Efficacy of Convalescent Plasma to Treat Long-Standing COVID-19 in Patients with B-Cell Depletion.

The use of antivirals, corticosteroids, and IL-6 inhibitors has been recommended by the WHO to treat COVID-19. CP has also been considered for severe and critical cases. Clinical trials on CP have shown contradictory results, but an increasing number of patients, including immunocompromised ones, have shown benefits from this treatment. We reported two clinical cases of patients with prolonged COVID-19 infection and B-cell depletion who showed rapid clinical and virological recovery after the administration of CP. The first patient in this study was a 73-year-old female with a history of follicular non-Hodgkin lymphoma previously treated with bendamustine followed by maintenance therapy with rituximab. The second patient was a 68-year-old male with chronic obstructive pulmonary disease, bipolar disorder, alcoholic liver disease, and a history of mantellar non-Hodgkin lymphoma treated with rituximab and radiotherapy. After the administration of CP, both patients showed a resolution of symptoms, improvement of their clinical conditions, and a negative result of the nasopharyngeal swab test. The administration of CP might be effective in resolving symptoms and improving clinical and virological outcomes in patients with B-cell depletion and prolonged SARS-CoV2 infections.

Reduced probability of improving viro-immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study.

INTRODUCTION: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients. METHODS: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm3 , and CD4+/CD8+ ratio ≥ 1. RESULTS: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). CONCLUSIONS: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years.

Long-Term Effectiveness of Rilpivirine-Based Single-Tablet Regimens in a Seven-Year, Two-Center Observational Cohort of People Living with HIV.

Data on the long-term durability of rilpivirine (RPV) are still scarce. A two-center retrospective study was performed, including all people living with HIV (PLWH) treated with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)/RPV or tenofovir alafenamide (TAF)/FTC/RPV in the period January 2013-December 2019. Aims of the study were to assess the rate of discontinuation of the RPV single-tablet regimen (STR) and identify factors associated with the risk of discontinuation according to Cox's regression analysis. A total of 684 PLWH were enrolled. Mean duration of RPV-STR treatment was 192.5 (±99.5) weeks for 123 antiretroviral therapy (ART)-naïve participants (18%) and 173.3 (± 85.6) weeks for 561 ART-experienced study participants (82%). During the study period, the incidence of discontinuation was 7.7 per 100 person-years. The estimated proportions of discontinuation after 48 and 96 weeks were 5.6% and 13.4%, respectively. Causes of discontinuation were loss to follow-up (30%), side effects (15%), ART optimization (14%), virological failure (VF) (12%), death or transfer to another center (9%), low adherence (7%), drug interactions (6%), simplification to dual therapy (3%), and unknown (3%). No differences were observed in cumulative probability of discontinuation between ART-naïve and -experienced PLWH. Heterosexual (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.4-6.8) and mother-to-child (HR 5.3, 95% CI 1.8-15.3) transmission of HIV infection and history of previous VF (HR 1.7, 95% CI 1.2-2.5) were associated with higher risk of discontinuation. High RPV-STR effectiveness and durability were confirmed in our real-life population of PLWH. Given these data, RPV has the potential to be a drug for life in patients selected according to current guidelines.

Viremia copy-years and risk of estimated glomerular filtration rate reduction in adults living with perinatal HIV infection.

Among people with perinatal HIV infection (PHIV), non-communicable diseases, such as chronic kidney disease, are increasing. Both HIV replication and antiretroviral therapy are recognised causes of renal impairment. Objective of the study is to describe the impact of viremia copy-years (VCY) and antiretroviral therapy on trend of estimated glomerular filtration rate (eGFR) in a cohort of adults with perinatal HIV infection. We conducted a multicentre observational study in sixty adults living with PHIV across a 9-year period, from January 2010 to December 2018. The mean values of eGFR were analysed at the first (T0) and last year of observation (T1). VCY was defined as the area under HIV-RNA curve during the study period. We analysed data according to antiretroviral therapy: tenofovir disoproxil (TDF), non-nucleoside reverse transcriptase inhibitors (NNRTI), boosted protease inhibitors (PI/b), integrase inhibitors (INI). We observed a mean overall eGFR reduction from 126.6 mL/min (95%CI: 119.6-133.5) to 105.0 mL/min (95%CI: 99.55-110.6) (p<0.001). Older age, higher baseline eGFR, higher VCY and longer exposure to INI treatment were associated with eGFR reduction at univariate analysis. In the multivariate model, older age (p = 0.039), baseline eGFR (p<0.001) and VCY (p = 0.069), were retained. We also observed a longer exposure to PI/b and INI in patients with lower control on HIV-RNA, expressed as VCY>2 log10. Our study outlines a progressive eGFR reduction in young adults with PHIV, related to the lower control on HIV-RNA VCY and related to aging.

Migrants and imported disease: Trends of admission in an Italian infectious disease ward during the migration crisis of 2015-2017.

BACKGROUND: Since 2014, the migrant population residing in Europe has dramatically increased. Migrants' unmet health needs represent a barrier to integration and should be promptly addressed, without stigma, in order to favour resettlement. METHODS: All-cause of admissions in the migrant population at the Infectious Disease Clinic of Policlinico San Martino Hospital in Genoa between 2015 and 2017 were analysed. Patients were classified by duration of residence in Italy according to the Recommendation on Statistics of International Migration, cause of hospitalization, and region of origin. All data were evaluated with SPSS Statistics. RESULTS: Two hundred thirty-five people were admitted, 86 (36.5%) of them residing in Italy for less than 1 year. Except for a significant increase in migrants from Africa, there was no change considering the area of origin, hospitalization reason or by comparing residency in Italy for more or less than 1 year. A considerable number of hospitalizations were related to non-communicable pathologies and latent tuberculosis infection. Residents in Italy for less than 1 year or with active tuberculosis had prolonged hospitalizations, while HIV-infected had shorter hospital stays. CONCLUSIONS: No difference in terms of diagnosis were found between migrants with longer or shorter period of residence in Italy. Adequate outpatient services for the management of communicable diseases could significantly reduce the length of hospitalizations in the migrant population.

Desirability of outcome ranking (DOOR) for comparing diagnostic tools and early therapeutic choices in patients with suspected candidemia.

Desirability of outcome ranking (DOOR) has been developed for assessing desirability of outcome in interventional studies. However, its possible use in observational studies of the diagnosis and early treatment of infectious diseases has not been explored so far, and it might introduce interesting features in specific scenarios. This was a post hoc analysis of a prospective observational study in intensive care unit patients with sepsis and at risk of candidemia. The probabilities that a randomly selected patient would have a more, less, and equally cost-effective early therapeutic choice following a BDG-based diagnostic strategy rather than the empirical administration of antifungals to all patients were calculated using DOOR methods. The probability of a more cost-effective therapeutic choice following the BDG-based rather than the empirical strategy was 67.81% (95% CI 67.32-68.30), whereas the probabilities of a less and equally cost-effective early therapeutic choice were 19.68% (95% CI 19.27-20.10) and 12.50% (95% CI 12.16-12.85), respectively. The application of DOOR methods to observational studies focused on diagnosis and early treatment is a novel field that could merit further investigation.

Trends in the annual incidence of carbapenem-resistant Klebsiella pneumoniae bloodstream infections: a 8-year retrospective study in a large teaching hospital in northern Italy.

BACKGROUND: Bloodstream infections (BSI) due to carbapenem-resistant (C-R) Klebsiella pneumoniae (Kp) are of global concern from both clinical and public health standpoints. This retrospective study aimed to describe C-R Kp BSI epidemiology in a large teaching hospital in northern Italy. METHODS: Between 1 January 2007 and 31 December 2014, annual incidences both of C-R Kp BSI and of carbapenem-susceptible (C-S) Kp BSI were calculated as the number of events per 10,000 patient-days. A Chi square test for linear trend was used to assess the change in the incidence of C-R Kp BSI and C-S Kp BSI over the study period. Crude 30-day mortality rates were provided both for C-R Kp BSI and for C-S Kp BSI. RESULTS: From 2007 to 2014, we observed 511 episodes of Kp BSI, 349 of which were caused by C-R Kp (68.3 %). The incidence of C-R Kp BSI considerably increased from 0.04/10,000 patient-days in 2007 to 1.77/10,000 patient-days in 2014 (Chi square for trend p < 0.001). The highest incidence of C-R Kp BSI was observed in intensive care units (ICUs), with a peak of 22.01 C-R Kp BSI/10,000 patient-days in 2012. A less marked but significant increase of C-S Kp BSI was also observed (Chi square for trend p = 0.004). Crude 30-day mortality was 36.1 % in patients with C-R Kp BSI and 23.5 % in those with C-S Kp BSI. CONCLUSIONS: During the study period, we observed a dramatic increase in the incidence of C-R Kp BSI in our hospital. More concerted infection-control efforts are needed to contain this alarming C-R Kp diffusion.