Background: Our aim was to estimate the rates of not achieving a robust/above-average humoral response to the COVID-19 mRNA vaccine in people living with HIV (PLWH) who received ≥2 doses and to investigate the role of the CD4 and CD4/CD8 ratio in predicting the humoral response. Methods: We evaluated the humoral anti-SARS-CoV-2 response 1-month after the second and third doses of COVID-19 mRNA vaccine as a proportion of not achieving a robust/above-average response using two criteria: (i) a humoral threshold identified as a correlate of protection against SARS-CoV-2 (<90% vaccine efficacy): anti-RBD < 775 BAU/mL or anti-S < 298 BAU/mL, (ii) threshold of binding antibodies equivalent to average neutralization activity from the levels of binding (nAb titer < 1:40): anti-RBD < 870 BAU/mL or anti-S < 1591 BAU/mL. PLWH were stratified according to the CD4 count and CD4/CD8 ratio at first dose. Logistic regression was used to compare the probability of not achieving robust/above-average responses. A mixed linear model was used to estimate the mean anti-RBD titer at various time points across the exposure groups. Results: a total of 1176 PLWH were included. The proportions of participants failing to achieve a robust/above-average response were significantly higher in participants with a lower CD4 and CD4/CD8 ratio, specifically, a clearer gradient was observed for the CD4 count. The CD4 count was a better predictor of the humoral response of the primary cycle than ratio. The third dose was pivotal in achieving a robust/above-average humoral response, at least for PLWH with CD4 > 200 cells/mm³ and a ratio > 0.6. Conclusions: A robust humoral response after a booster dose has not been reached by 50% of PLWH with CD4 < 200 cells mm³. In the absence of a validated correlate of protections in the Omicron era, the CD4 count remains the most solid marker to guide vaccination campaigns in PLWH.

Background: Mortality rate from COVID-19 in Italy is among the world’s highest. We aimed to ascertain whether there was any reduction of in-hospital mortality in patients hospitalised for COVID-19 in the second-wave period (October 2020–January 2021) compared to the first one (February–May 2020); further, we verified whether there were clusters of hospitalised patients who particularly benefitted from reduced mortality rate. Methods: Data collected related to in-patients’ demographics, clinical, laboratory, therapies and outcome. Primary end-point was time to in-hospital death. Factors associated were evaluated by uni- and multivariable analyses. A flow diagram was created to determine the rate of in-hospital death according to individual and disease characteristics. Results: A total of 1561 patients were included. The 14-day cumulative incidence of in-hospital death by competing risk regression was of 24.8% (95% CI: 21.3–28.5) and 15.9% (95% CI: 13.7–18.2) in the first and second wave. We observed that the highest relative reduction of death from first to second wave (more than 47%) occurred mainly in the clusters of patients younger than 70 years. Conclusions: Progress in care and supporting therapies did affect population over 70 years to a lesser extent. Preventive and vaccination campaigns should focus on individuals whose risk of death from COVID-19 remains high.

With the aim of describing the burden and epidemiology of community-acquired/healthcare-associated and hospital-acquired bloodstream infections (CA/HCA-BSIs and HA-BSIs) in patients hospitalised with COVID-19, and evaluating the risk factors for BSIs and their relative impact on mortality, an observational cohort study was performed on patients hospitalised with COVID-19 at San Paolo Hospital in Milan, Italy from 24 February to 30 November 2020. Among 1351 consecutive patients hospitalised with COVID-19, 18 (1.3%) had CA/HCA-BSI and 51 (3.8%) HA-BSI for a total of 82 episodes of BSI. The overall incidence of HA-BSI was 3.3/1000 patient-days (95% CI 2.4–4.2). Patients with HA-BSI had a longer hospital stay compared to CA/HCA-BSI and no-BSI groups (27 (IQR 21–35) vs. 12 (7–29) vs. 9 (5–17) median-days, p < 0.001) but a similar in-hospital mortality (31% vs. 33% vs. 25%, p = 0.421). BSI was not associated with an increased risk of mortality (CA/HCA-BSI vs. non-BSI aOR 1.27 95% CI 0.41–3.90, p = 0.681; HA-BSI vs. non-BSI aOR 1.29 95% CI 0.65–2.54, p = 0.463). Upon multivariate analysis, NIMV/CPAP (aOR 2.09, 95% CI 1.06–4.12, p = 0.034), IMV (aOR 5.13, 95% CI 2.08–12.65, p < 0.001) and corticosteroid treatment (aOR 2.11, 95% CI 1.06–4.19, p = 0.032) were confirmed as independent factors associated with HA-BSI. Development of HA-BSI did not significantly affect mortality. Patients treated with corticosteroid therapy had double the risk of developing BSI.

Whether vaccination confers a protective effect against progression after hospital admission for COVID-19 remains to be elucidated. Observational study including all the patients admitted to San Paolo Hospital in Milan for COVID-19 in 2021. Previous vaccination was categorized as: none, one dose, full vaccination (two or three doses >14 days before symptoms onset). Data were collected at hospital admission, including demographic and clinical variables, age-unadjusted Charlson Comorbidity index (CCI). The highest intensity of ventilation during hospitalization was registered. The endpoints were in-hospital death (primary) and mechanical ventilation/death (secondary). Survival analysis was conducted by means of Kaplan-Meier curves and Cox regression models. Effect measure modification by age was formally tested. We included 956 patients: 151 (16%) fully vaccinated (18 also third dose), 62 (7%) one dose vaccinated, 743 (78%) unvaccinated. People fully vaccinated were older and suffering from more comorbidities than unvaccinated. By 28 days, the risk of death was of 35.9% (95%CI: 30.1–41.7) in unvaccinated, 41.5% (24.5–58.5) in one dose and 28.4% (18.2–38.5) in fully vaccinated (p = 0.63). After controlling for age, ethnicity, CCI and month of admission, fully vaccinated participants showed a risk reduction of 50% for both in-hospital death, AHR 0.50 (95%CI: 0.30–0.84) and for mechanical ventilation or death, AHR 0.49 (95%CI: 0.35–0.69) compared to unvaccinated, regardless of age (interaction p > 0.56). Fully vaccinated individuals in whom vaccine failed to keep them out of hospital, appeared to be protected against critical disease or death when compared to non-vaccinated. These data support universal COVID-19 vaccination.

Background: HIV-associated neurocognitive disorders (HAND) still affects persons with HIV (PWH) and their pathogenesis is not completely understood. We aimed to explore the association between plasma and cerebrospinal fluid (CSF) markers of blood–brain barrier (BBB) impairment and HAND in untreated PWH. Design: Cross-sectional study. Methods: We enrolled untreated PWH, who underwent blood examinations and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, tight junction proteins: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria). Results: Twenty-one patients (21/78, 26.9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4⁺ T cells and increased CD4⁺ T-cell exhaustion (lower CD4⁺CD127⁺ and CD4⁺CD45RA⁺ T-cell percentages), in comparison to individuals without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15) but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules were not associated with HAND but with a poor performance in different cognitive domains. Conclusion: By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PWH.