Durability of the Effectiveness of Heterologous COVID-19 Vaccine Regimens in Thailand: Retrospective Cohort Study Using National Registration Data.

BACKGROUND: The durability of heterologous COVID-19 vaccine effectiveness (VE) has been primarily studied in high-income countries, while evaluation of heterologous vaccine policies in low- and middle-income countries remains limited. OBJECTIVE: We aimed to evaluate the duration during which the VE of heterologous COVID-19 vaccine regimens in mitigating serious outcomes, specifically severe COVID-19 and death following hospitalization with COVID-19, remains over 50%. METHODS: We formed a dynamic cohort by linking records of Thai citizens aged ≥18 years from citizen vital, COVID-19 vaccine, and COVID-19 cases registry databases between May 2021 and July 2022. Encrypted citizen identification numbers were used to merge the data between the databases. This study focuses on 8 common heterologous vaccine sequences: CoronaVac/ChAdOx1, ChAdOx1/BNT162b2, CoronaVac/CoronaVac/ChAdOx1, CoronaVac/ChAdOx1/ChAdOx1, CoronaVac/ChAdOx1/BNT162b2, BBIBP-CorV/BBIBP-CorV/BNT162b2, ChAdOx1/ChAdOx1/BNT162b2, and ChAdOx1/ChAdOx1/mRNA-1273. Nonimmunized individuals were considered for comparisons. The cohort was stratified according to the vaccination status, age, sex, province location, month of vaccination, and outcome. Data analysis employed logistic regression to determine the VE, accounting for potential confounders and durability over time, with data observed over a follow-up period of 7 months. RESULTS: This study includes 52,580,841 individuals, with approximately 17,907,215 and 17,190,975 receiving 2- and 3-dose common heterologous vaccines (not mutually exclusive), respectively. The 2-dose heterologous vaccinations offered approximately 50% VE against severe COVID-19 and death following hospitalization with COVID-19 for 2 months; however, the protection significantly declined over time. The 3-dose heterologous vaccinations sustained over 50% VE against both outcomes for at least 8 months, as determined by logistic regression with durability time-interaction modeling. The vaccine sequence consisting of CoronaVac/CoronaVac/ChAdOx1 demonstrated >80% VE against both outcomes, with no evidence of VE waning. The final monthly measured VE of CoronaVac/CoronaVac/ChAdOx1 against severe COVID-19 and death following hospitalization at 7 months after the last dose was 82% (95% CI 80.3%-84%) and 86.3% (95% CI 83.6%-84%), respectively. CONCLUSIONS: In Thailand, within a 7-month observation period, the 2-dose regimens could not maintain a 50% VE against severe and fatal COVID-19 for over 2 months, but all of the 3-dose regimens did. The CoronaVac/CoronaVac/ChAdOx1 regimen showed the best protective effect against severe and fatal COVID-19. The estimated durability of 50% VE for at least 8 months across all 3-dose heterologous COVID-19 vaccine regimens supports the adoption of heterologous prime-boost vaccination strategies, with a primary series of inactivated virus vaccine and boosting with either a viral vector or an mRNA vaccine, to prevent similar pandemics in low- and middle-income countries.

Breakthrough infections, hospital admissions, and mortality after major COVID-19 vaccination profiles: A prospective cohort study.

Background: Several COVID-19 vaccination rollout strategies are implemented. Real-world data from the large-scale, government-mandated Central Vaccination Center (CVC), Thailand, could be used for comparing the breakthrough infection, across all available COVID-19 vaccination profiles. Methods: This prospective cohort study combined the vaccine profiles from the CVC registry with three nationally validated outcome datasets to assess the breakthrough COVID-19 infection, hospitalization, and death among Thais individuals who received at least one dose of the COVID-19 vaccine. The outcomes were analyzed by comparing vaccine profiles to investigate the shot effect and homologous effect. Findings: Of 2,407,315 Thais who had at least one dose of COVID-19 vaccine, 63,469 (2.75%) had breakthrough infection, 42,001 (1.79%) had been hospitalized, and 431 (0.02%) died. Per one vaccination shot added, there was an 18% risk reduction of breakthrough infection (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.80-0.82), a 25% risk reduction of hospitalization (HR 0.75, 95% CI 0.73-0.76), and a 96% risk reduction of mortality (HR 0.04, 95% CI 0.03-0.06). The heterologous two-shot vaccine profiles had a higher protective effect against infection, hospitalization, and mortality compared to the homologous counterparts. Interpretation: COVID-19 breakthrough infection, hospitalization, and death differ across vaccination profiles that had a different number of shots and types of vaccines. Funding: This study did not involve any funding.

Real-World Effectiveness of Mix-and-Match Vaccine Regimens against SARS-CoV-2 Delta Variant in Thailand: A Nationwide Test-Negative Matched Case-Control Study.

The objective of this study is to explore the real-world effectiveness of various vaccine regimens to tackle the epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant in Thailand during September-December 2021. We applied a test-negative case control study, using nationwide records of people tested for SARS-CoV-2. Each case was matched with two controls with respect to age, detection date, and specimen collection site. A conditional logistic regression was performed. Results were presented in the form vaccine effectiveness (VE) and 95% confidence interval. A total of 1,460,458 observations were analyzed. Overall, the two-dose heterologous prime-boost, ChAdOx1 + BNT162b2 and CoronaVac + BNT162b2, manifested the largest protection level (79.9% (74.0-84.5%) and 74.7% (62.8-82.8%)) and remained stable over the whole study course. The three-dose schedules (CoronaVac + CoronaVac + ChAdOx1, and CoronaVac + CoronaVac + BNT162b2) expressed very high degree of VE estimate (above 80.0% at any time interval). Concerning severe infection, almost all regimens displayed very high VE estimate. For the two-dose schedules, heterologous prime-boost regimens seemed to have slightly better protection for severe infection relative to homologous regimens. Campaigns to expedite the rollout of third-dose booster shot should be carried out. Heterologous prime-boost regimens should be considered as an option to enhance protection for the entire population.

Pattern selection when a layer buckles on a soft substrate.

If a neo-Hookean elastic layer adhered to a neo-Hookean substrate grows equibiaxially, it will buckle into a topographic pattern. Here, we combine higher order perturbation theory and finite element numerics to predict the pattern formed just beyond the buckling threshold. More precisely, we construct a series of solutions corresponding to hexagonal, square and stripe patterns, and expand the elastic energy for each pattern as a Landau-like energy series in the topography amplitude. We see that, for square and stripe patterns, the elastic energy is invariant under topography inversion, making the instabilities supercritical. However, since patterns of hexagonal dents are physically different to patterns of hexagonal bumps, the hexagonal energy lacks this invariance. This lack introduces a cubic term which causes hexagonal patterns to be formed subcritically and are hence energetically favoured. Our analytic calculation of the cubic term allows us to determine that dents are favoured in incompressible systems, but bumps are favored in sufficiently compressible systems. Finally, we consider a stiff layer sandwiched between an identical substrate and superstrate pair. This system has topography inversion symmetry, so hexagons form supercritically, and square patterns are favoured. We use finite element calculations to verify our theoretical predictions for each pattern, and confirm which pattern is selected. Previous work has used a simplified elastic model (a plate & a linear elastic substrate) that possesses invariance under topography inversion, and hence incorrectly predicted square patterns. Our work demonstrates that large strain geometry is sufficient to break this symmetry and explain the hexagonal dent patterns observed in buckling experiments.

Peristaltic Elastic Instability in an Inflated Cylindrical Channel.

A long cylindrical cavity through a soft solid forms a soft microfluidic channel, or models a vascular capillary. We observe experimentally that, when such a channel bears a pressurized fluid, it first dilates homogeneously, but then becomes unstable to a peristaltic elastic instability. We combine theory and numerics to fully characterize the instability in a channel with initial radius a through an incompressible bulk neo-Hookean solid with shear modulus µ. We show instability occurs supercritically with wavelength 12.278…a when the cavity pressure exceeds 2.052…µ. In finite solids, the wavelength for peristalsis lengthens, with peristalsis ultimately being replaced by a long-wavelength bulging instability in thin-walled cylinders. Peristalsis persists in Gent strain-stiffening materials, provided the material can sustain extension by more than a factor of 6. Although naively a pressure driven failure mode of soft channels, the instability also offers a route to fabricate periodically undulating channels, producing, e.g., waveguides with photonic or phononic stop bands.