Unveiling therapeutic dynamics: An in-depth comparative analysis of neutralizing monoclonal antibodies and favipiravir in alleviating COVID-19 outpatients impacts among middle-aged and special populations (MA-FAST).

BACKGROUND: Neutralizing monoclonal antibodies (NMabs) are recognized for their efficacy against non-severe COVID-19. However, spike protein mutations may confer resistance. This study evaluates the effectiveness of favipiravir (FPV) versus NMabs in preventing severe COVID-19 in special populations. METHODS: A retrospective cohort was conducted on middle-aged, elderly, diabetic, or obese patients with COVID-19 treated with either FPV or NMabs. Propensity score matching (PSM) was used for analysis. RESULTS: The study included 1410 patients, resulting in four cohorts: middle-aged (36), elderly (48), diabetic (46), and obese (28) post-PSM. No significant differences were noted in 28-day emergency department (ED) visits across all groups between NMabs and FPV treatments, despite lower immunity in the FPV group. However, the diabetic group treated with FPV had higher 28-day hospitalization and oxygen supplemental, with no differences in the other groups. Intensive care unit (ICU) admissions, invasive mechanical ventilation, and mortality rates were similar between the two treatments. CONCLUSIONS: Early dose-adjusted FPV showed no difference from NMabs in preventing ED visits, ICU admissions, ventilator needs, or mortality among patients with major comorbidities. Diabetic patients on FPV experienced higher hospitalizations and oxygen needs, with no observed differences in other groups. FPV may be a viable alternative, especially in settings with limited resources.

Effect of Corticosteroid on Immunogenicity of SARS-CoV-2 Vaccines in Patients With Solid Cancer.

PURPOSE: Corticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed. METHODS: This was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti-spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level. RESULTS: Among the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti-S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti-S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti-SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL. CONCLUSION: Patients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed.

Sonographic appearance of focal liver lesions and likelihood of hepatocellular carcinoma in adult Thais with chronic hepatitis B virus infection.

PURPOSE: The objective of our study was to study and compare the sonographic findings of hepatocellular carcinoma (HCC) and benign liver lesions, and apply these to an HCC surveillance program in patient with chronic hepatitis B virus (HBV). METHODS: Sonographic findings of HCC and benign liver lesions were retrospectively reviewed following diagnosis based on either computer tomography or magnetic resonance imaging from July 2010 to December 2020. Multiple sonographic features were analyzed, including internal echogenicity, rim characteristics, and posterior acoustic enhancement. Associations between sonographic characteristics and HCC were assessed using uni- and multi-variate logistic regression analyses. RESULTS: Of the focal liver lesions in 337 chronic HBV patients, there were 25 HCC and 410 benign lesions, with median sizes of 1.6 and 1.0 cm, respectively. Three ultrasound patterns, homogeneous hypoechogenicity, heterogeneous echogenicity, and hypoechoic rims were more frequently found in HCC than in benign lesions. Moreover, the hypoechoic rim feature was the only sonographic pattern independently associated with HCC (Odds ratio, 68.05; 95% confidence interval, 7.37-628.10; p-values < 0.001). In a subgroup analysis of the lesions sized 2 cm or smaller, no sonographic findings were associated with HCC. CONCLUSION: A hypoechoic rim was a sonographic feature independently associated with HCC. These findings may aid in improving HCC detection and guiding management during HCC screening and surveillance with ultrasound.

Efficacy of combined COVID-19 convalescent plasma with oral RNA-dependent RNA polymerase inhibitor treatment versus neutralizing monoclonal antibody therapy in COVID-19 outpatients: a multi-center, non-inferiority, open-label randomized controlled trial (PlasMab).

IMPORTANCE: This pivotal study reveals that high neutralizing titer COVID-19 convalescent plasma therapy (CPT) combined with favipiravir (FPV) is non-inferior to sotrovimab in preventing hospitalization and severe outcomes in outpatients with mild-to-moderate COVID-19 and high-risk comorbidities. It underscores the potential of CPT-FPV as a viable alternative to neutralizing monoclonal antibodies like sotrovimab, especially amid emerging variants with spike protein mutations. The study's unique approach, comparing a monoclonal antibody with CPT, demonstrates the efficacy of early intervention using high neutralizing antibody titer CPT, even in populations with a significant proportion of elderly patients. These findings are crucial, considering the alternative treatment challenges, especially in resource-limited countries, posed by the rapidly mutating SARS-CoV-2 virus and the need for adaptable therapeutic strategies.

Efficacy of Andrographis paniculata extract treatment in mild to moderate COVID-19 patients being treated with favipiravir: A double-blind, randomized, placebo-controlled study (APFaVi trial).

BACKGROUND: While favipiravir had been the standard anti-SARS-CoV-3 drug for COVID-19 treatment in Thailand, the efficacy of favipiravir treatment is controversial. Andrographis paniculata extract (APE) inhibits viral entry, exhibits immunomodulatory effects, and proposes to have the potential for early-stage COVID-19 treatment. METHODS: A randomized, double-blind, placebo-controlled trial was performed in Thailand during June - September 2021. Non-severe COVID-19 patients were randomized 1:1 to groups receiving 180 mg/day of APE plus favipiravir (APE-FPV group) or placebo plus favipiravir (placebo-FPV group). Efficacy in preventing disease progression to severe COVID-19 was assessed on day 4, using World Health Organization Clinical Progression Scale (WHOCPS) score and visual analog scale (VAS) for acute respiratory tract infection symptoms. RESULTS: Of 146 patients, there were 73 patients in each group. Non-deterioration of WHOCPS scores on day 4 was 98.63% versus 97.26% of patients in the APE-FPV and placebo-FPV groups (p = 1.000). No difference in supplemental oxygen, hospitalization, and death was shown in both groups. The oxygen supplemental was 4.11% in the placebo-FPV group. The interleukin (IL)-1ß was significantly lower in the APE than in the placebo-FPV group throughout the study. We found no difference in virologic outcomes between groups and no substantial adverse events. CONCLUSIONS: APE treatment did not demonstrate additional clinical and virological benefits in patients with mild to moderate COVID-19 being treated with favipiravir. Early reduction of IL-1ß with APE may be advantageous in preventing cytokine storms in severe COVID-19 and requires further study.

Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective cohort study.

Protection against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection of inactivated vaccines is not well characterized in people with comorbidities, who are at high risk of severe infection. We compared the risk of SARS-CoV-2 infection after complete vaccination with Sinopharm/BBIBP in people with comorbidities (e.g., autoimmune diseases, cardiovascular disease, chronic lung disease, and diabetes) with healthy individuals using a Cox-proportional hazard model. In July-September 2021, a total of 10 548 people (comorbidities, 2143; healthy, 8405) receiving the complete primary series of vaccination with Sinopharm/BBIBP in Bangkok, Thailand were prospectively followed for SARS-CoV-2 infection through text messaging and telephone interviewing for 6 months. A total of 295 infections from 284 participants were found. HRs (95% CI) of individuals with any comorbidities did not increase (unadjusted, 1.02 (0.77-1.36), P = 0.89; adjusted, 1.04 (0.78-1.38), P = 0.81). HRs significantly increased in the subgroup of autoimmune diseases (unadjusted, 2.64 (1.09-6.38), P = 0.032; adjusted, 4.45 (1.83-10.83), P = 0.001) but not in cardiovascular disease, chronic lung disease, or diabetes. The protection against SARS-CoV-2 infection of the Sinopharm vaccine was similar in participants with any comorbidities vs. healthy individuals. However, the protection appeared lower in the subgroup of autoimmune diseases, which may reflect suboptimal immune responses among these people.

Dynamics of anti-RBD (anti-receptor binding domain) levels in diabetes patients following the ChAdOx1 nCoV-19 vaccine (AZD1222) in the Thai population.

The ChAdOx1 nCoV-19 vaccine (AZD1222) was used in Thailand during the early outbreak of coronavirus disease 2019 (COVID-19). A previous study showed a low immune response in diabetes patients after the first dose of the AZD1222 vaccine. Furthermore, humoral immune responses after the second vaccination were inconsistent. This study evaluated the immunogenicity following the first and second doses of the AZD1222 vaccine in people with type 2 diabetes (T2D) compared with the general population of Thailand. This was a prospective, single-center cohort study. 59 adults with T2D and 118 age- and sex-matched healthcare personnel were eligible. The participants received two doses of AZD1222 12 weeks apart. Antibodies against the receptor-binding domain (anti-RBD) of the SARS-CoV-2 spike protein, using an automated electrochemiluminesence immunoassay (ECLIA), were measured at baseline, 8 and 12 weeks after the first dose of vaccine, and 4 weeks after the second dose of vaccine. The anti-RBD levels were reported as the geometric mean concentration (GMC) and compared between groups using the geometric mean ratio (GMR). A total of 177 participants were included: The average age of 59 T2D patients was 60.1 years (SD: 11.4), and 31 (52.5%) of them were female. The GMC of anti-RBD 8 and 12 weeks after the first vaccination were significantly lower in T2D (week 8 60; 17.05 BAU/mL, 95% confidence interval [CI] 11.1-26.19, P = 0.035, week 12; 24.68 BAU/mL, 95% CI 16.4-37.0, P = 0.002) than in those without diabetes (week 8; 29.79 BAU/mL, 95% CI 22.07-40.42, week 12; 50.67 BAU/mL, 95% CI 40.62-63.20). However, there was no difference in the GMC of anti-RBD 4 weeks after the second vaccination among groups (T2D; 687.95 BAU/mL, 95% CI 462.7-1022.7, Normal; 697.95 BAU/mL, 95% CI 583.7-834.5, P = 0.947). In both groups, the GMC of anti-RBD was persistently high without decline 12 weeks after the first vaccination. Albuminuria was a major factor related to low humoral immune responses in T2D patients after the second dose of AZD122 vaccine (the GMR was 0.29, 95% CI 0.08-0.98, P = 0.047) whereas the HbA1C level and age were not. Immunogenicity in T2D cases was lower than in the normal population after the first dose of the AZD1222 vaccine. The two doses of AZD122 vaccine induced immunity in T2D equal to that of normal individuals in Thailand. People with diabetes should be boosted as soon as possible to induce adequate immunity to prevent COVID-19 infection.

Immune Response to CoronaVac and Its Safety in Patients with Type 2 Diabetes Compared with Healthcare Workers.

BACKGROUND: Vaccines for SARS-CoV-2 have been critical for preventing disease. Previous research showed patients with diabetes have impaired immunity. This study aimed to determine the immunity to coronavirus after CoronaVac by comparing patients with type 2 diabetes (T2D) and healthcare workers (HCW). MATERIALS AND METHODS: A prospective cohort study evaluated immune responses and safety after two doses of CoronaVac in T2D and HCW groups at Chulabhorn Hospital. The levels of total antibodies against the receptor-binding domain (anti-RBD) of the SARS-CoV-2 spike protein at baseline and 4 weeks after vaccination were collected. The level of anti-RBD concentrations was reported as geometric mean concentration (GMC) and compared between groups using the geometric mean ratio (GMR). RESULTS: 81 participants were included; 27 had T2D and 54 were HCW. After complete vaccination, anti-RBD concentrations were not significantly different between T2D (57.68 binding antibody units (BAU)/mL, 95% confidence interval (CI) = 29.08; 114.44) and HCW (72.49 BAU/mL, 95% CI = 55.77; 94.22) groups. Subgroup analysis showed the GMC of anti-RBD was significantly lower in T2D patients with dyslipidaemia (50.04 BAU/mL) than in T2D patients without dyslipidaemia (341.64 BAU/mL). CONCLUSIONS: The immune response at 4 weeks after two doses of CoronaVac did not significantly differ between patients with T2D and HCW.

Observational study investigating the relationship between maxillomandibular characteristics and temporomandibular disc conditions in female patients with a skeletal class III pattern.

OBJECTIVES: The objective of this study was to analyze the relationship between maxillomandibular characteristics and the severity of temporomandibular disc displacement in female patients with a skeletal class III (SKIII) pattern. METHODS: Fifty-seven samples were included in the study. The evaluation of articular disc conditions was conducted using magnetic resonance imaging, while 25 cephalometric variables from lateral and postero-anterior (P-A) cephalograms were measured to determine their maxillomandibular characteristics. The samples were categorized into three groups based on the articular disc conditions: (1) normal disc position (NDP), (2) disc displacement with reduction (DDwR), and (3) disc displacement without reduction (DDwoR). The relationship between the maxillomandibular characteristics and disc conditions was examined through both basic statistical analysis and multivariate analysis using principal component analysis (PCA). RESULTS: The Kruskal-Wallis and Dunn-Bonferroni tests revealed a significant difference between the groups in terms of the deviation of mandibular characteristics observed on the P-A cephalogram. The DDwoR group exhibited significantly larger menton deviation, ramal height asymmetry index, and total mandibular length asymmetry index compared to the NDP and DDwR groups. Moreover, the PCA successfully extracted all cephalometric variables into eight principal components. Among them, only the principal component related to mandibular asymmetry was able to differentiate the SKIII samples with DDwoR from the other groups. CONCLUSIONS: The findings of this study highlight a significant relationship between mandibular asymmetry and the severity of disc displacement, particularly DDwoR, in female patients with a SKIII pattern.

SARS-CoV-2 seroprevalence among cancer patients and household caregivers in a cancer hospital: Cross-sectional survey after the second COVID-19 wave in Thailand.

Objectives: Patients with cancer may be at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience more severe outcomes. Low vaccine coverage in the early phase of the coronavirus disease 2019 (COVID-19) pandemic meant that personal and social measures to reduce viral spread were the only methods of lowering the risk of infection among cancer patients. This study explored the prevalence of SARS-CoV-2 antibodies in cancer patients and caregivers in a cancer hospital after the second COVID-19 outbreak in Thailand. Study design: Cross-sectional study. Methods: A SARS-CoV-2 seroprevalence cross-sectional survey was conducted among 200 cancer patients and 200 household caregivers in a tertiary cancer care hospital in Bangkok, Thailand. The survey took place between 4 March and May 31, 2021 - a time period covering the end of the second COVID-19 wave and the early phase of the third wave in Thailand. Results: Rigorous personal and social measures to reduce viral spread among cancer patients and caregivers lead to an extremely low prevalence of SARS-CoV2 infection (0% among cancer patients and 1% among household caregivers). Conclusion: This study demonstrates the importance of social distancing and personal hygiene measures for the prevention of SARS-CoV-2 infection, even when vaccine coverage is low.

The clinical outcomes of high neutralizing antibodies titer convalescent plasma therapy in early developed severe COVID-19 patients; a case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes life-threatening pneumonia. Convalescent plasma therapy (CPT) is expected to be the effective COVID-19 treatment for passive immunity. The high neutralizing antibodies titer of CPT is needed to prove the benefit in early developed severe COVID-19. OBJECTIVE: This case-control study evaluated transfusion efficacy and adverse events with high-titer (≥ 1:320) COVID-19 convalescent plasma compared with standard care alone in severe COVID-19 pneumonia. RESULTS: Among 107 severe COVID-19 patients, 55 received CPT plus standard care, and 52 received standard care alone. All-cause mortality was 15.3% in the CPT group compared with 85.4% in the standard care group (p < 0.001). Univariate and multivariate analyses revealed reduced mortality with CPT (HR 0.14; 95% CI 0.07-0.31; p < 0.001 and HR 0.26; 95% CI 0.08-0.79; p = 0.018, respectively). CPT resulted in decreased use of mechanical ventilation, duration of supplemental oxygen, and high-flow oxygen requirement. Clinical and radiological outcomes improved. CONCLUSIONS: Immediate high neutralizing antibody titer CPT is safe and reduces mortality in early developed severe COVID-19 patients. The benefit of CPT in the early course of illness is challenging and requires additional study. Trial registration Thai clinical trials registry (TCTR) no. 20220101003.

Safety after BBIBP-CorV (Sinopharm) COVID-19 Vaccine in Adolescents Aged 10-17 Years in Thailand.

Coronavirus disease 2019 affected child health and impacted learning because of the resulting onsite school closures. This prospective cohort study included children aged 10-17 who received two 4 µg doses of BBIBP-CorV administered intramuscularly 21-28 days apart. To assess vaccine safety, 36,808 participants were then followed with paper- and web-based online questionnaire surveys that captured local and systemic reactogenicities following vaccine administration on days 1, 7, and 30. Among participants, 76% (27,880) reported reactogenicity within the first 24 h and 7 days following the first dose. Half (51.41%) of participants experienced pain at the injection site; the majority of cases were mild in severity. Injection site tenderness (37.93%) was another common local reaction. Fatigue (37.89%), myalgia (33.56%), and headache (26.76%) were the most common systemic reactions. On days 2-7 after the first dose, 25.85% of participants experienced adverse reactions. Following the second dose, reactogenicity was 7.6% and 1.09% within 24 h and between days 2-7. The majority of reactions were of mild to moderate severity. We report that two doses of the BBIBP-CorV caused mild to moderate side effects in adolescents in Thailand. The findings confirm the vaccine's safety profile in this age group.

Effect of Inactivated SARS-CoV-2 Vaccines and ChAdOx1 nCoV-19 Vaccination to Prevent COVID-19 in Thai Households (VacPrevent trial).

OBJECTIVES: SARS-CoV-2 is primarily transmitted within households, with massive healthcare system burdens. The role of inactivated vaccines and ChAdOx1 nCoV-19 vaccination in the prevention of within-household transmission remains unknown. METHODS: This observational case-control study tracked 408 SARS-CoV-2 polymerase chain reaction-confirmed index cases from April to September 2021. This study aimed to prove the benefit of inactivated and ChAdOx1 nCoV-19 vaccinated index cases in preventing within-household transmissibility. RESULTS: A total of 1178 household contacts were investigated. A total of 231 index cases were vaccinated with inactivated or ChAdOx1 nCoV-19 vaccine, and 177 were unvaccinated. The vaccinated index cases exhibited a 7.8% risk reduction in household transmission. There was no difference in the secondary attack rate of 50.77% in unvaccinated cases compared with 46.81% in vaccinated index cases (P-value = 0.177). Those who completed the two-dose SARS-CoV-2 vaccination demonstrated a 93% reduction in household transmissibility within 14-90 days. The effectiveness for preventing household transmission was 26.09%. The 87% reduced risk of household transmissibility was observed among those who wore masks. CONCLUSION: The completed two-dose SARS-CoV-2 inactivated and ChAdOx1 nCoV-19 vaccination within 14-90 days among index cases demonstrated benefits in preventing within-household transmissibility. Implementing high-efficacy vaccination and an appropriate booster dose can prevent household transmission.

Reactogenicity, immunogenicity, and humoral immune response dynamics after the third dose of heterologous COVID-19 vaccines in participants fully vaccinated with inactivated vaccine.

INTRODUCTION: Immunogenicity after the CoronaVac vaccine remains uncertain, especially regarding infections with the coronavirus variants of concern and waning immunity. METHODS: This was a single-center, open-label clinical trial designed to assess the immunogenicity and safety of BBIBP-CorV, AZD1222, or BNT162b2 as the third vaccination. The key eligible criteria were individuals at least 18 years old who were fully vaccinated with two doses of CoronaVac vaccine for 2-4 months. The primary endpoint was the ratio of the geometric mean concentration (GMC) of the total anti-receptor binding domain (RBD) antibody post-vaccination compared with that pre-vaccination. The secondary endpoint was reactogenicity within 7 days. RESULTS: Forty-one participants received AZD1222, 40 received BBIBP-CorV, and 40 received BNT162b2. The GMC of anti-RBD antibody at 2 weeks post-vaccination was 31,138.67 binding antibody units (BAU)/mL for BNT162b2, 6,412.10 BAU/mL for AZD1222, and 1,092.7 BAU/mL for BBIBP-CorV. Compared with pre-vaccination, the ratio of anti-RBD concentration was 690.24 for BNT162b2, 130.02 for AZD1222, and 17.79 for BBIBP-CorV. No potentially life-threatening adverse reaction were observed within 7 days. CONCLUSION: A third vaccination with the heterologous vaccine, BBIBP-CorV, AZD1222, or BNT162b2, can elicit a robust immune response, without serious adverse events in participants fully vaccinated with the CoronaVac vaccine.

Study of CALR, MPL, and c-kit Gene Mutations in Thai Patients with JAK2 V617F Negative Myeloproliferative Neoplasms.

OBJECTIVE: The aim of this study to determine the prevalence of CALR, MPL and c-kit gene mutations in JAK2 V617F negative-MPN patients. METHODS: The retrospective study of CALR, MPL and c-kit mutations were analyzed in 113 samples collected from March 2010 to May 2017 and identified as JAK2 V617F-negative MPN Thai patients. The samples were analysis by gel electrophoresis and direct sequencing. RESULTS: 28.3% of JAK2 V617F-negative MPN patients showed CALR gene mutations. Within the MPN patients with CALR mutation, 46.9% were classified as essential thrombocythemia (ET) and 20.9% were classified as primary myelofibrosis (PMF). Previous studies classified CALR mutations into three types using negatively charged amino acid stretches at the C-terminal domain. Type 1-like mutations were observed in 12 of 49 (24.5%) ET patients and type 2-like mutations were observed in 10 of 49 (20.4%) patients. In addition, 8 of 43 (18.6%) PMF patients showed type 1-like mutations and 1 of 43 (2.3%) showed type 2-like CALR mutation. Interestingly, platelet counts were higher in patients with CALR gene mutation than in patients without CALR gene mutation. MPL mutations (W515K and W515L) were identified in 2 of 109 (1.8%) MPN patients; the MPL mutations were only found in ET patients, which was consistent with previous studies. We did not detect exon 17 c-kit mutation in JAK2-negative MPN patients but detected intronic single nucleotide polymorphisms at c.74,978 and c.75,255 in these samples. Approximately 66% of patients did not have mutations in CALR and MPL genes, in addition to lacking JAK2 gene mutation, and these cases are classified as triple-mutations. CONCLUSION: Our results showed that 66% of cases were triple-negative mutation MPN because they lacked mutations in JAK2, CALR and MPL genes. The frequencies of CALR and MPL mutation in this study are similar to other CALR and MPL patient data.

Safety and Immunogenicity of the BBIBP-CorV Vaccine in Adolescents Aged 12 to 17 Years in the Thai Population: An Immunobridging Study.

Adolescents can develop a severe form of Coronavirus disease 2019 (COVID-19), especially with underlying comorbidities. No study has examined the efficacy or effectiveness of inactivated COVID-19 vaccines in adolescents. This single-center, prospective cohort study was performed to evaluate the safety and effectiveness of an inactivated COVID-19 vaccine in adolescents using the immunobridging approach at Chulabhorn Hospital. The key eligibility criterion was a healthy clinical condition or stable pre-existing comorbidity. The anti-receptor-binding domain (anti-RBD) antibody concentration at 4 weeks after dose 2 of the vaccine was compared between participants aged 12 to 17 years and those aged 18 to 30 years. Safety profiles included adverse events within 7 days after each dose of the vaccine and any adverse events through 1 month after dose 2 of the vaccine. In the adolescent and adult cohorts, the geometric mean concentration of anti-RBD antibody was 102.9 binding antibody unit (BAU)/mL (95% CI, 91.0−116.4) and 36.9 BAU/mL (95% CI, 30.9−44.0), respectively. The geometric mean ratio of the adolescent cohort was 2.79 (95% CI, 2.25−3.46, p < 0.0001) compared with the adult cohort, meeting the non-inferiority criterion. The reactogenicity was slightly lower in the adolescent than in the adult cohort. No serious adverse events occurred. The inactivated COVID-19 vaccine appears safe and effective in adolescents.

Oral vitamin A supplementation in preterm infants to improve health outcomes: A systematic review and meta-analysis.

OBJECTIVE: To determine the effects of oral vitamin A supplementation on clinical outcomes in preterm infants. DESIGN: We conducted the meta-analysis by searching PubMed/Medline, Scopus, Embase, CINAHL, and the Cochrane Library databases from inception to 12 August 2021, including reference lists of retrieved articles. Only randomized controlled trials (RCTs) evaluating the effects of oral vitamin A on premature babies were included. We used a random-effects model to calculate risk ratios (RRs) and weighted mean differences (MDs) with 95% confidence intervals (CIs). We used the GRADE approach to grade evidence quality and assess how oral vitamin A supplementation affects clinical outcomes. MAIN OUTCOMES MEASURES: The primary outcomes were respiratory outcomes, including the length of respiratory support, the need for oxygen at 36 weeks postmenstrual age (PMA), and moderate-to-severe bronchopulmonary dysplasia (BPD) at 36 weeks PMA. Secondary outcomes were hospitalization time, vitamin A status, mortality, other related outcomes, and potential adverse drug-related events. RESULTS: We included four RCTs, with 800 patients total. In all trials, oral vitamin A treatment was compared to a placebo. Oral vitamin A supplementation did not significantly affect mechanical ventilation duration (MD, -1.07 days; 95% CI, -2.98 to 0.83 days), oxygen requirement at 36 weeks PMA (RR, 0.65; 95% CI, 0.33 to 1.31), or moderate-to-severe BPD at 36 weeks PMA (RR, 0.53; 95% CI, 0.07 to 4.17). However, oral vitamin A supplementation yielded a slightly shorter noninvasive ventilation duration (MD, -0.96 days; 95% CI, -1.59 to -0.33 days). CONCLUSIONS: Administering oral vitamin A to preterm newborns did not alter the mechanical ventilation duration, oxygen needed at 36 weeks PMA, moderate-to-severe BPD at 36 weeks PMA, death, or short-term benefits. However, oral vitamin A supplementation may slightly affect the duration of noninvasive respiratory support without adverse drug-related events.

Persistence of immunogenicity, contributing factors of an immune response, and reactogenicities after a single dose of the ChAdOx1 (AZD1222) COVID-19 vaccine in the Thai population.

INTRODUCTION: Due to the vaccine's short supply and the efficacy of a single dose of the ChAdOx1 (AZD1222) vaccine, many governments delayed the interval between prime and boost dose from 4 to 8-12 weeks. However, the waning of immune response in this period is a concern. This study evaluated the durability, contributing factors of anti-RBD antibody concentration, and reactogenicities after the single dose of AZD1222 vaccine in the Thai population. METHODS: This was a single-center, prospective cohort study at Chulabhorn Hospital, Bangkok, Thailand. Individuals 18 years or older who were negative for anti-SARS-CoV-2 antibody were eligible. Anti- receptor-binding domain antibody concentrations were tested at least three weeks after the first vaccination and immediately before the second dose of vaccine. Information on reactogenicities was obtained via a questionnaire sent by a short message service. RESULTS: Anti-RBD Antibody concentration at 2 and 3 months post-vaccination were significantly higher than at 1 months post-vaccination (20.14 BAU/mL (95%CI; 16.37, 24.77) at 1 month, 48.08 BAU/mL (95%CI; 42.76, 54.08) at 2 month, and 65.01 BAU/mL (95%CI; 58.88,71.61) at 3 month). Adverse events occurred in approximately 60% of participants. Factors influencing vaccine immunogenicity include age, sex, the time elapsed from the first dose of vaccine, and underlying disease with diabetes and hematologic disease. CONCLUSION: A single dose of AZD1222 could elicit immune responses that did not decline within three months in Thai individuals. These data support the public health strategy of a delay between the prime and boost dose of AZD1222 of 4 to 12 weeks.

Immunogenicity and reactogenicity after heterologous prime-boost vaccination with CoronaVac and ChAdox1 nCov-19 (AZD1222) vaccines.

Mass vaccination with a safe and effective vaccine may be the best way to control the COVID-19 pandemic. Heterologous prime-boost vaccination with the CoronaVac and AZD1222 vaccines may increase the immunogenicity elicited by either vaccine alone. This study sought to compare the immunogenicity of a heterologous CoronaVac and AZD1222 prime-boost with a homologous CoronaVac prime-boost. From July 13 to September 2, 2021, 88 participants were enrolled in the study. Half (n = 44) of the participants were assigned to the AZD1222/CoronaVac cohort and half were assigned to the CoronaVac/AZD1222 cohort. Both cohorts had a prime-boost interval of 4 weeks. A control group of 136 health care personnel who received the homologous CoronaVac/CoronaVac prime-boost was matched by age and sex to the experimental cohorts. The primary endpoint was the geometric mean ratio (GMR) of the anti-receptor binding domain (RBD) antibody concentration 4 weeks after the booster dose was administered. The CoronaVac/CoronaVac cohort served as the reference group. Baseline age and sex were similar, and the median age was 42.5 years. The GMR was 2.58 (95% confidence interval [CI] 1.80-3.71) and 8.69 (95% CI 6.05-12.47) in the AZD1222/CoronaVac and CoronaVac/AZD1222 cohorts, respectively. Reactogenicity was similar following prime and booster doses with the same vaccine. Findings indicated that the heterologous CoronaVac and AZD1222 prime-boost combination elicited a more robust immune response than the homologous CoronaVac prime-boost. While both heterologous prime-boost combinations showed similar reactogenicity, the immunogenicity of the CoronaVac/AZD1222 cohort was higher, indicating that the order of prime-boost vaccine administration was important.

Immunogenicity and safety of an intradermal fractional third dose of ChAdOx1 nCoV-19/AZD1222 vaccine compared with those of a standard intramuscular third dose in volunteers who previously received two doses of CoronaVac: A randomized controlled trial.

INTRODUCTION: The CoronaVac vaccine is widely used in Thailand to combat the coronavirus disease 2019 (COVID-19) pandemic. The limited immunogenicity of this vaccine is a concern, especially because of expanding delta variant outbreaks. A third boost may enhance antiviral immune responses. METHODS: This non-inferiority randomized controlled trial evaluated the immunogenicity and safety of an intradermal (ID) fractional third dose of AZD1222 vaccine compared with those of a standard intramuscular (IM) third dose. Participants were enrolled from August 9, 2021 to August 13, 2021 at Chulabhorn Hospital, Bangkok, Thailand. The eligibility criteria were age 18 years or older and prior two-dose Coronavac vaccination completed at least 2 months previously. Participants were randomly assigned to one of three groups by block randomization: (i) standard dose by IM administration (IM), (ii) 20% of the standard dose ID (ID1), or (iii) 40% of the standard dose ID (ID2). The primary endpoint was the geometric mean ratio of anti-receptor binding domain antibody in the ID1/ID2 vs. the IM groups 14 days post-vaccination. RESULTS: A total of 125 participants were randomized (IM, n = 41; ID1, n = 41; and ID2, n = 43). One participant was lost to follow-up by day 14 post-vaccination in the ID1 group. The geometric mean ratio (95% confidence interval) of anti-receptor binding domain antibody was 0.94 (0.80-1.09) in the ID1 group and 1.28 (0.95-1.74) in the ID2 group. Immunogenicity in both ID groups met the non-inferiority criteria. Local adverse events were more common in the ID groups than in the IM group but were mostly mild to moderate in severity. CONCLUSION: An ID fractional third dose of AZD1222 was non-inferior to a standard IM third dose among individuals previously vaccinated with CoronaVac. Adverse events associated with the ID fractional third dose included mild to moderate local site reactions. This vaccination strategy may help conserve vaccine supply.