Changes in all-cause and cause-specific excess mortality before and after the Omicron outbreak of COVID-19 in Hong Kong.

Background: While coronavirus 2019 (COVID-19) deaths were generally underestimated in many countries, Hong Kong may show a different trend of excess mortality due to stringent measures, especially for deaths related to respiratory diseases. Nevertheless, the Omicron outbreak in Hong Kong evolved into a territory-wide transmission, similar to other settings such as Singapore, South Korea, and recently, mainland China. We hypothesized that the excess mortality would differ substantially before and after the Omicron outbreak. Methods: We conducted a time-series analysis of daily deaths stratified by age, reported causes, and epidemic wave. We determined the excess mortality from the difference between observed and expected mortality from 23 January 2020 to 1 June 2022 by fitting mortality data from 2013 to 2019. Results: During the early phase of the pandemic, the estimated excess mortality was -19.92 (95% confidence interval (CI) = -29.09, -10.75) and -115.57 (95% CI = -161.34, -69.79) per 100 000 population overall and for the elderly, respectively. However, the overall excess mortality rate was 234.08 (95% CI = 224.66, 243.50) per 100 000 population overall and as high as 928.09 (95% CI = 885.14, 971.04) per 100 000 population for the elderly during the Omicron epidemic. We generally observed negative excess mortality rates of non-COVID-19 respiratory diseases before and after the Omicron outbreak. In contrast, increases in excess mortality were generally reported in non-respiratory diseases after the Omicron outbreak. Conclusions: Our results highlighted the averted mortality before 2022 among the elderly and patients with non-COVID-19 respiratory diseases, due to indirect benefits from stringent non-pharmaceutical interventions. The high excess mortality during the Omicron epidemic demonstrated a significant impact from the surge of COVID-19 infections in a SARS-CoV-2 infection-naive population, particularly evident in the elderly group.

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.

Extracorporeal membrane oxygenation for paediatric refractory hypoxic respiratory failure caused by adenovirus in Shanghai: a case series.

BACKGROUND: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients. METHODS: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate. RESULTS: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes. CONCLUSIONS: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia.

Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone.

Objectives: This retrospective cohort study aims to explore head-to-head clinical outcomes and complications associated with tocilizumab or baricitinib initiation among hospitalized COVID-19 patients receiving dexamethasone. Methods: Among 10,445 COVID-19 patients hospitalized between January 21st 2020 and January 31st 2021 in Hong Kong, patients who had received tocilizumab (n = 165) or baricitinib (n = 76) while on dexamethasone were included. Primary study outcome was time to clinical improvement (at least one score reduction on WHO clinical progression scale). Secondary outcomes were disease progression, viral dynamics, in-hospital death, hyperinflammatory syndrome, and COVID-19/treatment-related complications. Hazard ratios (HR) of event outcomes were estimated using Cox regression models. Results: The initiation of tocilizumab or baricitinib had no significant differences in time to clinical improvement (HR = 0.86, 95%CI 0.57-1.29, p = 0.459), hospital discharge (HR = 0.85, 95%CI 0.57-1.27, p = 0.418), recovery without the need for oxygen therapy (HR = 1.04, 95%CI 0.64-1.67, p = 0.883), low viral load (HR = 1.49, 95%CI 0.85-2.60, p = 0.162), and positive IgG antibody (HR = 0.97, 95%CI 0.61-1.54, p = 0.909). Time to viral clearance (HR = 1.94, 95%CI 1.01-3.73, p = 0.048) was shorter in the tocilizumab group with marginal significance, compared to that of baricitinib. Meanwhile, the two treatment modalities were not significantly different in their associated risks of in-hospital death (HR = 0.63, 95%CI 0.29-1.35, p = 0.233), severe liver injury (HR = 1.15, 95%CI 0.43-3.08, p = 0.778), acute renal failure (HR = 2.33, 95%CI 0.61-8.82, p = 0.213), hyperinflammatory syndrome (HR = 2.32, 95%CI 0.87-6.25, p = 0.091), thrombotic and bleeding events (HR = 1.39, 95%CI 0.32-6.00, p = 0.658), and secondary infection (HR = 2.97, 95%CI 0.62-14.31, p = 0.173). Conclusion: Among hospitalized patients with moderate-to-severe COVID-19 on background dexamethasone, the initiation of tocilizumab or baricitinib had generally comparable effects on time to clinical improvement, hospital discharge, recovery, low viral load, and positive IgG antibody; risks of in-hospital death, hepatic and renal complications, hyperinflammatory syndrome, thrombotic and bleeding events, and secondary infection. On the other hand, tocilizumab users might achieve viral clearance slightly faster than baricitinib users. Further studies and clinical trials are needed to confirm our findings regarding the evaluation of tocilizumab and baricitinib in COVID-19 patients with different disease severities, at varying stages or timing of drug initiation, and considering the concomitant use of other therapeutics.

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.

Slower Recovery with Early Lopinavir/Ritonavir use in Pediatric COVID-19 Patients: A Retrospective Observational Study.

OBJECTIVES: There was initially insufficient understanding regarding suitable pharmacological treatment for pediatric Coronavirus Disease 2019 (COVID-19) patients. Lopinavir-ritonavir (LPV/r) was originally used for the treatment of Human Immunodeficiency Virus-1 (HIV-1) infection. It was also used in patients with severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) with positive results. Nonetheless, results from recent randomized controlled trials and observational studies on COVID-19 patients were unfavorable. We sought to evaluate the clinical outcomes associated with early treatment with LPV/r for pediatric COVID-19 patients. STUDY DESIGN: A total of 933 COVID-19 patients aged ≤ 18 years were admitted between 21 January 2020 and 31 January 2021 in Hong Kong. Exposure was receiving LPV/r within the first two days of admission. Time to clinical improvement, hospital discharge, seroconversion and hyperinflammatory syndrome, cumulative costs, and hospital length of stay were assessed. Multivariable Cox proportional hazard and linear models were performed to estimate hazard ratios (HR) and their 95% confidence intervals (CI) of time-to-event and continuous outcomes, respectively. RESULTS: LPV/r users were associated with longer time to clinical improvement (HR 0.51, 95% CI 0.38-0.70; p < 0.001), hospital discharge (HR 0.51, 95% CI 0.38-0.70; p < 0.001) and seroconversion (HR 0.59, 95% CI 0.43-0.80; p < 0.001) when compared with controls. LPV/r users were also associated with prolonged hospital length of stay (6.99 days, 95% CI 6.23-7.76; p < 0.001) and higher costs at 30 days (US$11,709 vs US$8270; p < 0.001) as opposed to controls. CONCLUSION: Early treatment with LPV/r for pediatric COVID-19 patients was associated with longer time to clinical improvement. Our study advocates the recommendation against LPV/r use for pediatric patients across age groups.

Remdesivir use and risks of acute kidney injury and acute liver injury among patients hospitalised with COVID-19: a self-controlled case series study.

BACKGROUND AND AIM: To investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS-CoV-2 infection. METHODS: This self-controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory-confirmed COVID-19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non-exposure period were estimated using the conditional Poisson regression models. RESULTS: Of 860 COVID-19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre-exposure period (ALI: IRR = 6.169, 95% CI = 4.549-8.365; AKI: IRR = 7.074, 95% CI = 3.763-13.298) and remained elevated during remdesivir treatment. Compared to the pre-exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915-1.737; AKI: IRR = 1.261, 95% CI = 0.889-1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793-1.489; AKI: IRR = 1.152, 95% CI = 0.821-1.616). CONCLUSION: The increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID-19 may be due to the underlying SARS-CoV-2 infection. The risks of AKI and ALI were elevated in the pre-exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre-exposure period.

Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort

Aim This study was conducted in order to evaluate the association between metformin use and clinical outcomes in type 2 diabetes mellitus (T2DM) patients hospitalized with coronavirus disease 2019 (COVID-19). Methods Patients with T2DM with confirmed diagnosis of COVID-19 and admitted between January 21, 2020, and January 31, 2021 in Hong Kong were identified in our cohort. Exposure was defined as metformin use within 90 days prior to admission until hospital discharge for COVID-19. Primary outcome was defined as clinical improvement of ≥1 point on the WHO Clinical Progression Scale (CPS). Other outcomes were hospital discharge, recovery, in-hospital death, acidosis, hyperinflammatory syndrome, length of hospitalization, and changes in WHO CPS score. Results Metformin use was associated with greater odds of clinical improvement (OR = 2.74, p = 0.009), hospital discharge (OR = 2.26, p = 0.009), and recovery (OR = 2.54, p = 0.005), in addition to lower odds of hyperinflammatory syndrome (OR = 0.71, p = 0.021) and death (OR = 0.41, p = 0.010) than control. Patients on metformin treatment had a shorter hospital stay (−2.76 days, p = 0.017) than their control counterparts. The average WHO CPS scores were significantly lower in metformin users than non-users since day 15 (p < 0.001). However, metformin use was associated with higher odds of acidosis. Conclusions Metformin use was associated with lower mortality and lower odds for hyperinflammatory syndrome. This provides additional insights into the potential mechanisms of the benefits of metformin use in T2DM patients with COVID-19.

Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization.

BACKGROUND: Safety after the second dose of the SARS-CoV-2 vaccine remains to be elucidated, especially among individuals reporting adverse events after their first dose. This study aims to evaluate the impact of a delayed second dose on all-cause mortality and emergency services. METHODS: A territory-wide, retrospective cohort of people who had completed two doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (CoronaVac) vaccine between February 23 and July 3, 2021, in Hong Kong was analyzed, with linkage to electronic health records retrieved from the Hong Kong Hospital Authority. Vaccine recipients were classified as receiving a second dose within recommended intervals (21-28 days for BNT162b2; 14-28 days for CoronaVac) or delayed. Study outcomes were all-cause mortality, emergency department (ED) visits, and unscheduled hospitalizations within 28 days after the second dose of vaccination. RESULTS: Among 417,497 BNT162b2 and 354,283 CoronaVac second dose recipients, 3.8% and 28.5% received the second dose beyond the recommended intervals (mean 34.4 and 31.8 days), respectively. During the study period, there were < 5 daily new cases of COVID-19 infections in the community. Delaying the second dose was not associated with all-cause mortality (hazard ratio [HR] = 1.185, 95% CI 0.478-2.937, P = 0.714), risk of ED visit (HR = 0.966, 95% CI 0.926-1.008, P = 0.113), and risk of unscheduled hospitalization (HR = 0.956, 95% CI 0.878-1.040, P = 0.294) compared to that within the recommended interval for CoronaVac recipients. No statistically significant differences in all-cause mortality (HR = 4.438, 95% CI 0.951-20.701, P = 0.058), ED visit (HR = 1.037, 95% CI 0.951-1.130, P = 0.411), and unscheduled hospitalization (HR = 1.054, 95% CI 0.867-1.281, P = 0.597) were identified between people who received a second dose of BNT162b2 within and beyond the recommended intervals. CONCLUSIONS: No significant association between delayed second dose of BNT162b2 or CoronaVac and all-cause mortality, ED visit, and unscheduled hospitalization was observed in the present cohort. Regardless of the recommended or delayed schedule for SARS-CoV-2 vaccination, a second dose of both vaccines should be administered to obtain better protection against infection and serious disease. The second dose should be administered within the recommended interval following the manufacturer's product information, until further studies support the benefits of delaying vaccination outweighing the risks.

Optimal Timing of Remdesivir Initiation in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Administered With Dexamethasone.

BACKGROUND: Evidence is lacking about any additional benefits of introducing remdesivir on top of dexamethasone, and the optimal timing of initiation. METHODS: In a territory-wide cohort of 10 445 coronavirus disease 2019 (COVID-19) patients from Hong Kong who were hospitalized between 21 January 2020 and 31 January 2021, 1544 had received dexamethasone during hospitalization. The exposure group consisted of patients who had initiated remdesivir prior to dexamethasone (n = 93) or co-initiated the 2 drugs simultaneously (n = 373), whereas the nonexposure group included patients who were given remdesivir after dexamethasone (n = 149) or those without remdesivir use (n = 929). Multiple imputation and inverse probability of treatment weighting for propensity score were applied and hazard ratios (HRs) of event outcomes were estimated using Cox regression models. RESULTS: Time to clinical improvement (HR = 1.23; 95% CI, 1.02-1.49; P = .032) and positive IgG antibody (HR = 1.22; 95% CI, 1.02-1.46; P = .029) were significantly shorter in the exposure group than that of nonexposure. The exposure group had a shorter hospital length of stay by 2.65 days among survivors, lower WHO clinical progression scale scores from 5 days of follow-up onwards, and lower risks of in-hospital death (HR = .59; 95% CI, .36-.98; P = .042) and composite outcomes; and without experiencing an increased risk of acute respiratory distress syndrome. Differences in the cumulative direct medical costs between groups were no longer significant from 17 days of follow-up onwards. CONCLUSIONS: Initiation of remdesivir prior to or simultaneously with dexamethasone was associated with significantly shorter time to clinical improvement and positive IgG antibody, lower risk of in-hospital death, in addition to shorter length of hospital stay in patients with moderate COVID-19.

Clinical Improvement, Outcomes, Antiviral Activity, and Costs Associated With Early Treatment With Remdesivir for Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Evidence remains inconclusive on any significant benefits of remdesivir in patients with mild-to-moderate COVID-19. This study explored the disease progression, various clinical outcomes, changes in viral load, and costs associated with early remdesivir treatment among COVID-19 patients. METHODS: A territory-wide retrospective cohort of 10 419 patients with COVID-19 hospitalized from 21 January 2020 to 31 January 2021 in Hong Kong was identified. Early remdesivir users were matched with controls using propensity-score matching in a ratio ≤1:4. Study outcomes were time to clinical improvement of at least 1 point on WHO clinical progression scale, hospital discharge, recovery, viral clearance, low viral load, positive IgG antibody, in-hospital death, and composite outcomes of in-hospital death requiring invasive ventilation or intensive care. RESULTS: After multiple imputation and propensity-score matching, median follow-up was 14 days for both remdesivir (n = 352) and control (n = 1347) groups. Time to clinical improvement was significantly shorter in the remdesivir group than that of control (HR: 1.14; 95% CI: 1.01-1.29; P = .038), as well as for achieving low viral load (1.51; 1.24-1.83; P < .001) and positive IgG antibody (1.50; 1.31-1.70; P < .001). Early remdesivir treatment was associated with lower risk of in-hospital death (HR: .58; 95% CI: .34-.99; P = .045), in addition to a significantly shorter length of hospital stay (difference: -2.56 days; 95% CI: -4.86 to -.26; P = .029), without increasing risks of composite outcomes for clinical deterioration. CONCLUSIONS: Early remdesivir treatment could be extended to hospitalized patients with moderate COVID-19 not requiring oxygen therapy on admission.

Use of DPP4i reduced odds of clinical deterioration and hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: Propensity score analysis of a territory-wide cohort in Hong Kong.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (T2DM) patients with Coronavirus Disease 2019 (COVID-19) have poorer prognosis. Inconclusive evidence suggested dipeptidyl peptidase-4 inhibitors (DPP4i) might reduce inflammation and prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry, hence further evaluation on DPP4i is needed. METHODS: 1214 Patients with T2DM were admitted with COVID-19 between 21st January 2020 and 31st January 2021 in Hong Kong. Exposure was DPP4i use within the 90 days prior to admission for COVID-19. Assessed outcomes included clinical deterioration, clinical improvement, low viral load, positive Immunoglobulin G (IgG) antibody, hyperinflammatory syndrome, proportion of IgG antibody, clinical status and length of hospitalization. Multivariable logistic and linear regression models were performed to estimate odds ratios (OR) and their 95% confidence intervals (CI) of event outcomes and continuous outcomes, respectively. RESULTS: DPP4i users (N = 107) was associated with lower odds of clinical deterioration (OR=0.71, 95%CI 0.54 to 0.93, P = 0.013), hyperinflammatory syndrome (OR=0.56, 95%CI 0.45 to 0.69, P < 0.001), invasive mechanical ventilation (OR=0.30, 95%CI 0.21 to 0.42, P < 0.001), reduced length of hospitalization (-4.82 days, 95%CI -6.80 to -2.84, P < 0.001), proportion of positive IgG antibody on day-3 (13% vs 8%, p = 0.007) and day-7 (41% vs 26%, P < 0.001), despite lack of association between DPP4i use and in-hospital mortality. CONCLUSION: DPP4i use was associated with reduced odds of clinical deterioration and hyperinflammatory syndrome. Prospective studies are warranted to elucidate the role of DPP4i in T2DM and COVID-19.

Impact of varying wave periods of COVID-19 on in-hospital mortality and length of stay for admission through emergency department: A territory-wide observational cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with excess mortality and reduced emergency department attendance. However, the effect of varying wave periods of COVID-19 on in-hospital mortality and length of stay (LOS) for non-COVID disease for non-COVID diseases remains unexplored. METHODS: We examined a territory-wide observational cohort of 563,680 emergency admissions between January 1 and November 30, 2020, and 709,583 emergency admissions during the same 2019 period in Hong Kong, China. Differences in 28-day in-hospital mortality risk and LOS due to COVID-19 were evaluated. RESULTS: The cumulative incidence of 28-day in-hospital mortality increased overall from 2.9% in 2019 to 3.6% in 2020 (adjusted hazard ratio [aHR] = 1.22, 95% CI 1.20 to 1.25). The aHR was higher among patients with lower respiratory tract infection (aHR: 1.30 95% CI 1.26 to 1.34), airway disease (aHR: 1.35 95% CI 1.22 to 1.49), and mental disorders (aHR: 1.26 95% CI 1.15 to 1.37). Mortality risk in the first- and third-wave periods was significantly greater than that in the inter-wave period (p-interaction < 0.001). The overall average LOS in the pandemic year was significantly shorter than that in 2019 (Mean difference = -0.40 days; 95% CI -0.43 to -0.36). Patients with mental disorders and cerebrovascular disease in 2020 had a 3.91-day and 2.78-day shorter LOS than those in 2019, respectively. CONCLUSIONS: Increased risk of in-hospital deaths was observed overall and by all major subgroups of disease during the pandemic period. Together with significantly reduced LOS for patients with mental disorders and cerebrovascular disease, this study shows the spillover effect of the COVID-19 pandemic.

Changes in Emergency Department Visits, Diagnostic Groups, and 28-Day Mortality Associated With the COVID-19 Pandemic: A Territory-Wide, Retrospective, Cohort Study.

STUDY OBJECTIVE: We aimed to evaluate and characterize the scale and relationships of emergency department (ED) visits and excess mortality associated with the early phase of the COVID-19 pandemic in the territory of Hong Kong. METHODS: We conducted a territory-wide, retrospective cohort study to compare ED visits and the related impact of the COVID-19 pandemic on mortality. All ED visits at 18 public acute hospitals in Hong Kong between January 1 and August 31 of 2019 (n=1,426,259) and 2020 (n=1,035,562) were included. The primary outcome was all-cause mortality in the 28 days following an ED visit. The secondary outcomes were weekly number of ED visits and diagnosis-specific mortality. RESULTS: ED visits decreased by 27.4%, from 1,426,259 in 2019 to 1,035,562 in 2020. Overall period mortality increased from 28,686 (2.0%) in 2019 to 29,737 (2.9%) in 2020. The adjusted odds ratio for 28-day, all-cause mortality in the pandemic period of 2020 relative to 2019 was 1.26 (95% confidence interval 1.24 to 1.28). Both sexes, age more than 45 years, all triage categories, all social classes, all ED visit periods, epilepsy (odds ratio 1.58, 95% confidence interval 1.20 to 2.07), lower respiratory tract infection, and airway disease had higher adjusted ORs for all-cause mortality. CONCLUSION: A significant reduction in ED visits in the first 8 months of the COVID-19 pandemic was associated with an increase in deaths certified in the ED. The government must make provisions to encourage patients with alarming symptoms, mental health conditions, and comorbidities to seek timely emergency care, regardless of the pandemic.

Limited role for meteorological factors on the variability in COVID-19 incidence: A retrospective study of 102 Chinese cities.

While many studies have focused on identifying the association between meteorological factors and the activity of COVID-19, we argue that the contribution of meteorological factors to a reduction of the risk of COVID-19 was minimal when the effects of control measures were taken into account. In this study, we assessed how much variability in COVID-19 activity is attributable to city-level socio-demographic characteristics, meteorological factors, and the control measures imposed. We obtained the daily incidence of COVID-19, city-level characteristics, and meteorological data from a total of 102 cities situated in 27 provinces/municipalities outside Hubei province in China from 1 January 2020 to 8 March 2020, which largely covers almost the first wave of the epidemic. Generalized linear mixed effect models were employed to examine the variance in the incidence of COVID-19 explained by different combinations of variables. According to the results, including the control measure effects in a model substantially raised the explained variance to 45%, which increased by >40% compared to the null model that did not include any covariates. On top of that, including temperature and relative humidity in the model could only result in < 1% increase in the explained variance even though the meteorological factors showed a statistically significant association with the incidence rate of COVID-19. In conclusion, we showed that very limited variability of the COVID-19 incidence was attributable to meteorological factors. Instead, the control measures could explain a larger proportion of variance.

Transmissibility of coronavirus disease 2019 in Chinese cities with different dynamics of imported cases.

BACKGROUND: Monitoring the reproduction number (Rt ) of the disease could help determine whether there is sustained transmission in a population, but areas with similar epidemic trends could have different transmission dynamics given the risk from imported cases varied across regions. In this study, we examined the Rt of coronavirus disease 2019 (COVID-19) by taking different dynamics of imported cases into account and compared the transmissibility of COVID-19 at different intervention periods in Hangzhou and Shenzhen. METHODS: We obtained the daily aggregated counts of laboratory-confirmed imported and local cases of COVID-19 infections in Hangzhou and Shenzhen from January 1 to March 13, 2020. Daily Rt and piecewise Rt before and after Wuhan lockdown were estimated, accounting for imported cases. RESULTS: Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was around 0.1 to 0.7 before the Wuhan lockdown. After the lockdown of Wuhan and the initialization of measures in response to the outbreak, local transmission was well-controlled as indicated by a low estimated value of piecewise Rt , 0.15 (95% CI [0.09-0.21]). On the contrary, Rt obtained for Hangzhou ranged from 1.2 to 4.9 with a piecewise Rt of 2.55 (95% CI [2.13-2.97]) before the lockdown of Wuhan due to the surge in local cases. Because of the Wuhan lockdown and other outbreak response measures, Rt dropped below unity in mid-February. CONCLUSIONS: Even though Shenzhen had more cases than Hangzhou, local transmission did not sustain probably due to limited transmission from imported cases owing to the reduction in local susceptibles as residents left the city during Chunyun. The lockdown measures and local outbreak responses helped reduce the local transmissibility.

Statistical Analysis of Dispelling Rumors on Sina Weibo

Analyzing the process and results of dispelling rumors is a prerequisite for designing an effective anti-rumor strategy. Current research on this subject focuses on the simulation experiments, short of empirical study. By using the False Information Publicity Results of Sina Weibo as the data source of empirical research, this article compares the typical features of rumor and anti-rumor accounts. Furthermore, taking COVID-19 as the target topic, distributions of the reported time, frequency, platform penalty levels, and diffusion parameters of rumors related to COVID-19 are given, and some interesting results are obtained.