Changes in the Adaptive Cellular Repertoire after Infection with Different SARS-CoV-2 VOCs in a Cohort of Vaccinated Healthcare Workers.

BACKGROUND: Currently approved vaccines are highly effective in protecting against hospitalization and severe COVID-19 infections. How pre-existing immunity responds to new variants with mutated antigens is crucial information for elucidating the functional interplay between antibodies and B and T cell responses during infection with new SARS-CoV-2 variants. METHODS: In this study, we monitored the dynamics and persistence of the immune response versus different SARS-CoV-2 variants of concern that emerged during the pandemic period (2021-2022) in a cohort of vaccinated healthcare workers, who experienced breakthrough infection in the Pre-Delta, Delta, and Omicron waves. We evaluated both the humoral and cell-mediated responses after infection. We also evaluated the anti-SARS-CoV-2 antibodies levels produced by infection in comparison with those produced after vaccination. RESULTS: Our results highlighted that the immune response against the Delta VOC mainly involved an adaptive humoral and switched memory B cells component, even 3 months after the last vaccine dose, conversely showing a high percentage of depleted adaptive T cells. Omicron infections triggered a consistent production of non-vaccine-associated anti-N antibodies, probably to balance the spike epitope immune escape mechanisms. CONCLUSION: Our results suggest a direct dependence between the VOC and different humoral and B and T cell balances in the post-infection period, despite the administration of a different number of vaccine doses and the elapsed time since the last vaccination.

Effect of long-acting injectable antipsychotics on emergency department visits and hospital admissions in people with bipolar disorder: A retrospective mirror-image analysis from the Northern Milan Area Cohort (NOMIAC) study.

BACKGROUND: Mood recurrences in bipolar disorder (BD) are often associated with poor treatment adherence. Despite long-acting injectable antipsychotics (LAIs) may favor treatment compliance, their use in BD is still poorly explored. METHODS: This mirror-image study investigated the effect of LAIs initiation on the number of emergency department (ED) visits and days of hospitalization, among individuals with BD from the mental health services of a large area of the Metropolitan City of Milan. The mirror periods were 365 days either side of the LAI initiation. Individual medical records were retrospectively reviewed. RESULTS: Sixty-eight individuals with BD initiating a LAI over the index period were included. We estimated that LAI initiation overall reduced both ED visits (p = 0.002) and days of hospitalization (p < 0.001). This remained true only for those participants who i) continued LAI for the entire 12-month period of observation and ii) were treated with a second-generation antipsychotic LAI. In addition, LAI initiation reduced number of hospitalization days during hypo/manic (p = 0.013), but not depressive (p = 0.641) episodes, as well as compulsory admission days (p = 0.002). LIMITATIONS: Due to the retrospective design, we could not collect systematic information on symptom severity and reasons of LAI discontinuation. Moreover, the limited sample size did not allow us to estimate effectiveness of single LAI agents. CONCLUSIONS: Our study provides additional insight on the effectiveness of LAIs in BD, supporting their clinical utility for pragmatic outcomes such as ED visits and hospitalizations. Further longitudinal research is needed to clarify the real-world effectiveness of LAIs for BD clinical management.

Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Clostridioides difficile Infections.

BACKGROUND: Limited and wide-ranging data are available on the recurrent Clostridioides difficile infection (rCDI) incidence rate. METHODS: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case-control study was performed to identify risk factors associated with 30-day onset rCDI. RESULTS: Three hundred nine patients with a first CDI were included in the study; 32% of the CDI episodes (99/309) were severe/complicated; complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up; rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7; 95% CI: 1.1-2.7, p = 0.03). CONCLUSION: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.

The Burden of Clostridioides Difficile Infection during the COVID-19 Pandemic: A Retrospective Case-Control Study in Italian Hospitals (CloVid).

Data on the burden of Clostridioides difficile infection (CDI) in Coronavirus Disease 2019 (COVID-19) patients are scant. We conducted an observational, retrospective, multicenter, 1:3 case (COVID-19 patients with CDI)-control (COVID-19 patients without CDI) study in Italy to assess incidence and outcomes, and to identify risk factors for CDI in COVID-19 patients. From February through July 2020, 8402 COVID-19 patients were admitted to eight Italian hospitals; 38 CDI cases were identified, including 32 hospital-onset-CDI (HO-CDI) and 6 community-onset, healthcare-associated-CDI (CO-HCA-CDI). HO-CDI incidence was 4.4 × 10,000 patient-days. The percentage of cases recovering without complications at discharge (i.e., pressure ulcers, chronic heart decompensation) was lower than among controls (p = 0.01); in-hospital stays was longer among cases, 35.0 versus 19.4 days (p = 0.0007). The presence of a previous hospitalisation (p = 0.001), previous steroid administration (p = 0.008) and the administration of antibiotics during the stay (p = 0.004) were risk factors associated with CDI. In conclusions, CDI complicates COVID-19, mainly in patients with co-morbidities and previous healthcare exposures. Its association with antibiotic usage and hospital acquired bacterial infections should lead to strengthen antimicrobial stewardship programmes and infection prevention and control activities.