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.

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.