Association of COVID-19 with acute and post-acute risk of multiple different complications and mortality in patients infected with omicron variant stratified by initial disease severity: a cohort study in Hong Kong.

BACKGROUND: Few studies have attempted to use clinical and laboratory parameters to stratify COVID-19 patients with severe versus non-severe initial disease and evaluate age-specific differences in developing multiple different COVID-19-associated disease outcomes. METHODS: A retrospective cohort included patients from the electronic health database of Hong Kong Hospital Authority between 1 January 2022 and 15 August 2022 until 15 November 2022. The cohort was divided into three cohorts by age (≤ 40, 41-64, and ≥ 65 years old). Each age cohort was stratified into four groups: (1) COVID-19 critically exposed group (ICU admission, mechanical ventilation support, CRP > 80 mg/L, or D-dimer > 2 g/mL), (2) severely exposed group (CRP 30-80 mg/L, D-dimer 0.5-2 g/mL, or CT value < 20), (3) mildly-moderately exposed group (COVID-19 positive-tested but not fulfilling the criteria for the aforementioned critically and severely exposed groups), and (4) unexposed group (without COVID-19). The characteristics between groups were adjusted with propensity score-based marginal mean weighting through stratification. Cox regression was conducted to determine the association of COVID-19 disease severity with disease outcomes and mortality in the acute and post-acute phase (< 30 and ≥ 30 days from COVID-19 infection) in each age group. RESULTS: A total of 286,114, 320,304 and 194,227 patients with mild-moderate COVID-19 infection; 18,419, 23,678 and 31,505 patients with severe COVID-19 infection; 1,168, 2,261 and 10,178 patients with critical COVID-19 infection, and 1,143,510, 1,369,365 and 1,012,177 uninfected people were identified in aged ≤ 40, 40-64, and ≥ 65 groups, respectively. Compared to the unexposed group, a general trend tending towards an increase in risks of multiple different disease outcomes as COVID-19 disease severity increases, with advancing age, was identified in both the acute and post-acute phases. Notably, the mildly-moderately exposed group were associated with either insignificant risks (aged ≤ 40) or the lowest risks (aged > 40) for the disease outcomes in the acute phase of infection (e.g., mortality risk HR (aged ≤ 40): 1.0 (95%CI: 0.5,2.0), HR (aged 41-64): 2.1 (95%CI: 1.8, 2.6), HR (aged > 65): 4.8 (95%CI: 4.6, 5.1)); while in the post-acute phase, these risks were largely insignificant in those aged < 65, remaining significant only in the elderly (age ≥ 65) (e.g., mortality risk HR (aged ≤ 40): 0.8 (95%CI: (0.5, 1.0)), HR (aged 41-64): 1.1 (95%CI: 1.0,1.2), HR (aged > 65): 1.5 (95%CI: 1.5,1.6)). Fully vaccinated patients were associated with lower risks of disease outcomes than those receiving less than two doses of vaccination. CONCLUSIONS: The risk of multiple different disease outcomes in both acute and post-acute phases increased significantly with the increasing severity of acute COVID-19 illness, specifically among the elderly. Moreover, future studies could improve by risk-stratifying patients based on universally accepted thresholds for clinical parameters, particularly biomarkers, using biological evidence from immunological studies.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Comparing the effectiveness of molnupiravir and nirmatrelvir-ritonavir in non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes: A target trial emulation study.

AIMS: To compare the effectiveness of molnupiravir and nirmatrelvir-ritonavir for non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: Territory-wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential trial approach. Patients (1) aged ≥18 years, (2) with T2DM, (3) with COVID-19 infection, and (4) who received molnupiravir or nirmatrelvir-ritonavir within 5 days of infection between 16 March 2022 and 31 December 2022 in non-hospital and hospital settings were included. Molnupiravir and nirmatrelvir-ritonavir initiators were matched using one-to-one propensity-score matching and followed for 28 days. Risk of outcomes was compared between groups by Cox regression adjusted for baseline characteristics. Subgroup analyses were performed on age (<70 years, ≥70 years), sex, Charlson comorbidity index (<4, ≥4), and number of COVID-19 vaccine doses (<2 doses, ≥2 doses). RESULTS: Totals of 17 974 non-hospitalized (8987 in each group) and 3678 hospitalized (1839 in each group) patients were identified. Non-hospitalized nirmatrelvir-ritonavir initiators had lower risk of all-cause mortality (absolute risk reduction [ARR] at 28 days 0.80%, 95% confidence interval [CI] 0.56-1.04; hazard ratio [HR] 0.47, 95% CI 0.30-0.73) and hospitalization (ARR at 28 days 4.01%, 95% CI 3.19-4.83; HR 0.73, 95% CI 0.66-0.82) as compared with molnupiravir initiators. Hospitalized nirmatrelvir-ritonavir initiators had reduced risk of all-cause mortality (ARR at 28 days 2.94%, 95% CI 1.65-4.23; HR 0.56, 95% CI 0.40-0.80) as compared with molnupiravir initiators. Consistent findings were found across all subgroups. CONCLUSIONS: The use of nirmatrelvir-ritonavir may be preferred to molnupiravir for COVID-19 patients with T2DM and without contraindication to either treatment.

Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study.

BACKGROUND: Molnupiravir and nirmatrelvir-ritonavir are orally administered pharmacotherapies for mild to moderate COVID-19. However, the effectiveness of these drugs among very old (≥80 years), hospitalised patients remains unclear, limiting the risk-benefit assessment of these antivirals in this specific group. This study investigates the effectiveness of these antivirals in reducing mortality among this group of hospitalised patients with COVID-19. METHODS: Using a territory-wide public healthcare database in Hong Kong, a target trial emulation study was conducted with data from 13 642 eligible participants for the molnupiravir trial and 9553 for the nirmatrelvir-ritonavir trial. The primary outcome was all-cause mortality. Immortal time and confounding bias was minimised using cloning-censoring-weighting approach. Mortality odds ratios were estimated by pooled logistic regression after adjusting confounding biases by stabilised inverse probability weights. RESULTS: Both molnupiravir (HR: 0.895, 95% CI: 0.826-0.970) and nirmatrelvir-ritonavir (HR: 0.804, 95% CI: 0.678-0.955) demonstrated moderate mortality risk reduction among oldest-old hospitalised patients. No significant interaction was observed between oral antiviral treatment and vaccination status. The 28-day risk of mortality was lower in initiators than non-initiators for both molnupiravir (risk difference: -1.09%, 95% CI: -2.29, 0.11) and nirmatrelvir-ritonavir (risk difference: -1.71%, 95% CI: -3.30, -0.16) trials. The effectiveness of these medications was observed regardless of the patients' prior vaccination status. CONCLUSIONS: Molnupiravir and nirmatrelvir-ritonavir are moderately effective in reducing mortality risk among hospitalised oldest-old patients with COVID-19, regardless of their vaccination status.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Here, we quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022. We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR: 1.66; 95% CI: 1.07, 2.59; p = 0.02) after the first dose. Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity: a territory-wide target trial emulation.

OBJECTIVES: Older individuals with multimorbidity are at an elevated risk of infection and complications from COVID-19. Effectiveness of post-COVID-19 interventions or care models in reducing subsequent adverse outcomes in these individuals have rarely been examined. This study aims to examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged 85 years or above with multimorbidity. DESIGN: Retrospective cohort study emulating a randomised target trial using electronic health records. SETTING: We used data from the Hospital Authority and the Department of Health in Hong Kong, which provided comprehensive electronic health records, COVID-19 confirmed case data, population-based vaccination records and other individual characteristics for the study. PARTICIPANTS: Adults aged 85 years or above with multimorbidity who were discharged after hospitalisation for COVID-19 between January 2020 and August 2022. INTERVENTIONS: Attending a general outpatient within 30 days of last COVID-19 discharge defined the exposure, compared to no outpatient visit. MAIN OUTCOME MEASURES: Primary outcome was all-cause mortality within one year. Secondary outcomes included mortality from respiratory, cardiovascular and cancer causes. RESULTS: A total of 6183 eligible COVID-19 survivors were included in the analysis. The all-cause mortality rate following COVID-19 hospitalisation was lower in the general outpatient visit group (17.1 deaths per 100 person-year) compared with non-visit group (42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI 8.1% to 14.4%). We also observed significantly better survival from respiratory diseases in the general outpatient visit group (difference in 1-year survival: 6.3%, 95% CI 3.5% to 8.9%). In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a general outpatient visit after COVID-19 discharge, the better the survival. CONCLUSIONS: Timely primary care consultations after COVID-19 hospitalisation may improve survival following COVID-19 hospitalisation among older adults aged 85 or above with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being.

Age-specific Multimorbidity Patterns and Burden on All-Cause Mortality and Public Direct Medical Expenditure: A Retrospective Cohort Study.

OBJECTIVE: To evaluate age-specific multimorbidity patterns and morbidity burden on mortality and healthcare expenditure across age groups. PATIENTS AND METHODS: Retrospective observational study between January 1, 2009 to December 31, 2017 using electronic health records in Hong Kong: Individuals were stratified by age (< 50, 50-64, 65-79, ≥ 80), and sub-classified by number of morbidities (0, 1, 2, 3, ≥ 4) out of 21 common chronic conditions. Clustering analyses were conducted to identify specific patterns of multimorbidity. Association between the number as well as combinations of morbidities and all-cause mortality and public expenditure was examined. RESULTS: 4,562,832 individuals with a median follow-up of 7 years were included. Mental disorders were the top morbidities among young individuals, while cardiovascular diseases were prevalent in the elderly. An increased number of morbidities was associated with a greater relative risk for mortality and medical expenditure, and this relationship was stronger among younger patients. Compared to individuals in the same age group without morbidity, the hazard ratios (HR; 95% CI) of all-cause mortality in patients aged < 50 and ≥ 80 with two comorbidities 3.81 (3.60-4.03) and 1.38 (1.36-1.40), respectively, which increased to 14.22 (9.87-20.47) and 2.20 (2.13-2.26), respectively, as the number of morbidities increased to ≥ 4. The stroke-hypertension cluster was shown to be associated with the highest HR of mortality 2.48 (2.43-2.53) among all identified clusters arising from the clustering analysis. CONCLUSION: Given the stronger association between multimorbidity and all-cause mortality and greater opportunity costs in younger populations, prevention and management of early-onset multimorbidity are warranted. (248 words).

Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.

BACKGROUND: Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited. OBJECTIVE: The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals. METHODS: Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not. RESULTS: A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. CONCLUSIONS: Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.

Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity: a territory-wide target trial emulation.

BACKGROUND: Older adults with multimorbidity are at high risk of mortality following COVID-19 hospitalisation. However, the potential benefit of timely primary care follow-up on severe outcomes post-COVID-19 has not been well established. AIM: To examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged ≥85 years, with multimorbidity. METHOD: We emulated a target trial using a comprehensive public healthcare database in Hong Kong. The cloning-censoring-weighting technique was used to minimise immortal time bias and confounding bias by adjusting for demographics, hospitalisation duration and ICU admission, baseline chronic conditions, and medication history. The outcome included all-cause and cause-specific mortality. RESULTS: Of 6183 eligible COVID-19 survivors, the all-cause mortality rate following COVID-19 hospitalisation was lower in general out-patient clinics (GOPC) group compared to non-GOPC group (17.1 versus 42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI = 8.1% to 14.4%). We also observed better survival from respiratory diseases in the GOPC group. In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a GOPC visit after COVID-19 discharge, the better the survival. CONCLUSION: Timely primary care consultations after discharge may improve survival following COVID-19 hospitalisation among older adults aged ≥85 years, with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being.

Comparative effectiveness and safety of BNT162b2 and CoronaVac in Hong Kong: A target trial emulation.

OBJECTIVES: To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety. METHODS: This target trial emulation study included individuals aged ≥12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization, and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups. RESULTS: A total of 639,818 and 1804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (95% confidence intervals [CI]) were 0.844 [0.833-0.856] and 0.749 [0.743-0.755] for COVID-19 infection, 0.692 [0.656-0.731] and 0.582 [0.559-0.605] for hospitalization, 0.566 [0.417-0.769] and 0.590 [0.458-0.76] for severe COVID-19, and 0.563 [0.456-0.697] and 0.457 [0.372-0.561] for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (incidence rate ratio [IRR] [95% CI]: 8.999 [1.14-71.017]) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR [95% CI]: 2.000 [0.500-7.996]). CONCLUSION: BNT162b2 has higher effectiveness among individuals aged ≥12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk.

Clinical subtypes of older adults starting long-term care in Japan and their association with prognoses: a data-driven cluster analysis.

We aimed to identify the clinical subtypes in individuals starting long-term care in Japan and examined their association with prognoses. Using linked medical insurance claims data and survey data for care-need certification in a large city, we identified participants who started long-term care. Grouping them based on 22 diseases recorded in the past 6 months using fuzzy c-means clustering, we examined the longitudinal association between clusters and death or care-need level deterioration within 2 years. We analyzed 4,648 participants (median age 83 [interquartile range 78-88] years, female 60.4%) between October 2014 and March 2019 and categorized them into (i) musculoskeletal and sensory, (ii) cardiac, (iii) neurological, (iv) respiratory and cancer, (v) insulin-dependent diabetes, and (vi) unspecified subtypes. The results of clustering were replicated in another city. Compared with the musculoskeletal and sensory subtype, the adjusted hazard ratio (95% confidence interval) for death was 1.22 (1.05-1.42), 1.81 (1.54-2.13), and 1.21 (1.00-1.46) for the cardiac, respiratory and cancer, and insulin-dependent diabetes subtypes, respectively. The care-need levels more likely worsened in the cardiac, respiratory and cancer, and unspecified subtypes than in the musculoskeletal and sensory subtype. In conclusion, distinct clinical subtypes exist among individuals initiating long-term care.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in CKD Patients With COVID-19.

Introduction: Even with effective vaccines, patients with CKD have a higher risk of hospitalization and death subsequent to COVID-19 infection than those without CKD. Molnupiravir and nirmatrelvir-ritonavir have been approved for emergency use, but their effectiveness for the CKD population is still unknown. This study was conducted to determine the effectiveness of these drugs in reducing mortality and severe COVID-19 in the CKD population. Methods: This was a target trial emulation study using electronic health databases in Hong Kong. Patients with CKD aged 18 years or older who were hospitalized with COVID-19 were included. The per-protocol average treatment effect among COVID-19 oral antiviral initiators, including all-cause mortality, intensive care unit (ICU) admission, and ventilatory support within 28 days, were compared to noninitiators. Results: Antivirals have been found to lower the risk of all-cause mortality, with Molnupiravir at a hazard ratio (HR) of 0.85 (95% confidence interval [CI], 0.77 to 0.95] and nirmatrelvir-ritonavir at an HR of 0.78 [95% CI, 0.60 to 1.00]. However, they do not significantly reduce the risk of ICU admission (molnupiravir: HR, 0.88 [95% CI, 0.59 to 1.30]; nirmatrelvir-ritonavir: HR, 0.86 [95% CI, 0.56 to 1.32]) or ventilatory support (molnupiravir: HR, 1.00 [95% CI, 0.76 to 1.33]; nirmatrelvir-ritonavir: HR, 1.01 [95% CI, 0.74 to 1.37]). There was a greater risk reduction in males and those with higher Charlson Comorbidity Index (CCI). The nirmatrelvir-ritonavir trial also showed reduced risk for those who had antiviral treatment and received 3 or more vaccine doses. Conclusion: Both molnupiravir and nirmatrelvir-ritonavir reduced mortality rates for hospitalized COVID-19 patients with CKD.

Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong.

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15-1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22-1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03-1.62]), and falls (13.83 vs 10.36; 1.28 [1.23-1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30 days) and post-acute phases (beyond 30 days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors.

Our study showed that older individuals with coronavirus 2019 (COVID-19) infection are at a higher risk of suffering from major osteoporotic fractures, ie serious bone fractures related to osteoporosis, compared to those not infected. The study analyzed the health records of 429 459 patients aged 50 and older in Hong Kong who had been diagnosed with COVID-19 between January 2020 and March 2022. These patients were compared with a matched group without COVID-19, considering age, sex, vaccination status, medical comorbidities, and concomitant medications. Findings indicated that individuals who had contracted COVID-19 experienced a higher risk of major osteoporotic fractures, hip fractures, and clinical vertebral fractures. The risk of falls, a common cause of these fractures, was also higher in the COVID-19 group. This increased risk of major osteoporotic fractures and falls persists both shortly after infection and in the following months, underscoring the lasting impact of COVID-19 on the bone health of older adults. These results support the recommendations for the assessment of bone health and fall risks, and an urgent review of the requirement for interventions to reduce the risk of fragility fractures in older adult COVID-19 survivors.

Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.

OBJECTIVE: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19. METHODS: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase. RESULTS: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses. CONCLUSION: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease.

BACKGROUND: Chronic liver disease (CLD) was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIM: To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma (HCC) among patients with CLD. METHODS: A retrospective, territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong. Patients with confirmed SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)+CLD] between January 1, 2020 and October 25, 2022 were identified and matched 1:1 by propensity-score with those without (COVID-19-CLD). Each patient was followed up until death, outcome event, or November 15, 2022. Primary outcome was incidence of HCC. Secondary outcomes included all-cause mortality, adverse hepatic outcomes, and different treatment strategies to HCC (curative, non-curative treatment, and palliative care). Analyses were further stratified by acute (within 20 d) and post-acute (21 d or beyond) phases of SARS-CoV-2 infection. Incidence rate ratios (IRRs) were estimated by Poisson regression models. RESULTS: Of 193589 CLD patients (> 95% non-cirrhotic) in the cohort, 55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching. Upon 249-d median follow-up, COVID-19+CLD was not associated with increased risk of incident HCC (IRR: 1.19, 95%CI: 0.99-1.42, P = 0.06), but higher risks of receiving palliative care for HCC (IRR: 1.60, 95%CI: 1.46-1.75, P < 0.001), compared to COVID-19-CLD. In both acute and post-acute phases of infection, COVID-19+CLD were associated with increased risks of all-cause mortality (acute: IRR: 7.06, 95%CI: 5.78-8.63, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.14-1.36, P < 0.001) and adverse hepatic outcomes (acute: IRR: 1.98, 95%CI: 1.79-2.18, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.13-1.35, P < 0.001), compared to COVID-19-CLD. CONCLUSION: Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC, they were more likely to receive palliative treatment than those without. The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

COVID-19 vaccine effectiveness against the Omicron variant of SARS-CoV-2 in multimorbidity: A territory-wide case-control study.

Multimorbidity entails a higher risk of SARS-CoV-2 infection and COVID-19 complications. We examined vaccine effectiveness (VE) stratified by multimorbidity using a case-control study of territory-wide electronic health records in Hong Kong. Cases of infection (testing positive), hospitalization, and mortality were identified from January to March 2022. Controls were matched by age, sex, outpatient attendance/hospitalization date, and Charlson Comorbidity Index. We demonstrated a consistently good VE among people with increased multimorbidity burden; even more so than among those with minimal such burden. There was also a significantly greater VE after a third dose of BNT162b2 or CoronaVac against infection. The difference in VE between those with multimorbidity and those without was less pronounced for hospitalization, and such difference for COVID-19-related mortality was negligible. In conclusion, VE of both examined vaccines against SARS-CoV-2 infection among people with more complex multimorbidity burden is significant. Further vaccine roll-out should prioritize people with multimorbidity.

Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection.

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

Risk of carditis among adolescents after extending the interdose intervals of BNT162b2.

Previous studies indicate an increased carditis risk among adolescents following the two-dose messenger RNA COVID-19 vaccine. Several jurisdictions have extended the interdose interval between the first and second doses to reduce the risk. However, the effectiveness of such an extension policy remains inconclusive. Using the territory-wide vaccine record-linked electronic health records in Hong Kong, we conducted a nested case-control study from February 23, 2021 to August 15, 2022. Adolescents aged between 12 and 17 who received two-dose BNT162b2 were included for comparing risks between standard interdose interval (21-27 days) versus extended interdose interval ( ≥ 56 days). The carditis cumulative incidence within 28 days following the second dose was calculated. The adjusted odds ratio was estimated from multivariable conditional logistic regression. We identified 49 adolescents with newly diagnosed carditis within 28 days following the second dose. The crude cumulative incidence is 37.41 [95% confidence interval (CI): 27.68-49.46] per million vaccinated adolescents. Compared to the standard interdose interval group, adolescents with an extended interval had a significantly lower risk of carditis [adjusted odds ratio (aOR) 0.34 (95% CI: 0.16-0.73)]. Sensitivity analysis of carditis occurring within 14 days following the second dose yielded a similar estimate [aOR 0.30 (95% CI: 0.13-0.73)]. Extending the interdose interval of the BNT162b2 vaccine from 21 to 27 days to 56 days or longer is associated with 66% lower risk of incident carditis among adolescents. Our findings contribute towards an evidence-based vaccination strategy for a vulnerable population and potentially informs product label updates.

Sedative-hypnotics and osteoporotic fractures: A systematic review of observational studies with over six million individuals.

We reviewed and meta-analyzed 20 observational studies to examine the relationship between sedative-hypnotic use and osteoporotic fractures. We searched PubMed, Embase, APA PsycINFO, and Web of Science™ for studies that used cohort, case-control, case-crossover, and self-controlled case series designs. We further assessed the quality of each study and performed meta-analyses of association estimates, e.g., odds ratios (ORs). The analysis included 6,084,083 participants and found a slight association between the use of sedative-hypnotics and osteoporotic fractures, with differing strength of associations between different classes of drugs and greater sedative-hypnotics exposure. The pooled estimates ORs for case-control studies were 1.33 (95% CI 0.98-1.80) with benzodiazepines (BZD) and any fractures, 1.32 (95% CI 1.05-1.66) with BZDs and hip fractures, and case-crossover studies were 1.15 (95% CI 0.95-1.41) with BZDs and any fractures, 1.41 (95% CI 1.08-1.85) with Z-drugs and any fractures. The study suggests that more research is needed to aid medical professionals in balancing this potential risk of osteoporotic fractures associated with sedative-hypnotic use against other reported adverse events and anticipated therapy outcomes.

Effectiveness and Respiratory Adverse Events Following Inactivated and mRNA COVID-19 Vaccines in Patients with COPD and Asthma: A Chinese Population-Based Study.

INTRODUCTION: Effectiveness and respiratory adverse events following coronavirus disease-2019 (COVID-19) vaccines have not been well investigated in Chinese patients with chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Using electronic health care records in Hong Kong, we included adults with COPD or asthma or both and hospitalised for severe respiratory exacerbation in a self-controlled case series (SCCS) study between 23/02/2021 and 30/11/2022. Conditional Poisson regression models were used to estimate the incidence of outcomes within exposure periods (28 days after each dose) compared with baseline periods. Cox proportional hazard models evaluated vaccine effectiveness (VE) against COVID-related mortality, hospitalisation, and severe complications, including admission to intensive care units or ventilatory support. The VE assessment was based on vaccine types and the number of doses. RESULTS: In the SCCS, 343 CoronaVac recipients and 212 BNT162b2 recipients were included. No increased risk of outcomes was observed within the exposure periods. In the cohort study, 108,423 and 83,323 patients received ≥ 2 doses of CoronaVac and BNT162b2, respectively. The VE (95% CI) against COVID-related mortality, hospitalisation, and severe complications after two-dose CoronaVac was 77% (74-80%), 18% (6-23%), and 29% (12-43%), respectively, while for the two-dose regimen of BNT162b2, it was 92% (91-94%), 33% (30-37%), and 57% (45-66%), respectively. Higher VE against COVID-related mortality, hospitalisation, and severe complications was found for the three-dose regimen of CoronaVac (94%, 40%, and 71%) and BNT162b2 (98%, 65%, and 83%). Administering a fourth dose of either vaccine showed additional reductions in COVID-related outcomes. CONCLUSIONS: Among people with COPD and asthma, the COVID-19 vaccines CoronaVac and BNT162b2 did not increase severe exacerbations and achieved moderate-to-high effectiveness against COVID-related outcomes. COVID-19 vaccination remains essential and should be encouraged to protect this vulnerable population in future epidemic waves.