The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial.

OBJECTIVES: To evaluate the immunogenicity of an extended interval regimen of BNT162b2 among healthy school-age children. METHODS: A randomized-control trial conducted among healthy Thai children aged 5-11 years. Participants received two doses of BNT162b2 with an 8-week (extended dosing) vs 3-week interval. Immunogenicity was determined by neutralization test (NT) against the Omicron variant, surrogate virus NT (sVNT; BA.1, % inhibition), and pseudovirus NT (BA.2, the half-maximal inhibition dilution or ID50). The third dose was offered to participants who had sVNT <68% inhibition. The immunogenicity outcome was evaluated at 14 days after the second and third doses. RESULTS: During February to April 2022, 382 children with a median age (interquartile range) of 8.4 years (6.6-10.0) were enrolled. At 14 days, after two doses of BNT162b2, the geometric means of sVNT in 8-week vs 3-week interval groups were 49.6 (95% confidence interval [CI] 44.8-54.9) vs 16.5 (95% CI 13.0-20.9), with a geometric means ratio of 3.0 (95% CI 2.4-3.8). Among 102 participants who received the third dose at a median of 15 weeks from the second dose, the geometric means of sVNT increased to 73.3 (95% CI 69.0-77.8) and pseudovirus NT increased to 326 (95% CI 256-415). CONCLUSION: The extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.

Good recovery of immunization stress-related responses presenting as a cluster of stroke-like events following CoronaVac and ChAdOx1 vaccinations.

BACKGROUND: Immunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand. METHODS: We conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site. RESULTS: Overall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores ≤2, indicating slight or no disability). CONCLUSIONS: Immunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases.

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12-18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7-16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7-74.2) and 233.6 (95% CI 79-690.6); adolescents with cancer 62.3 (95% CI 29.2-133.1) and 214.9(95% CI 34.2-1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4-84.8) and 849.8 (95% CI 393.4-1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3-98.8) and 3240.3 (95% CI 2699-3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3-98.9) and 3818.5 (95% CI 3490.4-4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8-62.4) and 178.7 (95% CI 91.2-350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4-92.8) and 1037.1 (95% CI 933.3-1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required.

Response of Severe EV71-Infected Patients to Hyperimmune Plasma Treatment: A Pilot Study.

Hand, foot, and mouth disease (HFMD) is highly prevalent in East and Southeast Asia. It particularly affects children under five years of age. The most common causative agents are coxsackieviruses A6 and A16, and enterovirus A71 (EV71). The clinical presentation is usually mild and self-limited, but, in some cases, severe and fatal complications develop. To date, no specific therapy or worldwide vaccine is available. In general, viral infection invokes both antibody and cell-mediated immune responses. Passive immunity transfer can ameliorate the severe symptoms of diseases such as COVID-19, influenza, MERS, and SARS. Hyperimmune plasma (HIP) from healthy donors with high anti-EV71 neutralizing titer were used to transfuse confirmed EV71-infected children with neurological involvement (n = 6). It resulted in recovery within three days, with no neurological sequelae apparent upon examination 14 days later. Following HIP treatment, plasma chemokines were decreased, whereas anti-inflammatory and pro-inflammatory cytokines gradually increased. Interestingly, IL-6 and G-CSF levels in cerebrospinal fluid declined sharply within three days. These findings indicate that HIP has therapeutic potential for HFMD with neurological complications. However, given the small number of patients who have been treated, a larger cohort study should be undertaken. Successful outcomes would stimulate the development of anti-EV71 monoclonal antibody therapy.