Abstract
Background
We studied immunological response against SARS-CoV-2 after two doses of vaccine in health care workers (HCW) at our Infectious Disease Unit
Methods
We enrolled prospectively HCW ...without (group A) and with previous infection (group B). We collected peripheral blood at baseline (before the BNT162b2 vaccine), T1 (before the 2nd dose), T2 and T6 (after 1 and 6 months after of 2nd dose). The activation induced cell marker assay (AIM) was performed with CD4 and CD8 Spike peptide megapools (MPs). We evaluated the Stimulation Index (SI) as AIM+ stimulated cells/negative control (positive response SI >= 2). Quantitative antibodies (Abs) to Spike-1 protein (S) and to nucleocapside protein (N) were detected with an electrochemiluminescence immunoassay. We tested at T6 the responses to alpha, beta, gamma, delta and epsilon variants MPs.We used the linear mixed model with random intercept adjusted for age and sex to compare specific times to T0. To assess differences over time between groups the interaction with time was tested.
Results
In group A 13/22 (59%) were female vs 5/7 (71%) group B, the mean age 40 vs 38 years, respectively. For CD4+ Spike the overall rate of change over time was significant at T1 (p=0.038) and at T2 (p< 0.001) vs T0 with a decreasing at T6 (p not significant) Figure 1 with a trend of higher response in group A. In group B the CD8+ Spike reactivity increased at T1(p=0.037) and at T6 (p=0.005) vs T0. The interaction between SI and time was statistically significant at T1 (p=0.033); T2 (p= 0.046) and T6 (p=0.035) (mean values in group B higher than A). For overall population, the anti-S Abs significantly increased at T1 vs T0, T2 vs T0 and at T6 vs T0 Figure 2A. The group B at T6 retained a higher anti S response but the rate of change significantly differs between the two group (overall interaction: p< 0.001) Figure 2B. At T6 in both groups we found a high CD4+ T cells response to epsilon variant, even if not detected as circulant virus.
Quantitative (U/ml) values of anti-S Antibodies.
Conclusion
The humoral response was persistent and increased in previous infected subjects. The CD4+T cells response after vaccination retained a response in uninfected subject, with an increasing trend and with a response to non-circulating variants. The vaccine could help the CD8+ T cells reactivity specific for Spike peptides.
Disclosures
Chiara Dentone, CD, Angelini: Advisor/Consultant|Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|Novartis: Advisor/Consultant Lucia Taramasso, LT, Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|ViiV: Advisor/Consultant Alessandro Sette, AS, Arcturus Therapeutics: Grant/Research Support|Astrazeneca: Advisor/Consultant|Avalia: Advisor/Consultant|CellCarta: Grant/Research Support|Flow Pharma: Grant/Research Support|Fortress: Advisor/Consultant|Gritstone Bio: Advisor/Consultant|ImmunoScape: Advisor/Consultant|Moderna: Advisor/Consultant|Repertoire: Advisor/Consultant Antonio Di Biagio, AD, Abbvie: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|MSD: Advisor/Consultant|ViiV: Advisor/Consultant Matteo Bassetti, PhD, Angelini: Advisor/Consultant|Astellas: Grant/Research Support|Bayer: Advisor/Consultant|Bayer: Honoraria|BioMe ́ rieux: Advisor/Consultant|BioMe ́ rieux: Honoraria|Cidara: Advisor/Consultant|Cidara: Honoraria|Cipla: Advisor/Consultant|Cipla: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Menarini: Advisor/Consultant|Menarini: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Tetraphase: Advisor/Consultant.
Highlights • Switch from unboosted protease inhibitor to an RPV/FTC/TDF-based single-tablet regimen among HIV-1-infected patients is proposed. • The switch is safe and associated with a reduction in ...plasma triglycerides and plasma cholesterol. • Decrease in cART-related costs and non-cART patient management is highlighted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The role of near-infrared spectroscopy (NIRS) for the evaluation of cerebral haemodynamics is gaining increasing popularity because of its noninvasive nature. The aim of this study was to evaluate ...the role of the integral components of regional cerebral oxygenation (rSO
) measured by NIRS i.e., arterial-oxyhemoglobin (O
Hbi) and venous-deoxyhemoglobin (HHbi)-components, as indirect surrogates of cerebral blood flow (CBF) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19). We compared these findings to the gold standard technique for noninvasive CBF assessment, Transcranial Doppler (TCD).
Mechanically ventilated patients with COVID-19 admitted to the Intensive Care Unit (ICU) of Policlinico San Martino Hospital, Genova, Italy, who underwent multimodal neuromonitoring (including NIRS and TCD), were included. rSO
and its components relative changes in O
Hbi, HHbi, and total haemoglobin (cHbi) were compared with TCD (cerebral blood flow velocity, CBFV). Changes (Δ) in CBFV and rSO
, ΔO
Hbi, ΔHHbi, and ΔcHbi after systemic arterial blood pressure (MAP) modifications induced by different manoeuvres (e.g., rescue therapies and haemodynamic manipulation) were assessed using mixed-effect linear regression analysis and repeated measures correlation coefficients. All values were normalised as percentage changes from the baseline (Δ%).
One hundred and four measurements from 25 patients were included. Significant effects of Δ%MAP on Δ%CBF were observed after rescue manoeuvres for CBFV, ΔcHbi, and ΔO
Hbi. The highest correlation was found between ΔCBFV and ΔΔO
Hbi (R = 0.88,
< 0.0001), and the poorest between ΔCBFV and ΔΔHHbi (R = 0.34, p = 0.002).
ΔO
Hbi had the highest accuracy to assess CBF changes, reflecting its role as the main component for vasomotor response after changes in MAP. The use of indexes derived from the different components of rSO
can be useful for the bedside evaluation of cerebral haemodynamics in mechanically ventilated patients with COVID-19.
HIV-associated immunodeficiency is related to loss of CD4+ T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater ...than 500 CD4+ T cells/μL. CD8+CD28−CD127loCD39+ T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients.
We sought to analyze the frequency of CD8+CD28−CD127loCD39+ Treg cells in the circulation of HIV-infected patients.
The frequency of circulating CD8+CD28−CD127loCD39+ Treg cells was analyzed and correlated with viral load and CD4+ T-cell counts/percentages in 93 HIV-1–infected patients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infected patients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus–infected patients (n = 17), and healthy donors (n = 173).
HIV-infected patients had increased circulating levels of functional CD8+CD28−CD127loCD39+ Treg cells. These cells showed antigen specificity against HIV proteins. Their frequency after antiretroviral therapy (ART) correlated with HIV viremia, CD4+ T-cell counts, and immune activation markers, suggesting their pathogenic involvement in AIDS- or non–AIDS-related complications. Their increase after initiation of ART heralded a lack of virologic or clinical response, and hence their monitoring is clinically relevant.
HIV infection induces remarkable expansion of CD8+CD28−CD127loCD39+ Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated
bloodstream infections ...(BSIs).
All episodes of uncomplicated
BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent
BSI and all-cause 1-year mortality) among patients who underwent SC (5-11 days) or PC (12-24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method.
A total of 114 patients with uncomplicated
BSI were included: 35 (30.7%) were classified into the SC group (median interquartile range {IQR}, 9 7-11 days) and 79 (69.3%) into the PC group (median IQR, 14 14-16 days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%;
= .02) or septic shock at the time of
BSI onset (11.4% vs 1.3%;
= .03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 22.9% vs 17 21.5%, respectively; IPTW-adjusted subdistribution hazard ratio sHR, 0.67; 95% CI, 0.31-1.47;
= .20). The risk for recurrent
BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20-5.80;
= .94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35-1.50;
= .38) did not differ between groups.
Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia.
In the last 20 years routine T CD4+ lymphocyte (CD4+) cell count has proved to be a key factor to determine the stage of HIV infection and start or discontinue of prophylaxis for opportunistic ...infections. However, several studies recently showed that in stable patients on cART a quarterly CD4+ cell count monitoring results in limited (or null) clinical relevance. The research is intended to investigate whether performing quarterly CD4+ cell counts in stable HIV-1 patients is still recommendable and to provide a forecast of the cost saving that could be achieved by reducing CD4+ monitoring in such a category of patients.
The study is based on data referring to all HIV-infected patients > 18 years of age being treated at two large infectious diseases units located in the metropolitan area of Genoa, Italy. The probability of CD4+ cell counts dropping below a threshold value set at 350 cells/mm
is assessed using confidence intervals and Kaplan-Meier survival estimates, whereas multivariate Cox analysis and logistic regression are implemented in order to identify factors associated with CD4+ cell count falls below 350 cells/mm
.
Statistical analysis reveals that among stable patients the probability of maintaining CD4+ >350 cell/mm
is more than 98%. Econometric models indicate that HCV co-infection and HIV-RNA values >50 copies/mL in previous examinations are associated with CD4+ falls below 350 cells/mm
. Moreover, results suggest that the cost saving that could be obtained by reducing CD4+ examinations ranges from 33 to 67%.
Empirical findings shows that patients defined as stable at enrollment are highly unlikely to experience a CD4+ value <350 cell/mm
in the space/arc of a year. The research supports a recommendation for annual CD4+ monitoring in stable HIV-1 patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the context of HIV-infected patients with several past antiretroviral therapies and multiple failures, it is possible to be faced with viruses resistant to all drug classes. We report on two HIV-1 ...infected patients in which the historical genotype showed mutations against all the major drug classes and in which viral suppression has been obtained by non-conventional antiretroviral therapy regimens, including the combination of darunavir at high dosage (800 mg bid), dolutegravir (50 mg bid) and a third agent, i.e. enfuvirtide in the first case and etravirine in the second one.
The number of patients newly infected by HIV-1 non-B subtypes and circulating recombinant forms (CRFs) is increasing worldwide, including in the western countries. We report on a primary HIV-1 ...infection in a Caucasian patient. A routine quantitative assay (Nuclisens EasyQ HIV-1 2.0, BioMérieux SA) showed 6,700 HIV-1 RNA copies/ml. A combined antiretroviral therapy (cART) consistent with low baseline HIV-1 RNA was started. Few days later, the analysis performed with REGA HIV-1 Subtyping Tool - Version 3.0 attributed the HIV-1 sequence to the CRF02_AG recombinant form. Therefore, a second real-time PCR assay was performed, using the Versant HIV-1 RNA 1.0 Assay (kPCR) (Siemens HealthCare Diagnostics) which revealed a HIV-1 RNA of 230,000 copies/ml. Consequently, the ongoing cART was potentiated. This case suggests that the wide genetic variability of HIV-1 subtypes may affect the capability of the commonly used assays to detect and accurately quantify HIV-1 RNA in non-B subtypes and CRFs. In presence of CRFs different commercial HIV-1 RNA tests should be performed to find the most reliable for viral load quantification at the diagnosis, because it influences the choice of cART, and during the follow-up. Indeed, international guidelines for HIV-1 infection management suggest to monitor patient' HIV-RNA with the same assay over the course of treatment. As different commercial tests can be performed in the same laboratory with considerable difficulty, the laboratory should select an assay that is suitable not only for the more prevalent strain, but also for less frequent ones that, nevertheless, can occur. Then, knowing and investigating the spread of non-B strains has essential clinical and laboratory implications.
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