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Background Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. Methods We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. Results Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction). Conclusions Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is challenging, and the role of Aspergillus-PCR in bronchoalveolar lavage (BAL) is unknown.This study evaluated diagnostic accuracy of Aspergillus-PCR in BAL in IPA in three different cohorts: ICU-admitted patients with COVID-19, ICU-admitted patients without COVID-19 and immunocompromised patients.All stored available BAL samples collected from three patient groups were tested with Aspergillus-PCR (AsperGeniusWe included 111 BAL samples from 101 patients: 52 (51%) patients admitted to ICU for COVID-19, 24 (24%) admitted to ICU for other reasons and 25 (25%) immunocompromised. There were 31 cases of IPA (28%). Aspergillus-PCR sensitivity was 64% (95% CI 47-79) and specificity 99% (95% CI 93-100). Aspergillus-PCR sensitivity was 40% (95%CI 19-64) in ICU COVID-19, 67% (95% CI 21-93) in non-COVID-19 ICU patients and 92% (95%CI 67-98) in the immunocompromised. The concordance between positive BAL-GM and BAL-PCR in patients with and without IPA was significantly lower in ICU patients (32%; 43% in COVID-19, 18% in non-COVID-19) than in the immunocompromised (92%), p .001.Aspergillus-PCR in BAL improves the diagnostic accuracy of BAL-GM in ICU patients.

Background It is 30 years since evidence-based medicine became a great support for individual clinical expertise in daily practice and scientific research. Electronic systems can be used to achieve the goal of collecting data from heterogeneous datasets and to support multicenter clinical trials. The Ligurian Infectious Diseases Network (LIDN) is a web-based platform for data collection and reuse originating from a regional effort and involving many professionals from different fields. Objectives The objective of this work is to present an integrated system of ad hoc interfaces and tools that we use to perform pseudonymous clinical data collection, both manually and automatically, to support clinical trials. Methods The project comprehends different scenarios of data collection systems, according to the degree of information technology of the involved centers. To be compliant with national regulations, the last developed connection is based on the standard Clinical Document Architecture Release 2 by Health Level 7 guidelines, interoperability is supported by the involvement of a terminology service. Results Since 2011, the LIDN platform has involved more than 8,000 patients from eight different hospitals, treated or under treatment for at least one infectious disease among human immunodeficiency virus (HIV), hepatitis C virus, severe acute respiratory syndrome coronavirus 2, and tuberculosis. Since 2013, systems for the automatic transfer of laboratory data have been updating patients' information for three centers, daily. Direct communication was set up between the LIDN architecture and three of the main national cohorts of HIV-infected patients. Conclusion The LIDN was originally developed to support clinicians involved in the project in the management of data from HIV-infected patients through a web-based tool that could be easily used in primary-care units. Then, the developed system grew modularly to respond to the specific needs that arose over a time span of more than 10 years.

Background The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). Methods All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5–11 days) or PC (12–24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. Results A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7–11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14–16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P = .02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P = .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31–1.47; P = .20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20–5.80; P = .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35–1.50; P = .38) did not differ between groups. Conclusions Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.

Background Clinical trial demonstrated that SARS-CoV-2 vaccines have the ability of reduce mortality and morbidity due to COVID-19. The aim of this study is to describe the effect of vaccination in term of mortality, type of ventilation and ICU admission among patients hospitalized for COVID-19 from May to December 2021 in a Ligurian Hospital. Methods This is a retrospective, single-center study conducted in San Martino Hospital (Genoa, Italy), including patients ≥ 18 years hospitalized for COVID-19 in Infectious Disease and Emergency Units from 1st May to 31st December 2021. We collected demographical data, multimorbidity and disability score, vaccination time (“vaccinated” all patients hospitalized ≥ 14 days after first dose or ≥ 7 days after second/third dose), therapy for COVID-19, mortality at 7 and 30 days, ICU admission, ventilation type. Characteristics of vaccinated (group A) versus non vaccinated (group B) patients were compared using Chi-squared/Fisher's exact test for categorical variables and t-test /Kruskal-Wallis test for the continuous ones. Cox proportional hazards models for death at 30 days were performed as univariate analysis as well as adjusting for age, Cumulative Illness Rating Scale [CIRS], gender, Remdesivir, Monoclonal antibodies, Tocilizumab use. Results Overall, 405 patients SARS-CoV-2 infected were enrolled. Data about timing of vaccination were available for 360 patients (89%). We compared clinical characteristics and outcomes of group A (32%) versus group B (68%). In group A patients were older (p< 0.001) and frailer (higher CIRS score and lower Barthel index, p< 0.001) than in group B. Among patients requiring oxygen, 76 (31.5%) in group B vs 26 (22.41%) in group A needed high flow ventilation (p=0.036); 33 (13.52%) vs 3 (2.59%) respectively were admitted to ICU (Figure 1). Mortality at 30 days after hospitalization was higher in group A at univariate analysis [HR(95%CI) 1.44(0.82; 2.53), p=0.208], lower at multivariate analysis [0.57(0.31; 1.02), p=0.059]. Conclusion The results of this study confirm that SARS-CoV-2 vaccination reduces rate of admission to ICU and 30 days mortality among patients hospitalized for COVID-19. In our cohort mortality among vaccinated patients remains high and we hypothesized this is due to high frailty of evaluated population. Disclosures Chiara Dentone, CD, Angelini: Advisor/Consultant|Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|Novartis: Advisor/Consultant Matteo Bassetti, PhD, Angelini: Advisor/Consultant|Astellas: Grant/Research Support|Bayer: Advisor/Consultant|Bayer: Honoraria|BioMe ́ rieux: Advisor/Consultant|BioMe ́ rieux: Honoraria|Cidara: Advisor/Consultant|Cidara: Honoraria|Cipla: Advisor/Consultant|Cipla: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Menarini: Advisor/Consultant|Menarini: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Tetraphase: Advisor/Consultant.

Background We studied immunological response against SARS-CoV-2 after two doses of vaccine in health care workers (HCW) at our Infectious Disease Unit Methods We enrolled prospectively HCW without (group A) and with previous infection (group B). We collected peripheral blood at baseline (before the BNT162b2 vaccine), T1 (before the 2nd dose), T2 and T6 (after 1 and 6 months after of 2nd dose). The activation induced cell marker assay (AIM) was performed with CD4 and CD8 Spike peptide megapools (MPs). We evaluated the Stimulation Index (SI) as AIM+ stimulated cells/negative control (positive response SI >= 2). Quantitative antibodies (Abs) to Spike-1 protein (S) and to nucleocapside protein (N) were detected with an electrochemiluminescence immunoassay. We tested at T6 the responses to alpha, beta, gamma, delta and epsilon variants MPs.We used the linear mixed model with random intercept adjusted for age and sex to compare specific times to T0. To assess differences over time between groups the interaction with time was tested. Results In group A 13/22 (59%) were female vs 5/7 (71%) group B, the mean age 40 vs 38 years, respectively. For CD4+ Spike the overall rate of change over time was significant at T1 (p=0.038) and at T2 (p< 0.001) vs T0 with a decreasing at T6 (p not significant) [Figure 1] with a trend of higher response in group A. In group B the CD8+ Spike reactivity increased at T1(p=0.037) and at T6 (p=0.005) vs T0. The interaction between SI and time was statistically significant at T1 (p=0.033); T2 (p= 0.046) and T6 (p=0.035) (mean values in group B higher than A). For overall population, the anti-S Abs significantly increased at T1 vs T0, T2 vs T0 and at T6 vs T0 [Figure 2A]. The group B at T6 retained a higher anti S response but the rate of change significantly differs between the two group (overall interaction: p< 0.001) [Figure 2B]. At T6 in both groups we found a high CD4+ T cells response to epsilon variant, even if not detected as circulant virus. Quantitative (U/ml) values of anti-S Antibodies. Conclusion The humoral response was persistent and increased in previous infected subjects. The CD4+T cells response after vaccination retained a response in uninfected subject, with an increasing trend and with a response to non-circulating variants. The vaccine could help the CD8+ T cells reactivity specific for Spike peptides. Disclosures Chiara Dentone, CD, Angelini: Advisor/Consultant|Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|Novartis: Advisor/Consultant Lucia Taramasso, LT, Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|ViiV: Advisor/Consultant Alessandro Sette, AS, Arcturus Therapeutics: Grant/Research Support|Astrazeneca: Advisor/Consultant|Avalia: Advisor/Consultant|CellCarta: Grant/Research Support|Flow Pharma: Grant/Research Support|Fortress: Advisor/Consultant|Gritstone Bio: Advisor/Consultant|ImmunoScape: Advisor/Consultant|Moderna: Advisor/Consultant|Repertoire: Advisor/Consultant Antonio Di Biagio, AD, Abbvie: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|MSD: Advisor/Consultant|ViiV: Advisor/Consultant Matteo Bassetti, PhD, Angelini: Advisor/Consultant|Astellas: Grant/Research Support|Bayer: Advisor/Consultant|Bayer: Honoraria|BioMe ́ rieux: Advisor/Consultant|BioMe ́ rieux: Honoraria|Cidara: Advisor/Consultant|Cidara: Honoraria|Cipla: Advisor/Consultant|Cipla: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Menarini: Advisor/Consultant|Menarini: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Tetraphase: Advisor/Consultant.

Background There is limited knowledge on the origin and development from CD34+ precursors of the ample spectrum of human natural killer (NK) cells, particularly of specialized NK subsets. Objective This study sought to characterize the NK-cell progeny of CD34+DNAM-1brightCXCR4+ and of other precursors circulating in the peripheral blood of patients with chronic viral infections (eg, HIV, hepatitis C virus, cytomegalovirus reactivation). Methods Highly purified precursors were obtained by flow cytometric sorting and cultured in standard NK-cell differentiation media (ie, SCF, FLT3, IL-7, IL-15). Phenotypic and functional analyses on progenies were performed by multiparametric cytofluorimetric assays. Transcriptional signatures of NK-cell progenies were studied by microarray analysis. Inhibition of cytomegalovirus replication was studied by PCR. Results Unlike conventional CD34+ precursors, Lin−CD34+DNAM-1brightCXCR4+ precursors from patients with chronic infection, rapidly differentiate into cytotoxic, IFN-γ–secreting CD94/NKG2C+KIR+CD57+ NK-cell progenies. An additional novel subset of common lymphocyte precursors was identified among Lin−CD34−CD56−CD16+ cells and characterized by expression of CXCR4 and lack of perforin and CD94. Lin−CD34−CD56−CD16+Perf−CD94−CXCR4+ precursors are also endowed with generation potential toward memory-like NKG2C+NK cells. Maturing NK-cell progenies mediated strong human cytomegalovirus–inhibiting activity. Microarray analysis confirmed a transcriptional signature compatible with NK-cell progenies and with maturing adaptive NK cells. Conclusions During viral infections, precursors of adaptive NK cells are released and circulate in the peripheral blood.

BackgroundThe primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors.Materials and methodsPatients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed.ResultsSixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759,p = 0.039).ConclusionsIn critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2-specific T cell responses in the early phase comparing mild, moderate, or severe COVID-19 disease outcomes. T cell responses to the spike (S) and non-S proteins were measured in a combined activation-induced marker (AIM) and intracellular cytokine staining (ICS) assay. Early CD4+ T cell responses to SARS-CoV-2 S correlated with milder disease by both AIM and IFNγ ICS readouts. The correlation of S-specific CD4+ T cell responses with milder disease severity was most striking within the first two weeks of symptom onset compared to later time points. Furthermore, donors with milder disease were associated with polyantigenic CD4+ T cell responses that recognized more prominently non-S proteins in addition to S, while severe acute COVID-19 was characterized by lower magnitudes of CD4+ T cell responses and a narrower repertoire. In conclusion, this study highlights that both the magnitude and breadth of early SARS-CoV-2-specific CD4+ T cell responses correlated with milder disease outcomes in acute COVID-19 patients.

Objective Few data exist about the effect of dolutegravir (DTG) on bone mineral density (BMD) in real life. The aim of this study was to determine rates of change in BMD over time in people living with HIV (PLWH) treated with DTG. Design The SCOLTA project is a multicenter observational study enrolling HIV-infected people who start newly commercialized drugs prospectively, with the aim of identifying toxicities and adverse events (AE) in a real-life setting. Methods Dual-energy X-ray absorptiometry at the femoral neck (FN) and lumbar spine (LS) was performed at study entry (baseline, BL) and after 96 weeks. Percentage BMD change from BL was evaluated using a general linear model, including factors potentially associated with bone loss. Results One hundred and sixty PLWH were enrolled (26.3% female, mean age 49.9 ± 11.2 years) from April 2015 to April 2017. Overall, we could calculate BMD change from baseline, for at least one site, in 133 subjects (83.1%). After a median of 102 weeks (IQR: 90-110), mean FN BMD increased, but not significantly, whereas LS BMD showed a significant mean increase of 13.1 (95% confidence interval, CI: 1.7-24.6) mg/cm3 (+1.6%, 95% CI: 0.3%, 2.8%) after a median time of 102 weeks (IQR: 84-110). As regards LS BMD, patients with osteopenia/osteoporosis at study entry experienced a high increase from baseline (20.6, 95% CI: 3.1, 38.1 mg/cm3), as well as experienced subjects (16.9, 95% CI: 4.7, 29.2 mg/cm3) and those on vitamin D supplementation (26.8, 95% CI: 7.7, 45.9 mg/cm3). Conclusion Dolutegravir-containing regimens could reduce the negative impact of antiretroviral therapy on bone, especially in patients with low BMD.

Patients with severe SARS-CoV-2 infection have an overwhelming inflammatory response characterized by remarkable organs monocyte infiltration. We performed an immunophenotypic analysis on circulating monocytes in 19 COVID-19 patients in comparison with 11 naïve HIV-1 patients and 10 healthy subjects. Reduced frequency of classical monocytes and increased frequency of intermediate monocytes characterized COVID-19 patients with respect to both HIV naïve patients and healthy subjects. Intensity of C-C motif chemokine receptor 2 (CCR2) monocyte expression highly correlated with parameters of kidney dysfunction. Our data indicate that highly activated monocytes of COVID-19 patients may be pathogenically associated to the development of renal disease.

Candida auris (C. auris) is an emerging nosocomial pathogen, and a sharp rise in cases of colonization and infection has been registered in intensive care units (ICUs) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The unfavorable resistance profile of C. auris and the potential high mortality of C. auris infections represent an important challenge for physicians.We conducted a single-center retrospective study including all patients admitted to ICUs with isolation of C. auris in any non-sterile body site between February 20, 2020, and May 31, 2021. The primary aim of the study was to assess the cumulative incidence of C. auris candidemia in colonized patients. The secondary aim was to identify predictors of C. auris candidemia in the study population.During the study period, 157 patients admitted to ICUs in our hospital became colonized with C. auris; 59% of them were affected by COVID-19. Overall, 27 patients (17%) developed C. auris candidemia. The cumulative risk of developing C. auris candidemia was 25% at 60 days after first detection of C. auris colonization. Seven patients with C. auris candidemia (26%) also developed a late recurrent episode. All C. auris blood isolates during the first occurring episode were resistant to fluconazole and susceptible to echinocandins, while 15 (56%) were resistant to amphotericin B. During late recurrent episodes, emergent resistance to caspofungin and amphotericin B occurred in one case each. In the final multivariable model, only multisite colonization retained an independent association with the development of C. auris candidemia.Candida auris candidemia may occur in up to one fourth of colonized critically ill patients, and multisite colonization is an independent risk factor for the development of candidemia. Implementing adequate infection control measures remains crucial to prevent colonization with C. auris and indirectly the subsequent development of infection.

Diagnosing people living with chronic viral hepatitis is challenging due to the absence of symptoms as long as liver decompensated cirrhosis come out. The aim of this retrospective study was to evaluate the prevalence of HBV and/or HCV infections in a non-selected population, hospitalised for SARS-CoV-2 infection in a tertiary care hospital in Northern Italy. During the study period 1,429 patients were admitted to hospital for SARS-CoV-2 infection, serologic tests for HBV and/or HCV were available for 382 (27%) patients and 3 were excluded due to their previous known serologic status. Among 379 patients, 235 (62%) were male, median age was 70 years (range 21–103), 360 (95%) were Caucasian. Among them, 372/379 (98%) were screened for HBsAg, 320/379 (84%) for HBcAb. HBsAg was positive in 2/372 (0.5%, 95% CI 0.0006–0.02) patients (only in one HBV-DNA was performed that was negative), while HBcAb was found positive in 55/320 (17%, 95% CI 0.13–0.22). Among 370/379 (98%) patients screened for HCV, 11/370 (3%, 95% CI 0.02–0.05) had positive HCV-Ab. Five out of 11 (45%) were tested for HCV-RNA that resulted positive in two patients (0.5%, 95% CI 0.0006–0.02). Considering this data, even though the screening was performed in only 27% of study population, a tailored screening in people with known risk factors for hepatitis might be preferable to universal screening in low prevalence areas. Also a prompt diagnostic workout should begin in case of clinical or laboratory suspicion of hepatitis and in those starting immunosuppressive treatments.

Serum (1,3)-beta-d-glucan (BDG) assay is a non-culture-based test recommended for the diagnosis of invasive candidiasis owing to its faster results and higher sensitivity than blood cultures. Its performance might vary for different Candida species. The aim of this study was to determine in vitro levels of BDG in Candida auris culture supernatants and evaluate BDG levels in patients with C. auris candidemia sustained by these stains.C. auris strains were collected from blood cultures of patients who had a concomitant (-24 to +72 hours) serum BDG test (Fungitell assay). Supernatants of broth media culture of C. auris strains and two Candida albicans (controls) strains were prepared and tested for BDG.Ten C auris strains were included. Supernatants of two C. albicans considered as controls had a mean BDG level of 1155 pg/mL (considered 100% reactivity). The median BDG level in supernatants of C. auris strains was 275 pg/mL (IQR 165-523 pg/mL), with a median reactivity of 24% (range 6%-72%). In vivo, the median BDG level was 129 pg/mL (IQR, 28-199 pg/mL). Sensitivity of BDG for C. auris candidemia was 60%. All patients received antifungal treatment with an echinocandin initiated a median of 2 days (IQR -8 to 0) before blood collection for BDG.Our C. auris strains released lower amounts of BDG when compared to C. albicans. Clinical implications include lower sensitivity of serum BDG for the diagnosis of C. auris candidemia with a consequent impact on management protocols in settings with high prevalence of this species.

No abstract present.

Monoclonal antibodies, such as bamlanivimab and etesevimab combination (BEC), have been proposed for patients with mild or moderate coronavirus disease 2019 (COVID-19). However, few studies have assessed the factors associated with the early administration of BEC or the impact of early BEC treatment on the clinical evolution of the patients. We conducted a retrospective cohort study of all adults with COVID-19 who received BEC at three institutions in the Liguria region. The primary endpoint was to investigate the clinical variables associated with early BEC infusion. Secondary endpoints were 30-day overall mortality and the composite endpoint of requirement of hospital admission or need for supplemental oxygen during the 30-day follow-up period. A total of 127 patients (median age 70 years, 56.7% males) received BEC. Of those, 93 (73.2%) received BEC within 5 days from symptoms onset (early BEC). Patients with a higher Charlson comorbidity index were more likely to receive early treatment (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.04–2.45, p = 0.03) in contrast to those reporting fever at presentation (OR 0.26, 0.08–0.82, p = 0.02). Early BEC was associated with lower likelihood of hospital admission or need for supplemental oxygen (OR 0.19, 0.06–0.65, p = 0.008). Five patients who received early BEC died during the follow-up period, but only one of them due to COVID-19-related causes. Early bamlanivimab and etesevimab combination was more frequently administered to patients with a high Charlson comorbidity index. Despite this, early BEC was associated with a lower rate of hospital admission or need for any supplementary oxygen compared to late administration. These results suggest that efforts should focus on encouraging early BEC use in patients with mild–moderate COVID-19 at risk for complications.

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response.

Objectives: The hypothesis of this study is that tocilizumab should affect common signs of infection due to its immunosuppressive properties. Primary aim of the study was to investigate whether the administration of tocilizumab to critically ill patients with COVID-19, led to a different clinical presentation of infectious complications compared to patients who did not receive tocilizumab. Secondary aim was investigating differences in laboratory parameters between groups. Methods: Single-centre retrospective study, enrolling COVID-19 patients who developed a microbiologically confirmed infectious complication [ventilator associated pneumonia or bloodstream infection] after intensive care unit [ICU] admission and either treated with tocilizumab or not [controls]. Results: A total of 58 patients were included, 25 treated with tocilizumab and 33 controls. Median time from tocilizumab administration to infection onset was 10 days [range 2-26]. Patients were 78% male, with median age 65 years [range 45-79]. At first clinical presentation of the infectious event, the frequency of hypotension [11/25, 44% vs. 11/33, 33%], fever [8/25, 32% vs. 10/33, 30%] or hypothermia [0/25,0%, vs. 2/33, 6%], and oxygen desaturation [6/25, 28% vs 4/33, 12%], as well as the frequency of SOFA score increase of ≥ 2 points [4/25, 16%,vs. 4/33, 12%] was similar in tocilizumab treated patients and controls [p>0.1 for all comparisons]. Among laboratory parameters, C-Reactive Protein elevation was reduced in tocilizumab treated patients compared to controls [8/25, 32% vs. 22/33, 67%, p=0.009]. Conclusion: The clinical features of infectious complications in critically ill patients with COVID-19 admitted to ICU were not affected by tocilizumab.

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16–21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43–7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05–57.26, p &lt, 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.

This study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG (p

Background An unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU). Materials and methods The primary objective was to describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI. Results During the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval [CI] 172–298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04–1.66, p = .021). Conclusions The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.KEY MESSAGESThe cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19.The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%.There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Candida auris among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital&ndash, IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with C. auris and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed C. auris candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.

In this observational study, 13 patients with severe COVID‐19 and 10 healthy controls were enrolled. The data concerning the analysis of circulating T cells show that, in severe COVID‐19 patients, the expansion of these cell compartments is prone to induce antibody response, inflammation (CCR4+ and CCR6+ TFH) and regulation (CD8+ Treg). This pathogenic mechanism could lead us to envision a possible new form of biological target therapy., Highlights In patients with severe COVID‐19 we found a relative expansion of T‐cell subsets (Th2‐ and Th17‐ oriented TFH and CD8+ Treg) with a relative reduction of Th1 cells, which are those associated with eradication of a viral infection. This pathogenic mechanism could lead us to envision a possible new form of biological target therapy.

Background Viral RNA amplification by real-time RT-PCR still represents the gold standard for the detection of SARS-CoV-2, but the development of rapid, reliable and easy-to-perform diagnostic methods is crucial for public health, because of the need of shortening the time of result-reporting with a cost-efficient approach. Objectives The aim of our research was to assess the performance of FREND™ COVID-19 Ag assay (NanoEntek, South Korea) as a ultra-rapid frontline test for SARS-CoV-2 identification, in comparison with RT-PCR and another COVID-19 antigen fluorescence immunoassay (FIA). Study design The qualitative FIA FREND™ test, designed to detect within 3 min the Nucleocapsid protein of SARS-CoV-2, was evaluated using nasopharyngeal swabs in Universal Transport Medium (UTM™, Copan Diagnostics Inc, US) from suspected COVID-19 cases who accessed the Emergency Room of the Ospedale Policlinico San Martino, Genoa, Liguria, Northwest Italy. Diagnostic accuracy was determined in comparison with SARS-CoV-2 RT-PCR and STANDARD F™ COVID-19 Ag FIA test (SD BIOSENSOR Inc., Republic of Korea). Results In November 2020, 110 nasopharyngeal samples were collected consecutively; 60 resulted RT-PCR positive. With respect to RT-PCR results, sensitivity and specificity of FREND™ COVID-19 Ag test were 93.3 % (95 % CI: 83.8−98.2) and 100 % (95 % CI: 92.9−100), respectively. FREND™and STANDARD F™ COVID-19 Ag FIA assays showed a concordance of 96.4 % (Cohen’s k = 0.93, 95 % CI: 0.86−0.99). Conclusions FREND™ FIA test showed high sensitivity and specificity in nasopharyngeal swabs. The assay has the potential to become an important tool for an ultra-rapid identification of SARS-CoV-2 infection, particularly in situations with limited access to molecular diagnostics.

The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Candida auris among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital–IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with C. auris and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed C. auris candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.

Background: Some patients affected by COVID-19 present a life-threatening hyperinflammatory state known as cytokine storm syndrome (CSS) associated with a high mortality rate. Our hypothesis is that a eucaloric ketogenic diet (EKD) may be a safe and efficacious treatment option to reduce CSS and consequently to reduce the need for CPAP, ICU admission and COVID-19 mortality.Aim of the study: The primary objective is to explore the effect of an EKD on mortality, admission to the ICU and the need for NIV in hospitalized patients with COVID-19 in comparison to a eucaloric standard diet (ESD). The secondary objectives are to collect data about the safety and feasibility of an EKD during hospitalization and to evaluate the effect of the diet on biological and inflammatory parameters, particularly interleukin-6 (IL-6).Patients and methods: The study is a retrospective explorative analysis of 34 patients fed with an EKD during hospitalization for COVID-19 in comparison to 68 patients fed an ESD selected and matched using propensity score one-to-two to avoid the confounding effect of interfering variables.Results: A trend of reduced 30-day mortality (HR 0.416, 95% CI 0.122 – 1.413, P = 0.160) and a trend regarding the need for ICU admission (HR 0.357, 95% CI 0.045 – 2.847, P = 0.331) were observed in subjects treated with the EKD compared to patients fed with the standard diet. No significantly different risks in the need for CPAP (HR 0.968, CI 0.289 – 3.242, P = 0.958 for EKD) or the composite endpoint (HR 0.674, CI 0.233 – 1.949, P = 0.446 for EKD) were detectable between the two groups of dietary patterns.Furthermore, IL-6 concentrations between t 0 and t 7 (seven days after the beginning of the diet) in the ketogenic nutrition group showed a median difference of -26.0 ȵg/mL and a mean difference of -164 ȵg/mL (data from 23 of the 34 pairs) compared to controls, with a trend toward significance (P = 0.062). EKD was safe and no adverse events were observed in patients fed an EKD.Discussion and conclusions: These preliminary data on the clinical results for mortality, need for ICU admission and the effect on the IL-6 concentration during EKD feeding, collected in a retrospective way during the most aggressive period of the COVID-19 pandemic, suggest a favorable role of this dietary treatment in COVID-19 clinical management. The EKD was safe and well accepted by patients during hospitalization and seems to be an interesting tool in controlling COVID-19 CSS. The results of the prospective controlled randomized trial, currently underway with a large number of subjects, are necessary to confirm these preliminary data.

Background: Some patients affected by Covid 19 present a life threatening hyperinflammatory state known as a cytokine storm syndrome (CSS) associated with a high mortality rate. Our hypothesis is that eucaloric ketogenic diet (EKD) may be a safe and efficacious treatment option to reduce CSS and consequently to reduce need of CPAP, ICU admission and mortality COVID-19 related.Aim of the study: Primary objective is to explore the effect of EKD on mortality, access to ICU and the need of NIV in COVID-19 hospitalized patients in comparison to a eucaloric standard dietstandard diet (ESDESD). Secondary objectives are to collect data about safety and feasibility of EKD during hospitalization and to evaluate the effect of the diet on biological and inflammatory parameters and particularly on interleukin -6 (IL-6).Patients and Methods: The study is a retrospective explorative analysis of 34 patients fed with EKD during hospitalization for COVID-19 in comparison to 68 patients in ESDESD selected and matched using propensity score one-to-two to avoid the confounding effect of interfering variables.Results: A trend of reduction of 30-day mortality (HR 0.416, 95% CI 0.122 – 1.413, P = 0.160) and a trend in need for ICU admission (HR 0.357, 95% CI 0.045 – 2.847, P = 0.331) were observed in subjects treated with EKD respect to patients fed with standard one. No significant different risks in need for CPAP (HR 0.968, CI 0.289 – 3.242, P = 0.958 for EKD) and composite endpoint (HR 0.674, CI 0.233 – 1.949, P = 0.446 for EKD) were detectable between the two groups of dietary patterns.Furthermore, IL-6 concentrations, between t 0 and t 7 (seven days after the beginning of the diet), collected in the ketogenic nutrition group, show a median IL-6 difference of -26.0 ȵg/mL or a mean IL-6 difference of -164 ȵg/mL (data from 23 of the 34 pairs) compared to controls, with a trend to (P = 0.062).Discussion and conclusions: These preliminar data, collected in a retrospective way during the most aggressive period of Covid-19 pandemia, on clinical results on mortality, need for ICU and effect on IL-6 concentration during EKD suggest a favorable role of this dietary treatment in COVID-19 clinical management. EKD resulted well accepted by patients during hospitalization and seems to be an interesting tool in controlling Covid-19-CSS. The results of the prospective controlled randomized trial, actually ongoing, in a largest number of subjects are necessary to confirm these preliminary data.