The efficiency of COVID-19 vaccines among taiwanese patients with varied comorbidities

Background/Aims: The global pandemic of COVID-19 has caused tremendous loss of human life since 2019. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control the pandemic. The vaccination efficacy in Taiwanese patients with different comorbidities is elusive and to be explored. Method(s): Uninfected subjects who received 3-doses of mRNA vaccines (Moderna, BioNTech), non-replicating viral vector-based vaccines (AstraZeneca, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine, MVC) were prospectively enrolled. SARSCoV2- IgG spike antibody level was determined (Abbott [SARS-CoV- 2 IgG II]) within 3 months after the last dose of vaccination. Charlson Comorbidity Index (CCI) was applied to disclose the association of vaccine titer and underlying comorbidities. Result(s): A total of 824 subjects were enrolled in the current study. The mean age was 58.9 years and males accounted for 48.7% of the population. The proportion of CCI with 0-1, 2-3 and>4 was 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%) and AZAZ- BioNTech (14.7%), respectively. The mean vaccination titer was 3.11 log BAU/mL after a median 48 days of the 3rd dose. Subjects of male gender, lower body mass index, chronic kidney disease, higher CCI, and receiving AZ-AZ based vaccination were likely to have a lower titer of antibody. There was a decreasing trend of antibody titer with the increase of CCT (trend P<0.001). Linear regression analysis revealed that AZ-AZ-based vaccination (beta: 0.341, 95% confidence intervals [CI]: 0.144, 0.21, P<0.001) and higher CCI (beta: - 0.055, CI: - 0.096, - 0.014, P = 0.009) independently correlated with low IgG spike antibody levels. Conclusion(s): Patients with more comorbidities had a poor response to 3 doses of COVID-19 vaccination. Further studies are warranted to clarify the efficacy of booster vaccination in the population. The vaccine titer did not differ between patient with or without chronic liver disease.

Comparison of the Effectiveness of Different Covid-19 Vaccines among Plwh

Background: Previous studies have demonstrated promising serologic responses in PLWH receiving a third dose of vaccine against SARS-CoV-2. However, real-world clinical effectiveness, especially during the pandemic caused by B.1.1.529 variant, remains less investigated. Method(s): PLWH seeking HIV care at our hospital from 2021/6 to 2022/6 were included and advised to receive the third dose of COVID-19 vaccine. Individuals were excluded from this study if they had been previously diagnosed with COVID-19. Different types of COVID-19 vaccines were available in the vaccination program, including BNT162b2, mRNA-1273 (either 50 or 100 mug), MVC-COV1901 and NVX-CoV2373 vaccines. PLWH were screening for the occurrence of COVID-19 through the reporting system of notifiable diseases of Taiwan CDC, and were tested for anti-nucleocapsid (anti-N) IgG every 1 to 3 months. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, occurrence of SARS-CoV-2 infection, seroconversion of anti-N IgG, death, or loss to follow-up, whichever occurred first. Result(s): 1,496 PLWH were included: 631 (42.2%) receiving 100 mug mRNA-1273 vaccine, 468 (31.3%) 50 mug mRNA-1273 vaccine, and 328 (21.9%) BNT162b2 vaccine, 65 (4.3%) MVC-COV1901 vaccine, and 4 (0.3%) NVX-CoV2373 vaccine for the third dose of SARS-CoV-2 vaccination. 297 (19.9%) PLWH were diagnosed with COVID-19 during the follow-up period, including 92 (14.6%) who received 100 mug mRNA-1273, 111 (23.7%) 50 mug mRNA-1273, 79 (24.1%) BNT162b2 and 15 (21.7%) either MVC-COV1901 or NVX-CoV2373;in addition, 98 PLWH had seroconversion of anti-N IgG during follow-up, including 23, 50, 19 and 6 PLWH who received 100 mug mRNA-1273, 50 mug mRNA-1273, BNT162b2, and either MVC-COV1901 or NVX-CoV2373, respectively. Similar rates of new infection with SARS-CoV-2 or seroconversion of anti-N IgG were demonstrated regardless the vaccine type of the third dose (log-rank test, p=0.46). Factors associated with a diagnosis of SARS-CoV-2 infection and seroconversion of anti-N IgG included an age >50 years (aOR, 0.67;95% CI, 0.49-0.91) and newly infected with hepatitis C virus (HCV) (aOR, 1.41;95% CI, 1.09-1.83). Conclusion(s): Our study demonstrated that clinical effectiveness of the third dose of different vaccines available to PLWH was similar in preventing SARSCoV- 2 infection or seroconversion of anti-N IgG Taiwan. PLWH aged less than 50 years and those with newly diagnosed HCV infection were at higher risk of acquiring COVID-19. Kaplan-Meier survival curve for acquiring COVID-19 or seroconversion of anti-N IgG in PLWH receiving different COVID-19 vaccination of the third dose (log-rank test, 4 groups, p = 0.46).

REAL-WORLD EFFECTIVENESS OF mRNA, SUBUNIT, AND VECTOR-BASED VACCINES AGAINST COVID-19

Background: Limited Covid-19 vaccine effectiveness (VE) studies address the mRNA, adenoviral vector-based, and protein subunit vaccines and their mix and match in real-world settings. BNT162v2 (Pfizer-BioNTech), mRNA- 1273 (Moderna), AZD1222 (AstraZeneca), and locally produced MVC-COV1901 (Medigen) are provided under the National Vaccination Program. Taiwan maintained a low circulation of Covid-19 infection until a major epidemic Omicron BA.2, began in April 2022. The study aimed to estimate the VE against moderate and severe (severity) and fatal diseases (death) associated with SARS-CoV-2 among individuals administered one, two, and three doses of vaccination and categorized by vaccine type combinations in this predominantly infection-naive population. Method(s): The study included CDC's administrative records from National Immunization Information System and National Infectious Disease Reporting System from March 21, 2021, to September 30, 2022. Criteria for Covid-19 severity followed WHO's guidelines, and the committee reviewed the records. The study calculated each individual's last administered date to disease onset (incidence rate (IR) per 100,000 person-days) to explore the incidence rate to compare the presence of risk probabilities. Multiple logistic regression was used for vaccine effectiveness analysis. Result(s): Of 23,933,482 individuals included in the study, and 6,202,496 infections, 30,976 severity, and 10,851 deaths were observed. Compared with three doses administered, three doses of AZD1222 or it as primary series plus mRNA or protein-based vaccines were at higher risk of severity (IR: 0.390-0.762), followed by mRNA-1273 (IR: 0.316-0.471), MVC-COV1901 (IR: 0.044-0.196) and BNT162v2 (IR: 0.061-0.197). As for the death outcome, AZD1222 was at higher fatal risk (IR: 0.127-0.269), followed by mRNA-1273 (IR: 0.086-0.125), MVC-COV1901 (IR: 0.013-0.064) and BNT162v2 (IR: 0.015-0.045). VE against the severity of AZD1222 or it as primary series ranged from 65.9% to 77.7%;mRNA vaccines ranged from 86.4% to 96.1%;and protein-based vaccines ranged from 91.4% to 96.2%. A similar pattern of VE against death ranged from 60.9% to 73.7%, 88.2% to 96.2%, and 90.3% to 95.6%. Conclusion(s): Individuals who received their primary series as AZD1222 might not have adequate protection against Covid-19 severity so encourage those vulnerable groups to receive additional booster doses. The study also indicated that protein subunit vaccines provide similar protection against severity and death as mRNA vaccines. (Table Presented).

Case report of new-onset ulcerative colitis after MVC-COVI1901 vaccine injection for SARS-CoV-2.

A 23-year-old man suffered from diarrhea after receiving the MVC-COVI1901 vaccine. The patient then presented to our emergency department due to swelling and pain in his right knee. Synovial effusion studies of the right knee revealed inflammation. Gram and acid-fast stains reported negative results and no crystals were found under a polarized light microscope. During his hospitalization, the patient underwent a colonoscopy and computed tomography (CT) due to bloody stool. Pancolitis was suspected under colonoscopy and an abdominal CT scan supported our diagnosis showing wall thickening and mucosal enhancement. Pathology showed distorted crypt architecture and acute cryptitis with abscesses. After excluding other causes of ulcerative colitis (UC), the patient was diagnosed with MVC-COV1901 vaccine-related UC and inflammatory bowel disease arthropathy. Subsequent presentation of UC and inflammatory bowel disease-related arthropathy after receiving the MVC-COVI1901 vaccine has not previously been reported. We speculate that the pathogenesis could be correlated to the vaccine's components (spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide) through the combination of 2 effects: the activation of Toll-like receptor (TLR) 4 by S-2P, and the activation of TLR9 and expression of interleukin-13 by CpG-1018 adjuvant. In conclusion, it is remarkable that the MVC-COVI1901 vaccine may lead to the incidence of autoinflammatory diseases such as UC.

Effectiveness of Booster and Influenza Vaccines against COVID-19 among Healthcare Workers, Taiwan.

Among previously uninfected healthcare workers in Taiwan, mRNA COVID-19 booster vaccine was associated with lower odds of COVID-19 after primary recombinant vaccine. Symptom-triggered testing revealed that tetravalent influenza vaccine was associated with higher odds of SARS-CoV-2 infection. COVID-19 vaccination continues to be most effective against SARS-CoV-2.

Safety and immunogenicity of MVC-COV1901 vaccine in older adults: Phase 2 randomized dose-comparison trial.

INTRODUCTION: Older adults are subject to higher COVID-19 infection and mortality rates. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine have been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age, however, older adults were under-represented. METHODS: A double-blind, randomized, multi-center study compared safety and immunogenicity of high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart in 420 participants of 65 years and older. The results have been stratified by the comorbidity status. RESULTS: Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities. CONCLUSION: Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommend high dose for immunization of elder adults with MVC-COV1901. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04822025).

EFFECTIVENESS of COVID-19 VACCINATION among PEOPLE LIVING with HIV during AN OUTBREAK

Background: A large-scale community COVID-19 outbreak occurred between April and August 2021 in Taiwan, where non-pharmaceutical interventions (NPIs) have been strictly implemented and COVID-19 vaccination program was not implemented until 1 March, 2021. Although COVID-19 vaccination is recommended for at-risk populations, the vaccine effectiveness in people living with HIV (PLWH) remains incompletely understood. We evaluated the effectiveness of COVID-19 vaccination among PLWH during a COVID-19 outbreak in Taiwan. Methods: From 1 March to 30 September, 2021, all adult PLWH without previous SARS-CoV-2 infection were included and advised to receive 2 doses of COVID-19 vaccine. The government-funded vaccination campaign provided different types of COVID-19 vaccine, including ChAdOx1 nCoV-19 (AZD1222), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and MVC-COV1901 (Medigen) vaccines. The primary endpoint of this study was the vaccine effectiveness in preventing COVID-19 among PLWH, which was estimated by comparing incidence rates between the unvaccinated, partially vaccinated, and fully vaccinated groups in a dynamic cohort. Results: During the study period, 3131 PLWH were included, with 99.9% on antiretroviral therapy, 99.8% being MSM and median CD4 count of 627 cells/mm3. In the dynamic cohort, 3128 PLWH contributed 516892 person-days of follow-up (PDFU) to the unvaccinated group, 2476 PLWH contributed 139163 PDFU to the partially vaccinated group, and 236 PLWH contributed 12011 PDFU to the fully vaccinated group (Table). During the follow-up, 37 PLWH (1.2%) acquired SARS-CoV-2 infections. The incidence rate of SARS-CoV-2 infection was 6.4 per 100,000 PDFU in the unvaccinated group, which decreased to 2.9 and 0 per 100,000 PDFU in the partially and fully vaccinated groups, respectively. The adjusted incidence rate ratios were 0.47 (95% CI, 0.17-1.32) in the partially vaccinated group and <0.01 in the fully vaccinated group compared with the unvaccinated group, resulting in vaccine effectiveness rates of 53.4% and 99.9% for single-and 2-dose COVID-19 vaccination, respectively. Conclusion: COVID-19 vaccination was clinically effective among PLWH during the outbreak setting where NPIs were strictly implemented.