Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

Prevention, diagnosis and pharmacological treatment of infections in pregnancy: The mobile app GAIA! for healthcare providers and patients.

OBJECTIVE: To develop and assess the GAIA! app, designed to assist pregnant women and healthcare professionals in managing infectious diseases during pregnancy, and to bridge the information gap between health professionals and expectant mothers. STUDY DESIGN: This collaborative initiative in Italy involved partnerships with the University of Florence, Careggi University Hospital, and other institutions. The app, built on the Ionic framework, is available on both Apple and Google App Stores. It offers two distinct modes: "healthcare providers" and "patients." Content for the app was derived from extensive literature reviews and clinical guidelines. RESULTS: Since its August 2022 launch, the GAIA! app has garnered over 2,500 downloads, indicating its effectiveness and acceptance within the community. The app differentiates itself from others, such as the Sanford Guide, by focusing specifically on the needs of pregnant women. It ensures cross-platform compatibility, a user-friendly interface, and offline functionality. CONCLUSIONS: The GAIA! app has successfully addressed a niche in infectious disease management for pregnant women, gaining significant traction within the community. While it has seen substantial success, challenges like continuous updates and potential language expansion remain. Future endeavors will address these challenges and further evaluate the app's impact on maternal and child health.

Indirect impact of SARS-CoV-2 pandemic on incidence of maternal primary cytomegalovirus and Toxoplasma gondii infection in pregnancy.

OBJECTIVE: Public health interventions promoted during the SARS-CoV-2 pandemic to control viral spread have impacted the occurrence of other communicable disease. Yet no studies have focused on perinatal infections with the potential for neonatal sequelae, including cytomegalovirus (CMV) and Toxoplasma gondii (TG). Here we investigate whether incidence rates of maternal primary CMV and TG infection in pregnancy were affected by the implementation of pandemic-related public health measures. METHODS: A retrospective study including all pregnant women with confirmed primary CMV or TG infection in pregnancy, managed between 2018 and 2021 at two university centers. The incidence rate was calculated as the number of CMV and TG infections per 100 consultations with a 95% confidence interval (CI). Data were compared between pre-pandemic (2018-2019) and pandemic (2020 and 2021) years. The Newcombe Wilson with Continuity Correction method was employed to compare incidence rates. RESULTS: The study population included 215 maternal primary CMV and 192 TG infections. Rate of maternal primary CMV infection decreased in 2021 compared with 2018-2019 (4.49% vs 6.40%, attributable risk [AR] 1.92, P = 0.019). By contrast, the rate of TG infection substantially increased in 2020 (6.95% vs 4.61%, AR 2.34, P = 0.006). Close contact with cats was more common among patients with TG infection in 2020 and 2021 than among pre-pandemic TG-infected women (26.3% and 24.4% vs 13.3%, P = 0.013). CONCLUSION: Pandemic-related public health interventions and associated behavioral and lifestyle changes exerted a divergent effect on the incidence of primary CMV and TG infection in pregnancy, likely due to modulation of exposure to risk factors for these infections.

Consensus definitions in imported human schistosomiasis: a GeoSentinel and TropNet Delphi study.

Terminology in schistosomiasis is not harmonised, generating misunderstanding in data interpretation and clinical descriptions. This study aimed to achieve consensus on definitions of clinical aspects of schistosomiasis in migrants and returning travellers. We applied the Delphi method. Experts from institutions affiliated with GeoSentinel and TropNet, identified through clinical and scientific criteria, were invited to participate. Five external reviewers revised and pilot-tested the statements. Statements focusing on the definitions of acute or chronic; possible, probable, or confirmed; active; and complicated schistosomiasis were managed through REDCap and replies managed in a blinded manner. Round 1 mapped the definitions used by experts; subsequent rounds were done to reach consensus, or quantify disagreement, on the proposed statements. Data were analysed with percentages, medians, and IQRs of a 5-point Likert scale. The study was terminated on the basis of consensus or stability-related and time-related criteria. 28 clinicians and scientists met the criteria for experts. 25 (89%) of 28 experts replied to Round 1, 18 (64%) of 28 to Round 2, 19 (68%) of 28 to Round 3, and 21 (75%) of 28 to at least two rounds. High-level consensus (79-100% agreement and IQRs ≤1) was reached for all definitions. Consensus definitions will foster harmonised scientific and clinical communication and support future research and development of management guidelines for schistosomiasis.

When it rains, it pours: Early treatment with tecovirimat of cardiac complications associated with monkeypox infection in a person with HIV and previously undiagnosed Lyme disease. A case report.

Cardiac involvement, such as myocarditis and pericarditis, can be a severe complication of monkeypox virus (mpox) infection and could be related to other co-infections with cardiac involvement. Tecovirimat is an antiviral specifically designed to inhibit smallpox infection diffusion and approved by the FDA for other Orthopoxvirus infections; its efficacy in mpox-infected patients is not well established. We present the case of a cardiac complication during mpox infection in a previously undiagnosed Lyme disease in a 42-year-old man living with HIV. Two days after the typical maculopapular rash, the patient reported a rise in body temperature up to 39 °C, chest pain without irradiation, and shortness of breath. We found an increase in troponin level, a slight reduction in ejection fraction, and grade 2 AV block (Mobitz 1 and 2) with frequent sinus pauses (the longest of 10.1 s). Given the suspicion of myopericarditis with cardiac conduction system involvement, the patient was admitted to the Intermediate Care Unit for continuous monitoring and further evaluation. Treatment included Ibuprofen 600 mg every 12 hours (bid) and colchicine 1 mg once daily for anti-inflammatory purposes. Concomitantly, treatment with tecovirimat was started at 600 mg bid for a total of 14 days. Cardiac MRI with gadolinium showed mild interstitial edema and pericardial enhancement. However, despite the clinical and laboratory resolution of the acute phase, bradycardia with episodes of AV block persisted at follow-up, suggesting the possibility of an additional etiology. Thus, the patient was investigated for Lyme disease because high-degree AV block is the most common presentation of Lyme carditis. Serological results evidenced a previous Borrelia burgdorferi senso latu. We decided to start treatment with doxycycline 100 mg every 12h, even pending the uncertainty of the role of a previous Lyme disease in determining the cardiac rhythm disturbances. At the evaluation on day 44, the patient was systemically well, and after cardiologist consultation, pace-maker implantation was not deemed indicated. This case underscores the importance of considering alternative causes of carditis when the clinical picture remains unclear or persists after the acute phase.

Identification of asymptomatic Leishmania infection in patients undergoing kidney transplant using multiple tests.

OBJECTIVES: In immunocompromised patients, asymptomatic Leishmania infection can reactivate, and evolve to severe disease. To date, no test is considered the gold standard for the identification of asymptomatic Leishmania infection. A combination of methods was employed to screen for Leishmania infection in patients undergoing kidney transplant (KT). METHODS: We employed polymerase chain reaction for the detection of parasitic DNA in peripheral blood, Western blot to identify serum immunoglobulin G and whole blood assay to detect cytokines/chemokines after stimulation of whole blood with parasitic antigen. RESULTS: One-hundred twenty patients residing in Italy were included in the study at the time of KT. Each patient that tested positive to at least one test was considered as Leishmania positive. Fifty out of 120 patients (42%) tested positive for one or more tests. The detection of specific cell-mediated response (32/111, 29%) was the most common marker of Leishmania infection, followed by a positive serology (24/120, 20%). Four patients (3%) harbored parasitic DNA in the blood. CONCLUSION: Our findings underline the high prevalence of asymptomatic Leishmania infection in patients undergoing KT in Italy, who are potentially at-risk for parasite reactivation and can benefit from an increased vigilance. Understanding the clinical relevance of these findings deserves further studies.

Visceral larva Migrans in a Young Italian Patient: A Diagnostic Dilemma.

BACKGROUND: The association of fever, focal hepatic lesions and peripheral hyper-eosinophilia (FHLH) can be observed in both infectious and non-infectious conditions. Fascioliasis, capillariasis, toxocariasis, all causes of visceral larva migrans (VLM), represent most of the former, whilst lymphomas, eosinophilic leukemias and mastocytosis belong in the non-infectious conditions. METHODS: We prospectively followed a young patient presenting with FHLH in the Tuscany region of Italy. RESULTS: The patient was subject to serological and parasitological examination in an attempt to clarify the origin of the lesions. Serologies for both Fasciola hepatica and Toxocara spp. were positive, with the latter presenting a higher index. We opted for treatment with a prolonged course of albendazole due to the serological results and being toxocariasis more frequent in our setting. The patient was then subject to radiological follow-up. The patient responded to treatment with albendazole as shown by a decrease in eosinophils, seronegativization for Toxocara spp., clinical and radiological improvement. Toxocariasis was hence considered the most likely diagnosis. CONCLUSIONS: Parasitic infections cannot be disregarded in the presence of FHLH. Differential diagnosis between these parasitic infections can be challenging due to the presence of similar clinical presentations and serological cross-reactions, and follow-up of the patient is needed to ensure optimal treatment outcomes.

Asymptomatic CMV infection at birth following maternal primary infection despite valacyclovir treatment and a subsequent negative amniocentesis. Case report.

Valacyclovir is currently the only pharmacological intervention demonstrated to reduce the risk of vertical CMV congenital infection within a randomized clinical trial in case of primary infection during pregnancy. So far, no data are available on the prognosis of children with congenital CMV infection diagnosed at birth after a negative amniocentesis whose mother were treated with valacyclovir during pregnancy, therefore it is essential to carry out a rigorous neurocognitive follow-up in these children in order to investigate the potential clinical consequence.

Scalp eschar and neck lymph adenopathy after a tick bite (SENLAT) in Tuscany, Italy (2015-2022).

INTRODUCTION: The Scalp Eschar and Neck Lymph Adenopathy After a Tick Bite (SENLAT) syndrome is frequently caused by Rickettsia slovaca and Rickettsia raoultii. Only six microbiologically confirmed SENLAT cases have been reported in Italy between 1996 and 2021. We report ten cases of SENLAT seen between 2015 and 2022 in a tertiary care center in Tuscany, Italy. CASES PRESENTATION: All patients were women; most common symptoms were scalp eschar on the site of tick bite (100%) and cervical lymphadenopathy (90%). No microbiological identification was obtained. Persistent alopecia, for several months to years, was observed in four patients. The known difficulty of microbiological diagnosis in SENLAT was worsened, in our cases, by factors as the absence of ticks available for identification and microbiological study, and antibiotic treatment administration previous to microbiological tests. CONCLUSION: The report highlights the presence of SENLAT in Italy, aiming to raise the awareness toward the emergence of this clinical entity.

Diagnosis and management of complicated urogenital schistosomiasis: a systematic review of the literature.

BACKGROUND: Currently, there are no standardized guidelines for the diagnosis or management of the complications of urogenital schistosomiasis (UGS). This systematic review of the literature aims to investigate the state of the art in reference to diagnostic approaches and the clinical management of this condition. METHODS: A systematic review of literature published between January 1990 and January 2021 was conducted in the MEDLINE database, scoping for articles regarding diagnostic means or therapeutic options for the complications of UGS, namely obstructive uropathy, bladder cancer, abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures. Relevant data were then extracted from the articles deemed eligible according to the inclusion criteria. MAIN RESULTS: In total, 3052 articles were identified by the research query, of which 167 articles fulfilling inclusion criteria after title/abstract screening and full-text evaluation were included, 35% on both diagnostic and therapeutic aspects, and 51% on diagnosis and 14% on therapy. Ultrasound was the most frequently tool employed for the diagnosis of UGS complications showing a good performance. Concerning the management of hydronephrosis, the majority of available evidences came from community-based studies where universal treatment with praziquantel was used leading to decrease of prevalence of obstructive uropathy. Concerning studies on surgical procedures, laser endoureterotomy followed by stenting was mostly employed in adult patients leading to a crude cure rate of 60% (43 of 71 patients). In the case of severe hydronephrosis, surgery consisting of ureteral re-implantation showed excellent results with a crude cure rate of 98% (157 cured patients of 160 treated). Concerning bladder cancer, data on 93 patients with a clear diagnosis of UGS-related bladder were available reporting a variable and sometime combined approach based on disease stage. Available data on diagnosis and management of abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures due to UGS are also presented. CONCLUSIONS: The review produced a complete picture of the diagnostic and therapeutic options currently available for complicated UGS. These results can be useful both for guiding clinicians towards correct management and for tracing the direction of future research.

Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study.

BACKGROUND: Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020. OBJECTIVE: This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus. STUDY DESIGN: The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth). RESULTS: A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension. CONCLUSION: Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

Seroconversion following empiric praziquantel treatment as confirmatory diagnostic tool for chronic schistosomiasis.

We report on six patients with suspected chronic schistosomiasis and negative microbiological findings at baseline. All patients were treated empirically with praziquantel and all seroconverted 20 days to two months after treatment. We suggest that seroconversion after praziquantel treatment may be used as a confirmatory diagnostic tool for chronic schistosomiasis.

Tuberculosis in the European Region.

Purpose of Review: Tuberculosis (TB) remains a major public health concern worldwide. The COVID-19 pandemic and migration flow due to socioeconomic conditions, climate change, and geopolitical issues, such as the war, are important drivers influencing TB epidemiology in Europe. This article aims to review the data about TB in this area and the new findings about treatment and prevention strategies. Recent Findings: During the COVID-19 pandemic, access to health facilities and retention in care were difficult for TB patients, with consequences on TB diagnosis and TB incidence. The ongoing conflict in Europe, in areas with high prevalence of TB and MDR-TB, has reduced the access to health services and the availability of anti-TB drugs and increased the migration of refugees. New data on short treatment regimens could change the length of therapy and adverse events. Summary: TB control programs are facing emerging challenges that could change TB incidence in the near future. Novel antibiotic strategies and improved preventive policies could offer new opportunities to reduce the TB impact on public health.

Combination regimen of nirmatrelvir/ritonavir and molnupiravir for the treatment of persistent SARS-CoV-2 infection: A case report and a scoping review of the literature.

Immunocompromised patients still experience unpredictable courses of COVID-19, despite that effective vaccines and drugs against SARS-CoV-2 are now available. Antiviral combination regimens may have a role in SARS-CoV-2 infection in immunocompromised hosts, but current knowledge is still limited. We describe the case of a 73-year-old Italian man affected by follicular lymphoma with persistent SARS-CoV-2 infection who was successfully treated with co-administration of oral antivirals (10-day molnupiravir and nirmatrelvir/ritonavir). The therapy was well tolerated both from a clinical and biochemical standpoint, with no signs of toxicity. We also performed a scoping review, to sum up available knowledge on combined antiviral regimens including remdesivir, molnupiravir, or nirmatrelvir/ritonavir. Pending further studies on larger cohorts of patients, our report is consistent with available pre-clinical and clinical data, supporting the possible use of combination therapy in selected difficult-to-treat COVID-19 cases.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Characteristics of COVID-19 vaccinated and unvaccinated patients admitted to Careggi University Hospital, Florence, Italy.

More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0%, breakthrough infections are common and may lead to severe outcome in fragile population. We conducted a real-world observational study on 420 COVID-19 admitted patients from July 2021 to January 2022 in a tertiary level Italian hospital. We collected patient's vaccination and SARS-CoV-2 serological status, SARS-CoV-2 treatments, oxygen supports, intensive (ICU) and subintensive (sub-ICU) care unit admissions, length of staying (LoS) and in-hospital mortality. One-hundred-seventy-two vaccinated and 248 unvaccinated patients were admitted during the study period. Vaccinated group (Vg) had a significantly more elevated Charlson Comorbidity Index than Unvaccinated group (UVg), and no statistical differences were found in terms of in-hospital mortality, LoS or ICU and sub-ICU admissions. Among Vg, anti-S antibodies were detected in 86.18% of patients (seropositives). Vaccinated seronegative patients' in-hospital mortality was significantly higher than vaccinated seropositive patients (33.33% vs 10.69%, p = 0.0055): in particular, mortality rate in 45-69 years old population was higher in vaccinated seronegative group, and comparable in patients ≥ 70 years old. No differences in terms of outcome were registered between Vg and UVg, taking into account that Vg was considerably older and with more comorbidities. In line with other recent observations, higher mortality rate was evidenced for seronegative vaccinated patients. Primary prophylaxis and early treatments result to be necessary, especially for older and immunosuppressed populations.

A Questionnaire Integrated with the Digital Medical Record Improved the Coverage of a Control Program for Congenital Chagas Disease in Tuscany, Italy.

The leading route of Chagas disease transmission in nonendemic countries is congenital. However, policies concerning screening, prevention, and management of congenital Chagas disease are rare in these settings. Since 2012, serological screening for Chagas disease should be provided for pregnant women at risk in Tuscany, Italy according to a Regional resolution. Due to difficulties in the implementation, in November 2019, a checklist aimed at identifying pregnant women at risk for Chagas disease was introduced in digital clinical records at Careggi University Hospital, Florence, Italy. In order to evaluate the effectiveness of the "Chagas checklist", data about the number of deliveries by women at risk and their screening coverage between 2012 and June 2022 were collected. Out of 1348 deliveries by women at risk, 626 (47%) Trypanosoma cruzi serology tests were performed during the study period. The annual screening coverage increased from an average of 40.3% between 2012 and 2019 to 75.7% between 2020 and June 2022, underlining the big impact of the checklist. Four Chagas disease serological tests out of 626 (0.6%) resulted positive, corresponding to 2 affected women. No cases of congenital transmission occurred. The study showed that a simple digital tool led to a tangible improvement in the coverage of the screening program; its application in a setting where digital charts are available will contribute to the control and elimination of congenital Chagas disease.

Effectiveness of tocilizumab in hospitalized moderate-to-severe COVID-19 patients: a real-life study.

BACKGROUND: To assess the clinical effectiveness of Tocilizumab (TCZ) in moderate-to-severe hospitalized COVID-19 patients and factors associated with clinical response. METHODS: Five hundred eight inpatients with moderate-to-severe SARS-CoV-2 infection were enrolled. TCZ effect in addition to standard medical therapy was evaluated in terms of death during hospital stay. Unadjusted and adjusted risk of mortality for TCZ treated patients versus TCZ untreated ones was estimated using robust Cox regression model. We considered the combination of TCZ and ICU as time-dependent exposure and created a model using duplication method to assess the TCZ effect in very severe COVID-19 patients. RESULTS: TCZ reduced death during hospital stay in the unadjusted model (HR 0.54, 95%CI 0.33-0.88) and also in the adjusted model, although with loss of statistical significance (HR 0.72, 0.43-1.20). Better effectiveness was observed in patients with low SpO2/FiO2 ratio (HR 0.35, 0.21-0.61 vs. 1.61, 0.54-4.82, P<0.05), and, without statistical significance, in patients with high CRP (HR 0.51, 0.30-0.87 vs. 0.41, 0.12-1.37, P=NS) and high IL-6 (HR 0.49, 0.29-0.82 vs. 1.00, 0.28-3.55, P=NS). TCZ was effective in patients not admitted to ICU, both in the unadjusted (HR 0.33, 0.14-0.74) and in the adjusted (HR 0.39, 0.17-0.91) model but no benefit was observed in critical ICU-admitted patients both in the unadjusted (HR 0.66, 0.37-1.15) and in the adjusted model (HR 0.95, 0.54-1.68). CONCLUSIONS: Our real-life study suggests clinical efficacy of TCZ in moderate-to-severe COVID-19 patients but not in end-stage disease. Thus, to enhance TCZ effectiveness, patients should be selected before grave compromise of clinical conditions.