Adequate duration of therapy in severe fungal infections.

PURPOSE OF REVIEW: To highlight recent findings on the adequate duration of antifungal therapy in patients with invasive fungal disease (IFD). RECENT FINDINGS: Plenty of published data available suggest that there is no additional clinical benefit at a certain point after initiation of antifungal treatment in patients with confirmed IFD. Moreover, the prolonged antifungal exposure can be associated with an increased risk of side effects and toxicity as well as striking risk for developing antifungal resistance or rising unnecessary healthcare costs. Recent data suggest that, in the presence of an adequate initial antifungal therapy and adequate source control of the infection, new stratified approaches integrating clinical judgment, biomarkers and microbiological eradication, should be considered as an alternative to the 'one-size-fits-all' treatment duration currently used worldwide. SUMMARY: The optimal duration of antifungal therapy is still an unresolved issue that depends by many key elements including the host; the pathogen and its microbiological eradication, the adequateness of initial antifungal therapy and the promptness of source control of the infection. In general, many patients with invasive candidiasis can be treated with a 2 weeks course of antifungal therapy. Longer antifungal course (6 weeks or more) is generally required for patients with invasive aspergilosis.

The role of fosfomycin for multidrug-resistant gram-negative infections.

PURPOSE OF REVIEW: In the last decade, an increasing interest in using fosfomycin for the treatment of multidrug-resistant gram-negative (MDR-GNB) infections have been registered, especially when none or only a few other active alternatives remained available. RECENT FINDINGS: Fosfomycin may remain active against a considerable proportion of MDR-GNB. In observational studies, a possible curative effect of oral fosfomycin monotherapy has been described for uncomplicated urinary tract infections (UTI) and bacterial prostatitis caused by MDR-GNB, whereas intravenous fosfomycin has been mostly used in combination with other agents for various type of severe MDR-GNB infections. The ZEUS randomized controlled trial (RCT) has started to provide high-level evidence about the possible use of fosfomycin for complicated UTI caused by extended-spectrum ß-lactamase-producing GNB, but no results of large RCT are currently available to firmly guide the use of fosfomycin for carbapenem-resistant GNB. SUMMARY: Fosfomycin is an important therapeutic option for MDR-GNB infections. Further pharmacokinetic/pharmacodynamic and clinical research is needed to optimize its use.

Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia.

Introduction: Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm. Methods: This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and ß-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality. Results: A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data. Conclusion: The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort.

Long-acting (LA) formulations have been designed to improve the quality of life of people with HIV (PWH) by maintaining virologic suppression. However, clinical trials have shown that patient selection is crucial. In fact, the HIV-1 resistance genotype test and the Body Mass Index of individual patients assume a predominant role in guiding the choice. Our work aimed to estimate the patients eligible for the new LA therapy with cabotegravir (CAB) + rilpivirine (RPV). We selected, from the Antiviral Response Cohort Analysis (ARCA) database, all PWH who had at least one follow-up in the last 24 months. We excluded patients with HBsAg positivity, evidence of non-nucleoside reverse transcriptase inhibitor (except K103N) and integrase inhibitor mutations, and with a detectable HIV-RNA (>50 copies/mL). Overall, 4103 patients are currently on follow-up in the ARCA, but the eligible patients totaled 1641 (39.9%). Among them, 1163 (70.9%) were males and 1399 were Caucasian (85.3%), of which 1291 (92%) were Italian born. The median length of HIV infection was 10.2 years (IQR 6.3-16.3) with a median nadir of CD4 cells/count of 238 (106-366) cells/mm3 and a median last available CD4 cells/count of 706 (509-944) cells/mm3. The majority of PWH were treated with a three-drug regimen (n = 1116, 68%). Among the 525 (30.3%) patients treated with two-drug regimens, 325 (18.1%) were treated with lamivudine (3TC) and dolutegravir (DTG) and only 84 (5.1%) with RPV and DTG. In conclusion, according to our snapshot, roughly 39.9% of virologically suppressed patients may be suitable candidates for long-acting CAB+RPV therapy. Therefore, based on our findings, many different variables should be taken into consideration to tailor the antiretroviral treatment according to different individual characteristics.

Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study.

INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.

Evaluating fostemsavir as a therapeutic option for patients with HIV.

ABSTRACIntroduction: Despite the unquestionable success of antiretroviral therapy achieved in recent years, there are still cases of heavily treated patients who do not achieve or struggle to maintain undetectable HIV-RNA due to drug resistance. New antiretroviral options are needed to address this issue.Area covered: The authors first provide an overview of fostemsavir and its role in the treatment of HTE PLWH. Data from pre-clinical and clinical studies are reviewed and the pharmacokinetic and farmacodynamic properties are highlited. Drug-drug interactions and safety data from available clinical studies are also discussed.Expert opinion: Fostemsavir is a promising antiretroviral belonging to the class of entry inhibitors; its novel mechanism of action represents a very important innovation. Its use will be limited to the heavy-treatment-experienced patient population. This use will have to be monitored to avoid abuse and waste of a molecule that for some patients may represent a life-saving drug.

Recent molecules in the treatment of severe infections caused by ESBL-producing bacteria.

Introduction: The widespread increase in resistance to ß-lactam antibiotics in Enterobacterales currently represents one of the main threats to human health worldwide. The primary mechanisms of resistance are the production of ß-lactamase enzymes that are able to hydrolyze ß-lactams.Areas covered: we summarize the most recent advances regarding the main characteristics and spectrum of activity of new available antibiotics and strategies for the treatment of ESBL-producing Enterobacterales infections.Expert opinion: ESBL-producing strains are recognized as a worldwide challenge in the treatment of both hospital- and community-acquired infections. Data from the literature point out the high mortality associated with severe infections due to ESBL strains, especially in patients who developed severe sepsis or septic shock, together with the importance of the source of infection and indicators of severity, as determinants of the patient's outcome. Carbapenems are currently considered the first-line therapy, although the diffusion of resistant strains is an evolving problem and is mandatory the introduction in clinical practice of new drug regimens and treatment strategies, based on clinical data, local epidemiology, and microbiology. As a possible carbapenem-sparing strategy, ceftolozane-tazobactam and ceftazidime-avibactam appear the best-available carbapenem-sparing therapies. The definitive role of new drugs should be definitively assessed.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography as a diagnostic and follow-up tool in Coxiella burnetii endocarditis of prosthetic valve and aortic valved tube: a case report.

BACKGROUND: European Society of Cardiology 2015 guidelines approved 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as a useful diagnostic imaging technique in prosthetic valve endocarditis (PVE) and recent evidence seems to suggest a role of nuclear imaging in the follow-up of cardiovascular infections, but nowadays there are no sufficient data available. CASE SUMMARY: A 67-year-old male presented with fever, weight loss, and fatigue. His medical history included ulcerative colitis and a previous Bentall-De Bono surgical procedure in 2014. A previous recent hospitalization to a small community hospital did not reveal a clear aetiology for the fever: transeosophageal echocardiography showed dubious peri-prosthetic tissue alterations, interpreted as post-surgical fibrosis; consequently, the patient was discharged with steroid therapy. At admission in our ward, we repeated transoesophageal echocardiography that confirmed the peri-prosthetic alterations. Moreover, 18F-FDG PET/CT showed two hypermetabolic areas, one around the prosthetic tube in the aortic bulb and the other in relation with the prosthetic aortic valve. Serological test was positive for Coxiella burnetii infection with consequent beginning of a targeted antimicrobial therapy with oral doxicycline and hydroxychloroquine. Echocardiography, serology, and 18F-FDG PET/CT follow-up demonstrated a progressive response to treatment and clinical conditions of the patient gradually improved. DISCUSSION: According to guidelines, 18F-FDG PET/CT can be used in ambiguous PVE to improve diagnostic accuracy of standard techniques. In this case, 18F-FDG PET/CT combined with echocardiography and serological tests is used not only to better define diagnosis but also for treatment response monitoring during follow-up.

Injectable Antiretroviral Drugs: Back to the Future.

Current HIV treatment regimens provide sustained virologic suppression, at least partially restore the immune system and have limited side effects; however, they do not allow viral eradication and they are burdened by daily pill intake with a life-long commitment for the people living with HIV (PHIV). Injectable agents might represent a turning point in the care of PHIV, allowing less frequent administration of antiretroviral treatment (ART), more widespread use of pre-exposure prophylaxis (PrEP) and more stable drug levels in the blood, thus increasing the odds to get closer to end the HIV pandemic. The aim of this manuscript is to give a comprehensive review of injectable antiretrovirals that have been used in the past, which are available now, will be available in the future, and their role in the treatment of HIV infection.

Use of Ceftaroline in Hospitalized Patients with and without COVID-19: A Descriptive Cross-Sectional Study.

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.

General Practitioners as partners for a shared management of chronic HIV infection: An insight into the perspectives of Italian People Living with HIV.

Is it possible to achieve a collaboration between Infectious Diseases (ID) Specialists and General Practitioners (GPs) in the management of chronic HIV infection? A cross sectional survey was conducted among People Living with HIV (PLWHIV) attending the outpatient services of four Italian Infectious Diseases Centers to understand to which extent patients trust their GPs and involve them in the management of their chronic condition. Information about level of communication with GPs, subjective perception of the disease, and presence of co-medications were collected and matched with socio-demographic data using χ2statistics. A p<0.05 was considered statistically significant. From December 2019 to February 2020, 672 patients completed the survey, 59% males and 56% >50 years. Overall, 508 patients (76%) had informed GPs about HIV-positivity. Communication of diagnosis was significantly associated with age >50years, lower education level, history of disease >10 years and residency in Northern Italy. The "Undetectable = Untrasmittable" (U = U) concept was investigated as an indirect measure of perceived stigma. 23% of subjects was unaware of its meaning. Despite undetectable status, 50% of PLWHIV found difficult to communicate their condition to GPs, especially married (52% vs 48% of unmarried, p = 0.003), well-educated patients (51% vs 48, p = 0.007), living in Southern vs Northern Italy (52% vs 46%, p< 0.001). More than 75% of the participants consulted the ID specialist for co-medications and DDIs management, often complaining a lack of communication of the former with GPs. Overall, a good level of communication between PLWHIV and GPs was outlined, even if a wider involvement of the latter in HIV care is desirable.

Early Administration of Bamlanivimab in Combination with Etesevimab Increases the Benefits of COVID-19 Treatment: Real-World Experience from the Liguria Region.

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.

Integrase Inhibitors Use and Cytomegalovirus Infection Predict Immune Recovery in People Living With HIV Starting First-Line Therapy.

BACKGROUND: We explored predictors of CD4/CD8 ratio improvement and optimal immunological recovery (OIR) after initiation of antiretroviral therapy (ART) in naive people living with HIV (PLWH). METHODS: Retrospective multicenter study including naive PLWH starting ART with 2 nucleos(t)ide reverse transcriptase inhibitors + 1 integrase strand transfer inhibitor (InSTI) or non-NRTI or protease inhibitor (PI). PLWH were followed from the time of ART initiation (baseline) to the discontinuation of first-line regimen, virological failure, death, or loss to follow-up. Estimated incidence and predictors of time to CD4/CD8 ratio normalization (defined as ≥1) and OIR (defined as CD4/CD8 ratio ≥ 1 plus CD4 ≥ 500 cells/µL plus CD4% ≥ 30%) were explored by Kaplan-Meier curves and Cox regression analysis. RESULTS: Overall, 1428 PLWH (77.8% males, median age 39 years, 55.1% with positive cytomegalovirus (CMV) antibodies, median HIV-RNA 4.80 log copies/mL, median CD4 323 cells/µL, median CD4/CD8 ratio 0.32) were included, of which 21.5% (n = 307), 44.5% (n = 636), and 34% (n = 485) treated with InSTI-, PI-, and NNRTI-based regimens, respectively. The estimated proportion of CD4/CD8 normalization and OIR at 36 months was 38.6% and 32.9%, respectively. Multivariate analysis showed that InSTI-based regimens had a higher probability of CD4/CD8 ratio normalization and OIR both in the total population (P < 0.001 versus PI) and in advanced naive PLWH (P ≤ 0.001 versus PI and NNRTI). Moreover, subjects with positive CMV serology showed a lower probability of CD4/CD8 ratio normalization and OIR (P < 0.001). CONCLUSIONS: InSTI-based regimens showed a better immune recovery, suggesting that the type of first-line ART can influence immune reconstitution. PLWH with positive CMV serology showed an increased risk of suboptimal immune recovery.

Prevalence and Clinical Significance of Persistent Viral Shedding in Hospitalized Adult Patients with SARS-CoV-2 Infection: A Prospective Observational Study.

BACKGROUND: The goal of this study was to investigate the prevalence and factors associated with persistent viral shedding (PVS) in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This was a prospective observational study including all consecutive adults hospitalized with SARS-CoV-2 infection. When the first nasopharyngeal swab was positive for SARS-CoV-2 RNA (day 0), additional samples were obtained on days + 3, + 5, + 7 and then once every 7 days until virus detection was negative. PVS was defined as the duration of shedding of at least 21 days after diagnosis. The primary endpoint of this study was the prevalence of PVS. RESULTS: Data were obtained regarding 121 consecutive hospitalized patients with SARS-CoV-2 infection (median age 66 years, male sex 65.3%). Overall, the prevalence of PVS was 38% (46/121 patients). According to univariate analysis, factors associated with PVS were immunosuppression (6.7% vs 21.7%, p = 0.02), increased interleukin-6 (IL-6) levels (≥ 35 ng/ml) at the time of diagnosis (43.4% vs 67.3%, p = 0.02), time from onset of symptoms to diagnosis (median days 7.0 vs 3.5, p = 0.001), intensive care unit admission (22.7% vs 43.5%, p = 0.02), and need for invasive mechanical ventilation (20.0% vs 41.3%, p = 0.01). The multivariate analysis indicated that immunosuppression, increased IL-6 levels at the time of diagnosis, time from onset of symptoms to diagnosis, and need for mechanical ventilation were independent factors associated with PVS. CONCLUSIONS: PVS was detected in up to 38% of hospitalized patients with SARS-CoV-2 infection and was strongly associated with immunosuppression, increased IL-6 levels, and the need for mechanical ventilation.

The switch from tenofovir disoproxil fumarate to tenofovir alafenamide determines weight gain in patients on rilpivirine-based regimen.

OBJECTIVE: To investigate whether the switch from tenofovir disoproxil fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) to tenofovir alafenamide (TAF)/FTC/RPV is associated with weight gain in people living with HIV (PLWHIV). DESIGN: Retrospective single-centre study. METHODS: All PLWHIV on TDF/FTC/RPV who switched to TAF/FTC/RPV from January 2017 to December 2018 were considered if they had at least two weight measures in the year before and two after the switch. The weight trend across the study was evaluated by a generalized linear model for repeated measures, with pair comparison performed by Bonferroni adjustment. RESULTS: Two hundred and fifty-two patients on TDF/FTC/RPV were included, 65% men, mean age 51.2 years (±9.6), history of 18 (±18.2) years of HIV infection and CD4 T-cell count of 744 (±329) cells/µl. All had HIV-RNA <50 copies/ml. Twelve months before the switch, baseline weight was 73.8 (±14.3) kg, and remained stable to 73.8 (±14.3) kg in the following 6 months. A weight increase was noticed 3 and 6 months after the switch, to 77.7 (±42.3) and 75.5 (±14.5) kg, respectively (P < 0.0001). A significant weight change exactly within the timeframe of the switch (between 6 months before and 3 months after) was found in women, patients with higher BMI (>25 kg/m), lower CD4 T-cell count (≤500 cells/µl) and history of previous drug abuse. The frequency of BMI greater than 25 kg/m rose from 122/252 patients (48.4%), to 133/252 (52.8%) (P < 0.0001). CONCLUSION: TAF appears to have an impact on weight gain, similarly to what observed in naïve patients, also in experienced PLWHIV with good virologic control.

Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors.

We aimed to assess the prevalence of and factors associated with anti- severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in a large population of adult volunteers from five administrative departments of the Liguria and Lombardia regions. A total of 3609 individuals were included in this analysis. Participants were tested for anti-SARS-CoV-2 antibodies [Immunoglobulin G (IgG) and M (IgM) class antibodies] at three private laboratories (Istituto Diganostico Varelli, Medical Center, and Casa della Salute di Genova). Demographic data, occupational or private exposure to SARS-CoV-2-infected patients, and prior medical history consistent with SARS-CoV-2 infection were collected according to a preplanned analysis. The overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0% [398/3609; confidence interval (CI) 10.0%-12.1%]. Seroprevalence was higher in female inmates than in male inmates (12.5% vs. 9.2%, respectively, p = 0.002), with the highest rate observed among adults aged >55 years (13.2%). A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59-3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19-6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75-6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94-88.71, p = 0.001). In conclusion, we found a high prevalence (11.0%) of SARS-CoV-2 infection that is significantly associated with residing in long-term care facilities or occupational exposure to the virus. These findings warrant further investigation into SARS-CoV-2 antibody prevalence among the Italian population.

Clinical characteristics, management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa, Italy.

OBJECTIVES: To describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality. METHODS: This retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020. RESULTS: Overall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An 'atypical' presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04-1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07-6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004-1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality. CONCLUSIONS: COVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.