We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost ...8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.
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•History of SARS-CoV-2 infection affects longitudinal responses to BNT162b2 vaccine•Lower humoral but enhanced cellular responses early after vaccine in naive subjects•Comparable humoral and cellular responses almost 8 months after vaccination•Similar S-specific B cells late after vaccine in those naive and recovered from COVID-19
Lozano-Rodríguez et al. show that naive subjects have enhanced SARS-CoV-2 spike-specific T reactions but reduced humoral-specific responses compared with individuals recovered from COVID-19. However, almost 8 months after vaccination, comparable specific responses are observed with equivalent levels of SARS-CoV-2-specific B cells and neutralizing antibodies.
BACKGROUND:Immune activation is an independent surrogate marker of CD4 T-cell depletion in HIV-infected patients. Highly active antiretroviral therapy (HAART) reduces disease progression as a direct ...consequence of suppressing HIV replication. Immune function does not normalize completely in most subjects on HAART, however, perhaps reflecting residual HIV replication. So far, it is unclear to what extent immune activation may influence the evolution of CD4 T-cell counts in patients on HAART.
PATIENTS AND METHODS:The expression of CD38 on naive and memory subsets of CD4 and CD8 T cells was measured quantitatively by flow cytometry in 62 drug-naive HIV-positive and 30 HIV-uninfected controls. In addition, the evolution of this marker as well as that of some virologic parameters (plasma viremia and proviral load) and CD4 counts were assessed in 25 HIV-infected individuals who initiated HAART and were followed for 12 months.
RESULTS:The mean level of CD38 on memory CD4 and CD8 T cells as well as in naive CD8 cells was significantly higher in drug-naive HIV-positive subjects than in HIV-negative controls. Moreover, it was highly correlated with viral load titers. In patients on successful HAART, immune activation declined in all T-cell subsets, particularly among memory CD8 cells. It remained elevated with respect to HIV-negative controls, however, even after 12 months of HAART. There was a significant correlation between the CD8 T-cell activation decay and the increase of CD4 T cells on HAART. Patients with the highest decline in CD8 activation were those showing the highest CD4 T-cell gains after 12 months of therapy.
CONCLUSIONS:The level of CD38 expression on different T-cell subsets is differentially upregulated in drug-naive HIV-infected patients. After successful HAART, immune activation decreases in all T-cell subsets, although it still remains elevated in most cases after 12 months of HAART. The extent of immune deactivation under successful HAART correlates with the ability to reconstitute CD4 counts.
The level of CD8+ CD38+ T lymphocytes in blood correlates with disease progression in HIV-infected individuals, independently of the CD4 count. Effective antiretroviral therapy reduces this ...lymphocyte subset in parallel with plasma viremia, although CD38 expression on CD8+ cells does not normalize completely in most subjects, and might reflect residual HIV replication. The expression of CD38 on CD8+ cells (as number of CD38 molecules per CD8+ cell) was measured quantitatively by flow cytometry in 200 individuals, of whom 170 were HIV positive and 30 were HIV-uninfected controls. Forty-six HIV-infected subjects were on antiretroviral therapy and had undetectable viral load. The remaining 124 HIV-positive persons were not on therapy and had detectable plasma viremia. The mean level of CD38 on CD8+ cells was higher in HIV-positive, untreated patients than in subjects on antiviral therapy and controls (5023, 2029, and 1978 molecules per CD8+ cell, respectively, p < 0.01). In HIV-positive, untreated subjects, the higher CD38 expression mainly occurred on CD45RO+ CD8+ cells. The level of CD38 strongly correlated with plasma HIV-RNA (r = 0.63, p < 0.001). The levels of CD38 on CD8+ cells declined steadily in HIV-positive subjects after beginning antiretroviral therapy. A few individuals presented viral blips whereas being on antiviral treatment, levels of CD38 on CD8+ cells increased transiently in parallel with episodes of viral replication. Levels of CD38 on CD8+ cells are increased in chronic HIV infection, and strongly correlate with plasma viremia. The slow decline of CD38 expression on CD8+ cells over time in subjects with undetectable plasma viremia while being on antiretroviral therapy suggests that CD38 expression on CD8+ cells could be used as a marker of residual virus replication.
Aims
Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary oedema ...(ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE.
Methods and results
A randomized, multicentre, open‐label, blinded endpoint clinical trial was performed in seven Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnoea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in‐hospital all‐cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and the composite endpoint included 30‐day mortality and SAE. Analyses were made on an intention‐to‐treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no significant differences in the primary endpoint (in‐hospital mortality for midazolam vs. morphine 12.7% vs. 17.9%; risk ratioRR 0.71, 95% confidence interval CI 0.29–1.74; p = 0.60). SAE were less common with midazolam versus morphine (18.2% vs. 42.9%; RR 0.42, 95% CI 0.22–0.80; p = 0.007), as were the composite endpoint (23.6% vs. 44.6%; RR 0.53, 95% CI 0.30–0.92; p = 0.03).
Conclusion
Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group.
There were no significant differences in mortality between morphine and midazolam but the rate of serious adverse events was significantly higher in the morphine group, although the number of patients was too small to draw final conclusions.
The MIMO clinical trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. Atrial ...fibrillation (AF) is a common comorbidity in heart failure and affects patient's outcome.
The primary endpoint of this substudy is to know if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. The first secondary endpoint is to know if AF modified the reduced risk of serious adverse events or death at 30 days in the midazolam arm. The second secondary objective of this substudy is to analyze whether AF modified the reduced risk of midazolam against morphine on the total number of serious adverse events per patient.
We conducted a secondary analysis of the MIMO trial. Patients more than 18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine.
In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without AF. Calculating the Cochran-Mantel-Haenszel interaction test, we evaluated if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine.
One hundred eleven patients (median = 78.9 years; IQR, 72.3-83.7; women, 52.2%) were randomized in the MIMO trial, 55 to receive midazolam and 56 to morphine. All randomized patients received the assigned drug and there were no losses to follow-up. Forty-four patients (39.6%) had AF. In the AF group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.42 (95% CI, 0.14-1.3). In the group without AF, the RR was 0.46 (95% CI, 0.21-1). The presence of AF did not modify the reduced risk of serious adverse events in the midazolam arm compared with morphine ( P for interaction = 0.88).
This post hoc analysis of the MIMO trial suggests that the reduced risk of serious adverse events in the midazolam group compared to morphine is similar in patients with and without AF.
Objective
To investigate the relationship between ambient temperature and atmospheric pressure (AP) and the severity of heart failure (HF) decompensations.
Methods
We analysed patients coming from ...the Epidemioloy Acute Heart Failure Emergency (EAHFE) Registry, a multicentre prospective cohort study enrolling patients diagnosed with decompensated HF in 26 emergency departments (EDs) of 16 Spanish cities. We recorded patient and demographic data and maximum temperature (
T
max
) and AP (AP
max
) the day before ED consultation. Associations between temperature and AP and severity endpoints were explored by logistic regression. We used restricted cubic splines to model continuous non-linear associations of temperature and AP with each endpoint.
Results
We analysed 16,545 patients. Daily
T
max
and AP
max
(anomaly) of the day before patient ED arrival ranged from 0.8 to 41.6° and from − 61.7 to 69.9 hPa, respectively. A total of 12,352 patients (75.2%) were hospitalised, with in-hospital mortality in 1171 (7.1%). The probability of hospitalisation by HF decompensation showed a U-shaped curve versus
T
max
and an increasing trend versus AP
max
. Regarding temperature, hospitalisation significantly increased from 20 °C (reference) upwards (25 °C: OR = 1.12, 95% CI = 1.04–1.21; 40 °C: 1.65, 1.13–2.40) and below 5.4 °C (5 °C: 1.21, 1.01–1.46). Concerning the mean AP of the city (anomaly = 0 hPa), hospitalisation increased when AP
max
(anomaly) was above + 7.0 hPa (atmospheric anticyclone; + 10 hPa: 1.14, 1.05–1.24; + 30 hPa: 2.02. 1.35–3.03). The lowest probability of mortality also corresponded to cold-mild temperatures and low AP, with a significant increased risk only found for
T
max
above 24.3 °C (25 °C: 1.13, 1.01–1.27; 40 °C: 2.05, 1.15–3.64) and AP
max
(anomaly) above + 3.4 hPa (+ 10 hPa: 1.21, 1.07–1.36; + 30 hPa: 1.73, 1.06–2.81). Sensitivity analysis confirmed the main analysis results.
Conclusion
Temperature and AP are independently associated with the severity of HF decompensations, with possible different effects on the need for hospitalisation and in-hospital mortality.
To analyze whether the high levels of air pollutants are related to a greater severity of decompensated heart failure (HF).
Patients diagnosed with decompensated HF in the emergency department of 4 ...hospitals in Barcelona and 3 in Madrid were included. Clinical data (age, sex, comorbidities, baseline functional status), atmospheric (temperature, atmospheric pressure) and pollutant data (SO
, NO
, CO, O
, PM
, PM
) were collected in the city on the day of emergency care. The severity of decompensation was estimated using 7-day mortality (primary indicator) and the need for hospitalization, in-hospital mortality, and prolonged hospitalization (secondary indicators). The association adjusted for clinical, atmospheric and city data between pollutant concentration and severity was investigated using linear regression (linearity assumption) and restricted cubic spline curves (no linearity assumption).
A total of 5292 decompensations were included, with a median age of 83 years (IQR=76-88) and 56% women. The medians (IQR) of the daily pollutant averages were: SO
=2.5μg/m
(1.4-7.0), NO
=43μg/m
(34-57), CO=0.48mg/m
(0.35-0.63), O
=35μg/m
(25-48), PM
=22μg/m
(15-31) and PM
=12μg/m
(8-17). Mortality at 7 days was 3.9%, and hospitalization, in-hospital mortality, and prolonged hospitalization were 78.9, 6.9, and 47.5%, respectively. SO
was the only pollutant that showed a linear association with the severity of decompensation, since each unit of increase implied an OR for the need for hospitalization of 1.04 (95% CI 1.01-1.08). The restricted cubic spline curves study also did not show clear associations between pollutants and severity, except for SO
and hospitalization, with OR of 1.55 (95% CI 1.01-2.36) and 2.71 (95% CI 1.13-6.49) for concentrations of 15 and 24μg/m
, respectively, in relation to a reference concentration of 5μg/m
.
Exposure to ambient air pollutants, in a medium to low concentration range, is generally not related to the severity of HF decompensations, and only SO
may be associated with an increased need for hospitalization.
To analyze whether the high levels of air pollutants are related to a greater severity of decompensated heart failure (HF).
Patients diagnosed with decompensated HF in the emergency department of 4 ...hospitals in Barcelona and 3 in Madrid were included. Clinical data (age, sex, comorbidities, baseline functional status), atmospheric (temperature, atmospheric pressure) and pollutant data (SO2, NO2, CO, O3, PM10, PM2.5) were collected in the city on the day of emergency care. The severity of decompensation was estimated using 7-day mortality (primary indicator) and the need for hospitalization, in-hospital mortality, and prolonged hospitalization (secondary indicators). The association adjusted for clinical, atmospheric and city data between pollutant concentration and severity was investigated using linear regression (linearity assumption) and restricted cubic spline curves (no linearity assumption).
A total of 5292 decompensations were included, with a median age of 83 years (IQR=76–88) and 56% women. The medians (IQR) of the daily pollutant averages were: SO2=2.5μg/m3 (1.4–7.0), NO2=43μg/m3 (34–57), CO=0.48mg/m3 (0.35–0.63), O3=35μg/m3 (25–48), PM10=22μg/m3 (15–31) and PM2.5=12μg/m3 (8–17). Mortality at 7 days was 3.9%, and hospitalization, in-hospital mortality, and prolonged hospitalization were 78.9, 6.9, and 47.5%, respectively. SO2 was the only pollutant that showed a linear association with the severity of decompensation, since each unit of increase implied an OR for the need for hospitalization of 1.04 (95% CI 1.01–1.08). The restricted cubic spline curves study also did not show clear associations between pollutants and severity, except for SO2 and hospitalization, with OR of 1.55 (95% CI 1.01–2.36) and 2.71 (95% CI 1.13–6.49) for concentrations of 15 and 24μg/m3, respectively, in relation to a reference concentration of 5μg/m3.
Exposure to ambient air pollutants, in a medium to low concentration range, is generally not related to the severity of HF decompensations, and only SO2 may be associated with an increased need for hospitalization.
Analizar si la exposición a contaminantes del aire en 2 grandes ciudades españolas está relacionada con la gravedad de las descompensaciones de la insuficiencia cardiaca (IC).
Se estudiaron pacientes con IC descompensada en urgencias de 4 hospitales de Barcelona y 3 de Madrid. Se recogieron datos clínicos (edad, sexo, comorbilidades, situación funcional basal), atmosféricos (temperatura, presión atmosférica) y de contaminantes (SO2, NO2, CO, O3, PM10, PM2,5) el día de atención en urgencias. La gravedad de la descompensación se estimó mediante la mortalidad a 7 días (indicador primario) y la necesidad de hospitalización, mortalidad intrahospitalaria y hospitalización prolongada (indicadores secundarios). Se investigó la asociación ajustada por datos clínicos, atmosféricos y ciudad entre concentración de contaminantes y gravedad, mediante regresión logística (asunción de linealidad) y curvas spline cúbicas restringidas (no asunción de linealidad).
Se incluyeron 5.292 descompensaciones, con edad mediana de 83 años (RIC=76–88) y 56% mujeres. Las medianas (RIC) de los promedios diarios de contaminantes fueron: SO2=2,5μg/m3 (1,4–7,0), NO2=43μg/m3 (34–57), CO=0,48mg/m3 (0,35–0,63), O3=35μg/m3 (25–48), PM10=22μg/m3 (15–31) y PM2,5=12μg/m3 (8–17). La mortalidad a 7 días fue del 3,9%, y la hospitalización, la mortalidad intrahospitalaria y la hospitalización prolongada, del 78,9, 6,9 y 47,5%, respectivamente. El SO2 fue el único contaminante que mostró asociación lineal con la gravedad de la descompensación, ya que cada unidad de incremento supuso una OR para necesidad de hospitalización de 1,04 (IC 95% 1,01–1,08). El estudio mediante curvas spline cúbicas restringidas tampoco mostró asociaciones nítidas entre contaminantes y gravedad, excepto para SO2 y hospitalización, con OR de 1,55 (IC 95% 1,01–2,36) y de 2,71 (IC 95% 1,13–6,49) para concentraciones de 15 y 24μg/m3, respectivamente, en relación con una concentración de referencia de 5μg/m3.
La exposición a contaminantes del aire ambiente, en un rango de concentraciones medio a bajo, en general no está relacionado con la gravedad de las descompensaciones de la IC, y solo el SO2 podría estar asociado a una mayor necesidad de hospitalización.
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