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1.
Nature Medicine ; 18:18, 2023.
Article in English | MEDLINE | ID: covidwho-2185966

ABSTRACT

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. While first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January-July 2022. We estimated that Omicron infected 45% (41-48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection (VE of 48% (95% credible interval 34-64%) and 69% (46-98%) for three and four doses of BNT162b2 respectively;VE of 30% (1-66%) and 56% (6-97%) for three and four doses of CoronaVac respectively) seven days after vaccination. 100 days after immunization, VE waned to 26% (7-41%) and 35% (10-71%) for three and four doses of BNT162b2, and to 6% (0-29%) and 11% (0-54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlights the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.

3.
Gut ; 70(SUPPL 2):A9-A10, 2021.
Article in English | EMBASE | ID: covidwho-1467715

ABSTRACT

Background Evidence regarding the use of proton-pump inhibitors (PPIs) in COVID-19 patients remains elusive. We examined the impact of PPI use on clinical outcomes of COVID-19 patients in a territory-wide cohort. Methods We performed a retrospective cohort study using data from an electronic healthcare database managed by the Hospital Authority, Hong Kong. COVID-19 patients diagnosed virologically between 23 January 2020 and 1 January 2021 in Hong Kong were identified. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. PPI user was identified by PPI use within 12 months before the diagnosis of COVID-19. In subgroup analysis, current PPI users were defined as patients who used PPIs within 1 month before the diagnosis of COVID-19;past PPI users were defined as patients who used PPIs 1 to 12 months before COVID-19 diagnosis. We performed sensitivity analysis after excluding patients with short-term new NSAID use within 1 month before COVID-19 diagnosis to minimize reverse causation bias. Results We identified 8,675 COVID-19 patients (mean age 46 years, 49% male, 97.6% of all the reported cases in Hong Kong);579 (6.7%) patients had used PPI. PPI users were older, more likely to have comorbidities, concomitant medications and unfavorable laboratory parameters than non-users. Of 8,675 COVID-19 patients, 500 (5.8%) developed the primary endpoint. After propensity score (PS) balancing for patients' demographics, comorbidities, laboratory parameters, and use of medications, PPI use was not associated with the development of primary endpoint in PS weighting (weighted hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.83-1.47, P=0.482) (IDDF2021-ABS- 0122 Figure 1. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton- pump inhibitor (PPI) users after propensity score (PS) weighting in a single multiple imputation data set.), and PS matching analysis (weighted HR 0.81, 95%CI 0.57-1.14, P=0.228) (IDDF2021-ABS-0122 Figure 2. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton-pump inhibitor (PPI) users after propensity score (PS) matching in a single multiple imputation data set). Consistent non-association was observed after multivariable adjustment (adjusted HR 0.84, 95%CI 0.66- 1.07, P=0.151), in subgroups of current and past PPI users, and in sensitivity analysis after excluding short-term new NSAID users. Conclusions PPI use is not associated with adverse clinical outcomes in COVID-19 patients. The result remains robust after PS weighting, PS matching, multivariable adjustment, and subgroup analyses.

6.
Open Forum Infectious Diseases ; 7(SUPPL 1):S340, 2020.
Article in English | EMBASE | ID: covidwho-1185909

ABSTRACT

Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report baseline characteristics associated with clinical improvement at day (d) 14. Methods: We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. For this analysis, patients were followed through discharge, d14, or death. Baseline demographic and disease characteristics associated with clinical improvement in oxygen support (≥2-point improvement on a 7-category ordinal scale ranging from discharge to death) were evaluated using multivariable logistic regression methods. Results: 584 patients were randomized and treated (5/10d RDV, n=384;SoC: n=200). 159 (27%) were ≥65y, 227 (39%) female, 328 (61%) white, 102 (19%) Asian, and 99 (19%) Black. 252 participants (43%) were enrolled in Europe, 260 (45%) North America (NA), and 72 (12%) in Asia. Most patients (483 [83%]) were not on supplemental oxygen but required medical care at baseline. In a multivariable model, 5/10d RDV was significantly positively associated with clinical improvement (adjusted odds ratio [OR] 1.69, 95% CI: 1.08, 2.65;p=0.0226). Significant covariables positively associated with clinical improvement included age < 65y (p< 0.0001) and region of treatment (Europe and NA vs Asia, p< 0.0001 each;Table);other examined factors were not significantly associated with clinical improvement, including gender, race, ethnicity, baseline oxygen support, duration of symptoms and hospitalization, obesity, and baseline transaminase levels. Conclusion: In moderate COVID-19 patients, after adjusting for treatment arm, age < 65y and region (NA vs Asia;Europe vs Asia) were associated with higher rates of clinical improvement. These observations recapitulate younger age as positive prognostic factor, and highlight the differences in the impact of the pandemic globally.

7.
Open Forum Infectious Diseases ; 7(SUPPL 1):S166-S167, 2020.
Article in English | EMBASE | ID: covidwho-1185704

ABSTRACT

Background: Remdesivir (RDV) shortens time to recovery time in patients with severe COVID-19. Its effect in patients with moderate COVID-19 remains unclear. Methods: We conducted an open-label, phase 3 trial (NCT04252664) involving hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned 1:1:1 to receive up to 5d or 10d of RDV with standard of care (SoC), or SoC alone;patients could be discharged prior to completing per-protocol assigned treatment duration. RDV was dosed intravenously at 200 mg on d1, 100 mg daily thereafter. Patients were evaluated daily while hospitalized, and via telephone if discharged. The primary endpoint was clinical status on d11 assessed on a 7-point ordinal scale. Results regarding the primary endpoint are expected to be published before IDWeek 2020;we plan to present d28 results at the meeting. Results: In total, 584 patients underwent randomization and started their assigned treatment (191, 5d RDV;193, 10d RDV;200, SoC). By d11, 3 2 point improvement on the ordinal scale occurred in 70% of patients in the 5d arm, 65% in the 10d arm, and 61% in the SoC arm. Patients in the 5d RDV arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65;95% confidence interval [CI], 1.09-2.48;P=0.017);OR of improvement for the 10d RDV arm compared to SoC was 1.31 (95% CI, 0.88-1.95];p=0.183). This improvement in the 5-day arm over the SOC arm was noted from d6 through d11. We observed a peak of discharges corresponding with the assigned treatment duration of RDV, with increased discharges at d6 in the 5-day arm and at d11 in the 10-day arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n=19, 10%) versus the 5d RDV (n=7, 4%) and 10d RDV (n=9, 5%). Conclusion: RDV for up to 5 days was superior to SoC in improving the clinical status of patients with moderate COVID-19 by d11. We will report d28 outcomes at the meeting. (Table Presented).

8.
Hepatology ; 72(1 SUPPL):284A-285A, 2020.
Article in English | EMBASE | ID: covidwho-986163

ABSTRACT

Background: Different degrees of liver injury were reported in patients infected by Coronavirus disease 2019 (COVID-19) It is possibly caused by systemic inflammation and adverse drug reactions in severe COVID-19 patients under different medical treatments However, the impact of liver injury on adverse clinical outcomes remains unclear We aimed to examine the impact of liver injury on clinical outcomes in COVID-19 patients Methods: All COVID-19 patients reported to the Department of Health between 23 January 2020 and 1 May 2020 in Hong Kong were identified using an electronic database managed by Hospital Authority, Hong Kong, and retrospectively studied Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2x upper limit of normal (ULN) (i.e. 80 U/L) Acute liver injury was defined as ALT and/or AST ≥2xULN, with total bilirubin ≥2xULN (i.e. 38 μmol/L) and/or international normalized ratio (INR) ≥1.7. The primary endpoint was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation, and/or death Results: 1,040 COVID-19 patients were identified. Their mean age was 38±18 years, 560 (53 8%) were male, 4 1% and 0 3% had hepatitis B and C virus infection, respectively;53 (5 1%) were admitted to ICU, 22 (2 1%) received invasive mechanical ventilation, and 4 (0 4%) died Among 816 COVID-19 patients who had serial measurement of liver biochemistries, 184 (22 5%) had ALT/ AST elevation and 15 (1 8%) had acute liver injury Acute liver injury was more common in patients who had hepatitis B/C virus infection than those who did not have (9 4% vs. 1 8%, P=0 026) ALT/AST elevation (adjusted odds ratio [aOR] 7 92, 95% CI 4 14-15 14, P<0 001) and acute liver injury (aOR 6 40, 95% CI 1 78-23 07, P=0 005) were independently associated with development of primary endpoint (Table) Use of lopinavirritonavir ± ribavirin + interferon beta (aOR 1 94, 95% CI 1 20- 3 13, P=0 006) and corticosteroids (aOR 3 92, 95% CI 2 14- 7 16, P<0 001) were independently associated with ALT/AST elevation Use of corticosteroids was associated with acute liver injury (aOR 4 76, 95% CI 1 56-14 50, P=0 006), while all 15 patients who developed acute liver injury also usedlopinavir-ritonavir ± ribavirin ± interferon beta Conclusion: ALT/AST elevation and acute liver injury were independently associated with adverse clinical outcomes in COVID-19 patients Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids were associated with ALT/AST elevation and acute liver injury in COVID-19 patients.

9.
Hepatology ; 72(1 SUPPL):279A, 2020.
Article in English | EMBASE | ID: covidwho-986086

ABSTRACT

Background: Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated potent in vitro and in vivo activity against SAR-CoV-2 and favorable clinical efficacy and tolerability in patients with moderate and severe COVID-19 Elevated transaminase levels are commonly seen in patients with severe COVID-19 prior to treatment Here we report safety and clinical outcomes after RDV treatment in patients with normal versus elevated baseline alanine aminotransferase (ALT) levels Methods: We conducted a randomized, open-label, phase 3 trial, involving hospitalized patients with confirmed COVID-19 pneumonia with Sat<94% Patients with screening ALT or AST> 5x the upper limit of normal (ULN) were excluded from the study Patients were randomized 1:1 to receive either 5 or 10 days of intravenous RDV once daily We compared patients with baseline ALT below and above the ULN based on AASLD criteria (ALT 35 U/L for males and 25 U/L for females) Covariates for adjustment included age, sex, race and baseline oxygen support Clinical recovery and all-cause mortality were evaluated using logistic regression Clinical outcomes and adverse events (AEs) were assessed through day 28 Results: Of 397 patients treated with RDV, 215 (54%) had elevated baseline ALT Median ALT was 53 U/L (IQR: 40 - 78 U/L) in the high ALT group Patients with high ALT at time of RDV initiation were younger (median 58 vs 65 years, p<0 001), required less oxygen (p=0 02), and had longer symptom duration (median 10 vs 8 days, p<0.001) prior to first dose of RDV. Incidence of serious AEs, grade ≥3 AEs, and AE leading to discontinuation were similar between groups (Table1). Grade ≥3 hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher in the high ALT group (8 8% vs 3 3%, p=0 068) Time to clinical recovery, 2-point clinical improvement, 1-point clinical improvement, room air, and death were similar between groups Conclusion: In severe COVID-19 patients, adverse events and clinical outcomes after RDV initiation were similar among patients with baseline normal ALT and those with elevated ALT (1-5x ULN)(Table Presented).

10.
J Hosp Infect ; 105(4): 682-685, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-350041

ABSTRACT

Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine whether an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically linked coronavirus disease 2019 (COVID-19) cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Outbreaks/prevention & control , Disease Transmission, Infectious/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , COVID-19 , Hong Kong/epidemiology , Humans , Japan/epidemiology , Pandemics , SARS-CoV-2 , Singapore/epidemiology
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