Intradermal Fractional ChAdOx1 nCoV-19 Booster Vaccine Induces Memory T Cells: A Follow-Up Study.

The administration of viral vector and mRNA vaccine booster effectively induces humoral and cellular immune responses. Effector T cell responses after fractional intradermal (ID) vaccination are comparable to those after intramuscular (IM) boosters. Here, we quantified T cell responses after booster vaccination. ChAdOx1 nCoV-19 vaccination induced higher numbers of S1-specific CD8+ memory T cells, consistent with the antibody responses. Effector memory T cell phenotypes elicited by mRNA vaccination showed a similar trend to those elicited by the viral vector vaccine booster. Three months post-vaccination, cytokine responses remained detectable, confirming effector T cell responses induced by both vaccines. The ID fractional dose of ChAdOx1 nCoV-19 elicited higher effector CD8+ T cell responses than IM vaccination. This study confirmed that an ID dose-reduction vaccination strategy effectively stimulates effector memory T cell responses. ID injection could be an improved approach for effective vaccination programs.

Efficacy of Moraceae with chlorhexidine mouthwash on the microbial flora of critically ill intubated patients: a randomized controlled pilot study.

Critically ill intubated patients are routinely provided with chlorhexidine (CHX) for their mouth washing, but CHX mouthwash induces several complications. In this study, we aimed to evaluate the efficacy and safety of Moraceae with CHX mouthwash in the reduction of oral bacterial count in critically ill patients and to compare it with CHX-alone mouthwash. This double-blind, randomized, controlled trial included critically ill patients receiving mechanical ventilation. The patients were randomly divided into two groups based on the Modified Beck oral assessment score. The primary endpoint was a reduction in oral bacterial counts after mouth washing on day 1 and day 4. Thirty patients were included in this study; 15 patients received Moraceae with CHX mouthwash and 15 patients received CHX-alone mouthwash. The oral bacterial counts in the Moraceae with CHX group did not differ from the CHX group after mouth washing on day 1 and day 4 of admission. The patients in the CHX group experienced more intolerable taste than those in the Moraceae group (60% vs. 13.3%, P = 0.008). Moraceae with CHX mouthwash had the same effectiveness as CHX alone on bacterial flora but exhibited less intolerable side effects than CHX alone.Trial registration: TCTR20190530003; 30/05/2019.

T-Cell Responses Induced by an Intradermal BNT162b2 mRNA Vaccine Booster Following Primary Vaccination with Inactivated SARS-CoV-2 Vaccine.

A practical booster vaccine is urgently needed to control the coronavirus disease (COVID-19) pandemic. We have previously reported the safety and immunogenicity of a fractional intradermal booster, using the BNT162b2 mRNA vaccine in healthy volunteers who had completed two doses of inactivated SARS-CoV-2 vaccine. In this study, an intramuscular booster at full dosage was used as a control, and a half-dose vaccination was included for reciprocal comparison. Detailed T-cell studies are essential to understand cellular responses to vaccination. T-cell immunity was examined using S1 peptide restimulation and flow cytometry. The fractional dose (1:5) of the BNT162b2 mRNA vaccine enhanced antigen-specific effector T-cells, but the responses were less remarkable compared to the intramuscular booster at full dosage. However, the intradermal regimen was not inferior to the intramuscular booster a month after boosting. An intradermal booster using only one-fifth of the standard dosage could provide comparable T-cell responses with the fractional intramuscular booster. This work confirms the efficacy of intradermal and fractional vaccination in terms of T-cell immunogenicity in previously immunised populations.

The incidence of phlebitis development of high concentration of continuous amiodarone infusion with in-line filter compared to the low concentration without in-line filter: a retrospective propensity score-matched analysis.

BACKGROUND: Phlebitis-associated peripheral infusion of intravenous amiodarone is common in clinical practice, with an incidence between 5% and 65%. Several factors, including drug concentration, catheter size, and in-line filter used, are significantly associated with phlebitis occurrence. We performed a retrospective propensity score-matched analysis to find out whether in-line filter will reduce the incidence of amiodarone-induced phlebitis (AIP) in high concentration of amiodarone infusion compared to low concentration without in-line filter. METHODS: Clinical records of all patients who required intravenous amiodarone infusion for cardiac arrhythmias, between January 2017 to December 2019 were retrieved. The incidence of AIP was recorded and subsequently compared among high concentration (2 mg/ml) with an in-line filter and low concentration (1.5 mg/ml) infusion without an in-line filter after a 1 to 2 propensity score matched. RESULTS: The data indicated that among the 214 cases of amiodarone infusion collected, 28 cases used an in-line filter with high concentration while 186 cases received a low concentration of amiodarone infusion without an in-line filter. After 1:2 propensity score matching, the incidence of phlebitis in the high concentration with in-line filter group was significantly higher than the low concentration without in-line filter group (28.6% vs. 3.6%, P<0.01). CONCLUSIONS: Despite the usage of in-line filter, the high concentration of amiodarone infusion resulted in a higher incidence of peripheral phlebitis. Central venous catheterization for a high concentration of amiodarone infusion is recommended.

Immunogenicity and safety of an intradermal ChAdOx1 nCoV-19 boost in a healthy population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Two doses of an inactivated SARS-CoV-2 vaccine (CoronaVac) have been shown to be insufficient to protect against variants of concern (VOCs), while viral vector vaccines remain protective against the infection. Herein, we conducted a preliminary study to evaluate the safety and immunity in an adult population who received the conventional 2 dosage-regimen of inactivated SARS-CoV-2 vaccine; with an additional intradermal ChAdOx1 nCoV-19 reciprocal dosage (1:5). An Intramuscular ChAdOx1 nCoV-19 booster was also included as a control. Immediate and delayed local reactions were frequently observed in the fractional intradermal boost, but systemic side effects were significantly decreased compared to the conventional intramuscular boost. The anti-RBD-IgG levels, the neutralising function against delta variants, and T cell responses were significantly increased after boosting via both routes. Interestingly, the shorter interval elicited higher immunogenicity compared to the extended interval. Taken together, a reciprocal dosage of intradermal ChAdOx1 nCoV-19 booster reduces systemic adverse reactions and enhances non inferiority humoral and cellular immune responses compared to a full dose of intramuscular boosting. These findings provide for an effective vaccine management during the shortages of vaccine supply.

Immunogenicity and Safety of an Intradermal BNT162b2 mRNA Vaccine Booster after Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthy Population.

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.

National Early Warning Score (NEWS) at ICU discharge can predict early clinical deterioration after ICU transfer.

OBJECTIVE: This study aims to determine the ability of the National Early Warning Score at ICU discharge (NEWSdc) to predict the development of clinical deterioration within 24h. METHODS: A prospective observational study was conducted. The NEWS was immediately recorded before discharge (NEWSdc). The development of early clinical deterioration was defined as acute respiratory failure or circulatory shock within 24h of ICU discharge. The discrimination of NEWSdc and the best cut off value of NEWSdc to predict the early clinical deterioration was determined. RESULTS: Data were collected from 440 patients. The incidence of early clinical deterioration after ICU discharge was 14.8%. NEWSdc was an independent predictor for early clinical deterioration after ICU discharge (OR 2.54; 95% CI 1.98-3.26; P<0.001). The AUROC of NEWSdc was 0.92±0.01 (95% CI 0.89-0.94, P<0.001). A NEWSdc>7 showed a sensitivity of 93.6% and a specificity of 82.2% to detect an early clinical deterioration after ICU discharge. CONCLUSION: Among critically ill patients who were discharged from ICU, a NEWSdc>7 showed the best sensitivity and specificity to detect early clinical deterioration 24h after ICU discharge.

Quality of Dying in the Medical Intensive Care Unit: Comparison between Thai Buddhists and Thai Muslims.

BACKGROUND AND AIMS: Religious belief is an important aspect that influences the life of a patient, especially in Asia. We aim to compare the quality of death in an Intensive Care Unit (ICU) between Buddhists and Muslims from the perspectives of the relatives of the patients and the nurses and physicians. SUBJECTS AND METHODS: This was a cohort study of critically ill patients who died after admission to a medical ICU in Songklanagarind Hospital in Thailand between 2015 and 2016. We interviewed by telephone the relatives of patients. The nurses and physicians who cared for the patients responded to a self-questionnaire. RESULTS: A total of 112 patients were enrolled in the study. The quality of death and dying-1 scores in Thai Buddhists and Muslim patients rated by the relatives (8 vs. 8, P = 0.55), nurses (8 vs. 8, P = 0.28), and physicians (7 vs. 7, P = 0.74) were not different. The ratings by the nurses correlated with the relatives (rs = 0.41, P < 0.001) but did not correlate with the physicians (rs = 0.15, P = 0.12). Compared with Buddhist patients, Muslim patients were more likely to have documentation in place at the time of the death of do not resuscitate (100% vs. 80.2%, P = 0.02) and withholding and withdrawing life support (100% vs. 80.2%, P = 0.02). CONCLUSION: There was no difference in the quality of dying and death between Thai Buddhists and Muslims. However, some elements of palliative care were not similar.