A longitudinal environmental surveillance study for SARS-CoV-2 from the emergency department of a teaching hospital in Hong Kong.

BACKGROUND: Understanding factors associated with SARS-CoV-2 exposure risk in the hospital setting may help improve infection control measures for prevention. AIM: To monitor SARS-CoV-2 exposure risk among healthcare workers and to identify risk factors associated with SARS-CoV-2 detection. METHODS: Surface and air samples were collected longitudinally over 14 months spanning 2020-2022 at the Emergency Department (ED) of a teaching hospital in Hong Kong. SARS-CoV-2 viral RNA was detected by real-time reverse-transcription polymerase chain reaction. Ecological factors associated with SARS-CoV-2 detection were analysed by logistic regression. A sero-epidemiological study was conducted in January-April 2021 to monitor SARS-CoV-2 seroprevalence. A questionnaire was used to collect information on job nature and use of personal protective equipment (PPE) of the participants. FINDINGS: SARS-CoV-2 RNA was detected at low frequencies from surfaces (0.7%, N = 2562) and air samples (1.6%, N = 128). Crowding was identified as the main risk factor, as weekly ED attendance (OR = 1.002, P=0.04) and sampling after peak-hours of ED attendance (OR = 5.216, P=0.03) were associated with the detection of SARS-CoV-2 viral RNA from surfaces. The low exposure risk was corroborated by the zero seropositive rate among 281 participants by April 2021. CONCLUSION: Crowding may introduce SARS-CoV-2 into the ED through increased attendances. Multiple factors may have contributed to the low contamination of SARS-CoV-2 in the ED, including hospital infection control measures for screening ED attendees, high PPE compliance among healthcare workers, and various public health and social measures implemented to reduce community transmission in Hong Kong where a dynamic zero COVID-19 policy was adopted.

Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan, and Singapore.

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.

Identification of chronic obstructive pulmonary disease subgroups in 13 Asian cities.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment. OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup. METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis. RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score. CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

Probable transmission routes of the influenza virus in a nosocomial outbreak.

Influenza is a long-standing public health concern, but its transmission remains poorly understood. To have a better knowledge of influenza transmission, we carried out a detailed modelling investigation in a nosocomial influenza outbreak in Hong Kong. We identified three hypothesised transmission modes between index patient and other inpatients based on the long-range airborne and fomite routes. We considered three kinds of healthcare workers' routine round pathways in 1140 scenarios with various values of important parameters. In each scenario, we used a multi-agent modelling framework to estimate the infection risk for each hypothesis and conducted least-squares fitting to evaluate the hypotheses by comparing the distribution of the infection risk with that of the attack rates. Amongst the hypotheses tested in the 1140 scenarios, the prediction of modes involving the long-range airborne route fit better with the attack rates, and that of the two-route transmission mode had the best fit, with the long-range airborne route contributing about 94% and the fomite route contributing 6% to the infections. Under the assumed conditions, the influenza virus was likely to have spread via a combined long-range airborne and fomite routes, with the former predominant and the latter negligible.

Virological response to peramivir treatment in adults hospitalised for influenza-associated lower respiratory tract infections.

An open-label trial on intravenous peramivir was conducted among adult patients hospitalised for influenza-associated lower respiratory tract complications (LRTCs). Virus culture and quantitative reverse transcription PCR (qRT-PCR) were performed serially until Day 10. Peramivir treatment was associated with viral RNA decline as well as culture and RNA negativity, which occurred at rates comparable with those of oseltamivir: by Day 5, viral load decline -2.5 log10 copies/mL [ßinteraction -0.071, standard error (SE) 0.121, 95% confidence interval (CI) -0.309 to 0.167]; culture-negative, 94% (vs. 95%); and RNA-negative, 44% (vs. 36%). Extended treatment of >5 days was required in 69% of cases because of slow clinical resolution and viral clearance in LRTCs. Peramivir was well tolerated. These data are useful for future trial design in this unique population.

A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections.

BACKGROUND: It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. METHODS: A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. CONCLUSIONS: We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01052961.

High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections.

BACKGROUND: Better understanding of complications and outcomes of adults hospitalized with respiratory syncytial virus (RSV) infection is necessary. METHODS: A retrospective cohort study was conducted on all adults (≥ 18 years) admitted to 3 acute care general hospitals in Hong Kong with virologically confirmed RSV infection during 2009-2011 (N = 607). Adults hospitalized for seasonal influenza during the period were used for comparison (n = 547). Both infections were prospectively diagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists. Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalization duration. Cox proportional hazards models were used for analyses. RESULTS: The mean age of RSV patients was 75 (SD, 16) years; 87% had underlying conditions. Lower respiratory and cardiovascular complications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic obstructive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterial superinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively. Crude all-cause mortality was 9.1% and 11.9% within 30 days and 60 days, respectively; mean length of stay of survivors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superinfection, and elevated urea level and white blood cell count were independently associated with poorer survival. Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall outcomes of survival and length of stay were not significantly different from those in influenza. CONCLUSIONS: RSV can cause severe lower respiratory complications in older adults, resulting in respiratory failure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.

Tuberculosis is associated with increased lung cancer mortality.

SETTING: Elderly persons living in the community in Hong Kong. OBJECTIVE: To examine the association between tuberculosis (TB) and lung cancer. DESIGN: Elderly clients enrolled in a health programme from 2000 to 2003 were retrospectively cross-matched with the territory-wide TB notification registry for TB before enrolment. The cohort was followed up prospectively through linkage with the territory-wide death registry for cause of death until 31 December 2011. All subjects with suspected malignancy or recent weight loss (≥5%) at enrolment and deaths within the first 2 years of follow-up were excluded. RESULTS: Of the 61,239 subjects included, 516 had TB before enrolment. After 490,258 person-years of follow-up, respectively 1344, 910 and 2003 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. TB before enrolment was associated with death due to lung cancer (Mantel-Haenszel weighted relative risk 2.61, 95%CI 1.82-3.74, P < 0.001) but not other malignancies after stratification by sex. TB remained an independent predictor of lung cancer death (adjusted hazard ratio 2.01, 95%CI 1.40-2.90; P < 0.001), after adjustment for multiple potential confounders. CONCLUSIONS: TB was independently associated with subsequent mortality due to lung cancer. This finding calls for intensification of tobacco control and better targeting of lung cancer screening in high TB burden areas.

Comparison of empirical continuous positive airway pressure (CPAP) treatment versus initial portable sleep monitoring followed by CPAP treatment for patients with suspected obstructive sleep apnoea.

BACKGROUND: Polysomnography is labour-intensive for diagnosing obstructive sleep apnoea (OSA). We compared two algorithms for initiating continuous positive airway pressure (CPAP) treatment for patients with suspected OSA. METHODS: Symptomatic OSA patients were randomised into either algorithm I or II. Algorithm I consisted of an empirical CPAP trial whereas algorithm II utilised an Apnea Risk Evaluation System, a wireless device applied on the forehead, for establishing a diagnosis before a CPAP trial for 3 weeks. Primary outcome was success of CPAP trial, defined as CPAP usage > 4 h/night and willingness to continue CPAP. Subjective usefulness of CPAP, accuracy of Apnea Risk Evaluation System versus polysomnography and CPAP adherence at 6 months were secondary end-points. RESULTS: Altogether 138 patients in algorithm I and 110 patients in algorithm II completed the CPAP trial. There were no significant differences between these algorithms with respect to the primary end-point. The sensitivity and specificity of algorithm I versus II as a diagnostic test for OSA were 0.3, 0.8 versus 0.31, 1.00 respectively. In predicting CPAP adherence at 6 months, the likelihood ratio positive for algorithms I and II was 2.7 and 5.27 respectively. The mean (SE) time taken from the first consultation to the end of CPAP trial in algorithm I and algorithm II was 60 (2) and 98 (5) days, respectively, P < 0.01. CONCLUSION: An ambulatory approach with portable sleep monitoring for diagnosing OSA before a CPAP trial can identify more patients who would adhere to CPAP at 6 months than empirical CPAP treatment alone.

Interferon gamma release assay for differentiating tuberculosis among pneumonia cases in acute healthcare setting.

OBJECTIVES: Early diagnosis of smear-negative tuberculosis remains challenging. The role of an interferon-gamma release assay (IGRA) in discriminating active pulmonary tuberculosis (PTB) among cases of 'pneumonia' was investigated. METHODS: Consecutive patients admitted to an acute hospital in Hong Kong (intermediate TB burden) during 2006-2008 because of pneumonia and suspected PTB were recruited for IGRA (Quantiferon-TB Gold, QFN-G) study. Diagnosis of tuberculosis was confirmed by mycobacterial culture or histology. RESULTS: Altogether 179 patients were recruited (median (IQR) age 59 (44-75), 68.7% male); active PTB was confirmed in 63 (35.2%). Among the AFB-smear-negative 'pneumonias' (n = 152), age>50 (OR 0.27, 95% CI 0.09-0.84), absence of weight loss (OR 0.30, 95% CI 0.10-0.88), and negative IGRA (OR 0.08, 95% CI 0.03-0.25) were independently associated with lower risks of PTB. The overall sensitivity, specificity, positive and negative predictive values for the IGRA in diagnosing active PTB were 60%, 87%, 72% and 80% respectively. Among smear-negative 'pneumonias' (n = 152), the performance values of IGRA were 64%, 87%, 62% and 88% respectively; in the absence of characteristic clinical or radiographic features of PTB, the negative predictive value (NPV) improved to 90-95%. CONCLUSIONS: The high NPV of QFN-G among smear-negative 'pneumonias' can be useful for risk stratification in hospitalized patients suspected of PTB. Further investigation on the role of these assays in patient management is warranted.

Outcomes of adults hospitalised with severe influenza.

BACKGROUND: The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza. METHODS: A prospective, observational cohort study was conducted over 24 months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates. RESULTS: 754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70+/-18 years; co-morbidities and serious complications were common (61-77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation. CONCLUSIONS: Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.

Endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases: local experience of a novel investigation.

OBJECTIVE: To study the efficacy and safety of endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases in Hong Kong. DESIGN: Retrospective review of prospectively collected data. SETTING: University teaching hospital, Hong Kong. PATIENTS: A total of 125 consecutive patients with various mediastinal and pulmonary lesions that underwent trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration from July 1998 to June 2007. MAIN OUTCOME MEASURES: The diagnostic accuracy and safety of the procedure and its influence in patient management. RESULTS: Malignancy was confirmed in 62 (50%) of the patients and excluded in 42 (34%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of endoscopic ultrasonography-guided fine-needle aspiration in diagnosing mediastinal malignancies were 75% (95% confidence interval, 64-83%), 100% (90-100%), 100% (93-100%), 67% (54-78%), and 83%, respectively. Eighty-six (69%) of the patients had their initial plan of invasive investigations changed. Only one (0.8%) patient developed a septic complication in a mediastinal cyst after puncturing, and was treated surgically. CONCLUSIONS: Trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration is a minimally invasive, effective, and safe method of diagnosing malignant mediastinal disease. It may reduce the need for other invasive investigations.

Activation of peripheral Th17 lymphocytes in patients with asthma.

A recently identified interleukin (IL)-17-producing T-helper (Th) lymphocyte subset, which comprises Th17 cells producing hallmark cytokines IL-17A, IL-17F and IL-22, is involved in chronic inflammatory diseases. Elevated gene and protein expressions of IL-17 are manifested in allergic asthma. We further characterized the activation of Th17 cells in asthmatic patients. Peripheral blood mononuclear cells (PBMC) were purified from 31 asthmatic patients and 20 sex- and age-matched control subjects. The number of IL-17A secreting cells in peripheral blood was enumerated by enzyme-linked immunosorbent spot assay. Cell surface expression of Th17-related chemokine receptor CCR6, and plasma level of IL-17A, IL-17F and IL-22, and ex vivo production of IL-17A and IL-22 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The number of peripheral Th17 lymphocytes, expression of CCR6 on Th cells, and ex vivo IL-23, anti-CD3 and anti-CD28 induced production of IL-22 by PBMC were significantly elevated in asthmatic patients compared with control subjects (all p < 0.01). This clinical study further confirmed increased number of peripheral Th17 lymphocytes and cell surface expression of CCR6 receptors on Th cells in asthmatic patients. Pro-inflammatory cytokine IL-23 can exacerbate disease severity by activating pathogenic Th17 lymphocytes to release downstream inflammatory cytokine IL-22 in asthma.