Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults.

BACKGROUND: We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019. METHODS: CoronaVac-immunized adults (18-72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events. RESULTS: In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182-227) and 939 IU/mL (95% CI, 841-1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95-5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240-325), 1044 IU/mL (95% CI, 898-1213), and 668 IU/mL (95% CI, 520-829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported. CONCLUSIONS: Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants. Clinical Trials Registration. NCT05188677.

SCB-2019 protein vaccine as heterologous booster of neutralizing activity against SARS-CoV-2 Omicron variants after immunization with other COVID-19 vaccines.

We assessed the non-inferiority of homologous boosting compared with heterologous boosting with the recombinant protein vaccine, SCB-2019, in adults previously immunized with different COVID-19 vaccines. Three equal cohorts (N ~ 420) of Philippino adults (18-80 years) previously immunized with Comirnaty, CoronaVac or Vaxzevria COVID-19 vaccines were randomized 1:1 to receive homologous or heterologous (SCB-2019) boosters. Neutralizing antibodies against prototype SARS-CoV-2 (Wuhan-Hu-1) were measured in all participants and against Delta variant and Omicron sub-lineages in subsets (30‒50 per arm) 15 days after boosting. Participants recorded solicited adverse events for 7 days and unsolicited and serious adverse events until Day 60. Prototype SARS-CoV-2 neutralizing responses on Day 15 after SCB-2019 were statistically non-inferior to homologous Vaxzevria boosters, superior to CoronaVac, but lower than homologous Comirnaty. Neutralizing responses against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants after heterologous SCB-2019 were higher than homologous CoronaVac or Vaxzevria, but lower than homologous Comirnaty. Responses against Omicron BF.7, BQ.1.1.3, and XBB1.5 following heterologous SCB-2019 were lower than after homologous Comirnaty booster but significantly higher than after Vaxzevria booster. SCB-2019 reactogenicity was similar to CoronaVac or Vaxzevria, but lower than Comirnaty; most frequent events were mild/moderate injection site pain, headache and fatigue. No vaccine-related serious adverse events were reported. Heterologous SCB-2019 boosting was well tolerated and elicited neutralizing responses against all tested SARS-COV-2 viruses including Omicron BA.1, BA.2, BA.4, BA.5, BF.7, BQ.1.1.3, and XBB1.5 sub-lineages that were non-inferior to homologous boosting with CoronaVac or Vaxzevria, but not homologous Comirnaty booster.

Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD. METHODS: Patients with COPD were randomized 1:1 to enter a 12-week treatment period and receive either oral roflumilast, 500 µg once daily, or placebo, following a single-blind, 4-week baseline period in which all patients received placebo. The primary end point was mean change in FEV1 from baseline to each postrandomization visit during the treatment period. Other spirometric lung function measurements were evaluated as secondary end points. COPD exacerbations were monitored. Safety was assessed from clinical laboratory tests, vital signs, physical examination (including electrocardiogram) and monitoring of adverse events (AEs). RESULTS: Of 551 patients recruited, 410 were randomized and received at least one dose of study medication (roflumilast, n = 203; placebo, n = 207). Superiority of roflumilast over placebo was demonstrated by a statistically significant difference in postbronchodilator FEV1 (79 mL, P < 0.0001). Other spirometry end points, including prebronchodilator FEV1, pre-and postbronchodilator FEV6, forced vital capacity and peak expiratory flow significantly favoured roflumilast over placebo. AEs were more common with roflumilast than with placebo, but were comparable with those reported in previous studies. CONCLUSIONS: Roflumilast, 500 µg once daily, improves pulmonary function in Asian patients with COPD. The safety and tolerability of roflumilast in this population was similar to that in a Caucasian population.

Burden of obstructive lung disease in a rural setting in the Philippines.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the prevalence of and risk factors associated with COPD in a rural setting in the Philippines. METHODS: The study was conducted in two municipalities in Nueva Ecija province in the Philippines. Using the Burden of Obstructive Lung Disease (BOLD) protocol and study design, non-hospitalized men or women, aged 40years or older, were recruited by multi-stage random sampling procedures. Participants completed questionnaires on respiratory symptoms and exposure to potential risk factors for COPD, including smoking, occupation and exposure to burning of biomass fuel. Spirometry was performed according to American Thoracic Society criteria. RESULTS: Of the 1188 individuals selected for recruitment, 722 had acceptable post-bronchodilator spirometry and were classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The overall prevalence of COPD for all stages was 20.8%. The prevalence of COPD at GOLD Stage I or higher was greater in men compared with women (26.5% vs 15.3%), and increased between the ages of 40 to >70years. Logistic regression analysis showed a significant association between all stages of COPD and farming for >40years (odds ratio (OR) 2.48, 95% confidence interval (CI): 1.43-4.30), use of firewood for cooking for >60years (OR 3.48, 95% CI: 1.57-7.71), a smoking history of ≥20 pack-years (OR 2.86; 95% CI: 1.78-4.60), and a history of tuberculosis (OR 6.31, 95% CI: 2.67-15.0). CONCLUSIONS: The prevalence COPD in a rural community in Nueva Ecija, Philippines was 20.8% for GOLD Stage I or higher, and 16.7% for GOLD Stage II or higher. In addition to smoking history, the use of firewood for cooking, working on a farm and a history of tuberculosis were significantly associated with fixed airflow obstruction, as assessed by spirometry.

The gastroprotective effect of tannins extracted from duhat (Syzygium cumini Skeels) bark on HCl/ethanol induced gastric mucosal injury in Sprague-Dawley rats.

The gastroprotective effect of quantified tannins (13.4%) from Syzygium cumini was determined. Gastric mucosal damage was induced in sixty eight rats by oral gavage administration of HCl/ethanol solution. For macroscopic and microscopic studies, 30 rats were divided into three groups consisting of a negative control, an Omeprazole group and a Tannins group. There was no significant difference in the number, size and surface area of macroscopic lesions between the three groups. Microscopic examination using Best's Ulcer Staging Index showed that Tannins had a very significant decrease in gastric mucosal damage with p<0.01. Average lymphocyte populations in the three groups showed no significant difference, although both the Tannins and Omeprazole group had fewer lymphocytes. Thirty-eight rats were studied for the amount of free radicals present after induction of gastric damage. A dose which consisted of 20.0 g tannins/kg rat weight showed significantly lower stomach free radical concentrations. These findings suggest that tannins extracted from S. cumini have gastroprotective and anti-ulcerogenic effects.