The effect of dose-interval on antibody response to mRNA COVID-19 vaccines: a prospective cohort study

BackgroundVaccination against COVID-19 is highly effective in preventing severe disease and hospitalization, but primary COVID mRNA vaccination schedules often differed from those recommended by the manufacturers due to supply chain issues. We investigated the impact of delaying the second dose on antibody responses to COVID mRNA-vaccines in a prospective cohort of health-care workers in Quebec.MethodsWe recruited participants from the McGill University Health Centre who provided serum or participant-collected dried blood samples (DBS) at 28-days, 3 months, and 6 months post-second dose and at 28-days after a third dose. IgG antibodies to SARS-CoV2 spike (S), the receptor-binding domain (RBD), nucleocapsid (N) and neutralizing antibodies to the ancestral strain were assessed by enzyme-linked immunosorbent assay (ELISA). We examined associations between long (≤89 days) versus short (<89 days) between-dose intervals and antibody response through multivariable mixed-effects models adjusted for age, sex, prior covid infection status, time since vaccine dose, and assay batch.FindingsThe cohort included 328 participants who received up to three vaccine doses (>80% Pfizer-BioNTech). Weighted averages of the serum (n=744) and DBS (n=216) cohort results from the multivariable models showed that IgG anti-S was 31% higher (95% CI: 12% to 53%) and IgG anti-RBD was 37% higher (95% CI: 14% to 65%) in the long vs. short interval participants, across all time points.InterpretationOur study indicates that extending the covid primary series between-dose interval beyond 89 days (approximately 3 months) provides stronger antibody responses than intervals less than 89 days. Our demonstration of a more robust antibody response with a longer between dose interval is reassuring as logistical and supply challenges are navigated in low-resource settings

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Optical Studies Of Inp/inalas/inp Interface Recombinations

We report on the photoluminescence characterization of a metalorganic vapour phase epitaxy grown InP/InAlAs/InP structure. The energy band alignment of the InAlAs/InP interface is of type II. The PL arising from the first grown interface (InAlAs grown on InP) is clearly seen at 1.2 eV. The localization was possible by scanning the laser beam on a angle-bevelled sample whose bevel crosses all the layers of the InP/InAlAs/InP structure. For the second interface, called the inverse interface (InP grown on InAlAs), a different PL behaviour is observed. The energy of the observed PL peak is 1.3 eV. It is very sensitive to the excitation power. From this behaviour, the Auger depth profiling measurements and the wedge transmission electron microscopy performed on this sample we conclude that this recombination does not originate from a type II interface band structure but from an InAsxP1-x layer located at the inverse interface. This intermediate layer originates from the higher incorporation coefficient of As compared to that of P. © 1993.65-66C777783Quillec, (1990) SPIE's Int. Conf. Aachen, FRGSacilotti, Motisuke, Monteil, Abraham, Iikawa, Montes, Furtado, Waldman, Growth and characterization of type-II/type-I AlGaInAs/InP interfaces (1992) Journal of Crystal Growth, 124, p. 584Kroemer, Griffiths, (1983) IEEE Electron Device Lett., 4 EDL, p. 20Huber, Di Persio, Di Forte-Poisson, Brylinski, Bisaro, Grattepain, Lagorsse, Defect Characterization In InP Epitaxial Layers Grown By LP-MOCVD (1987) Proc. SPIE, 796, p. 182Faist, Ganière, Buffat, Sampson, Reinhart, (1989) J. Appl. Phys., 66, p. 1023Caine, Subbanna, Kroemer, Merz, (1984) Appl. Phys. Lett., 45, p. 1123Brasil, Nahory, Quinn, Tamargo, Farrell, (1992) Appl. Phys. Lett., 60, p. 1981Krawczky, Hollinger, Photoluminescence and x-ray photoelectron spectroscopy measurements of InP surface treated by acid and base solutions (1984) Applied Physics Letters, 45, p. 870Böhrer, Krost, Bimberg, InAsP islands at the lower interface of InGaAs/InP quantum wells grown by metalorganic chemical vapor deposition (1992) Applied Physics Letters, 60, p. 2258Schwedler, Gallmann, Wolter, Kohl, Leo, Kurz, Juillaguet, Baumann, (1993) Appl. Surf. Sci., 63, p. 187Adachi, (1982) J. Appl. Phys., 53, p. 8775Tiwari, Frank, (1992) Appl. Phys. Lett., 60, p. 63

Intravenous immunoglobulin exerts reciprocal regulation of Th1/Th17 cells and regulatory T cells in Guillain-Barré syndrome patients

International audienceGuillain-Barré syndrome (GBS) is an acute, autoimmune inflammatory disorder of peripheral nervous system characterized by a severe functional motor weakness. Treatment with intravenous immunoglobulin (IVIg) is one of the approved and preferred therapeutic strategies for GBS. However, the mechanisms underlying the therapeutic benefit with IVIg in GBS are not completely understood. In the present study, we observed that GBS patients have increased frequencies of Th1 and Th17 cells, but reduced number of Foxp3(+) regulatory T cells (Treg cells) with defective functions. We show that IVIg treatment in GBS patients results in a marked reduction in the frequency of Th1 and Th17 cells with a concomitant expansion of Treg cells. Importantly, IVIg-expanded Treg cells exhibited an increased T cell suppressive function. Together our results demonstrate that therapeutic benefit of IVIg in GBS patients implicates the reciprocal regulation of Th1/Th17 and Treg cells

Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients

Background: Deep sedation may hamper the detection of neurological deterioration in brain-injured patients. Impaired brainstem reflexes within the first 24 h of deep sedation are associated with increased mortality in non-brain-injured patients. Our objective was to confirm this association in brain-injured patients. Methods: This was an observational prospective multicenter cohort study involving four neuro-intensive care units. We included acute brain-injured patients requiring deep sedation, defined by a Richmond Assessment Sedation Scale (RASS) < -3. Neurological assessment was performed at day 1 and included pupillary diameter, pupillary light, corneal and cough reflexes, and grimace and motor response to noxious stimuli. Pre-sedation Glasgow Coma Scale (GCS) and Simplified Acute Physiology Score (SAPS-II) were collected, as well as the cause of death in the Intensive Care Unit (ICU). Results: A total of 137 brain-injured patients were recruited, including 70 (51%) traumatic brain-injured patients, 40 (29%) vascular (subarachnoid hemorrhage or intracerebral hemorrhage). Thirty patients (22%) died in the ICU. At day 1, the corneal (OR 2.69, p = 0.034) and cough reflexes (OR 5.12, p = 0.0003) were more frequently abolished in patients that died in the ICU. In a multivariate analysis, abolished cough reflex was associated with ICU mortality after adjustment to pre-sedation GCS, SAPS-II, RASS (OR: 5.19, 95% CI [1.92-14.1], p = 0.001) or dose of sedatives (OR: 8.89, 95% CI [2.64-30.0], p = 0.0004). Conclusion: Early (day 1) cough reflex abolition is an independent predictor of mortality in deeply sedated brain-injured patients. Abolished cough reflex likely reflects a brainstem dysfunction that might result from the combination of primary and secondary neuro-inflammatory cerebral insults revealed and/or worsened by sedation