Objectives Aim of our study was to describe the incidence and predictive factors of secondary infections in patients with COVID-19. Methods Cohort study on patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between February 25 th and April 6th, 2020 (NCT04318366). We considered secondary bloodstream (BSIs) or possible lower respiratory tract infections (pLRTIs) occurred after 48 hours since hospital admission until death or discharge. We calculated multivariable Fine-Gray models, to assess factors associated with risk of secondary infections. Results Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%): 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. Overall 28-day cumulative incidence was 16.4% (95% CI 12.4% - 21.0%). The majority of BSIs was due to gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were mainly caused by gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count ( < 0.7 vs >0.7 per 10 9 /L: subdistribution hazard ratios (sdHRs) 1.93 [95% CI 1.11-3.35]), baseline PaO 2 /FiO 2 (per 100-points lower: sdHRs 1.56 [95% CI 1.21-2.04]), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51 [95% CI 1.04-6.05]). Conclusions Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia, were identified as risk factors for secondary infections.

Type 2 diabetes mellitus is a growing problem in HIV population and a comparison with the general population may help screening and prevention. In this cross-sectional study the authors determined the prevalence of type 2 diabetes mellitus in 4,249 HIV-infected subjects attending the San Raffaele Infectious Diseases Department compared with 9,148 healthy controls recruited in 15 Italian regions, and identified risk factors associated with of type 2 diabetes mellitus. Type 2 diabetes mellitus was defined as reported diabetes, a fasting plasma glucose concentration ≥7.0 mmol/l, or current use of anti-diabetic medication. Prevalence of type 2 diabetes mellitus was higher in HIV-infected than healthy subjects (4.1 vs. 2.5 %; P < 0.0001). At multivariable analysis, HIV-infected subjects (odds ratio 1.70, 95 % CI, 1.12-2.51; P = 0.009), older age (P < 0.0001), higher BMI (P < 0.0001) and hypertension (P = 0.039) were associated with a higher risk of diabetes. Among HIV-infected patients, the risk of type 2 diabetes mellitus increased with older age (P < 0.0001), higher BMI (P = 0.003), higher triglycerides (P = 0.015) lower total cholesterol (P = 0.008), longer duration of HIV infection (P = 0.036) lower nadir CD4 (P = 0.027). Prevalence of type 2 diabetes mellitus in HIV-infected subjects was almost two-fold increased than healthy subjects and it was associated with the typical risk factors of the general population and also to longer duration of HIV infection and lower nadir CD4.

We prospectively evaluated 28 triple-class experienced HIV-1-infected patients harbouring R5 virus, who received maraviroc, raltegravir and etravirine. By on-treatment analysis, 26 (92%) had less than 50 copies HIV-RNA/ml at week 48. The median (interquartile range) 48-week increase in CD4 cell counts was 267 (136-355) cells/microl. Three serious adverse events occurred: one recurrence of mycobacterial spondylodiscitis, one anal cancer, one Hodgkin lymphoma. Although long-term safety needs further study, this protease inhibitor and nucleoside analogue-sparing regimen showed sustained efficacy.

Objectives Despite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir. Patients and methods This was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA <50 copies/mL for ≥10 years, without residual viraemia for ≥5 years, CD4+ >500 cells/mm3, HIV-DNA <100 copies/106 PBMCs and without comorbidities or AIDS-defining diseases. Enrolled patients were strictly monitored. The ART regimen in use at ATI was resumed in the case of confirmed viral rebound (CVR, two consecutive HIV-RNA >50 copies/mL). Results are reported as median (IQR). Results Nine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47–6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14–56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA <50 copies/mL in a median of 88 days (range 15–197). No serious adverse event occurred; one subject experienced acute retroviral syndrome. No significant correlation between baseline factors and time to viral rebound was observed, while the magnitude of viral rebound was significantly associated with pre-ART HIV-1 RNA (Spearman r = 0.786, P = 0.036), nadir CD4+ (Spearman r = −0.800, P = 0.010), baseline CD4+ (Spearman r = −0.667, P = 0.049) and years with undetectable viral load (Spearman r = −0.717, P = 0.030). Conclusions Despite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.

The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.