Risk of glomerular diseases, proteinuria and hematuria following mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines.

BACKGROUND: With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines. METHODS: A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100 000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment. RESULTS: Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100 000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100 000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR = 0.76, 95% CI 0.56-1.03; CoronaVac: IRR = 0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR = 0.92, 95% CI 0.72-1.17; CoronaVac: IRR = 0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR = 0.39. 95% CI 0.15-1.03; CoronaVac: IRR = 1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines. CONCLUSIONS: There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines.

Risk of carditis after three doses of vaccination with mRNA (BNT162b2) or inactivated (CoronaVac) covid-19 vaccination: a self-controlled cases series and a case–control study

Background Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac. Methods We conducted a self-controlled case series (SCCS) and a case–control study using electronic health and vaccination records in Hong Kong. Carditis incidents within 28 days of covid-19 vaccination were included as cases. In the case–control study, up to 10 hospitalized controls were selected with stratified probability sampling by age, sex, and hospital admission (±1 day). The incidence rate ratios (IRRs) were reported from conditional Poisson regressions for SCCS, and adjusted odds ratios (ORs) were reported from multivariable logistic regressions. Findings A total of 8,924,614 doses of BNT162b2 and 6,129,852 doses of CoronaVac were administered from February 2021 to March 2022. The SCCS detected increased carditis risks after BNT162b2: 4.48 (95%confidence interval [CI]:2.99–6.70] in 1–14 days and 2.50 (95%CI:1.43–4.38) in 15–28 days after first dose;10.81 (95%CI:7.63–15.32) in 1–14 days and 2.95 (95%CI:1.82–4.78) in 15–28 days after second dose;4.72 (95%CI:1.40–15.97) in 1–14 days after third dose. Consistent results were observed from the case–control study. Risks were specifically found in people aged below 30 years and males. No significant risk increase was observed after CoronaVac in all primary analyses. Interpretations We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were not higher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed. Funding : This study was funded by Hong Kong 10.13039/501100005407Health Bureau (COVID19F01).

Effectiveness of BNT162b2 and CoronaVac vaccines in preventing SARS-CoV-2 Omicron infections, hospitalizations, and severe complications in the pediatric population in Hong Kong: a case-control study.

Severe COVID-19 appears to be disproportionately more common in children and adolescents since the emergence of Omicron. More evidence regarding vaccine effectiveness (VE) is urgently needed to assist policymakers in making decisions and minimize vaccine hesitancy among the public. This was a case-control study in the pediatric population using data extracted from the electronic health records database in Hong Kong. Individuals aged 3-17 with COVID-19 confirmed by polymerase chain reaction were included in the study. Each case was matched with up to 10 controls based on age, gender, and index date (within 3 calendar days). The VE of BNT162b2 and CoronaVac in preventing COVID-19, hospitalizations, and severe outcomes were estimated using conditional logistic regression adjusted by patients' comorbidities and medication history during the outbreak from January to August 2022. A total of 36,434 COVID-19 cases, 2231 COVID-19-related hospitalizations, and 1918 severe COVID-19 cases were matched to 109,004, 21,788, and 18,823 controls, respectively. Compared to the unvaccinated group, three doses of BNT162b2 or CoronaVac was associated with reduced risk of infection [VE: BNT162b2: 56.0% (95% CI: 49.6-61.6), CoronaVac: 39.4% (95% CI: 25.6-50.6)], hospitalization [VE: BNT162b2: 58.9% (95% CI: 36.1-73.6), CoronaVac: 51.7% (11.6-73.6)], and severe outcomes [VE: BNT162b2: 60.2% (95% CI: 33.7-76.1), CoronaVac: 42.2% (95% CI: -6.2-68.6)]. Our findings showed that three doses of BNT162b2 or CoronaVac was effective in preventing COVID-19, hospitalizations, and severe outcomes among the pediatric population during Omicron-dominant pandemic, which was further enhanced after a booster dose.

Risk of carditis after three doses of vaccination with mRNA (BNT162b2) or inactivated (CoronaVac) covid-19 vaccination: a self-controlled cases series and a case-control study.

Background: Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac. Methods: We conducted a self-controlled case series (SCCS) and a case-control study using electronic health and vaccination records in Hong Kong. Carditis incidents within 28 days of covid-19 vaccination were included as cases. In the case-control study, up to 10 hospitalized controls were selected with stratified probability sampling by age, sex, and hospital admission (±1 day). The incidence rate ratios (IRRs) were reported from conditional Poisson regressions for SCCS, and adjusted odds ratios (ORs) were reported from multivariable logistic regressions. Findings: A total of 8,924,614 doses of BNT162b2 and 6,129,852 doses of CoronaVac were administered from February 2021 to March 2022. The SCCS detected increased carditis risks after BNT162b2: 4.48 (95%confidence interval [CI]:2.99-6.70] in 1-14 days and 2.50 (95%CI:1.43-4.38) in 15-28 days after first dose; 10.81 (95%CI:7.63-15.32) in 1-14 days and 2.95 (95%CI:1.82-4.78) in 15-28 days after second dose; 4.72 (95%CI:1.40-15.97) in 1-14 days after third dose. Consistent results were observed from the case-control study. Risks were specifically found in people aged below 30 years and males. No significant risk increase was observed after CoronaVac in all primary analyses. Interpretations: We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were not higher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed. Funding: : This study was funded by Hong Kong Health Bureau (COVID19F01).

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.

Comparing hybrid and regular COVID-19 vaccine-induced immunity against the Omicron epidemic.

Evidence on the effectiveness of COVID-19 vaccines among people who recovered from a previous SARS-CoV-2 infection is warranted to inform vaccination recommendations. Using the territory-wide public healthcare and vaccination records of over 2.5 million individuals in Hong Kong, we examined the potentially differential risk of SARS-CoV-2 infection, hospitalization, and mortality between those receiving two homologous doses of BNT162b2 or CoronaVac versus those with a previous infection receiving only one dose amid the Omicron epidemic. Results show a single dose after a SARS-CoV-2 infection is associated with a lower risk of infection (BNT162b2: adjusted incidence rate ratio [IRR] = 0.475, 95% CI: 0.410-0.550; CoronaVac: adjusted IRR = 0.397, 95% CI: 0.309-0.511) and no significant difference was detected in the risk of COVID-19-related hospitalization or mortality compared with a two-dose vaccination regimen. Findings support clinical recommendations that those with a previous infection could receive a single dose to gain at least similar protection as those who received two doses without a previous infection.

Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients.

BACKGROUND: In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset. METHODS: We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves' disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression. RESULTS: A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670-1.114; CoronaVac: IRR 0.707, 95% CI 0.549-0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716-1.159; CoronaVac: IRR 0.778, 95% CI 0.618-0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744-1.023; CoronaVac: IRR 0.830, 95% CI 0.713-0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838-1.199; CoronaVac: IRR 0.963, 95% CI 0.807-1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770-1.227; CoronaVac: IRR 0.879, 95%CI 0.693-1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833-1.246; CoronaVac: IRR 0.768, 95% CI 0.613-0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899-1.201; CoronaVac: IRR 0.911, 95% CI 0.786-1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794-1.102; CoronaVac: IRR 0.945, 95% CI 0.799-1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines. CONCLUSIONS: Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.

Risk of acute liver injury following the mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines.

BACKGROUND & AIMS: Case reports of severe acute liver injury (ALI) following COVID-19 vaccination have recently been published. We evaluated the risks of ALI following COVID-19 vaccination (BNT162b2 or CoronaVac). METHODS: We conducted a modified self-controlled case series analysis using the vaccination records in Hong Kong with data linkage to electronic medical records from a territory-wide healthcare database. Incidence rate ratios (IRRs) for ALI outcome in the 56-day period following first and second doses of COVID-19 vaccines in comparison to the non-exposure period were estimated and compared to the ALI risk in patients with SARS-CoV-2 infection. RESULTS: Among 2,343,288 COVID-19 vaccine recipients who were at risk, 4,677 patients developed ALI for the first time between 23rd February 2021 to 30th September 2021. The number of ALI cases within 56 days after the first and second dose of vaccination were 307 and 521 (335 and 334 per 100,000 person-years) for BNT162b2, and 304 and 474 (358 and 403 per 100,000 person-years) for CoronaVac, respectively, compared to 32,997 ALI cases per 100,000 person-years among patients within 56 days of SARS-CoV-2 infection. Compared to the non-exposure period, no increased risk was observed in the 56-day risk period for first (IRR 0.800; 95% CI 0.680-0.942) and second (IRR 0.944; 95% CI 0.816-1.091) dose of BNT162b2, or first (IRR 0.689; 95% CI 0.588-0.807) and second (IRR 0.905; 95% CI 0.781-1.048) dose of CoronaVac. There were no severe or fatal cases of ALI following COVID-19 vaccination. CONCLUSION: There was no evidence of an increased risk of ALI associated with BNT162b2 or CoronaVac vaccination. Based on all current available evidence from previous studies and our study, the benefit of mass vaccination far outweighs the ALI risk from vaccination. LAY SUMMARY: There have been some recent reports that COVID-19 vaccination could be associated with acute liver injury. In our study, we found no evidence that COVID-19 vaccination increased the risk of acute liver injury, which was much more common after SARS-CoV-2 infection than after vaccination. Hence, our study provides further data indicating that the benefits of mass COVID-19 vaccination outweigh the potential risks.

Adverse events of special interest and mortality following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines in Hong Kong: A retrospective study.

BACKGROUND: Safety monitoring of coronavirus disease 2019 (COVID-19) vaccines is crucial during mass vaccination rollout to inform the choice of vaccines and reduce vaccine hesitancy. Considering the scant evidence directly comparing the safety profiles of mRNA and inactivated SARS-CoV-2 vaccines, this territory-wide cohort study aims to compare the incidence of various adverse events of special interest (AESIs) and all-cause mortality between CoronaVac (inactivated vaccine) and BNT162b2 (mRNA-based vaccine). Our results can help vaccine recipients make an informed choice. METHODS AND FINDINGS: A retrospective, population-based cohort of individuals who had received at least 1 dose of BNT162b2 or CoronaVac from 23 February to 9 September 2021 in Hong Kong, and had data linkage to the electronic medical records of the Hong Kong Hospital Authority, were included. Those who had received mixed doses were excluded. Individuals were observed from the date of vaccination (first or second dose) until mortality, second dose vaccination (for first dose analysis), 21 days after vaccination, or 30 September 2021, whichever came first. Baseline characteristics of vaccinated individuals were balanced between groups using propensity score weighting. Outcome events were AESIs and all-cause mortality recorded during 21 days of post-vaccination follow-up after each dose, except anaphylaxis, for which the observation period was restricted to 2 days after each dose. Incidence rate ratios (IRRs) of AESIs and mortality comparing between CoronaVac and BNT162b2 recipients were estimated after each dose using Poisson regression models. Among 2,333,379 vaccinated individuals aged 18 years or above, the first dose analysis included 1,308,820 BNT162b2 and 955,859 CoronaVac recipients, while the second dose analysis included 1,116,677 and 821,560 individuals, respectively. The most frequently reported AESI among CoronaVac and BNT162b2 recipients was thromboembolism (first dose: 431 and 290 per 100,000 person-years; second dose: 385 and 266 per 100,000 person-years). After the first dose, incidence rates of overall AESIs (IRR = 0.98, 95% CI 0.89-1.08, p = 0.703) and mortality (IRR = 0.96, 95% CI 0.63-1.48, p = 0.868) associated with CoronaVac were generally comparable to those for BNT162b2, except for Bell palsy (IRR = 1.95, 95% CI 1.12-3.41, p = 0.018), anaphylaxis (IRR = 0.34, 95% CI 0.14-0.79, p = 0.012), and sleeping disturbance or disorder (IRR = 0.66, 95% CI 0.49-0.89, p = 0.006). After the second dose, incidence rates of overall AESIs (IRR = 0.97, 95% CI 0.87-1.08, p = 0.545) and mortality (IRR = 0.85, 95% CI 0.51-1.40, p = 0.516) were comparable between CoronaVac and BNT162b2 recipients, with no significant differences observed for specific AESIs. The main limitations of this study include residual confounding due to its observational nature, and the possibility of its being underpowered for some AESIs with very low observed incidences. CONCLUSIONS: In this study, we observed that the incidences of AESIs (cumulative incidence rate of 0.06%-0.09%) and mortality following the first and second doses of CoronaVac and BNT162b2 vaccination were very low. The safety profiles of the vaccines were generally comparable, except for a significantly higher incidence rate of Bell palsy, but lower incidence rates of anaphylaxis and sleeping disturbance or disorder, following first dose CoronaVac versus BNT162b2 vaccination. Our results could help inform the choice of inactivated COVID-19 vaccines, mainly administered in low- and middle-income countries with large populations, in comparison to the safety of mRNA vaccines. Long-term surveillance on the safety profile of COVID-19 vaccines should continue.

Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study.

Background: Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. Results: In total, 47,086 LT4 users were identified (BNT162b2: n = 12,310; CoronaVac: n = 11,353; and unvaccinated: n = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. Conclusions: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.