Assessing the performance of LumiraDx™ SARS-CoV-2 Ag test in detecting Omicron lineages: 2022-2023 study.

Background: The introduction of rapid antigen tests revolutionized the approach to SARS-CoV-2 diagnosis, offering prompt and accurate results with high sensitivity and specificity. Although it is more cost- and time-saving than the gold standard, real-time polymerase chain reaction (RT-PCR), the efficacy in general population screening in both hospital- and community-based settings remains unknown. Moreover, rapid antigen testing is limited by qualitative results. This study aims to evaluate the diagnostic reliability of the LumiraDx™ rapid antigen test during the Omicron era and to investigate its quantitative (analogue-to-digital converter (ADC)) results in comparison with RT-PCR Ct values. Methods: This prospective study included all adult patients with mild-to-moderate SARS-CoV-2 symptoms who were not hospitalised and did not require oxygen supplementation, consented to participate, and attended the Infectious and Tropical Diseases Unit of Padua University Hospital from July 14th, 2022 to January 3rd, 2023. The patients underwent two different tests simultaneously: a nasal LumiraDx™ swab and a real-time RT-PCR assay performed on a nasopharyngeal swab. Sampling was repeated several times for a subset of subjects. Results: We enrolled 266 consecutive participants and collected 601 pairs of LumiraDx™ and RT-PCR samples. The most prevalent variant was BA.4/BA.5 Omicron (60.2 %). The sensitivity and specificity of LumiraDx™ test when compared to real-time RT-PCR results as the reference standard were 93.1 % and 79.75 %, respectively. No significant differences in diagnostic reliability were found based on the available characteristics, age, sex, symptom status, or COVID-19 variant, except for the days from symptom onset. According to the multilevel logistic regression analysis, the only independent variable significantly associated with test concordance was the Ct value (adjusted odds ratio (OR) = 0.56, p < 0.001). Significant differences in quantitative ADC values were found between false negative (FN) versus true negative (TN), and false positive (FP) and true positive (TP) tests. Conclusions: This study showed that LumiraDx™ test is reliable for SARS-CoV-2 diagnosis in patients with mild-to-moderate SARS-CoV-2 symptoms. This finding confirms the efficacy of rapid antigen tests in monitoring vulnerable individuals during the current post-vaccination era. When compared with the RT-PCR, LumiraDx™ test effectively quantitatively distinguishes between FN and TN cases, as well as FP and true TP tests, despite inaccuracies in qualitative results.

Weight excess and obesity are associated with binge eating behaviours in people with HIV.

OBJECTIVE: Binge eating (BE) is a mental health disorder related to weight gain (WG), whose prevalence/correlation with weight excess in people with HIV (PWH) have been scarcely investigated.Design: A cross-sectional study of PWH who underwent the validated Binge eating scale (BES) questionnaire. METHODS: We included adult PWH during routine visits from October 2022 to February 2023. The BES questionnaire was administered with the support of a psychiatrist (score <17 BE very unlikely, BE≥17 possible/very likely). We performed a logistic regression for the binary outcome BES≥17 and being overweighted/obese as effect measure of risk association, and then adjusted for possible confounders (as integrase inhibitor exposure) and performed a sensitivity analysis fitting the regression model including and excluding depression (which may drive BE). RESULTS: We included 1204 PWH, 75.2% males, median age 53 years (IQR:44-60), 95.6% with undetectable HIV-RNA. As for BMI, we had overweight and obesity in 35.1% and 19.4% cases. Considering BES, 1089 (90.4%) PWH had a score<17, 115 (9.6%) ≥17. Multivariable analysis showed that obesity (OR = 6.21, p�< 0.0001), overweight (OR = 2.21, p = 0.006) and depression (OR�=�1.98, p�=�0.028) were significantly associated with high BES score. By excluding depression, our results were confirmed, and obesity/overweight remained significantly associated with BE (obesity OR = 6.58, p < 0.0001, overweight OR = 2.17, p = 0.023). CONCLUSIONS: BE should be considered among possible causes of WG in PWH. Our results push towards an in-depth study of this topic for a better understanding of the phenomenon in PWH, possibly identifying subgroups of this population who could benefit from a psychoeducational/psychological intervention to preventing WG.

Multidrug-resistant bacterial infections in the liver transplant setting.

Bacterial infections pose a life-threatening complication in patients with decompensated liver cirrhosis and acute-on-chronic liver failure. An increasing prevalence of infections caused by multidrug-resistant organisms (MDROs) has been observed in these patients, significantly impacting prognosis. A growing body of evidence has identified the most common risk factors for such infections, enabling the development of preventive strategies and therapeutic interventions. MDRO infections may also occur after liver transplantation (most commonly in the early post-operative phase), affecting both graft and patient survival. This review provides an overview of MDRO infections before and after liver transplantation, discussing epidemiological aspects, risk factors, prevention strategies, and novel therapeutic approaches. Furthermore, it examines the implications of MDRO infections in the context of prioritizing liver transplantation for the most severe patients, such as those with acute-on-chronic liver failure.

Impact of switching to injectables cabotegravir and rilpivirine on sleep disturbances in a cohort of people living with HIV.

BACKGROUND: Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. METHODS: A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. RESULTS: To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41-57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5-19.5) years and 360 (205-500) cell/mm3, respectively. The reason to start a long-acting strategy was person's choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. CONCLUSIONS: To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

Achievement of Primary Prevention Cardiometabolic Targets in Women with HIV: An Urgent Call to Action to Pursue Cardiovascular Health.

BACKGROUND: Cardiometabolic health has become crucial, especially for women with HIV (WWH). We assessed the achievement of targets for hypertension, dyslipidemia, and diabetes (H/Dy/DT) in primary prevention in a WWH cohort. METHODS: Cross-sectional analysis including all WWH in our clinic, excluding those who had a myocardial infarction. H/Dy/DT achievement was assessed by both EACS guidelines and individual cardiovascular risk, CVR (measured by ESC calculator), using logistic regression to evaluate differences in H/Dy/DT achievement between migrant and Italian women. RESULTS: We included 292 WWH, 55.5% Italian and 44.5% migrant women; the median age was 50 (IQR:42-58) years, 94.5% had undetectable HIV-RNA, 55.1% had a high level of education, 27.1% were smokers, and 19.2% did regularly physical exercise. Overall, 76%, 19%, and 5% of women presented a low, a high, and a very high CVR, respectively. Among Italians, 28.4% and 6.2% women presented a high and a very high CVR, respectively. Considering migrants, 7.7% and 3.8% women presented a high and a very high CVR, respectively. Overall, among migrant women, those with a high CVR were more likely to be not at target than those with a low risk (especially for LDL-c and blood pressure among people on treatment), despite the fact that we did not detect a statistically significant difference. By contrast, migrants were more likely to achieve glycemic targets than Italians (p = 0.032). CONCLUSIONS: H/Dy/DT target achievement is suboptimal, especially in migrants. A more aggressive pharmacological treatment, also assessing adherence to medical prescriptions, and promotion of healthy lifestyle should be urgently implemented, possibly redrawing the current model of care.

Immune System Deficiencies Do Not Alter SARS-CoV-2 Evolutionary Rate but Favour the Emergence of Mutations by Extending Viral Persistence.

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral therapies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants which strongly challenged containment measures and some therapeutic treatments. To assess whether impaired immunity could lead to the increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimise the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients experienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low-frequency mutations. This study suggests that a compromised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

Use of different anticholinergic scales and their correlation with anticholinergic symptom burden in a cohort of people living with HIV.

OBJECTIVES: How to detect the clinical impact of anticholinergic (AC) burden in people with HIV (PWH) remains poorly investigated. We cross-sectionally described the prevalence and type of AC signs/symptoms and the screening accuracy of three AC scales in detecting their presence in a modern cohort of PWH. METHODS: We calculated AC Burden Scale (ABS), AC Risk Score (ARS) and AC Drug Score (ADS) in 721 adult PWH and recorded the presence of AC signs/symptoms over the previous 3 months. High AC risk was defined by ABS score ≥2, and ARS or ADS score ≥3. Comparisons among the scale were based on Cohen's inter-rater agreement, and their screening accuracy was assessed by receiver operating characteristics (ROC) curves and performance measures. RESULTS: We enrolled 721 PWH, of whom 72.0% of participants were male; the median age was 53 years, and 164 participants (22.7%) were on at least one AC drug. Among these, 28.6% experienced at least one AC sign/symptom. Agreement in AC risk classification was substantial only between ARS and ADS (k = 0.6). Lower and higher risk of AC signs/symptoms was associated with dual regimens [adjusted OR (aOR) = 0.12 versus three-drug regimens, P = 0.002] and increasing number of AC drugs (aOR = 12.91, P < 0.001). Depression and COPD were also associated with higher risk of AC signs/symptoms in analysis unadjusted for number of AC drugs. ABS and ADS showed the best area under the ROC curve (AUROC) of 0.85 (0.78-0.92) and 0.84 (0.75-0.92; P < 0.001 for both). However, at the cut-off used for the general population, the sensitivity of all three scales was very low (34.0%, 46.8% and 46.8%). CONCLUSIONS: Up to one-fourth of participants in our cohort were exposed to at least one AC drug, and among them AC signs/symptoms affected more than one-fourth. Both polypharmacy (as number of antiretrovirals and of co-medications with AC properties) and to a lesser extent specific comorbidities shaped the risk of developing AC signs/symptoms. Sensitive screenings for AC risk in PWH should prefer ABS or ADS based on lower cut-offs than those suggested for the general population.

Real-Life Experience on Dolutegravir and Lamivudine as Initial or Switch Therapy in a Silver Population Living with HIV.

BACKGROUND: Clinical trials and real-life studies have granted the efficacy and safety of dolutegravir and lamivudine (DTG/3TC) in naïve and experienced people living with HIV (PLWH), but there are no long-term data in elderly people. We herein describe our real-life cohort of PLWH who were ≥65 years of age (PLWH ≥ 65) who started or were switched to DTG/3TC, single-tablet regimen, or DTG plus 3TC. METHODS: We considered laboratory/clinical parameter changes from the baseline to the last follow-up time point available for each person by the paired Wilcoxon test and analyzed factors associated with virological failure (VF) and discontinuation. RESULTS: We included 112 PLWH with a median age of 66 (IQR: 65-70) years, 77.6% males; 84.8% of people had multimorbidity, 34.8% were on polypharmacy, and only 5.4% were naïve to treatment. Reasons to be switched to DTG/3TC were: abacavir removal (38.7%), treatment simplification (33.1%), and PI discontinuation (28.2%). The median treatment durability was 6 (IQR: 5.4-7) years. No significant changes were detected in metabolic, renal, immunological, or cardiovascular biomarkers during follow-up. HIV RNA undetectability was maintained in 104 (92.8%) individuals for whom follow-up evaluation was available. We observed eight discontinuations (two deaths, two VFs, two early intolerances, one significant weight gain, and one switch to long-acting therapy). No factors were significantly associated with VF or discontinuation. CONCLUSIONS: This is the first study on DTG/3TC in PLWH ≥ 65 with a follow-up longer than 5 years. DTG/3TC was found to be safe and effective, neutral on metabolic parameters, and with a low discontinuation rate for toxicity or VF.

Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic.

BACKGROUND: A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. METHODS: We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. RESULTS: We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR). CONCLUSIONS: Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

Risk of hospitalization and sequelae in patients with COVID-19 treated with 3-day early remdesivir vs. controls in the vaccine and Omicron era: A real-life cohort study.

Recently, a benefit from administration of a 3-day course of early remdesivir (ER) in the outpatients' setting was reported. However, real-life data on its use is scarce. Therefore, we explored the ER clinical outcome in our outpatients' s cohort, compared to untreated controls. We included all patients who were prescribed ER from February to May 2022 and followed them up for 3 months and compared patients who received treatment with untreated controls. In the two groups the following outcomes were investigated: hospitalization and mortality rate, time of negativization and symptom's resolution, and postacute coronavirus disease 19 (COVID-19) syndrome prevalence. Overall, 681 patients were analyzed, mostly females (53.6%), and with a median age of 66 years (interquartile range: 54-77), 316 (46.4%) patients received ER, and 365 (53.6%) did not receive antiviral treatment (control group). Overall, 8.5% patients eventually required oxygen support, 8.7% were hospitalized for COVID-19, and 1.5% died. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and ER (adjusted odds ratio [aOR]: 0.049 [0.015; 0.16], p < 0.001) independently reduced hospitalization risk. ER was significantly associated with a shorter duration of SARS-CoV-2 positivity at nasopharyngeal swabs (aß -8.15 [-9.21; -7.09], p < 0.001) and of symptoms (aß -5.11 [-5.82; -4.39], p < 0.001), and with lower rate of COVID-19 sequelae compared to control group (aOR: 0.18 [0.10; 0.31], p < 0.001). Even in the SARS-CoV-2 vaccination and Omicron era, in patients at high risk of developing severe disease, ER demonstrated to have a good safety profile and to significantly reduce the risk of disease progression and COVID-19 sequelae compared to untreated controls.

Changing patterns and clinical outcomes of hospitalized patients with COVID-19 severe pneumonia treated with remdesivir according to vaccination status: results from a real-world retrospective study.

Since the beginning of Coronavirus Disease 2019 (COVID-19) pandemic, many drugs have been purposed for the treatment of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Remdesivir emerged as an encouraging antiviral drug for patients with documented severe COVID-19-related pneumonia. Although several studies about remdesivir effectiveness exist, no study investigated the effect of the combination of remdesivir with the vaccination status. The aim of this study was to assess whether the administration of remdesivir could show some differences in terms of clinical outcomes in patients vaccinated against SARS-CoV-2 versus those who were not. The primary outcome was the in-hospital mortality. The secondary outcomes were 30-days mortality, the need for ICU admission and for oxygen supplementation. This is a retrospective cohort study including all consecutive adult patients hospitalized for severe COVID-19 at the Padua University Hospital (Italy), between September 1st, 2020, and January 31st, 2022, and who received a 5-days course of remdesivir. A total of 708 patients were included, 467 (66%) were male, and the median age was 67 (IQR: 56-79) years. To better estimate the outcomes of interest, a propensity score weighted approach was implemented for vaccination status. A total of 605/708 patients (85.4%) did not complete the vaccination schedule. In-hospital mortality rate was 5.1% (n = 36), with no statistically significant difference between the unvaccinated (n=29, 4.8%) and vaccinated (n=7, 6.8%; p=0.4) patients. After propensity score matching, mortality between the two groups remained similar. However, both the need for ICU and oxygen supplementation were significantly lower in the vaccinated group. Our finding suggests that a complete vaccination course could have an impact in reducing the need for transfer in ICU and for high-flow therapy in moderate-to-severe COVID-19 patients treated with remdesivir.

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

BACKGROUND: Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce. METHODS: We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded. RESULTS: We included 909 patients, 48.3% males and 95.2% vaccinated against SARS-CoV-2. The median age was 73 (IQR: 62-82) years. MOL and NIR were prescribed in 407 (44.8%) and 502 (55.2%) patients, respectively. Overall, 124/909 (13.6%) patients experienced any AEs following antivirals intake: 98/124 (79%) patients reporting adverse events presented grade 1 AEs, 23/124 (18.5%) grade 2 AEs and 3 (2.5%) grade 3 AEs. Treatment discontinuation was recorded in 4.8% of patients. AEs were significantly higher in women, in patients treated with NIR compared to MOL and in people who were not vaccinated. CONCLUSIONS: In our real-life setting, AEs were higher than those reported by clinical trials, and were particularly associated with NIR use and with not being vaccinated. Further analyses are needed to better assess safety of oral antivirals and to define which patient's profile may benefit most from MOL and NIR.

Sleep disturbances and their correlation with cardiovascular risk, obesity, and mood disorders in people with HIV.

BACKGROUND: The relationship between sleep disorders (SDs), cardiovascular risk (CVR), and mood disorders (MDs) has been studied in detail in the general population, but far less in people with HIV (PWH). METHODS: Cross-sectional analysis in single centre cohort of PWH. Sleep quality was assessed using by Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Berlin Questionnaire (BQ), Pittsburgh Sleep Quality Index (PSQI); anxiety and depression were evaluated by the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9. Demographic, clinical and HIV-related data were collected, and Framingham and Data collection on Adverse effects of anti-HIV Drugs (DAD)-10 scores were computed in modelling associations with each SDs scale. RESULTS: Data were collected for 721 PWH on stable combination antiretroviral therapy (cART) (median age of 53 years, 71.8% males, 96% with undetectable HIV RNA, 50.3% on cART potentially affecting sleep, and 20.4% on hypno-inducing drugs), 76.9% had SDs 60.3, 31.3, 31.1, and 7.9% at PSQI, BQ, ISI, and ESS, respectively. Anxiety and depression were detected in 28.3 and 16.1% participants, respectively. BQ score was independently associated with high BMI ( P  < 0.001), Framingham risk >10% ( P  < 0.001), and both DAD-10R and -10F score >10% ( P  < 0.001 and P  = 0.031). PSQI and ISI scores were independently associated with depression and anxiety ( P  < 0.001). No association between SDs and specific antiretroviral regimens, nor HIV-related parameters was detected. CONCLUSIONS: In our cohort of PWH on stable ART, despite the alarmingly higher prevalence, SDs were associated with the same determinants (cardiovascular risk factors and MDs) observed in the general population.

Changing Prevalence of AIDS and Non-AIDS-Defining Cancers in an Incident Cohort of People Living with HIV over 28 Years.

BACKGROUND: The introduction and evolution of antiretrovirals has changed the panorama of comorbidities in people living with HIV (PLWH) by reducing the risk of AIDS-defining cancers (ADC). By contrast, due to ageing and persistent inflammation, the prevalence and incidence of non-AIDS-defining cancers have significantly increased. Therefore, we aimed at describing cancer epidemiology in our cohort over 28 years. METHODS: We retrospectively included all PLWH in our clinic who ever developed cancers, considering features of ADC and NADC, from January 1996 to March 2023. Demographic, clinical characteristics, and survival were analyzed, comparing three observation periods (1996-2003, 2004-2013, and 2014-2023). RESULTS: A total of 289 PLWH developed 308 cancers over the study period; 77.9% were male, the mean age was 49.6 years (SD 12.2), and 57.4% PLWH developed NADC and 41.5% ADC. Kaposi (21.8%) and non-Hodgkin lymphoma (20.1%) were the most frequent cancers. Age at the time of cancer diagnosis significantly increased over time (41.6 years in the first period vs. 54.4 years in the third period, p < 0.001). In the first period compared with the last, a simultaneous diagnosis of HIV infection and cancer occurred in a higher proportion of persons (42.7 vs. 15.3, p < 0.001). While viro-immunological control at cancer diagnosis significantly improved over time, the proportions of cancer progression/remission remained stable. Overall survival significantly increased, but this trend was not confirmed for ADC. CONCLUSIONS: The probability of survival for ADC did not decrease as significantly as the number of ADC diagnoses over time. By contrast, NADC dramatically increased, in line with epidemiological studies and other literature data. The changing patterns of malignancies from ADC to NADC underline the need for public health interventions and the fostering of screening programs aimed at the prevention and early detection of NADC in PLWH.

Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern.

Background: Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods: The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results: Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01). Conclusions: Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn. Funding: This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number: NCT05205759.

Epidemiological and Clinical Features of SARS-CoV-2 Variants Circulating between April-December 2021 in Italy.

SARS-CoV-2 is constantly evolving, leading to new variants. We analysed data from 4400 SARS-CoV-2-positive samples in order to pursue epidemiological variant surveillance and to evaluate their impact on public health in Italy in the period of April-December 2021. The main circulating strain (76.2%) was the Delta variant, followed by the Alpha (13.3%), the Omicron (5.3%), and the Gamma variants (2.9%). The B.1.1 lineages, Eta, Beta, Iota, Mu, and Kappa variants, represented around 1% of cases. There were 48.2% of subjects who had not been vaccinated, and they had a lower median age compared to the vaccinated subjects (47 vs. 61 years). An increasing number of infections in the vaccinated subjects were observed over time, with the highest proportion in November (85.2%). The variants correlated with clinical status; the largest proportion of symptomatic patients (59.6%) was observed with the Delta variant, while subjects harbouring the Gamma variant showed the highest proportion of asymptomatic infection (21.6%), albeit also deaths (5.4%). The Omicron variant was only found in the vaccinated subjects, of which 47% had been hospitalised. The diffusivity and pathogenicity associated with the different SARS-CoV-2 variants are likely to have relevant public health implications, both at the national and international levels. Our study provides data on the rapid changes in the epidemiological landscape of the SARS-CoV-2 variants in Italy.

Viro-Immunological, Clinical Outcomes and Costs of Switching to BIC/TAF/FTC in a Cohort of People Living with HIV: A 48-Week Prospective Analysis.

To date, therapeutic switches are performed to reduce and prevent toxicity, improve adherence, promote virological control, and save costs. Drug switches are a daily challenge in the management of people living with HIV (PLWH), especially in those with multiple comorbidities and on polypharmacy. The objectives of this prospective analysis were: (I) to evaluate the viro-immunological efficacy of BIC/FTC/TAF in a cohort of PLWH who switched to this regimen from any other previous, at the Infectious and Tropical Diseases Unit of the Padua University Hospital; (II) to assess the impact on body weight, lipids, and renal function parameters at week 48; and (III) to evaluate daily costs changes, adherence, and the rate and causes of discontinuation of the regimen. We included all adult PLWH who switched to BIC/FTC/TAF from 1 February 2020 to 31 October 2021. We collected demographic, clinical, and laboratory data at baseline and week 48 after the switch. In addition, the estimated cART-related cost changes over the follow-up period were calculated. Over the study period, 290 individuals who switched to BIC/FTC/TAF, 76.9% were males, with a median age of 52 years, and 94.8% had an undetectable baseline HIV viremia. After a median time of 35 days (IQR: 1-55), 41 (14.1%) individuals discontinued the regimen. Factors significantly associated with discontinuation were switching from dual regimens, and neurological disorders. At week 48, we detected a significant increase in body weight, BMI, CD4 T-cell count, and CD4/CD8 ratio, and a significant reduction in triglycerides and costs; all patients had undetectable HIV RNA. Our results showed that switching to BIC/FTC/TAF may favor slightly immunological recovery and cost saving (-4.2 EUR/day from baseline to week 48, equivalent to a mean saving of 1533 EUR/year/person). The reduction in triglycerides does not appear to be clinically relevant, even if statistically significant, nor do both the increase in body weight and BMI (+1 kg and +0.29 BMI, respectively) and the increase in CD4 T-cell count (+45 cells/mmc). Further studies are needed to confirm our results.