Prevalence and associating factors of long COVID in pediatric patients during the Delta and the Omicron variants.

Introduction: The number of pediatric COVID-19 infections is increasing; however, the data on long COVID conditions in children is still limited. Our study aimed to find the prevalence of long COVID in children during the Delta and Omicron waves, as well as associated factors. Methods: A single-center prospective cohort study was conducted. We included 802 RT-PCR-confirmed COVID-19 pediatric patients in the Delta and Omicron periods. Long COVID was defined as having symptoms for ≥3 months after infection. Parents and/or patients were interviewed by phone. Multivariable logistic regression was performed to find associated factors with long COVID. Results: The overall prevalence of long COVID was 30.2%. The Delta period had more prevalence than the Omicron (36.3% vs. 23.9%). Common symptoms for patients 0-3 years' old were loss of appetite, rhinorrhea, and nasal congestion. Conversely, patients 3-18 years' old had hair loss, dyspnea on exertion, rhinorrhea, and nasal congestion. However, there was no significant negative impact on daily life. Most symptoms improved after a 6-month follow-up. Factors associated with long COVID-19 conditions were infection during the Omicron period (adjusted OR: 0.54; 95% CI: 0.39-0.74, P < 0.001), fever (adjusted OR: 1.49, 95% CI: 1.01-2.20, P = 0.04) and rhinorrhea (adjusted OR: 1.47, 95% CI: 1.06-2.02, P = 0.02). Conclusion: Infection during the Omicron wave has a lower prevalence of long COVID. The prognosis is often favorable, and most symptoms gradually become less. However, pediatricians may schedule appointments to surveil long COVID in children with fever or rhinorrhea as an initial symptom.

Prevalence, risk factors, and vaccine effectiveness of COVID-19 infection in thai children, adolescents, and young adults in the omicron era.

Background and objectives: The study of prevalence, risk factors, and vaccine effectiveness (VE) in children, adolescents, and young adults during the Omicron era has been limited, making this the objectives of the study. Methods: A prospective, test-negative case-control study was conducted on patients aged 0-24 years old classified as patients under investigation (PUI) from January to May 2022. PUI with positive RT-PCR within 14 days were classified as cases, whilst PUI with negative RT-PCR in 14 days were controls. Univariate and multivariate analyses determined risk factors; VE was calculated using [1-adjusted odds ratio (OR)] × 100. Results: The final analyses included 3,490 patients with a PUI infection rate of 45.6%. Heterologous vaccination regimens, including inactivated vaccines, viral vectors, and mRNA were utilized during the study period. A total of 2,563 patients (73.5%) had received at least 2 vaccine doses, regardless of regimen. Male gender and household infections were independent risk factors for the development of infection, with an adjusted OR of 1.55 and 1.45, respectively. Underlying comorbidities and obesity were not significantly associated with the development of infection. Patients with underlying comorbidities were more likely to have at least moderate severity of infection with the adjusted OR of 3.07. Age older than 11 years was associated with lower infection risk and development of at least moderate infection with adjusted OR of 0.4 and 0.34, respectively. Vaccinated participants also had a lower risk of developing at least moderate infection: adjusted OR of 0.40. The adjusted VE of any vaccination regimen for infection prevention for one, two, three, or more than four doses was 21.8%, 30.6%, 53.5%, and 81.2%, respectively. The adjusted VE of any vaccination regimen for prevention of at least moderate severity of the disease for one, two, three, or more than four doses was 5.7%, 24.3% 62.9%, and 90.6%, respectively. Conclusion: Disease prevalence among PUI was substantially high during the Omicron wave. A two-dose vaccination regimen does not appear sufficient to ensure protection against infection.

Dengue amid COVID-19 pandemic

The increasing in dengue cases nowadays is a global threat concern. Fifty per cent of the world's population is vulnerable to dengue infection with Asia contributing over two-thirds of the global burden. The double trouble of Coronavirus disease 2019 (COVID-19) arising from novel severe respiratory syndrome coronavirus (SARS-CoV-2) and dengue virus is a major challenge, particularly in developing countries due to overburdened public health systems and economic constraints including the ability to diagnose. The objective of this study was to analyze the prevalence of dengue in Thailand during the outbreak of COVID-19. We studied data on dengue cases reported at epidemiological information centers, the Bureau of Epidemiology, and the Ministry of Public Health, Thailand during 2019 to 2021. Patients can be observed across all age groups, particularly adolescents and adults. Dengue was seen year-round, with highest incidence in the rainy seasons between June and September. Total number of cases was markedly declined by nearly 93 percentage from 2019 to 2011. Taken together, Thailand is still at risk of spreading of dengue in the midst of COVID-19 pandemic. Continuous status updates on dengue patients in Thailand should be incorporated into global health advisory on preventive measures before travelling.

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.

Immunogenicity and Safety of the Third Booster Dose with mRNA-1273 COVID-19 Vaccine after Receiving Two Doses of Inactivated or Viral Vector COVID-19 Vaccine.

The changes in the severe acute respiratory syndrome coronavirus 2 and the tapering of immunity after vaccination have propelled the need for a booster dose vaccine. We aim to evaluate B and T cell immunogenicity and reactogenicity of mRNA-1273 COVID-19 vaccine (100 µg) as a third booster dose after receiving either two doses of inactivated COVID-19 vaccine (CoronaVac) or two doses of viral vector vaccine (AZD1222) in adults not previously infected with COVID-19. The anti-receptor-binding-domain IgG (anti-RBD IgG), surrogate virus neutralization test (sVNT) against the Delta variant, and Interferon-Gamma (IFN-γ) level were measured at baseline, day (D)14 and D90 after vaccination. In D14 and D90, the geometric means of sVNT were significantly increased to 99.4% and 94.5% inhibition in CoronaVac, respectively, whereas AZD1222 showed inhibition of 99.1% and 93%, respectively. Anti-RBD IgG levels were 61,249 to 9235 AU/mL in CoronaVac and 38,777 to 5877 AU/mL in AZD1222 after D14 and D90 vaccination. Increasing median frequencies of S1-specific T cell response by IFN-γ concentration were also elevated in D14 and were not significantly different between CoronaVac (107.8-2035.4 mIU/mL) and AZD1222 (282.5-2001.2 mIU/mL). This study provides evidence for the high immunogenicity of the mRNA-1273 booster after two doses of CoronaVac or AZD1222 in the Thai population.

Real-life effectiveness of COVID-19 vaccine during the Omicron variant-dominant pandemic: how many booster doses do we need?

The surge in coronavirus disease 2019 (COVID-19) caused by the Omicron variants of the severe acute respiratory syndrome coronavirus 2 necessitates researches to inform vaccine effectiveness (VE) and other preventive measures to halt the pandemic. A test-negative case-control study was conducted among adults (age ≥18 years) who were at-risk for COVID-19 and presented for nasopharyngeal real-time polymerase chain reaction testing during the Omicron variant-dominant period in Thailand (1 January 2022-15 June 2022). All participants were prospectively followed up for COVID-19 development for 14 days after the enrolment. Vaccine effectiveness was estimated and adjusted for characteristics associated with COVID-19. Of the 7971 included individuals, there were 3104 cases and 4867 controls. The adjusted VE among persons receiving 2-dose, 3-dose, and 4-dose vaccine regimens for preventing infection and preventing moderate-to-critical diseases were 33%, 48%, 62% and 60%, 74%, 76%, respectively. The VE were generally higher among those receiving the last dose of vaccine within 90 days compared to those receiving the last dose more than 90 days prior to the enrolment. The highest VE were observed in individuals receiving the 4-dose regimen, CoronaVac-CoronaVac-ChAdOx1 nCoV-19-BNT162b2 for both preventing infection (65%) and preventing moderate-to-critical diseases (82%). Our study demonstrated increased VE along with an increase in number of vaccine doses received. Current vaccination programmes should focus on reducing COVID-19 severity and mandate at least one booster dose. The heterologous boosters with viral vector and mRNA vaccines were highly effective and can be used in individuals who previously received the primary series of inactivated vaccine.

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.

Development and validation of the predictive score for pediatric COVID-19 pneumonia: A nationwide, multicenter study.

BACKGROUND: Due to the possibility of asymptomatic pneumonia in children with COVID-19 leading to overexposure to radiation and problems in limited-resource settings, we conducted a nationwide, multi-center study to determine the risk factors of pneumonia in children with COVID-19 in order to create a pediatric pneumonia predictive score, with score validation. METHODS: This was a retrospective cohort study done by chart review of all children aged 0-15 years admitted to 13 medical centers across Thailand during the study period. Univariate and multivariate analyses as well as backward and forward stepwise logistic regression were used to generate a final prediction model of the pneumonia score. Data during the pre-Delta era was used to create a prediction model whilst data from the Delta one was used as a validation cohort. RESULTS: The score development cohort consisted of 1,076 patients in the pre-Delta era, and the validation cohort included 2,856 patients in the Delta one. Four predictors remained after backward and forward stepwise logistic regression: age < 5 years, number of comorbidities, fever, and dyspnea symptoms. The predictive ability of the novel pneumonia score was acceptable with the area under the receiver operating characteristics curve of 0.677 and a well-calibrated goodness-of-fit test (p = 0.098). The positive likelihood ratio for pneumonia was 0.544 (95% confidence interval (CI): 0.491-0.602) in the low-risk category, 1.563 (95% CI: 1.454-1.679) in the moderate, and 4.339 (95% CI: 2.527-7.449) in the high-risk. CONCLUSION: This study created an acceptable clinical prediction model which can aid clinicians in performing an appropriate triage for children with COVID-19.

An epidemiological study of pediatric COVID-19 in the era of the variant of concern.

BACKGROUND: There were limited epidemiological data of pediatric COVID-19 in Asia outside China, especially during the era of the variants of concern such as the Delta and Alpha variants. The objective was to describe the clinical epidemiology of pediatric COVID-19 in a tertiary care center in Thailand from April to August 2021. The identification of risk factors for the development of pneumonia in these children was also performed. METHODS: This retrospective cohort study was conducted by retrospective chart review of all children aged 0-15 years admitted to Thammasat University Hospital care system during the study period. The risk factors for the development of pneumonia were analyzed using logistic regression. RESULTS: A total of 698 children were included for analysis, of which 52% were male. The mean age of the cohort was 7.2 + 4.5 years old. Radiographic pneumonia was identified in 100 children (14.3%) and a total of 16 children (2.3%) were diagnosed with severe and critical diseases. The mortality rate was 0.1%. Children younger than 1 year and children with comorbidity were at higher risk of developing pneumonia (Adjusted odds ratios 2.99 (95% confidence interval (CI): 1.56-5.74) and 2.32 (95% CI: 1.15-4.67), respectively). CONCLUSION: In the era of the variants of concern, the proportion of children with severe and critical diseases remained low. However, prudence must be taken in caring for younger children and children with comorbidity.

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.

Epidemiological and Clinical Characteristics of Pediatric COVID-19 in the Tertiary Care System in Thailand: Comparative Delta and pre-Delta Era.

Background: Few studies had focused on the epidemiological and clinical characteristics of pediatric COVID-19 (SARS-CoV-2) during Delta and pre-Delta eras in Asia, despite it being a pandemic. Objective: To study the epidemiological and clinical characteristics of three waves of pediatric COVID-19 infections in a tertiary-care setting in Thailand. Methods: This retrospective study reviewed all PCR-confirmed pediatric (0-18 years of age) COVID-19 infections between January 13, 2020, and October 31, 2021, in a tertiary care system in Thailand. Results: 1,019 patients, aged 0.02 - 18 years, 552 (54.2%) male, and 467 (45.8%) female, with a median age of 9.2 years, were enrolled. Asymptomatic cases accounted for 35.7%, of which 106 (18.9%) had abnormal chest X-ray findings. Most cases were classified as having mild clinical symptoms, with only 8 (0.8%) and 4 (0.4%) developing a severe and critical illness, respectively. There were no deaths. The Delta variant appeared more transmissible than previous ones, but we did not see any difference in disease severity. Upper respiratory tract symptoms were predominant, while few cases had lower respiratory tract involvement. The sensitivity and specificity of dyspnea symptoms to predict radiologically confirmed pneumonia were 14% and 95%, respectively, with a likelihood ratio of 3.37. The overall prognosis was good, with only 13 (1.3 %) needing respiratory support. All cases showed clinical improvement with a decent recovery. Conclusion: Pediatric COVID-19 during the Delta variant predominance era generally appeared more transmissible but benign. One-fifth of cases had pneumonia, but few cases needed respiratory support. Prevention remains important for disease control.

A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines.

BACKGROUND: Immunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed. OBJECTIVE: To evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults. METHODS: A double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x1010 viral particles) or low dose (LD, 2.5x1010 viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms. RESULTS: From July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD. CONCLUSION: Half-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings.

Comparing real-life effectiveness of various COVID-19 vaccine regimens during the delta variant-dominant pandemic: a test-negative case-control study.

Data on real-life vaccine effectiveness (VE), against the delta variant (B.1.617.2) of the severe acute respiratory syndrome coronavirus 2 among various coronavirus disease 2019 (COVID-19) vaccine regimens are urgently needed to impede the COVID-19 pandemic. We conducted a test-negative case-control study to assess the VE of various vaccine regimens for preventing COVID-19 during the period when the delta variant was the dominant causative virus (≥ 95%) in Thailand (25 July 2021-23 Oct 2021). All individuals (age ≥18 years) at-risk for COVID-19, presented for nasopharyngeal real-time polymerase chain reaction (RT-PCR) testing, were prospectively enrolled and followed up for disease development. Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. Of 3353 included individuals, there were 1118 cases and 2235 controls. The adjusted VE among persons receiving two-dose CoronaVac plus one BNT162b2 booster was highest (98%; 95% confidence interval [CI] 87-100), followed by those receiving two-dose CoronaVac plus one ChAdOx1 nCoV-19 booster (86%; 95% CI 74-93), two-dose ChAdOx1 nCoV-19 (83%; 95% CI 70-90), one CoronaVac dose and one ChAdOx1 nCoV-19 dose (74%; 95% CI 43-88) and two-dose CoronaVac (60%; 95% CI 49-69). One dose of CoronaVac or ChAdOx1 nCoV-19 had a VE of less than 50%. Our study demonstrated the incremental VE with the increase in the number of vaccine doses received. The two-dose CoronaVac plus one BNT162b2 or ChAdOx1 nCoV-19 booster regimens was highly effective in preventing COVID-19 during the rise of delta variant.