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.

Can selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitor antidepressants decrease the "cytokine storm" in the course of COVID-19 pneumonia?

BACKGROUND: Lots of research has been conducted to fight COVID-19 since the outbreak of the pandemic in 2020. The role of "cytokine storm" in the pathogenesis of COVID-19 pneumonia is well known. Relationship between interleukins and depression is still subject matter of the research, but a correlation between interleukin-6 and depressive disorders is proven by now. The aim of this study is to verify differences among interleukin-6 blood levels of inpatients treated with selective serotonin reuptake inhibitors and/or serotonin and norepinephrine reuptake inhibitor before and during hospitalization and of inpatients not treated with these drugs. METHODS: This is an observational study performed during the first wave of SARS Cov-2 pandemic in Italy for three months. The hospitalized patients of Internal Medicine wards and Infectious and Tropical Diseases ward of Azienda Ospedaliero-Universitaria Careggi of Florence for COVID-19 pneumonia have been divided into two subgroups (treated / not treated with antidepressants). Patients admitted to Intensive Care Unit previously have been excluded. Each patient has been evaluated concerning demographic, clinical and therapeutic features. The first dosage of interleukin-6 detected during hospitalization has been noticed. RESULTS: The entire sample included 402 patients and 8.5% (N.=34) had been treated with an antidepressant of the two considered categories before admission until discharge from hospital. Significant lower levels of interleukin-6 of recovered patients of the treated subgroup have been highlighted as compared to recovered patients of not-treated subgroup (12.1 vs. 25.4 P<0.001). These results have been pointed out in spite of higher mean age and more serious comorbidities of the treated subgroup. Nevertheless, the incidence of severe acute respiratory distress syndrome is significantly lower in the subgroup of patients with antidepressant treatment (20.6% vs. 43.2% P<0.02) as well as endotracheal intubation employment (0.0% vs. 11.7% P<0.04). The rate of deceased patients of treated-subgroup is not significantly lower than the rate of not-treated subgroup (23.5% vs. 26.4% P=0.13). CONCLUSIONS: During COVID-19 pneumonia, the production of interleukin-6 seems to be modulated in presence of antidepressant therapy. Further proofs and broader surveys are necessary.

Male reproductive system inflammation after healing from coronavirus disease 2019.

BACKGROUND: There is evidence that, after severe acute respiratory syndrome coronavirus 2 infection, male reproductive function and semen quality may be damaged OBJECTIVES: To evaluate a panel of inflammatory mediators in semen in patients recovered from coronavirus disease 2019. MATERIAL AND METHODS: Sexually active men with previous severe acute respiratory syndrome coronavirus 2 infection and proven recovery from coronavirus disease 2019 were enrolled in a prospective cohort study. Clinical, uro-andrological data and semen specimens were prospectively collected. For previously hospitalized coronavirus disease 2019 patients, data on serum inflammatory markers were retrospectively collected. RESULTS: A total of 43 men were enrolled in the study. Of these, 32 men were normozoospermic, three were oligozoospermic, and eight were crypto-azoospermic. Serum inflammatory markers (procalcitonin and C-reactive protein) were analyzed in previously hospitalized patients both at admission and at peak of infection. Levels at admission were statistically significantly higher in patients resulting in crypto-azoospermic with respect to those resulting in normozoospermic (p = 0.05; p = 0.03 and p = 0.02, respectively) after healing. Seminal cytokine levels were similar among all groups. Interleukin-1ß and tumor necrosis factor-α levels were significantly negatively related to sperm total number and concentration, whereas interleukin-4 was correlated with sperm motility. DISCUSSION AND CONCLUSION: Negative correlations between interleukin-1ß and tumor necrosis factor-α and sperm number and the overall high levels of semen cytokines indicate a potential detrimental role of severe acute respiratory syndrome coronavirus 2 driven inflammation on spermatogenesis. Overall, our results indicate that male patients recovering from coronavirus disease 2019 deserve accurate follow-up for their fertility status.

Has COVID-19 changed the approach to HIV diagnosis?: A multicentric Italian experience.

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

Transgender people living with HIV: characteristics and comparison to homosexual and heterosexual cisgender patients in two Italian teaching hospitals.

Regarding people living with HIV (PLHIV), little is known about the epidemiological characteristics and management decisions for transgender individuals. This retrospective study compared transgender and cisgender (homosexual and heterosexual) PLHIV at both the S. Maria della Misericordia of Perugia and Careggi of Firenze Teaching Hospitals from 2000 to 2018. Multivariate logistic regression was performed to analyse possible relationships between viral suppression (dependent variable) and age, sexually transmitted infections (STIs), and hepatitis diagnosis (independent variables). After analysing and comparing epidemiological and clinical data for 124 transgender, 180 homosexual cisgender and 188 heterosexual cisgender PLHIV, we found that transgender PLHIV, mostly Latin American sex workers, were more likely to have other STIs. Likewise, this subgroup, on average, was younger at the time of HIV diagnosis and more likely to be less adherent to care, consequently jeopardizing the achievement of viral suppression. Finally, the use of hormone therapy and gender confirmation surgery in transgender PLHIV contributed to specific management issues. To date, major attention has focused on studying the epidemiological characteristics of homosexual and heterosexual PLHIV. Our analysis found that transgender PLHIV were the least likely group to be adequately retained in the continuum of care and presented specific issues in part due to social and behavioural realities.

Results of comprehensive cardiovascular diagnostic work-up in HIV positive patients.

Cardiovascular disease (CVD) in the HIV population accounts for a large proportion of morbidity and mortality and, with the increased life expectancy, the burden of CVD is expected to rise. Inflammation, immune dysfunction, side effects of HIV medications, high prevalence of other risk factors are the likely pathogenic mechanisms for accelerated atherosclerosis. We aimed to evaluate the diagnostic yield of a cardiovascular multimodality diagnostic work-up in a contemporary cohort of HIV-infected patients. From November 2017 to October 2019, HIV infected patients were screened in a cardiovascular diagnostic work-up program including clinical history, physical examination, arterial blood pressure measurement, 12-lead ECG, and Transthoracic Echocardiogram (TTE). Advanced non-invasive cardiovascular imaging tests, like Coronary Computed Tomography Angiography (CCTA), stress-echocardiography, Cardiac Magnetic Resonance (CMR), were performed in patients with suspicion of chronic coronary syndrome (CCS) or non-ischemic heart disease (NIHD). 117 HIV-infected consecutive patients underwent this cardiovascular diagnostic work-up and were included in our study. Fifty-two patients (45%) had evidence of CVD. Of them, 22 presented Coronary Artery Disease (CAD), whereas 47 cases showed NIHD. In 17 cases both conditions were present. Among patients with CAD, 8 showed critical coronary stenosis; among them, 5 were treated with percutaneous coronary intervention, 2 with Aorto-Coronary By-Pass Grafting (CABG), and one with medical therapy. Hypertension and diabetes were significantly associated with the development of CVD (respectively p<0.001 and p< 0.05), while current smoking (p<0.02) and hypertension (p<0.007) were positively associated to CAD. A comprehensive cardiovascular diagnostic work-up including advanced multimodality diagnostic imaging modalities led to early detection of CVD in nearly half of an HIV population with immediate interventions required in 6.8% of them, and aggressive prevention treatment started in the remaining HIV patients.

Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study.

BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.