Molnupiravir versus favipiravir in at-risk outpatients with COVID-19: A randomized controlled trial in Thailand.

OBJECTIVES: Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. METHODS: In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. RESULTS: Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (-1.0%; Newcombe 95.2% CI: -2.4% to -0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). CONCLUSIONS: Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. THAI CLINICAL TRIALS REGISTRY ID: TCTR20230111009.

A randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV).

BACKGROUND: The efficacy of the viral clearance and clinical outcomes of favipiravir (FPV) in outpatients being treated for coronavirus disease 2019 (COVID-19) is unclear. Ivermectin (IVM), niclosamide (NCL), and FPV demonstrated synergistic effects in vitro for exceed 78% inhibiting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) replication. METHODS: A phase 2, open-label, 1:1, randomized, controlled trial was conducted on Thai patients with mild-to-moderate COVID-19 who received either combination FPV/IVM/NCL therapy or FPV alone to assess the rate of viral clearance among individuals with mild-to-moderate COVID-19. RESULTS: Sixty non-high-risk comorbid patients with mild-to-moderate COVID-19 were randomized; 30 received FPV/IVM/NCL, and 30 received FPV alone. Mixed-effects multiple linear regression analysis of the cycle threshold value from SARS-CoV-2 PCR demonstrated no statistically significant differences in viral clearance rates between the combined FPV/IVM/NCL therapy group and the FPV-alone group. World Health Organization Clinical Progression scores and symptomatic improvement did not differ between arms on days 3, 6, and 10, and no adverse events were reported. No patients required hospitalization, intensive care unit admission, or supplemental oxygen or died within 28 days. C-reactive protein on day 3 was lower in the FPV/IVM/NCL group. CONCLUSION: Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects. TRIAL REGISTRATION: TCTR20230403007, Registered 3 April 2023 - Retrospectively registered,https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20230403007.

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.

The real-world effectiveness of fluvoxamine therapy in mild to moderate COVID-19 patients; A historical cohort study (Fluvoxa Trial).

BACKGROUND: Fluvoxamine (FVX) has been proposed as a potential treatment for severe COVID-19 by the σ-1 receptor agonist, which can reduce cytokine production. However, the efficacy of FVX remains controversial. METHODS: A historical retrospective cohort study was conducted in mild to moderate COVID-19 patients, 2:1 ratio of standard of care (SOC) and FVX treatments to assess the effectiveness of FVX in preventing deterioration by the fifth day of treatment. RESULTS: Of 752 eligible patients, 234 received FVX while 518 received SOC, and there was no significant difference in the effectiveness of FVX and SOC in preventing clinical deterioration. On the fifth day after treatment, 86.1 % of patients in the FVX-treated group did not experience clinical deterioration compared to 78.7 % in the SOC group. Notably, the FVX group had higher rates of pneumonia development and hospitalization, requiring more oxygen supplementation while showing less reduction in viral shedding than the SOC group. However, no difference in mechanical ventilation use, ICU admission, and survival was observed. CONCLUSION: Fluvoxamine treatment is failed to demonstrate effectiveness in preventing deterioration in mild to moderate COVID-19 and may lead to a higher incidence of pneumonia, hospitalization, and oxygen supplementation, necessitating careful consideration before prescribing the drug for COVID-19.

The immunogenicity of the ChAdOx1 nCoV-19 vaccination in participants with underlying comorbidity diseases: A prospective cohort study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases mortality rates in older adults and those with comorbidities. Individuals with certain comorbidities may have a poor immune response and require early booster vaccines. We aimed to assess the immune response after two doses of ChAdOx1 nCoV-19 vaccine, at 84-day intervals, in participants with the following comorbidities; diabetes mellitus; obesity; cardiovascular disease; chronic kidney disease; rheumatological disease; cirrhosis; hematological disease; hematological malignancy; or solid malignancy. The study was conducted at Chulabhorn Hospital in Thailand, with healthy healthcare workers serving as the control group. Of the 769 participants, 352 were in the healthy cohort and 417 were in the comorbidity cohort, all received at least one dose of vaccine. Anti-RBD total antibody levels were evaluated on Day 0, Day 84, and Day 112. The results at Day 112 (4 weeks after the second dose) showed that individuals with comorbidities had a poor immune response compared to healthy individuals, especially those with hematological malignancy and solid malignancy. The geometric mean concentration (GMC) of anti-RBD antibody in the comorbidity cohort was significantly lower than that in the healthy cohort: 433.66 BAU/ml (95% CI 334.62-562.01) versus 1096.14 BAU/ml (95% CI 1010.26-1189.33), respectively. The geometric mean ratio (GMR) between the two cohorts was 0.40 (95% CI 0.30-0.52, p < .001). This study concluded that individuals with comorbidities, particularly hematological and solid malignancies, had poor immune responses and may require an early booster vaccine to prevent infection and death.

Favipiravir treatment in non-severe COVID-19: promising results from multicenter propensity score-matched study (FAVICOV).

This study aimed to evaluate the efficacy of favipiravir (FPV) in preventing the development of severe COVID-19 in patients with mild-to-moderate symptoms. The study evaluated 1037 COVID-19 patients treated with FPV or standard treatment between April and September 2021, analyzed by propensity score matching. 149 patients were included in each arm after propensity score matching. The clinical outcomes showed no deterioration of the WHO clinical progression scale in the FPV group compared to the standard treatment group on day 5 (83.2% vs. 69.1%, p < 0.001). The WHO clinical progression scale also showed improvements on day 14 in the FPV group compared to the standard treatment group (66.4% vs. 46.3%, p < 0.001). The rates of oxygen supplementation and hospitalization were significantly lower in the FPV group compared to the standard treatment group (0% vs. 12.1% and 0.7% vs. 17.4%, respectively, p < 0.001 for both). There were no differences in adverse events between the two groups. The study highlights the effectiveness of FPV in preventing severe COVID-19 and hospitalization in patients with mild-to-moderate symptoms. The findings emphasize the importance of personalized treatment plans for COVID-19 patients, starting FPV treatment early, and adjusting dosages based on ethnicity and body weight.

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.

Efficacy of combination therapy of fluvoxamine and favipiravir vs favipiravir monotherapy to prevent severe COVID-19 among mild to moderate COVID-19 patients: Open-label randomized controlled trial (EFFaCo study).

OBJECTIVES: Fluvoxamine (FVX) is an antidepressant proposed to its immunomodulatory effects in preventing deterioration in mild and moderate COVID-19. METHODS: An open-label, 1:1 randomized controlled trial was assigned either combination therapy 50 mg twice daily of FVX for 10 days and favipiravir (FPV) or FPV alone to assess the efficacy in preventing disease progression in mild to moderate COVID-19 on the 5th day. RESULTS: In total, 134 patients with mild COVID-19 received FPV and 132 received FVX/FPV, 31 patients with moderate COVID-19 received FPV/dexamethasone (FPV/Dex), and 30 received FVX/FPV/Dex. The intention-to-treat (ITT) analysis showed no difference of no clinical deterioration on the 5th day in both mild COVID-19 (100% in FPV vs 97% in FVX/FPV) and moderate COVID-19 (83.9% in FPV/Dex vs 86.7% in FVX/FPV/Dex). However, there was a low rate of oxygen supplemental, hospitalization, or intensive care in both groups and zero death in all groups. No significant difference in oxygen supplemental, hospitalization, radiological, virological, or biochemical outcomes, and the immunomodulatory effect was observed between the group. CONCLUSION: The combined fluvoxamine treatment did not add benefit in preventing deterioration in patients with mild to moderate COVID-19 without the immunomodulatory effect observed, although it demonstrated low hospitalization rates, oxygen supplemental, intensive care needed, and zero mortality. TRIAL REGISTRATION: Thai clinical trials registry (TCTR) no. 20210615002.

The Real-World Clinical Outcomes of Favipiravir Treatment with Telemedicine Monitoring in Preventing Disease Progression in Mild to Moderate COVID-19 Patients; A Retrospective Cohort Study.

Background: Favipiravir has complex pharmacokinetics, and varied efficacy has been reported in treating COVID-19. Telehealth and telemonitoring are disruptive challenges used for COVID-19 care during pandemics. Objective: This study aimed to assess the outcome of favipiravir treatment to prevent clinical deterioration in mild to moderate COVID-19 cases with adjunctive telemonitoring during the COVID-19 surge. Methods: This was a retrospective observational study of PCR-confirmed mild to moderate COVID-19 cases subjected to home isolation. Chest computed tomography (CT) was performed in all cases, and favipiravir was administrated. Results: This study involved 88 PCR-confirmed COVID-19 cases. In addition, 42/42 (100%) cases were Alpha variants. COVID-19 pneumonia was found in 71.5% of the cases, according to chest X-rays and chest CT on the first visit. Favipiravir started 4 days after symptoms, which was part of the standard of care. The 12.5% of the patients required supplemental oxygen and intensive care unit admission rate was 1.1%; 1.1% required mechanical ventilation, and the rate of all-cause mortality was 1.1%, with a value of 0% of severe COVID-19 deaths. All mild illness cases showed no clinical deterioration or requirement for supplemental oxygen. No significant deterioration in either obesity or diabetes mellitus was observed. Conclusions: Favipiravir treatment for mild to moderate COVID-19 cases in outpatient settings, coupled with telemonitoring, was both safe and effective in preventing clinical deterioration, including the need for oxygen supplementation. This approach proved valuable during surges of COVID-19 cases.

Immunogenicity and reactogenicity of heterologous prime-boost vaccination with inactivated COVID-19 and ChAdOx1 nCoV-19 (AZD1222) vaccines, a quasi-experimental study.

The global supply of COVID-19 vaccines has been limited, and concerns have arisen about vaccine supply chain disruptions in developing countries. Heterologous prime-boost vaccination, which involves using different vaccines for the first and second doses, has been proposed to enhance the immune response. We aimed to compare the immunogenicity and safety of a heterologous prime-boost vaccination using an inactivated COVID-19 vaccine and AZD1222 vaccine with that of a homologous vaccination using AZD1222. This pilot involved 164 healthy volunteers without prior SARS-CoV-2 infection aged 18 years or older assigned to receive either the heterologous or homologous vaccination. The results showed that the heterologous approach was safe and well-tolerated, although the reactogenicity of the heterologous approach was higher. At 4 weeks after receiving the booster dose, the heterologous approach elicited a non-inferior immune response compared to the homologous approach in neutralizing antibody and cell-mediated immune response. The percentage of inhibition was 83.88 (79.72-88.03) in the heterologous and 79.88 (75.50-84.25) in the homologous group, a mean difference of 4.60 (-1.67-10.88). The geometric mean of interferon-gamma was 1072.53 mIU/mL (799.29-1439.18) in the heterologous group and 867.67 mIU/mL (671.94-1120.40) in the homologous group, a GMR of 1.24 (0.82-1.85). However, the binding antibody test of the heterologous group was inferior to the homologous group. Our findings suggest that the use of heterologous prime-boost vaccination with different types of COVID-19 vaccines is a viable strategy, especially in settings where vaccine supply is limited or where vaccine distribution is challenging.

Pharmacokinetic Comparison of Favipiravir Oral Solution and Tablet Formulations in Healthy Thai Volunteers.

This study compared the pharmacokinetics and safety of favipiravir oral solution with those of tablet formulations, which were agents repurposed to treat nonsevere coronavirus disease 2019 in Thailand. In an open-label, single-dose, randomized, crossover study, 24 healthy subjects under fasting conditions were randomly assigned to a single dose of 200 mg of favipiravir, either as an oral solution of 200 mg/15 mL (test product) or a tablet (reference product), separated by a 7-day washout period. Fifteen plasma samples were collected over 12 hours after drug administration. Plasma favipiravir levels were quantified using in-house developed ultra-high-performance liquid chromatography-tandem mass spectrometry. The test/reference geometric mean ratio along with 90%CI for the maximum plasma concentration, area under the concentration-time curve (AUC) to the time of the last quantifiable concentration, and AUC after single-dose administration, extrapolated to infinity were 115.3% (90%CI, 107.7%-123.3%), 100.4% (90%CI, 96.9%-104.0%), and 100.4% (90%CI, 96.8%-104.2%), respectively. These results were within the predefined acceptance criteria for bioequivalence (80.0%-125.0%). No adverse events were observed in either group. The oral solution formulation could offer the advantage of easier swallowing in broader patient groups.

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.

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.

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.

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.

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 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.

Abnormality Pattern of F-18 FDG PET Whole Body with Functional MRI Brain in Post-Acute COVID-19.

Purpose: The study aimed to investigate imaging abnormalities associated with post-acute COVID-19 using F-18 FDG PET/CT and PET/ rsfMRI brain. Methods: We retrospectively recruited 13 patients with post-acute COVID-19. The post-acute COVID-19 symptoms and neuropsychiatric tests were performed before F-18 FDG PET/CT whole body with PET/rsfMRI brain. Qualitative and semiquantitative analyses were also conducted in both whole body and brain images. Results: Among the 13 patients, 8 (61.5%) had myositis, followed by 8 (61.5%) with vasculitis (mainly in the thoracic aorta), and 7 (53.8%) with lung abnormalities.. Interestingly, one patient with a very high serum RBD IgG antibody demonstrated diffuse myositis throughout the body which potentially associated with immune-mediated myositis. One patient experienced psoriasis exacerbation with autoimmune-mediated after COVID-19. Most patients had multiple areas of abnormal brain connectivity involving the frontal and parieto-temporo-occipital lobes, as well as the thalamus. Conclusion: The whole body F-18 FDG PET can be a potential tool to assess inflammatory process and support the hyperinflammatory etiology, mainly for lesions in skeletal muscle, vascular wall, and lung, as well as, multiple brain abnormalities in post-acute COVID-19. Nonetheless, further studies are recommended to confirm the results.

Alterations in 18F-FDG PET/MRI and 15O-Water PET Brain Findings in Patients With Neurological Symptoms After COVID-19 Vaccination: A Pilot Study.

PURPOSE: This study aimed to investigate functional abnormalities in the brain of patients with neurological adverse effects following COVID-19 (coronavirus disease 2019) vaccination using 18F-FDG PET/MRI and 15O-water PET. METHODS: Eight patients (1 man and 7 women, aged 26-47 years [median age, 36.5 years]) who experienced neurological symptoms after the first COVID-19 vaccination underwent CT, MRI, 18F-FDG PET/MRI, and 15O-water PET of the brain. After 7 days, each patient underwent a follow-up 18F-FDG PET/MRI and 15O-water PET of the brain. Imaging data were analyzed using visual and semiquantitative analyses, which included a cluster subtraction workflow (P = 0.05). RESULTS: There was no evidence of vascular abnormalities, acute infarction, or hemorrhage on the CT or MRI scans. On the 15O-water PET images, 1 patient had mildly significant decreases in perfusion in the bilateral thalamus and bilateral cerebellum, and another patient showed a diffuse increase in perfusion in the cerebral white matter. The visual and semiquantitative analyses showed hypometabolism in the bilateral parietal lobes in all 8 patients on both the first and follow-up 18F-FDG PET/MRI scans. Metabolic changes in the bilateral cuneus were also observed during the first visit; all patients exhibited neurological symptoms. Moreover, 6 patients showed hypometabolism, and 2 patients showed hypermetabolism. CONCLUSION: All regions of metabolic abnormality were part of the fear network model that has been implicated in anxiety. Our study findings support the concepts of and provide evidence for the immunization stress-related response and the biopsychosocial model.