density lipoprotein (HDL)-c ratio, while alanine aminotransferase (ALT) decreased significantly, mainly in those with altered baseline level. The treatment interruptions were 45 (8.4%) over the whole observation period, 13 (2.4%) due to AEs. The most frequent AEs were related to the central nervous system (6 events of depression, insomnia, headache, agitation) and 3 PLWH discontinued the regimen because of grade 1-2 weight gain. CONCLUSIONS: In ART-experienced PLWH switching to FTC/TAF/BIC a significant improvement of lipid profile occurred but with significant BG and ALT variation without clinical relevance. In ART-naïve PLWH, blood lipids increased even though lipid profile did not worsen, and a trend towards normalization of liver enzymes was suggested. FTC/TAF/BIC is well tolerated in the real life setting.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting.

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (-0.36, p < 0.0001) than in the RPV cohort (-0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (-14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

Lipids and transaminase elevations in ARV-experienced PLWH switching to a doravirine-based regimen from rilpivirine or other regimens.

BACKGROUND: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. METHODS: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. RESULTS: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. CONCLUSIONS: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF.

Incident diabetes in course of antiretroviral therapy.

OBJECTIVE: Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset. DESIGN: Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort. METHODS: All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM. RESULTS: 4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4 + 460 [interquartile range (IQR) 256-710] cells/mm 3 cells/mm 3 . During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30-6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM. CONCLUSIONS: Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort.

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study.

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients' decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions.

Are monoclonal antibodies effective in patients with severe obesity in SARS-CoV-2 infected?

It is important to block SARS-CoV-2 infection immediately with early therapies, such as monoclonal antibodies (MonoAbs). Also, several studies show that obesity is associated with a high risk of severe COVID-19 disease. We enrolled 32 SARS-CoV-2 infected patients who received MonoAbs, all patients were not vaccinated for SARS-CoV-2, and they received therapy after 7 ± 2 days from the onset of COVID-19 symptoms. In the days following administration, patients followed home therapy with Pidotimod 800 mg bid for 10 days and cholecalciferol 2000 UI for 20 days, prescribed the same day they received MonoAbs therapy. Our study found that there are no differences in the therapeutic response between obese and nonobese patients with SARS-CoV-2 infection undergoing MonoAbs therapy, in fact, none of them underwent hospitalization. Furthermore, the effect of the immunostimulant Pidotimod and cholecalciferol may have contributed to the resolution of COVID-19 symptoms in these patients.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

Neuroprotective Potential of Bacopa monnieri: Modulation of Inflammatory Signals.

BACKGROUND: To date, much evidence has shown the increased interest in natural molecules and traditional herbal medicine as alternative bioactive compounds to fight many inflammatory conditions, both in relation to immunomodulation and in terms of their wound healing potential. Bacopa monnieri is a herb that is used in the Ayurvedic medicine tradition for its anti-inflammatory activity. OBJECTIVE: In this study, we evaluate the anti-inflammatory and regenerative properties of the Bacopa monnieri extract (BME) in vitro model of neuroinflammation. METHODS: Neuronal SH-SY5Y cells were stimulated with TNFα and IFNγ and used to evaluate the effect of BME on cell viability, cytotoxicity, cytokine gene expression, and healing rate. RESULTS: Our results showed that BME protects against the Okadaic acid-induced cytotoxicity in SH-SY5Y cells. Moreover, in TNFα and IFNγ primed cells, BME reduces IL-1ß, IL-6, COX-2, and iNOS, mitigates the mechanical trauma injury-induced damage, and accelerates the healing of wounds. CONCLUSION: This study indicates that BME might become a promising candidate for the treatment of neuroinflammation.

New Therapeutic Options in Mild Moderate COVID-19 Outpatients.

Background: In recent years, the therapeutic options for COVID have significantly improved; however, the therapies are expensive with restricted access to drugs, and expeditious and difficult to manage at home. We investigated the effect of pidotimod in preventing hospitalization in patients with mild-moderate COVID-19. Methods: A total of 1231 patients between January and June 2021 were screened. A total of 184 patients with mild-moderate COVID-19 were enrolled and divided into two groups: group-A (97) had undergone therapy with pidotimod 800 mg bid for 7−10 days and group-B (87) had other therapies. We excluded those who had undergone complete vaccination course, monoclonal anti-spike/antivirals or the co-administration of pidotimod-steroid. The primary outcome chosen was the emergency room, hospitalization, and deaths for COVID-related causes; the secondary outcome chosen was the duration of COVID-19 illness. Results: A total of 34 patients (18.5%) required hospital treatment, 11 in group-A and 23 in group-B (11.3% vs. 26.4%, p = 0.008). The median disease duration in group-A was 21 days (IQR 17−27) vs. 23 (IQR 20−31) in group-B (p = 0.005). Patients in the pidotimod group had higher SpO2 in the walking test (IQR 96−99% vs. IQR 93−98%, p = 0.01) and a lower need for steroid rescue therapy (11.5% vs. 60.9%, p < 0.001). Conclusions: In the first phase of disease, pidotimod can represent an effective, low-cost, weapon, without restrictions of use, that is able to prevent a second aggressive phase and promote faster virological recovery.

Molnupiravir as an Early Treatment for COVID-19: A Real Life Study.

OBJECTIVES: Below we report our experience in the use of molnupiravir, the first antiviral drug against SARS-CoV-2 available to us, in the treatment of patients with COVID-19. MATERIALS AND METHODS: We enrolled patients diagnosed with COVID-19 and comorbidities who were candidates for antiviral drug therapy. All patients received molnupiravir (800 mg twice daily). Blood chemistry checks were carried out at T0 and after 7/10 days after starting therapy (T1). RESULTS: There were enrolled within the cohort 100 patients. There was 100.0% compliance with the antiviral treatment. No patient required hospitalization due to worsening of respiratory function or the appearance of serious side effects. The median downtime of viral load was ten days (IQR 8.0-13.0), regardless of the type of vaccination received. The patients who had a shorter distance from vaccination more frequently presented vomiting/diarrhea. During baseline and T1 we found significant differences in the median serum concentrations of the main parameters, in particular of platelets, RDW CV, neutrophils and lymphocytes, the eGFR, liver enzymes, as well as of the main inflammatory markers, CRP and Ferritin. CONCLUSION: Participants treated with molnupiravir, albeit in risk categories, demonstrated early clinical improvement, no need for hospitalization, and a low rate of adverse events.

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

BACKGROUND: In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). METHODS: To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years). RESULTS: In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. CONCLUSIONS: Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age.

Risk Factors Associated with Poor Outcome in Patients with Infective Endocarditis: An Italian Single-Center Experience.

Background: Nowadays, infective endocarditis (IE) is still burdened by a high mortality. In the absence of an adequate prognostic stratification system, it is important to assess new predictors of poor outcomes. The aim of our study is to evaluate which factors were associated with higher mortality in IE patients. Methods: A retrospective cohort study enrolled patients with an IE diagnosis at the Infectious Diseases Clinic of the University 'G. D'Annunzio', Chieti, Italy from January 2013 to December 2019. For each patient, demographic, anamnestic and clinical information, embolic phenomena, laboratory and microbiologic data, treatment, and outcomes were collected and analyzed. A correlation analysis was performed. Results: Sixty-eight patients with EI were studied; among them, the mortality was 17.6%, 20.6%, and 23.5%, intra-hospital, at 1 month from discharge and at 6 months from discharge, respectively. Mortality was significantly correlated with age, estimated glomerular filtration rate, and procalcitonin values when considering either basal values (r = 0.266, p = 0.029), or values at 48−72 h from the start of an antibiotic therapy (r = 0.222; p < 0.05), cerebral embolization for 6-month mortality (r = 0.284; p = 0.019), and inadequate antibiotic therapy (r = 0.232, p < 0.05). Conclusions: Procalcitonin values, at EI diagnosis and at 48−72 h after starting antibiotics, are prognostic factors useful for stratifying patient risk, and for setting up a personalized treatment. Of note, cerebral embolization and an inappropriate empirical treatment were associated with a higher mortality in the short- and long-term.

Atypical Sites of Lymphadenopathy after Anti-COVID-19 Vaccine: Ultrasound Features.

Background and Objectives: Several authors have reported cervical and axillary lymphadenopathies as known side effects following anti-COVID-19 vaccine administration. Few data are available about atypical locations of post-anti-COVID-19 vaccine lymphadenopathy. In this investigation, we evaluated the incidence and prevalence of postvaccine lymphadenopathy ultrasound (US) features in atypical sites. Materials and Methods: In this retrospective study, we retrospectively selected 64 patients on whom US was performed between January and October 2021 due to COVID-19 vaccine-related lymphadenopathy. We investigated lymph node anatomical sites, presence, number, size, shape, cortical profile, hilum outline, superb microvascular imaging (SMI), and elastosonography. Results: A total of 170 nodes were assessed. Atypical location was demonstrated in 5/64 patients (7.8%). In all these cases, atypical nodal involvement was associated with lymphadenopathy in a typical site (axillary, supraclavicular) ipsilateral to the vaccine injection site. Two patients presented lymphadenopathy in the infraclavicular station (3.1%), one in the pectoralis major muscle (1.6%), one in the left arm (1.6%), and one in the nuchal site (1.6%). All lymphadenopathies were oval-shaped, with a median size of 0.9 ± 0.2 cm. US features included a symmetric cortex with hilum evidence (4/6, 60%), vascular signal at SMI in both the hilar region and periphery of lymph node (5/6, 83.3%), and a US elastography pattern resembling that of adjacent tissues (5/6, 83.3%). The median age of patients with lymphadenopathies in an atypical location was 23 years. The main type of vaccine associated with lymph node appearance in atypical sites was Moderna's mRNA-1273 (60% of patients, 4/6 lymph nodes accounting for 66.7% among atypical locations). Conclusion: Post-COVID-19 vaccine administration lymphadenopathies in an atypical location represent an intense immune response to antigenic stimuli and they may show alarming US traits superimposed on malignant pathologies, which may complicate the patient's clinical and diagnostic pathway. Despite no distinctive US features between reactive post-COVID-19 vaccination and malignant lymph nodes being available, careful examination of atypical lymph node locations associated with accurate knowledge of patients' clinical background and delay of US exam to four to six weeks after vaccine injection should be considered.

Evaluation of Cell Migration and Cytokines Expression Changes under the Radiofrequency Electromagnetic Field on Wound Healing In Vitro Model.

Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive faster healing, evaluating the keratinocytes migration, cytokines, and matrix metalloproteinases (MMPs) expression. The results showed that RF-EMF treatment promotes keratinocytes' migration and regulates the expression of genes involved in healing, such as MMPs, tissue inhibitors of metalloproteinases, and pro/anti-inflammatory cytokines, to improve WH.

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.

Effects of Probiotic Mixture Supplementation on the Immune Response to the 13-Valent Pneumococcal Conjugate Vaccine in People Living with HIV.

BACKGROUND: In people living with HIV, combination antiretroviral therapy (cART) reduces the risk of death, but the persistent immune-deficient state predisposes them to pneumococcal infections. Current guidelines encourage administering pneumococcal vaccine Prevenar 13 to patients living with HIV. Since probiotic supplementation could act as adjuvants and improve vaccine immunogenicity by modulating gut microbiota, the present study aimed to assess whether the effect of a formulation containing a combination of specific probiotics (Vivomixx®) could improve the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) in adult people living with HIV. METHODS: Thirty patients who were clinically stable and virologically suppressed, without opportunistic infections during this time and no ART changes in the 12 months before the study started were enrolled. Patients were divided into two groups: (1) received a placebo dose and (2) received Vivomixx® (1800 billion CFU) for four weeks before and after the vaccination with a single dose of PCV13. RESULTS: Vivomixx® supplementation induced a better response to PCV13 immunization, as shown by greater change in anti-Pn CPS13 IgG and increase in salivary IgA, IL-10 and IL-8. CONCLUSIONS: Additional investigations will help to clearly and fully elucidate the optimal strains, doses, and timing of administration of probiotics to improve protection upon vaccination in immunocompromised individuals and the elderly.

BNT162b2 mRNA Vaccination Leads to Long-Term Protection from COVID-19 Disease.

The efficacy of SARS-CoV-2 mRNA-based vaccines in preventing COVID-19 disease has been extensively demonstrated; however, it is of uttermost importance to acquire knowledge on the persistence of immune-protection both in terms of levels of neutralizing antibodies and specialized memory cells. This can provide important scientific basis for decisions on the need of additional vaccine doses and on when these should be administered thus resulting in an improvement in vaccination schedules. Here, we briefly report the changes in antibody levels and cellular immunity following BNT162b2 administration. We show an important fall in anti S1-Spike antibodies in BNT162b2 vaccinated subjects overtime, paralleled by a contextual consolidation of specific spike (S) T-cells, mainly of the CD8+ compartment. Contrariwise, CD4+ S-specific response shows a considerable interindividual variability. These data suggest that the well-known antibody drop in vaccinated subjects is replaced by memory cell consolidation that can protect from severe adverse effects of SARS-CoV-2 infection.