Global COVID-19 Vaccination in Infants and Children: Effectiveness, Safety, and Challenges.

COVID-19 Vaccines, which include mRNA and inactivated vaccines, have been proven effective and safe for infants and children aged more than six months in reducing the severity of the disease, hospitalization, multisystem inflammatory syndrome in children, and death. Nonetheless, the real-world effectiveness of these vaccines in preventing infection is generally lower than in clinical trials due to the emergence of variants of concern, especially the Omicron strains. Despite the availability of vaccines for children, their uptake remains low globally, particularly among parents who are hesitant to vaccinate their children. This review article aims to provide a comprehensive overview of COVID-19 vaccine safety and efficacy from clinical trials and the current COVID-19 vaccine recommendations for infants and children aged 6 months to < 12 years for 2023-2024, discuss the progress made in vaccine implementation and real-world effectiveness, and address the knowledge gap and future directions.

Short-term immune response after inactivated SARS-CoV-2 (CoronaVac®, Sinovac) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-AstraZeneca) vaccinations in health care workers.

BACKGROUND: Inactivated SARS-CoV-2 (CoronaVac®, Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs). OBJECTIVE: To determine the short-term immune response after the SV and AZ vaccinations in HCWs. METHODS: In this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included. Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody. Blood samples were analyzed at 4 and 12 weeks after the complete vaccination. The primary outcome was the seroconversion rate at 4-weeks after complete immunization. RESULTS: Overall, 185 HCWs with a median (IQR) age of 40.5 (30.3-55.8) years (94 HCWs in the SV group and 91 in the AZ group) were included. At 4 weeks after completing the SV vaccination, 60.6% (95%CI: 50.0-70.6%) had seroconversion evaluated by sVNT (≥ 68% inhibition), comparable to the patients recovered from mild COVID-19 infection (69.0%), with a rapid reduction to 12.2% (95%CI: 6.3-20.8) at 12 weeks. In contrast, 85.7% (95%CI: 76.8-92.2%) HCWs who completed two doses of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients (92.5%), with a reduction to 39.2% (95%CI: 28.4-50.9%) at 12 weeks. When using the anti-SARS-CoV-2 total antibody level (≥ 132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group at 4 weeks. CONCLUSIONS: A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SARS-CoV-2 variants of concern.

Immunogenicity of BNT162b2 in children 6 months to under 5 years of age with previous SARS-CoV-2 infection, in the era of Omicron predominance.

Background: Children 6 months to < 5 years old are recommended to receive 3-dose regimen of BNT162b2. Children previously infected with Omicron variant of SARS-CoV-2 develop immunity from natural infection, therefore may require fewer doses of vaccine. Objective: To compare immunogenicity of 1- or 2-dose BNT162b2 in healthy children post COVID-19 with 3-dose BNT162b2 in COVID-naïve children. Methods: Children aged 6 months to < 5 years who developed COVID-19 during the Omicron-predominant period were enrolled; Group A 3-6 months(N = 40) and Group B > 6 months(N = 40) prior to vaccination. Participants in Group A and B received 2-dose BNT162b2 intramuscularly 1 month apart. COVID-naïve children were enrolled as a control group (N = 40) and received 3-dose BNT162b2 at month 0,1,3. Neutralizing antibody against Omicron variant(BA.2.75 and BA.4/5) was determined by pseudovirus assays(pVNT) as reported by neutralization dilution for 50%inhibition (ID50) at 28 days after the 1st and 2nd dose. Results: From October-November 2022, 120 children with a median age of 2.8 years (IQR 1.6-4.0) were enrolled. The median duration since COVID-19 to vaccination was 4.4 months(IQR 3.8-5.4) in Group A and 7.9 months(7.0-8.5) in Group B. In Group A, the geometric means(GMs) of pVNT-BA.2.75 ID50 were 553 (95%CI 338-906) and 753(516-1098) after 1 and 2 doses, respectively, and the GMs of pVNT-BA.4/5 ID50 were 1936(1402-2673) and 1885(1414-2512), respectively. In Group B, the GMs of pVNT-BA.2.75 ID50 were 1383(1100-1742) and 1419 (1104-1823), and the GMs of pVNT-BA.4/5 ID50 were 2627(2048-3367) and 2056(1546-2735), respectively. Meanwhile in COVID-naïve group, the GMs of pVNT-BA.2.75 and pVNT-BA.4/5 ID50 were 158(98-255) and 59(31-114) after the 3rd dose, respectively. The geometric mean ratio(GMR) of pVNT-BA.2.75 ID50 after 1 dose in Group A and B compared with after 3 doses in COVID-naïve group were 3.50 (1.93-6.34) and 8.74 (4.79-15.95), respectively. The GMR of pVNT-BA.2.75 ID50 after 1 dose in Group B compared with Group A was 2.50 (1.45-4.31). Conclusions: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.

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.

Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children.

Objective: To compare the immune response of hybrid immunity - arising from SARS-CoV-2 infection and mRNA BNT162b2 vaccination - to that of 2-doses of vaccine. Methods: In a subanalysis of BNT162b2 vaccine trial in 5 to 11-year-old children, There were 179 children who had hybrid immunity compared with 134 children with solely 2-dose vaccine. The immunological outcome was a surrogate virus neutralization test (sVNT) against the Omicron strain, BA.1, (%inhibition). An sVNT level ≥68 % inhibition was considered as protective immune response. Results: From February to April 2022, 179 children had COVID-19 natural infection resulting in hybrid immunity included: Group1;prior vaccination(n = 17), Group2;after the first dose(n = 61), and Group3;after the second dose(n = 97). The proportion of children with protective immune response was higher in Group 3 and Group 1 - 61.9 % and 58.8 %, compared to 36.1 % and 34.3 % in Group 2 and comparator group (2 doses of vaccine), respectively. The geometric mean % inhibition of sVNT was higher in Group 1 (68.5, 95 %CI 55.5-84.6) and Group 3 (63.5, 95 %CI 55.5-72.6), followed by comparator group (49.6, 95 %CI 44.8-54.9) and Group 2 (42.1, 95 %CI 34.6-51.3), p < 0.001. Conclusions: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.

Immunogenicity and reactogenicity of fractional, heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5-11-year-old Thai children: A multicenter, prospective, double-blind, randomized control trial.

OBJECTIVE: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children. METHODS: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-µg) or half-dose (5-µg) BNT162b2 vaccines as follows: CoronaVac/10-µg-BNT162b2 (Group 1), CoronaVac/5-µg-BNT162b2 (Group 2), 10-µg-BNT162b2/10-µg-BNT162b2 (Group 3), or 10-µg-BNT162b2/5-µg-BNT162b2 (Group 4). A subset of participants from each arm received 10-µg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported. RESULTS: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter. CONCLUSION: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.

High Transmission Rates of Early Omicron Subvariant BA.2 in Bangkok, Thailand.

The emergence of Omicron as the fifth variant of concern within the SARS-CoV-2 pandemic in late 2021, characterized by its rapid transmission and distinct spike gene mutations, underscored the pressing need for cost-effective and efficient methods to detect viral variants, especially given their evolving nature. This study sought to address this need by assessing the effectiveness of two SARS-CoV-2 variant classification platforms based on RT-PCR and mass spectrometry. The primary aim was to differentiate between Delta, Omicron BA.1, and Omicron BA.2 variants using 618 COVID-19-positive samples collected from Bangkok patients between November 2011 and March 2022. The analysis revealed that both BA.1 and BA.2 variants exhibited significantly higher transmission rates, up to 2-3 times, when compared to the Delta variant. This research presents a cost-efficient approach to virus surveillance, enabling a quantitative evaluation of variant-specific public health implications, crucial for informing and adapting public health strategies.

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.

Immunogenicity to SARS-CoV-2 Omicron variant among school-aged children with 2-dose of inactivated SARS-CoV-2 vaccines followed by BNT162b2 booster.

Background: A primary series of 2-dose SARS-CoV-2 vaccines based on an ancestral strain generate inadequate neutralizing antibodies against the SARS-CoV-2 Omicron variant. This study aimed to describe the immune response from giving healthy school-aged children who previously received 2 inactivated vaccines an mRNA BNT162b2 booster. Methods: Healthy children aged 5-11 years who received 2 doses of CoronaVac or Covilo were enrolled and received 10 µg BNT162b2 intramuscularly. Neutralizing antibody against Omicron variant was measured at pre-booster and 14-21 days post-booster by surrogate virus neutralization test (sVNT, %inhibition) and pseudovirus neutralization test (pVNT, ID50). Antibody responses were compared with a parallel cohort of children who received 2 doses of BNT162b2 3 weeks apart. Results: From April to May 2022, 59 children with a mean age (SD) of 8.5 years (1.7) were enrolled: 20 CoronaVac and 39 Covilo recipients. The median interval from the primary series was 49 days (IQR 33-51). After booster, the geometric means (GMs) of sVNT and pVNT were 72.2 %inhibition (95 %CI 67.2-77.6) and 499 (95 %CI 399-624), respectively. The proportion of children with sVNT against Omicron strain ≥68 %inhibition increased from none to 70.2 %. The geometric mean ratio (GMR) of sVNT and pVNT compared with a parallel cohort were 4.3 and 12.2, respectively. The GMR of sVNT and pVNT between children who received booster dose at >6-week interval were 1.2 (95 %CI 1.1-1.3). and 1.8 (95 %CI 1.2-2.7) compared with 4-6 weeks interval. Conclusion: A regimen of 2-dose of inactivated vaccine followed by BNT162b2 booster dose elicited high neutralizing antibody against the Omicron variants in healthy school-aged children.

Heterologous Prime-boost of SARS-CoV-2 inactivated vaccine and mRNA BNT162b2 among Healthy Thai Adolescents.

Background: Heterologous prime-boost SARS-CoV-2 vaccination is a widely accepted strategy during the COVID-19 pandemic, which generated a superior immune response than homologous vaccination strategy. Objective: To describe immunogenicity of heterologous prime-boost vaccination with inactivated vaccine, CoronaVac, followed by BNT162b2 and 5-month booster dose with BNT162b2 in healthy Thai adolescents. Methods: Adolescents aged 12-18 years were randomized 1:1:1:1 to receive CoronaVac (SV) followed by BNT162b2 (PZ) 30 or 20 µg at either 3- or 6-week interval (SV3w/PZ30µg, SV3w/PZ20µg, SV6w/PZ30µg or SV6w/PZ20µg). During the Omicron-predominant period, participants were offered a BNT162b2 booster dose 30, 15, or 10 µg. Immunogenicity was determined using IgG antibody against spike-receptor-binding domain of wild type(anti-S-RBD IgG) and surrogate virus neutralization test(sVNT) against Delta variant at 14 days and 5 months after the 2nd dose. Neutralization tests(sVNT and pseudovirus neutralization test; pVNT) against Omicron strain were tested pre- and 14 days post-booster dose. Results: In October 2021, 76 adolescents with a median age of 14.3 years (IQR 12.7-16.0) were enrolled: 20 in SV3w/PZ30µg; 17 in SV3w/PZ20µg; 20 in SV6w/PZ30µg; 19 in SV6w/PZ20µg. At day 14, the geometric mean(GM) of anti-S-RBD IgG in SV3w/PZ30µg was 4713 (95 %CI 4127-5382) binding-antibody unit (BAU)/ml, while geometric mean ratio(GMR) was 1.28 (1.09-1.51) in SV6w/PZ30µg. The GMs of sVNT against Delta variants at day 14 among participants in SV3w/PZ30µg and SV6wk/PZ30µg arm were 95.3 % and 99.7 %inhibition, respectively. At 5 months, GMs of sVNT against Delta variants in SV3w/PZ30µg were significantly declined to 47.8 % but remained at 89.0 % inhibition among SV6w/PZ30µg arm. In April 2022, 52 adolescents received a BNT162b2 booster dose. Proportion of participants with sVNT against Omicron strain > 80 %inhibition was significantly increased from 3.8 % pre-booster to 67 % post-booster. Proportion of participants with pVNT ID50 > 185 was 42 % at 14 days post 2nd dose and 88 % post booster, respectively. Conclusions: Heterologous prime-boost vaccination with CoronaVac followed by BNT162b2 induced high neutralizing titer against SARS-CoV-2 Delta strain. After 5-month interval, booster with BNT162b2 induced high neutralizing titer against Omicron strain.Thai Clinical Trials Registry (thaiclinicaltrials.org): TCTR20210923012.

Immunogenicity of BNT162b2 Vaccination against SARS-CoV-2 Omicron Variant and Attitudes toward a COVID-19 Booster Dose among Healthy Thai Adolescents.

Despite the BNT162b2 vaccination coverage, rapid transmission of Omicron SARS-CoV-2 has occurred, which is suspected to be due to the immune escape of the variant or waning vaccine efficacy of multiple BNT162b2 vaccination doses. Our study aims to compare immunogenicity against Omicron prior to and post a booster dose of BNT162b2 in healthy adolescents, and to evaluate their attitudes toward booster dose vaccination. A cross sectional study was conducted among healthy adolescents aged 12-17 who received two doses of BNT162b2 more than 5 months ago. Participants and their guardians performed self-reported questionnaires regarding reasons for receiving the booster. A 30 ug booster dose of BNT162b2 was offered. Immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against the Omicron variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) taken pre-booster and 14-days post-booster. From March to April 2022, 120 healthy Thai adolescents with a median age of 15 years (IQR 14-16) were enrolled. sVNT against Omicron pre- and post-booster had 11.9 (95%CI 0-23.9) and 94.3 (90.6-97.4) % inhibition. Geometric means (GMs) of anti-S-RBD IgG increased from 837 (728, 953) to 3041 (2893, 3229) BAU/mL. Major reasons to receive the booster vaccination were perceived as vaccine efficacy, reduced risk of spreading infection to family, and safe resumption of social activities. A booster dose of BNT162b2 elicits high immunogenicity against the Omicron variant. Motivation for receiving booster doses is to reduce risk of infection.

Immunogenicity of a Fractional Dose of mRNA BNT162b2 COVID-19 Vaccine for Primary Series and Booster Vaccination among Healthy Adolescents.

Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12-18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 µg. A booster was given at 5 months after the second dose using either 10 or 15 µg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID50) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9-16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761-3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67-0.97) in 3wPZ30/20; 1.00 (95% CI 0.83-1.20) in 3wPZ20/20; 1.37 (95% CI 1.13-1.65) in 6wPZ30/30; 1.24 (95% CI 1.02-1.50) in 6wPZ30/20; and 1.36 (1.13-1.64) in 6wPZ20/20. After a booster dose with 15 µg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4-94.9) and 331 (95% CI 221-495), respectively. In the group that received 10 µg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0-91.6) and pVNT was 397 (95% CI 267-590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option.

Dynamics of Neutralizing Antibody and T-Cell Responses to SARS-CoV-2 and Variants of Concern after Primary Immunization with CoronaVac and Booster with BNT162b2 or ChAdOx1 in Health Care Workers.

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declines within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants who received ChAdOx1 and forty-two participants who received BNT162b2 were enrolled into this study, which evaluated immune responses, including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript), five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization, as well as 4 and 12 weeks after receiving the booster. This study showed a significant increase in anti-SARS-CoV-2 spike total antibodies, sVNT, and T-cell immune response after the booster, including against the Omicron variant. Immune responses rapidly decreased in the booster group at 12 weeks after booster but were still higher than post-primary vaccination. A fourth dose or a second booster should be recommended, particularly in health care workers.

Differential escape of neutralizing antibodies by SARS-CoV-2 Omicron and pre-emergent sarbecoviruses.

The SARS-CoV-2 B.1.1.529 lineage, Omicron variant, was first detected in November 2021 and carries 32 amino acid mutations in the spike protein (15 in RBD) and exhibits significant escape of neutralizing antibodies targeting the parental SARS-CoV-2 virus. Here, we performed a high-resolution multiplex (16-plex) surrogate virus neutralization assay covering all major SARS-CoV-2 variants and pre-emergent ACE2-binding sarbecoviruses against 20 different human serum panels from infected, vaccinated and hybrid immune individuals which had vaccine-breakthrough infections or infection followed by vaccination. Among all sarbecoviruses tested, we observed 1.1 to 4.7-, 2.3 to 10.3- and 0.7 to 33.3-fold reduction in neutralization activities to SARS-CoV-2 Beta, Omicron and SARS-CoV-1, respectively. Among the SARS-CoV-2 related sarbecoviruses, it is found that the genetically more distant bat RaTG13 and pangolin GX-P5L sarbecoviruses had less neutralization escape than Omicron. Our data suggest that the SARS-CoV-2 variants emerged from the changed immune landscape of human populations are more potent in escaping neutralizing antibodies, from infection or vaccination, than pre-emergent sarbecoviruses naturally evolved in animal populations with no or less immune selection pressure.

SARS-CoV-2 Omicron variant emerged under immune selection.

The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.

Clinical outcomes of pediatric COVID-19 in a tertiary care center in Bangkok, Thailand.

Objective: To describe the clinical characteristics and outcomes of pediatric COVID-19 in Thailand, where favipiravir is the mainstay of antiviral treatment. Methods: We conducted a hospital based observational cohort study of COVID-19 among children. The study included children (age <15 years) with confirmed positive reverse transcriptase-polymerase chain reaction for SARS-CoV-2 from nasopharyngeal swab. Results: From April to July 2021, 416 cases with a median age of 7.1 (interquartile range 2.7-11.6) years were included in the study. The spectrum of disease included 82 (20%) asymptomatic, 232 (56%) mild and 102 (24%) with pneumonia. Abnormal chest x-ray findings included ground-glass opacities (46%), focal infiltrations (27%), perihilar opacities (19%), reticular infiltrations (15%) and other non-specific findings (4%). Only 12 children (3%) required oxygen support. Favipiravir was prescribed to 129 children (31%); 102 patients with pneumonia and 27 patients at risk for disease progression. Pneumonia was more common in age <3 years compared with those aged 3-<12 years (adjusted odds ratio (aOR) 0.30, 95% CI 0.17-0.52), 12-15 years (aOR 0.40, 95% CI 0.21-0.77) and in patients with comorbidities (aOR 2.36, 95% CI 1.09-5.12). Conclusions: One-fourth of pediatric COVID-19 patients had pneumonia, but few required oxygen support. Off-label use of Favipiravir in pediatric COVID-19 patients in a recent outbreak in Bangkok is reported.

Immunogenicity of 2-dose pre-exposure rabies vaccine co-administered with quadrivalent influenza vaccine in children.

OBJECTIVES: The World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). METHODS: Children aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. RESULTS: From November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). CONCLUSIONS: The 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.