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An assay for the large-scale screening of viral pathogens is reported, named Fragment Length Identification of Pooled Nucleic Acid Samples (FLIPNAS), which is demonstrated to be more cost-effective and efficient than Dorfman-based group testing.

Background and objective Few head-to-head evaluations of immune responses to different vaccines have been reported. Methods Surrogate virus neutralization test (sVNT) antibody levels of adults receiving either two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 [n = 49] vs. CoronaVac [n = 49]) was tested for plaque reduction neutralization (PRNT) and spike-binding antibody and T-cell reactivity in peripheral blood mononuclear cells. Results One month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT50 , PRNT90 , sVNT, spike receptor binding, spike N-terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT50 titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45, while PRNT90 titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT90. Allowing for an expected seven-fold waning of antibody titres over 6 months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT90 antibody titres. Both vaccines induced SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at 1 month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4+ and CD8+ T-cell responses. Conclusion Vaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induces higher CD4+ and CD8+ T-cell responses to the structural protein than BNT162b2.

As the life expectancy of people living with HIV (PLWH) approaches that of the general population, the burden of comorbidities such as cardiovascular disease (CVD) is increasing. Regardless of HIV status, about 50% of CVD deaths worldwide occur in Asia, and Asian PLWH have a high prevalence of conventional CVD risk factors, such as smoking, dyslipidaemia, hypertension and insulin resistance or diabetes. As well as conventional CVD risk factors, PLWH have HIV-specific risk factors such as chronic inflammation, immune activation and endothelial damage, as well as risk factors related to antiretroviral therapy. This review describes the current knowledge on the epidemiology and risk factors of CVD in Asian PLWH and provides an Asian perspective on the recommendations for managing CVD risk in PLWH.

This study examined the latent structure of the broad range of complex neuropsychiatric morbidities occurring one year after COVID-19 infection. As part of the CU-COVID19 study, 248 (response rate = 39·3%) of 631 adults hospitalized for COVID-19 infection in Hong Kong completed an online survey between 3-2021 and 1-2022. Disorder prevalence was compared against a random non-infected household sample (n = 1837). 248 surveys were received on average 321 days post-infection (Mean age: 48·9, 54% female, moderate/severe/critical infection: 58·2%). 32·4% were screened to have > = one mental disorder, 78·7% of whom had concurrent fatigue/subjective cognitive impairment (SCI). Only PTSD (19·1%) was significantly more common than control (14%, p = 0·047). Latent profile analysis classified individuals into P1(12·4%)-no current neuropsychiatric morbidities, P2 (23·1%)-SCI/fatigue, P3 (45·2%)-anxiety/PTSD, P4 (19·3%)-depression. SCI and fatigue pervaded in all profiles (P2-4) with neuropsychiatric morbidities one-year post-infection. SHAP: PTSD, anxiety and depressive symptoms were most important in differentiating P2-4. Past mental health and P4 independently predicted functional impairment. Neuropsychiatric morbidity was associated with past mental health, reduced resilience, financial problems, but not COVID-19 severity. Their confluence with depressive and anxiety symptoms predicted impairment and are associated with psychological and environmental factors.

BACKGROUND AND AIMS The uptake of antiviral treatment for patients with chronic hepatitis B (CHB) has been suboptimal. We aimed to determine the secular trend of treatment uptake in the territory-wide CHB cohort in Hong Kong from 2000 to 2017 and the factors for no treatment despite fulfilling treatment criteria. METHODS Chronic hepatitis B patients under public clinics and hospitals were identified through electronic medical records. The treatment indications were defined according to the Asian-Pacific guidelines published at the time of patients' first appearance in four periods: 2000-2004, 2005-2009, 2010-2013, and 2014-2017. RESULTS There were 135 395 CHB patients were included; 1493/12472 (12.0%), 7416/43426 (17.1%), 10 129/46559 (21.8%), 8051/32 938 (24.4%) patients fulfilled treatment criteria in the four periods, respectively. The treatment uptake rate increased with time: 35.1%, 43.4%, 60.2%, and 68.6% respectively. High fibrosis indices (APRI, FIB-4, and Forns indices) appeared to be the main factors for treatment indication in non-cirrhotic patients, with over 90% fulfilling treatment criteria due to high fibrosis indices alone. Of those fulfilling treatment criteria by high fibrosis indices, less than 60% of patients (25.2%, 36.1%, 46.0%, and 58.9%, respectively) had antiviral treatment initiated. Normal platelet count (odds ratio 0.42, P

BACKGROUND AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P

Background Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need. Methods We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters. Results Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. Conclusions Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.

Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients.Methods: Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort.Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence

BACKGROUND: Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear. METHODS: This retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. RESULTS: We identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event. CONCLUSIONS: AKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.

Surveillance of C. difficile infections suggests correlation of incidence to antibiotic stewardship programs., We conducted a territorywide survey to investigate the epidemiology, risk factors, and clinical outcomes of Clostridioides difficile infection (CDI) among hospitalized patients in Hong Kong. A total of 17,105 cases of CDI were identified, of which 15,717 (91.9%) were healthcare-associated and 1,025 (6.0%) were community-associated. Although CDI incidence increased substantially from 2006 to 2017, it plateaued in 2018 and 2019. The 30-day mortality rates decreased from 20.1% in 2015 to 16.8% in 2019, whereas the 60-day recurrence rates remained constant at ≈11% during the study period. Cross-correlation statistic showed significant correlations between incidence trend and overall antimicrobial drug use (r = 0.865, p

Coronavirus disease 2019 (COVID-19) is affecting millions of patients worldwide. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the family Coronaviridae, with 80% genomic similarities to SARS-CoV. Lymphopenia was commonly seen in infected patients and has a correlation to disease severity. Thrombocytopenia, coagulation abnormalities, and disseminated intravascular coagulation were observed in COVID-19 patients, especially those with critical illness and non-survivors. This pandemic has caused disruption in communities and hospital services, as well as straining blood product supply, affecting chemotherapy treatment and haematopoietic stem cell transplantation schedule. In this article, we review the haematological manifestations of the disease and its implication on the management of patients with haematological disorders.

Background & Aims PAGE-B and modified PAGE-B (mPAGE-B) scores were developed to predict the risk of hepatocellular carcinoma (HCC) in patients on nucleos(t)ide analogue therapy. However, how and when to use these risk scores in clinical practice is uncertain. Methods Consecutive adult patients with chronic hepatitis B who had received entecavir or tenofovir for at least 6 months between January 2005 and June 2018 were identified from a territory-wide database in Hong Kong. The performance of PAGE-B and mPAGE-B scores for HCC prediction at 5 years was assessed by area under the time-dependent receiver operating characteristic curve (AUROC), and different cut-off values of these 2 scores were evaluated by survival analysis. Results Of 32,150 identified patients with chronic hepatitis B, 20,868 (64.9%) were male. Their mean age was 53.0 ± 13.2 years. At a median (IQR) follow-up of 3.9 (1.8–5.0) years, 1,532 (4.8%) patients developed HCC. The AUROCs (95% CI) for the prediction of HCC at 5 years were 0.77 (0.76–0.78) and 0.80 (0.79–0.81), with PAGE-B and mPAGE-B scores, respectively (p Conclusions PAGE-B and mPAGE-B scores can be applied to identify patients on antiviral therapy who are at low risk of developing HCC. These patients could be exempted from HCC surveillance due to their very low HCC risk. Lay summary Risk scores have been developed to predict the likelihood of patients with chronic hepatitis B developing hepatocellular carcinoma (HCC). We investigated the role of 2 such scores, PAGE-B and modified PAGE-B, in predicting the risk of HCC in 32,150 nucleos(t)ide analogue-treated patients with chronic hepatitis B. These scores identified a group of patients at very low risk of developing HCC who could therefore be exempted from HCC surveillance.

Background and aims Improvement in Model for End-Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)-related cirrhosis. We aimed to identify factors associated with transplant-free survival and on-treatment MELD score improvement. Methods We identified patients with CHB-related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant-free survival at month 6. The secondary endpoints at month 6 were transplant-free survival with > 5-point improvement in MELD score and transplant-free survival with MELD score Results Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant-free survival at month 6. Proportion of transplant-free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant-free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant-free survival, 276 (45.6%) achieved > 5-point improvement in MELD score; 183 (30.2%) had 1-point to 5-point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant-free survival had a MELD score Conclusion On top of lower MELD score, patients with CHB-related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant-free survival after 6 months of antiviral treatment.

Background & Aims Systemic corticosteroids may cause HBV reactivation, but the impact on patients with previous HBV exposure is poorly defined. We aimed to study the risk of HBsAg seroreversion and hepatitis flare in patients with previous HBV exposure. Methods Patients who were negative for HBsAg and received corticosteroids between 2001–2010 were included. Patients who were positive for antibody to HBsAg (anti-HBs) and/or to HBcAg (anti-HBc) were defined as having previous HBV exposure. The primary endpoint was HBsAg seroreversion; the secondary endpoint was hepatitis flare (alanine aminotransferase >80 U/L) at 1 year. Results A total of 12,997 patients fulfilled the inclusion criteria: anti-HBs positive only (n = 10,561); anti-HBc positive only (n = 970); anti-HBs & anti-HBc positive (n = 830) and anti-HBs & anti-HBc negative (n = 636). HBsAg seroreversion occurred in 165 patients. Patients who were anti-HBc positive only had a higher risk of HBsAg seroreversion (1-year incidence 1.8%) than those negative for both anti-HBs & anti-HBc (0%; p = 0.014). Patients with previous HBV exposure had a similarly low risk of liver failure as unexposed individuals (1.1% vs. 0.9%). The risk of a hepatitis flare started to increase in those receiving corticosteroids at peak daily doses of 20–40 mg (adjusted hazard ratio [HR] 2.19, p = 0.048) or >40 mg (aHR 2.11, p = 0.015) prednisolone equivalents for 28 days (aHR 2.02–3.85; p Conclusions In HBsAg-negative patients who were only anti-HBc positive, high peak daily doses of corticosteroids increased the risk of hepatitis flare, but not seroreversion. The rate of liver failure was low and similar in HBV exposed and unexposed individuals; there were no deaths, nor any requirement for liver transplantation. Lay summary It is important to know the hepatitis B virus (HBV) status before starting corticosteroid therapy. Patients with resolved HBV infection without detectable immunity are at an increased risk of HBV surface antigen seroreversion after corticosteroid therapy. High peak daily doses of corticosteroids (>40 mg prednisolone equivalents) increase the risk of hepatitis flare, but not seroreversion, in patients with previous exposure to HBV, irrespective of the duration of treatment. Interval monitoring of liver biochemistries is essential for the early detection of hepatitis flares in these patients.

Molecular surveillance of infections is essential in monitoring their transmission in the population. In this study, newly diagnosed HIV patients' phylogenetic, clinical and behavioural data were integrated, and an information diffusion model was incorporated in analysing transmission dynamics. A genetic network was constructed from HIV sequences, from which transmission cascades were extracted. From the transmission cascades, CRF01_AE had higher values of information diffusion metrics, including scale, speed and range, than that of B, signifying the distinct transmission patterns of two circulating subtypes in Hong Kong. Patients connected in the network, were more likely male, younger, of main circulating subtypes, to have acquired HIV infection locally, and a higher CD4 level at diagnosis. Genetic connections varied among men who have sex with men (MSM) who used different channels of sex networking and varied in their engagement in risk behaviours. MSM using recreational drugs for sex held positions of greater importance within the network. Significant differences in network metrics were observed among MSM as differentiated by their mobile apps usage patterns, evidencing the impact of social network on transmission networks. The applied model in the presence of consistently collected longitudinal data could enhance HIV molecular epidemiologic surveillance for informing future intervention planning.

Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients.This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5.Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-α), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5.This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients.

COVID-19 is caused by s-coronavirus SARS-CoV-2. Recent reports suggested that neurological diseases, in particular stroke, dementia and advanced Parkinson’s disease (PD), were important predictors of COVID-19-related mortality.1–3 SARS-CoV was another s-coronavirus which resulted in the epidemic of SARS in late 2002 to early 2003. Apparently, it remained quiescent since 2004 but its re-emergence is possible. Patients with SARS at advanced age and with multiple comorbidities were at higher risk of mortality.4 Given mortality rates and predictors may vary with regions, we investigated the impact of pre-existing neurological diseases on the mortality of patients with COVID-19 and SARS in Hong Kong, one of the most densely populated cities in the world. Studying the impact of neurological diseases on COVID-19 and SARS mortalities would have important implications on possible future pandemics caused by coronaviruses. We believe the data would provide guidance on resource allocation and healthcare policy making. With the availability of effective vaccination against COVID-19, the finding could implicate on the prioritisation of vaccination for patients with chronic neurological diseases. ### Study design and data retrieval We performed a territory-wide retrospective cohort study using data from the Clinical Data Analysis and Reporting System (CDARS) under the management of the Hospital Authority, Hong Kong. CDARS is an electronic healthcare database that covers the patients’ demographic, death, diagnoses, procedures, drug prescription and dispensing history, and laboratory results from all public hospitals and clinics in Hong Kong. It represents in-patient data of about 80%–90% of the 7.49 million population in Hong Kong. All confirmed patients with COVID-19 and SARS were reported to the Department of Health and hospitalised in public hospitals in Hong Kong. Patients were anonymised in CDARS to ensure confidentiality. ### Subjects Consecutive patients with laboratory-confirmed COVID-19 from 23 January 2020 to 31 July 2020 and patients with SARS from March to June 2003 were identified by International …

BackgroundFew head-to-head evaluations of immune responses to difference vaccines have been reported.MethodsSurrogate virus neutralization test (sVNT) antibody levels of adults receiving either 2 doses of BNT162b2 (n=366) or CoronaVac (n=360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 (n=49) vs CoronaVac (n=49)) were tested for plaque reduction neutralizing (PRNT) and spike binding antibody and T cell reactivity in peripheral blood mononuclear cells (PBMC).FindingsOne month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT50, PRNT90, sVNT, spike receptor binding, spike N terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT50 titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45 while PRNT90 titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT90. Allowing for an expected seven-fold waning of antibody titres over six months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT90 antibody titres. Both vaccines induced SARS-CoV-2 specific CD4+ and CD8+ T cell responses at 1-month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4+ and CD8+ T cell responses.ConclusionVaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induce higher CD4+ and CD8+ T cell responses to the structural protein than BNT162b2.Summary At a GlanceThrough the head-to-head comparison, vaccination with BNT162b2 induces significantly higher levels of SARS-CoV-2 specific binding and neutralizing antibody responses when compared to CoronaVac. CoronaVac induce higher CD4+ and CD8+ T cell responses to the structural protein than BNT162b2.

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.

Introduction Both daily and on‐demand regimens have been proven effective for pre‐exposure prophylaxis (PrEP) against HIV in men who have sex with men (MSM). We aimed to compare the two regimens on their coverage of condomless anal intercourse (CLAI) in MSM. Methods A randomized, controlled, open‐label, crossover trial was conducted in a teaching hospital in Hong Kong. Participants were sexually active HIV‐negative MSM aged 18 years or above with normal renal function and without chronic hepatitis B infection. Oral tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC) tablets were prescribed for PrEP. After a 2‐week lead‐in with daily TDF/FTC for treatment‐naïve MSM for tolerance assessment, participants were randomly assigned in a 1:1 ratio with a block size of four to either daily‐first or on‐demand‐first arm based on the IPERGAY study, for receiving PrEP for 16 weeks, then crossed‐over to the alternative regimen for another 16 weeks. The primary outcome was the proportion of days with PrEP‐covered CLAI by intention‐to‐treat analysis. The trial is registered with the CCRB Clinical Trials Registry, CUHK, CUHK_CCRB00606, and is closed to accrual. Results Between 25 August 2018 and 23 March 2019, 119 eligible participants were assigned to daily‐first arm (n = 59) and on‐demand‐first arm (n = 60) with an 87% overall completion rate (n = 103). With 96% and 54% of days on PrEP during daily and on‐demand periods, respectively, the proportion of days with PrEP‐covered CLAI between two arms were not statistically different (92% vs. 92%, p = 0.93). About half (47%) were diagnosed with at least one episode of incident sexually transmitted infection. Mild and time‐limited adverse events, including diarrhoea, headache, nausea and dizziness, were reported in 37 (31%) and 10 (8%) during the daily and on‐demand periods, respectively. At the end of the study, a similar proportion favoured daily or on‐demand regimen. Conclusions High prevention‐effective adherence, as reflected from the coverage of CLAI, was achievable by either daily or on‐demand PrEP among MSM, albeit a higher number of tablets taken for daily PrEP. As both regimens were well accepted, a flexible approach adopting either or both regimens with possible switching is warranted in order to suit individual health needs.

Failure of pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine may occur despite perfect adherence, although this is uncommon. Failure results in breakthrough HIV infection. Delayed seroconversion associated with antiretroviral use may complicate the picture, causing uncertainties in interpreting adherence patterns for establishing the true cause of PrEP failure.

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO ‘End TB’ targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI. Keywords: Latent tuberculosis infection, Asia, Awareness, Optimization