Waning effectiveness against COVID-19-related hospitalization, severe complications, and mortality with two to three doses of CoronaVac and BNT162b2: a case-control study.

BACKGROUND: This study aims to evaluate waning effectiveness against severe and fatal COVID-19 with two to three doses of CoronaVac/BNT162b2, where data are limited. METHODS: A case-control study included individuals aged ≥18 years, unvaccinated or received two to three doses of CoronaVac/BNT162b2, using electronic healthcare databases in Hong Kong. Those with first COVID-19-related hospitalization, severe complications, or mortality between 1 January and 15 August 2022 were defined as cases and matched with up-to-10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness (VE) against COVID-19-related outcomes was estimated at different time intervals from second and third-dose vaccination (0-13 up-to 210-240 days) using conditional logistic regression adjusted for comorbidities and medications. RESULTS: By 211-240 days after second dose, VE against COVID-19-related hospitalization reduced to 46.6% (40.7-51.8%) for BNT162b2 and 36.2% (28.0-43.4%) for CoronaVac, and VE against COVID-19-related mortality were 73.8% (55.9-84.4%) and 76.6% (60.8-86.0%). After third dose, VE against COVID-19-related hospitalization decreased from 91.2% (89.5-92.6%) for BNT162b2 and 76.7% (73.7-79.4%) for CoronaVac at 0-13 days, to 67.1% (60.4-72.6%) and 51.3% (44.2-57.5%) at 91-120 days. VE against COVID-19-related mortality for BNT162b2 remained high from 0-13 days [98.2% (95.0-99.3%)] to 91-120 days [94.6% (77.7-98.7%)], and for CoronaVac reduced from 0-13 days [96.7% (93.2-98.4%)] to 91-120 days [86.4% (73.3-93.1%)]. CONCLUSIONS: Significant risk reduction against COVID-19-related hospitalization and mortality after CoronaVac or BNT162b2 vaccination was observed for >240 and >120 days after second and third doses compared to unvaccinated, despite significant waning over time. Timely administration of booster doses could provide higher levels of protection.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.

BACKGROUND: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain. OBJECTIVE: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak. DESIGN: Target trial emulation study. SETTING: Electronic health databases in Hong Kong. PARTICIPANTS: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119). INTERVENTION: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir. MEASUREMENTS: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days. RESULTS: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people. LIMITATION: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist. CONCLUSION: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed. PRIMARY FUNDING SOURCE: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

mRNA (BNT162b2) and Inactivated (CoronaVac) COVID-19 Vaccination and Risk of Adverse Events and Acute Diabetic Complications in Patients with Type 2 Diabetes Mellitus: A Population-Based Study.

INTRODUCTION: In Hong Kong, CoronaVac and BNT162b2 have been approved for emergency use owing to the coronavirus disease 2019 (COVID-19) pandemic. Reactions towards the vaccine and the risk of post-vaccination adverse events may be different between recipients with and without type 2 diabetes mellitus (T2DM). OBJECTIVE: The aim of this study was to evaluate the risk of adverse events of special interest (AESI) and acute diabetic complications in the T2DM population after COVID-19 vaccination in Hong Kong. RESEARCH DESIGN AND METHODS: Self-controlled case-series analysis was conducted. Patients with T2DM who received at least one dose of BNT162b2 or CoronaVac between 23 February 2021 and 31 January 2022 from electronic health records in Hong Kong were included. The incidence rates of 29 AESIs and acute diabetic complications (any of severe hypoglycemia, diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome) requiring hospitalization within 21 days after the first or second dose of vaccination were reported. The risks of these outcomes were evaluated using conditional Poisson regression. RESULTS: Among 141,224 BNT162b2 recipients and 209,739 CoronaVac recipients with T2DM, the incidence per 100,000 doses and incidence per 100,000 person-years of individual AESIs and acute diabetic complications ranged from 0 to 24.4 and 0 to 438.6 in BNT162b2 group, and 0 to 19.5 and 0 to 351.6 in CoronaVac group. We did not observe any significantly increased risk of individual AESIs or acute diabetic complications after first or second doses of BNT162b2 or CoronaVac vaccine. Subgroup analysis based on HbA1c < 7% and ≥ 7% also did not show significantly excess risk after vaccination. CONCLUSIONS: Patients with T2DM do not appear to have higher risks of AESI and acute diabetic complications after BNT162b2 or CoronaVac vaccination. Moreover, given the low incidence of AESIs and acute diabetic complications after vaccination, the absolute risk increment was likely minimal.

Effectiveness of BNT162b2 and CoronaVac vaccinations against SARS-CoV-2 omicron infection in people aged 60 years or above: a case-control study.

BACKGROUND: In view of limited evidence that specifically addresses vaccine effectiveness (VE) in the older population, this study aims to evaluate the real-world effectiveness of BNT162b2 and CoronaVac in older adults during the Omicron BA.2 outbreak. METHODS: This case-control study analysed data available between January and March 2022 from the electronic health databases in Hong Kong and enrolled individuals aged 60 or above. Each case was matched with up to 10 controls by age, sex, index date and Charlson Comorbidity Index for the four outcomes (COVID-19 infection, COVID-19-related hospitalisation, severe complications, and all-cause mortality) independently. Conditional logistic regression was conducted to evaluate VE of BNT162b2 and CoronaVac against COVID-19-related outcomes within 28 days after COVID-19 infection among participants stratified by age groups (60-79, ≥ 80 years old). RESULTS: A dose-response relationship between the number of vaccine doses received and protection against severe or fatal disease was observed. Highest VE (95% CI) against COVID-19 infection was observed in individuals aged ≥80 who received three doses of BNT162b2 [75.5% (73.1%-77.7%)] or three doses of CoronaVac [53.9% (51.0%-56.5%)] compared to those in the younger age group who received three doses of BNT162b2 [51.1% (49.9%-52.4%)] or three doses of CoronaVac [2.0% (-0.1%-4.1%)]. VE (95% CI) was higher for other outcomes, reaching 91.9% (89.4%-93.8%) and 86.7% (84.3%-88.8%) against COVID-19-related hospitalisation; 85.8% (61.2%-94.8%) and 89.8% (72.4%-96.3%) against COVID-19-related severe complications; and 96.4% (92.9%-98.2%) and 95.0% (92.1%-96.8%) against COVID-19-related mortality after three doses of BNT162b2 and CoronaVac in older vaccine recipients, respectively. A similar dose-response relationship was established in younger vaccine recipients and after stratification by sex and Charlson Comorbidity Index. CONCLUSION: Both BNT162b2 and CoronaVac vaccination were effective in protecting older adults against COVID-19 infection and COVID-19-related severe outcomes amidst the Omicron BA.2 pandemic, and VE increased further with the third dose.

Effectiveness of BNT162b2 and CoronaVac vaccinations against mortality and severe complications after SARS-CoV-2 Omicron BA.2 infection: a case-control study.

Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case-control study to evaluate the risk of severe complications and mortality following 1-3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6-92.3) and 74.8% (72.5-76.9) in those aged ≥65, 87.6% (81.4-91.8) and 80.7% (72.8-86.3) in those aged 50-64, 86.6% (71.0-93.8) and 82.7% (56.5-93.1) in those aged 18-50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6-87.3) and 58.9% (50.3-66.1) in those aged ≥65, 83.0% (69.6-90.5) and 67.1% (47.1-79.6) in those aged 50-64, 78.3% (60.8-88.0) and 77.8% (49.6-90.2) in those aged 18-50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5-98.9) for BNT162b2 and 95.5% (93.7-96.8) for CoronaVac against mortality, 90.8% (83.4-94.9) and 88.0% (80.8-92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose.

Safety of an inactivated, whole-virion COVID-19 vaccine (CoronaVac) in people aged 60 years or older in Hong Kong: a modified self-controlled case series.

Background: Because evidence on the safety of COVID-19 vaccines in older adults is scarce, we aimed to evaluate the incidence and risk of adverse events after CoronaVac (Sinovac Biotech) vaccination in adults aged 60 years or older. Methods: In this modified self-controlled case series, we enrolled adults aged 60 years or older who had received at least one dose of CoronaVac in Hong Kong between Feb 23, 2021, and Jan 31, 2022. We extracted population-based, electronic health record data from the clinical management system of the Hospital Authority on adverse events of special interest (from Jan 1, 2005, to Feb 23, 2022) and patients' demographic information (from Jan 1, 2018, to Jan 31, 2022), previous diagnoses (from Jan 1, 2018, to Jan 31, 2022), medication history (from Jan 1, 2018, to Jan 31, 2022), and laboratory tests, including those for SARS-CoV-2 infection (from Jan 1, 2018, to Jan 31, 2022). Details of vaccination status were provided by the Department of Health of the Hong Kong Government and were linked to data from the Hospital Authority with identity card numbers or passport numbers. Our outcomes were the overall incidence of any adverse event of special interest and the incidence rates of 30 adverse events of special interest, as suggested by the WHO Global Advisory Committee on Vaccine Safety, in the inpatient setting within 21 days (2 days for anaphylaxis) of either the first, second, or third CoronaVac dose compared with a baseline period. Individuals who had a history of a particular event between Jan 1, 2005, and Feb 23, 2021, were excluded from the corresponding analysis. We evaluated the risk of an adverse event of special interest using conditional Poisson regression, adjusting for seasonal effects. Findings: Of 1 253 497 individuals who received at least one dose of CoronaVac during the study period, 622 317 (49·6%) were aged at least 60 years and were included in the analysis. Our analysis sample received 1 229 423 doses of CoronaVac and had a mean age of 70·40 years (SD 8·10). 293 086 (47·1%) of 622 317 participants were men and 329 231 (52·9%) were women. The incidence of individual adverse events of interest ranged from 0·00 per 100 000 people to 57·49 per 100 000 people (thromboembolism). The first and third doses of CoronaVac were not associated with a significant excess risk of an adverse event of special interest within 21 days (or 2 days for anaphylaxis) of vaccination. After the second dose, the only significantly increased risk was for anaphylaxis (adjusted incidence rate ratio 2·61, 95% CI 1·08-6·31; risk difference per 100 000 people 0·61, 95% CI 0·03-1·81). Interpretation: Because older age is associated with poor outcomes after SARS-CoV-2 infection, the benefits of CoronaVac vaccination in older adults outweigh the risks in regions where COVID-19 is prevalent. Ongoing monitoring of vaccine safety is warranted. Funding: The Food and Health Bureau of the Government, Hong Kong Special Administrative Region, China and AIR@InnoHK, administered by the Innovation and Technology Commission. Translation: For the Chinese translation of the abstract see Supplementary Materials section.