Elevated risk of multimorbidity post-COVID-19 infection: protective effect of vaccination.

BACKGROUND: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association. AIM: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination. DESIGN: Nested case-control study. METHODS: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity. RESULTS: In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger. CONCLUSIONS: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Factors affecting stability and infectivity of SARS-CoV-2.

BACKGROUND: In late 2019, a novel human coronavirus - severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) - emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: To investigate the infectivity of SARS-CoV-2 under various environmental and pH conditions. The efficacies of various laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on to Vero E6 cells on days 0, 1, 3, 5 and 7 after incubation at different temperatures. Viral viability was determined after treatment with various disinfectants and pH solutions at room temperature (20-25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH 4 to pH 11 for several days, and for 1-2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrated the stability of SARS-CoV-2 on environmental surfaces, and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to reduce viral infectivity significantly, which could ensure hospital and laboratory safety during the SARS-CoV-2 pandemic.

Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study.

OBJECTIVES: To determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection. METHODS: This prospective cohort study was conducted during the 2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG™ Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel. RESULTS: A total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04). CONCLUSIONS: Respiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study.

OBJECTIVES: Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva. METHODS: This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated. RESULTS: Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776-0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%-96.2%) and 100% (97.3%-100%), respectively, for saliva, and were 96.1% (88.9%-99.2%) and 98.5% (94.7%-99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA. CONCLUSIONS: Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.

Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates.

This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.

Budget impact and cost-effectiveness analyses of direct-acting antivirals for chronic hepatitis C virus infection in Hong Kong.

The purpose of this investigation was to evaluate the budget impact and cost-effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection in Hong Kong. A decision analytic model was developed to compare short-term costs and health outcomes of patients with chronic HCV genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based treatments (sofosbuvir or ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171 per course while improving the rate of sustained virologic response (SVR) from 59-66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments ranged from $9724 to $29,189 per treatment success, which were all below the cost-effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection management over 5 years. A 50% change in DAA medication costs reflected a change in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs to the public hospital formulary yields a considerable budget increase but is still economically favorable to the local government.

Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia.

BACKGROUND: Gut dysbiosis may contribute to pain and bloating in patients with functional gastrointestinal disease. AIMS: To determine if treatment with rifaximin would improve the symptoms of functional dyspepsia in Chinese patients in a double-blinded, randomised, placebo-controlled trial. METHODS: Consecutive subjects with a diagnosis of functional dyspepsia as per the Rome III criteria were randomised to receive rifaximin 400 mg or placebo, all taken three times daily for 2 weeks. The investigators and study subjects were blinded to the treatment allocation. Subjects were followed up for 8 weeks. The primary end point was adequate relief of global dyspeptic symptoms (GDS). Secondary endpoints were relief of individual dyspeptic symptoms. RESULTS: Eighty-six subjects were recruited. At week 8, there were significantly more subjects in the rifaximin than in the placebo group who experienced adequate relief of GDS (78% vs. 52%, P = 0.02). A trend favouring rifaximin group was also noted in the preceding 4 weeks. Rifaximin was also superior to placebo in providing adequate relief of belching and post-prandial fullness/bloating (PPF) in subjects at week 4. Subgroup analysis revealed that female subjects had more significant response to rifaximin treatment (adequate relief of GDS at week 4: 76% vs. 42%, P = 0.006; week 8: 79% vs. 47%, P = 0.008), as well as improvements in their belching and PPF at week 4. The incidences of adverse effects were similar in both groups. CONCLUSIONS: Treatment with 2 weeks of rifaximin led to adequate relief of global dyspeptic symptoms, belching and post-prandial fullness/bloating in subjects with functional dyspepsia. The difference was more marked in females. (clinicaltrials.org NCT01643083).

Effects of nucleoside analogue prescription for hepatitis B on the incidence of liver cancer in Hong Kong: a territory-wide ecological study.

BACKGROUND: The temporal relationship between nucleoside analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level. AIM: To investigate the impact of nucleoside analogue prescription on liver cancer incidence in a CHB-prevalent region. METHODS: We obtained territory-wide nucleoside analogue prescription data from 1999, when nucleoside analogue was first available in Hong Kong, to 2012 and the population-based liver cancer incidence data from 1990 to 2012. We compared the liver cancer incidences from 1990 to 1998 and 1999 to 2012 with adjustment for local hepatitis B surface antigen seroprevalence. RESULTS: Nucleoside analogue prescription patient headcount increased from 2006 per year in 1999 to 26 411 in 2012. Prescription volume in 2012 was highest among 55-64 years (30.3%), higher than 65-74 years (13.0%) and ≥75 years (5.8%). Age-standardised liver cancer incidence 1999-2012 decreased by 1.88%/year (95% CI 3.34% to 0.42%/year). NA therapy was associated with decline in age-adjusted liver cancer incidence (2.7 per 100 000 persons, P < 0.001, 95% CI 1.4-4.0 per 100 000 persons). Fifty-five to sixty-four years age group had the most significant decline (men: 24.0 per 100 000 persons, P = 0.001, 95% CI 11.4-36.6 per 100 000 persons; women: 8.5 per 100 000 persons, P = 0.009, 95% CI 2.3-14.6 per 100 000 persons). No significant association was noted in age groups 65-74 years and ≥75 years (both P > 0.05). CONCLUSIONS: Nucleoside analogue prescription was associated with a reduction of overall liver cancer incidence in a CHB-prevalent region. The lack of association among individuals of ≥65 years was consistent with the low nucleoside analogue prescription volume in elderly patients, mitigating the impact of CHB treatment on liver cancer.

Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii.

Gastrointestinal colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Acinetobacter baumannii (MRAB) provides an important reservoir for clinical infections and hospital outbreaks. We conducted a 7-month study in a 3200-bed healthcare network to investigate the prevalence of gastrointestinal colonization of CRAB and MRAB in Hong Kong. Between 1 June and 31 December 2014, a total of 17,760 fecal specimens from 9469 patients were screened. Testing showed that 340 (1.9%) specimens from 224 (2.6%) patients were CRAB-positive, which included 70 (0.39%) MRAB-positive specimens from 54 (0.57%) patients. The presence of wound or ulcer, use of broad-spectrum antibiotics in the preceding 6 months, and residence in elderly homes are independent risk factors for gastrointestinal colonization of CRAB. Quantitative bacterial counts in various body sites (rectal, nasal, axilla, wound, catheterized urine, if available) were performed in 33 (61.1%) of 54 MRAB patients. Ten (30.3%) and 8 (24.2%) patients had high bacterial load (defined as over 3 log10) in rectal and nasal swabs, with a median of 5.04 log10 cfu/ml of rectal swab and 4.89 log10 cfu/ml of nasal swab in saline diluent, respectively. Nine (81.8%) of 11 patients with wounds had high bacterial load in wound swabs, with a median of 5.62 log10 cfu/ml. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs. With the implementation of directly observed hand hygiene before meals and medications to all conscious hospitalized patients, no hospital outbreaks were observed during our study period.

Containment of Clostridium difficile infection without reduction in antimicrobial use in Hong Kong.

Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0%, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47% (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8% from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2% vs. 25/152, 16.4%, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.

Control of hospital endemicity of multiple-drug-resistant Acinetobacter baumannii ST457 with directly observed hand hygiene.

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.

Sunitinib-induced hyperammonaemia in a patient with pancreatic neuroendocrine tumour.

WHAT IS KNOWN AND OBJECTIVE: Sunitinib can improve progression-free survival and overall survival in patients with advanced pancreatic neuroendocrine tumor (PNET). From clinical trial, most commonly reported adverse events of sunitinib were neutropenia (12%), diarrhea (10%), asthenia (7%), erythrodysesthesia (7%), hypertension (7%) and thrombocytopenia (6%). CASE SUMMARY: We report a patient with PNET with liver metastases who developed hyperammonemia with a low dosage of sunitinib probably contributed by the presence of liver metastases. WHAT IS NEW AND CONCLUSIONS: We would like to draw attention to the potential risk of sunitinib induced hyperammonemic encephalopathy even with a low dosage of sunitinib. The absence of sunitinib-induced hyperammonemia during its initial course does not rule out this possibility if there is increased in liver metastases. We suggest checking the ammonia level if patient on sunitinib presented with altered sensorium even if the liver function is normal.