Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines

Immunogenicity and reactogenicity of heterologous COVID-19 vaccination in pregnant women

This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18–45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0–35.5) years and gestational age of 23.5 (IQR 18.0–30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery (r = 0.719, P < .001) and inversely correlated with elapsed time after the second vaccination (r = −0.366, P < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings

Long-term multiple metabolic abnormalities among healthy and high-risk people following nonsevere COVID-19

Abstract Few studies have identified the metabolic consequences of the post-acute phase of nonsevere COVID-19. This prospective study examined metabolic outcomes and associated factors in nonsevere, RT-PCR-confirmed COVID-19. The participants’ metabolic parameters, the prevalence of long-term multiple metabolic abnormalities (≥ 2 components), and factors influencing the prevalence were assessed at 1, 3, and 6 months post-onset. Six hundred individuals (mean age 45.5 ± 14.5 years, 61.7% female, 38% high-risk individuals) with nonsevere COVID-19 attended at least one follow-up visit. The prevalence of worsening metabolic abnormalities was 26.0% for BMI, 43.2% for glucose, 40.5% for LDL-c, 19.1% for liver, and 14.8% for C-reactive protein. Except for lipids, metabolic-component abnormalities were more prevalent in high-risk hosts than in healthy individuals. The prevalence of multiple metabolic abnormalities at the 6-month follow-up was 41.3% and significantly higher in high-risk than healthy hosts (49.2% vs 36.5%; P = 0.007). Factors independently associated with a lower risk of these abnormalities were being female, having dyslipidemia, and receiving at least 3 doses of the COVID-19 vaccine. These findings suggest that multiple metabolic abnormalities are the long-term consequences of COVID-19. For both high-risk and healthy individuals with nonsevere COVID-19, healthcare providers should monitor metabolic profiles, encourage healthy behaviors, and ensure complete vaccination