ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection.

The SARS-CoV-2 virus emerged in December 2019 and has caused a worldwide pandemic due to the lack of any pre-existing immunity. Accurate serology testing is urgently needed to help diagnose infection, determine past exposure of populations and assess the response to a future vaccine. The landscape of antibody responses to SARS-CoV-2 is unknown. In this study, we utilized the luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19. We identified new targets of the immune response to SARS-CoV-2 and show that nucleocapsid, open reading frame (ORF)8 and ORF3b elicit the strongest specific antibody responses. ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity. Our findings could be used to develop second-generation diagnostic tests to improve serological assays for COVID-19 and are important in understanding pathogenicity.

Author Correction: ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Implementation of evidence on management of pleural diseases: insights from a territory-wide survey of clinicians in Hong Kong.

BACKGROUND: Major advances in management of common pleural diseases have taken place in the past decade. However, pleural diseases are often managed by physicians of diverse training background and research on implementation of new knowledge is scanty. We aim to evaluate the practice pattern in pleural medicine among physicians in Hong Kong, for identification of possible gaps for clinical service improvement. METHODS: The Hong Kong Thoracic Society undertook a cross-sectional questionnaire survey in 2019, targeting clinicians of various subspecialties in internal medicine and levels of experience (basic and higher trainees, specialists) from twelve regional hospitals of diverse service scopes throughout Hong Kong. Respondents were selected by non-probability quota sampling. The questionnaire tool consisted of 46 questions covering diagnostic and therapeutic aspects of common pleural diseases. The responses were anonymous, and analysed independently using SPSS statistics software. RESULTS: The survey collected 129 responses, 47(36%) were from clinicians specialized in respiratory medicine. Majority of the respondents (98%) managed pleural diseases, including performing pleural procedures in their practice. Fifty-five percent of all the respondents had not received any formal training in transthoracic ultrasonography. A significant proportion of clinicians were unaware of pleuroscopy for investigation of exudative pleural effusion, indwelling pleural catheter for recurrent malignant pleural effusion, and combined intra-pleural Alteplase plus DNase for treatment of pleural infection (30%, 15% and 70% of non-respiratory clinicians respectively). Significant heterogeneity was found in the management of pleural infection, malignant pleural effusion and pneumothorax among respiratory versus non-respiratory clinicians. Contributing factors to the observed heterogeneity included lack of awareness or training, limited accessibility of drugs, devices, or dedicated service support. CONCLUSION: Significant heterogeneity in management of pleural diseases was observed among medical clinicians in Hong Kong. Continuous medical education and training provision for both specialists and non-specialists has to be strengthened to enhance the implementation of advances, improve quality and equity of healthcare provision in pleural medicine.

Kikuchi-Fujimoto disease following SARS-CoV-2 infection: A rare disease with increased incidence during the COVID-19 pandemic?

Kikuchi-Fujimoto Disease (KFD), also known as Kikuchi disease or Kikuchi histiocytic necrotizing lymphadenitis, is a rare and self-limiting condition characterized by cervical lymphadenopathy and fever, primarily affecting young Asian adults. The aetiology of KFD remains unknown, although various infectious agents have been suggested as potential triggers. With the emergence of the COVID-19 pandemic, cases of post-COVID-19 KFD and post-COVID-19 vaccine KFD have been reported. In this article, we present the first case of post-COVID-19 KFD in Hong Kong. A 24-year-old man developed fever and painful neck swelling 1 month after recovering from COVID-19. Diagnostic evaluation, including ultrasound-guided fine needle aspiration cytology (FNAC), confirmed the diagnosis of KFD. The patient's symptoms resolved spontaneously with supportive care. This case underscores the importance of considering KFD as a potential differential diagnosis in patients presenting with cervical lymphadenopathy and fever following COVID-19 recovery or vaccination.

A case series of three patients with histologically proven post COVID-19 organizing pneumonia.

Organizing pneumonia, a form of interstitial lung disease, may occur in patients who have recovered from COVID-19. In this article, we report three cases of post COVID-19 organizing pneumonia, proven histologically with transbronchial biopsies showing fibroblastic plugs in the alveolar spaces. Our patients received a range of 86-166 days of continuous corticosteroid therapy and all of them made excellent recovery.

Use of high flow nasal cannula oxygen therapy for patients infected with SARS-CoV-2 outside intensive care setting.

Background: In early 2022, there was a sudden surge of patients infected by the Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Hong Kong (HK), resulting in 9,163 deaths as of 29 May 2022. Many of the local population had not been vaccinated before this wave. The number of patients who developed coronavirus disease 2019 (COVID-19) related respiratory failure outnumbered the capacity of intensive care unit (ICU) beds. Some of these patients had to be supported with high flow nasal cannula (HFNC) therapy outside ICU setting. HK was in crisis situation. The primary objective of this study is to assess the 28-day mortality of this group of patients. The secondary objective is to explore any predictors of non-survivors to help clinical decision-making in future crisis. Methods: This is a retrospective observational study of patients suffering from COVID-19 related respiratory failure who received HFNC therapy in general medical wards of two hospitals during the period of 17 Mar to 30 Apr 2022. Survival and risk factors were reviewed. Results: Forty-nine patients were recruited. Twenty-six patients (53%) survived at 28-day after initiation of HFNC support. Three clinical parameters were found to be significantly associated with mortality at 28-day: (I) SpO2/FiO2 (SF) ratio <160 at 48 hours; (II) SF ratio <191 at 72 hours; (III) serial SF ratio at 48 or 72 hours showing no improvement over that at the time of initiation of HFNC therapy. Conclusions: Use of HFNC outside ICU setting showed benefit to patients suffering from COVID-19 related acute hypoxemic respiratory failure (AHRF). Serial SF ratio monitoring at 48 and 72 hours after therapy initiation might serve as predictors of outcome and thus guide clinical decision-making for medical resource allocation in outbreak situation.

A Multi-Center Study of the Prevalence and Characteristics of Eosinophilic Phenotype and High IgE Levels Among Chinese Patients with Severe Asthma.

Background: Patients with severe asthma have higher total- and asthma-related health burden than those whose disease is not severe. Recent medical advances in biologic therapies allow better control of asthma characterized by type 2 inflammation. Objective: To study the prevalence of eosinophilic phenotype and IgE levels in Chinese with severe asthma, and the relationship of these type 2 characteristics with asthma control, exacerbations and lung function. Methods: This was a multicenter cross-sectional observational study in Hong Kong, in Chinese adults with asthma on Step 4 or 5 of GINA treatment. Their blood eosinophil counts and total IgE levels were measured, and the relationship of these phenotypic parameters to the number of exacerbations in the past 12 months, and to symptom control in the past 4 weeks, were investigated. Results: A total of 232 subjects were recruited from 6 centers. The mean age was 53.9±12.9 years, with 86 (37.1%) male, and the duration of diagnosed asthma was 26.2±15.7 years. A T-helper 2 (Th2) phenotype indicated by elevated eosinophils and/or IgE was present in 169 (72.8%) of patients. Of 232 patients, 43% had an eosinophilic phenotype (blood eosinophil count ≥300 cell/mm3), while 59% had high total IgE levels of >100 IU/mL (overlap with eosinophilic phenotype in 30%) and 44% had IgE levels of >150 IU/mL (overlap with eosinophilic phenotype in 22%). Subjects with eosinophilic phenotype and IgE >150 IU/mL had a higher rate (1.8 times) of uncontrolled asthma compared with those without such a combination. Conclusion: In Chinese adults with severe asthma defined by the use of conventional maintenance medication regimens, the prevalence of Th2 inflammation is comparable to that reported from other ethnic populations. Those with both eosinophil count ≥300 cell/mm3 and high IgE levels >150 IU/mL had a higher rate of uncontrolled asthma compared with those without a combination of these features.

Good's syndrome presenting with CMV pneumonitis and oesophageal candidiasis: A case report.

Good's syndrome is an acquired combined T- and B-cell immunodeficiencies and patients are prone to opportunistic infections. The diagnosis is based on a characteristic immunoglobulin and lymphocyte subset profile, with clinical features of thymoma. Despite thymectomy, the immunodeficiencies persist and lifelong immunoglobulin replacement is necessary to prevent infections.

Airway pathogens detected in stable and exacerbated COPD in patients in Asia-Pacific.

Background: The burden of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region is projected to increase. Data from other regions show bacterial and viral infections can trigger acute exacerbations of COPD (AECOPD). Methods: This 1-year prospective epidemiological study (ClinicalTrials.gov identifier: NCT03151395) of patients with moderate to very severe COPD in Hong Kong, the Philippines, South Korea and Taiwan assessed the prevalence in sputum samples (by culture and PCR) of bacterial and viral pathogens during stable COPD and AECOPD. The odds of experiencing an exacerbation was evaluated for pathogen presence, acquisition and apparition. Health-related quality of life (HRQOL) was assessed. Results: 197 patients provided 983 sputum samples, with 226 provided during exacerbation episodes. The mean yearly AECOPD incidence rate was 1.27 per patient. The most prevalent bacteria by PCR at exacerbation were Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mcat); Mcat prevalence was higher at exacerbation than at stable state. Virus prevalence was low, other than for human rhinovirus (HRV) (8.1%, stable state; 16.6%, exacerbation). The odds ratio (95% CI) for an exacerbation (versus stable state) was statistically significant for the presence, acquisition and apparition of Hi (2.20, 1.26-3.89; 2.43, 1.11-5.35; 2.32, 1.20-4.46, respectively), Mcat (2.24, 1.30-3.88; 5.47, 2.16-13.86; 3.45, 1.71-6.98, respectively) and HRV (2.12, 1.15-3.91; 2.22, 1.09-4.54; 2.09, 1.11-3.91, respectively). HRQOL deteriorated according to the number of exacerbations experienced. Conclusion: In patients with COPD in the Asia-Pacific region, the presence of Hi, Mcat or HRV in sputum samples significantly increased the odds of an exacerbation, providing further evidence of potential roles in triggering AECOPD.

Associations between Preserved Foods and Breast Cancer Risk in Hong Kong Chinese Women.

Preserved food such as cured foods may contain nitrate and nitrite that may contribute to the breast cancer development. Evidence on the associations between these preserved food intakes and risk of breast cancer is sparse. This study aimed to examine the associations between preserved foods (i.e., cured meat, pickled vegetables, canned meat, and canned fruit/vegetables) and breast cancer risk in Hong Kong Chinese women. A total of 1,307 breast cancer cases and 1,050 age-matched controls were recruited from three hospitals during November 2011 through January 2018. We used a standardized questionnaire to collect information on dietary factors, including preserved foods. Unconditional multiple logistic regression was performed to calculate the adjusted odds ratio (AOR) of breast cancer in relation to preserved food with adjustment of potential confounders. We further performed stratified analysis according to the breast cancer biology subtypes. We found that cured meat consumption was significantly associated with the risk of breast cancer [AOR, 1.32; 95% confidence interval 95% (CI), 1.06-1.64]. Compared with no cured meat consumption, cured meat intake ≥ once per week was associated with an AOR of 2.66 (95% CI, 1.38-5.35). Women with canned fruit/vegetable ≥ consumption once per week had a higher risk of breast cancer (OR, 1.19; 95% CI, 1.00-1.41), particularly for the HER2-positive subtypes, but it became borderline after adjustment of confounders. Our study reveals a positive association between consumption of cured meat and breast cancer risk in Chinese population. Cured meat intake might be a potential novel risk factor for breast cancer but this would have to be confirmed by large prospective cohort studies. PREVENTION RELEVANCE: The main finding of this case-control study, an association between cured meat intake and a higher risk of breast cancer in Hong Kong Chinese women, contributes to the growing evidence for population-level health benefits of reducing cured meat consumption.

First reported case of late recurrence of pulmonary mucormycosis in a renal transplant recipient with poorly controlled diabetes mellitus.

Pulmonary mucormycosis (PM) is a rare, life-threatening fungal infection usually affecting immunocompromised patients. Its incidence is rising, with a recent outbreak associated with COVID-19 co-infection. Amphotericin B along with early surgery are considered the standard treatment. Recurrence has been reported in patients without adequate treatment and without permanent reversal of predisposing factors. We report a case of late recurrence of PM in a renal transplant recipient. In 2012, he was diagnosed with PM. Imaging at the time showed a lingular mass. He was treated with antifungal for 1 year until complete radiological resolution. Surgical intervention was considered but no further follow-up action was taken. In 2020, he presented with fever and haemoptysis. Imaging again showed a lingular mass, which was confirmed to be PM by bronchoscopic lung biopsy. This case highlights the importance of secondary antifungal prophylaxis for PM if permanent reversal of immunosuppression is not possible.

New pneumothorax complicating successful treatment of persistent air leak by endobronchial valves.

Endobronchial one-way valves (EBV) have been proposed as a treatment option for persistent air leak (PAL) complicating spontaneous pneumothorax when surgical intervention is considered not feasible. Published case series showed this form of treatment to be generally safe. We report two such cases in which both achieved immediate cessation of air leak and post-procedural chest radiograph showed significant collapse of the treated lobe, but developed sudden onset of shortness of breath within 24 h after EBV insertion. Chest radiograph showed continued collapse of the treated lobes with enlarged ipsilateral pneumothorax in one patient and new contralateral pneumothorax in the other. Pulmonologists and thoracic surgeons inserting EBV for treatment of PAL should be aware of this possible and important complication.

Clamping of chest drain before removal in spontaneous pneumothorax.

BACKGROUND: In spontaneous pneumothorax, clamping the chest drain before its removal may avoid reinsertion in case of early recurrence, but may be unsafe and may prolong hospital stay. The objective of this study was to examine the incidence of early recurrence in both clamped and unclamped pneumothorax episodes, and factors associated with it. METHODS: Retrospective chart review of primary and secondary spontaneous pneumothorax episodes in which chest drain was inserted during the period April 2012 to March 2014. RESULTS: Data of 122 episodes were analysed. There were 36 primary pneumothorax and 86 secondary pneumothorax episodes. Mean age was 59 years with 92% males. Clamping of the chest drain was done in 68 episodes (55.7%), and not done in 54. The clamping group was significantly younger, had more primary pneumothorax, and had shorter time from cessation of air leak to clamp/removal. Recurrence within 24 h were seen in 12 (17.6%) clamped episodes and 4 (7.4%) non-clamped episodes, although in only eight episodes were reinsertion of chest drain saved. Significantly more previous pneumothorax episodes were seen in the early recurrence group. We observed no new onset of tension pneumothorax or subcutaneous emphysema associated with clamping. CONCLUSION: The practice of clamping the chest drain before removal in spontaneous pneumothorax appear safe. Clamping saved chest drain reinsertion in 11.8% of cases, and has the potential to save more if clamped for up to 24 h. However, clamping may result in more early recurrences. Prospective randomised studies are needed.

Machine learning application for the prediction of SARS-CoV-2 infection using blood tests and chest radiograph.

Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9-95.8%; Sensitivity: 55.5-77.8%; Specificity: 91.5-98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.

Blood Eosinophil and Risk of Exacerbation in Chronic Obstructive Pulmonary Disease Patients: A Retrospective Cohort Analysis.

Purpose: Blood eosinophil is a readily available biomarker to reflect the eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) patients, yet its association with exacerbation is inconclusive. It is uncertain which measurement, eosinophil percentage or absolute eosinophil count, should be used and what is the optimal cutoff for exacerbation prediction. Patients and Methods: A total of 247 COPD patients were included in this retrospective cohort study. Blood eosinophil during stable disease state, baseline demographics, and clinical characteristics in 12 months after the index complete blood count (CBC) were recorded. Exacerbation frequencies were compared between patients with high and low blood eosinophil percentage using 2% as cut-off. Logistic regression and receiver operating characteristics (ROC) curve analyses were conducted. Results: Patients with blood eosinophil ≥2% were associated with more frequent exacerbations than patients with eosinophil <2% in the 12 months after the index CBC (mean exacerbation 1.07 vs 0.34, p < 0.001). Higher blood eosinophil percentage conferred a higher risk of exacerbation. Adjusted odds ratio for exacerbation in 12 months after the index CBC for blood eosinophil ≥2% was 2.98 (95% confidence interval = 1.42-6.25). The area under the ROC curve of eosinophil percentage was significantly higher than that of absolute eosinophil count (0.678 vs 0.640, p = 0.010). The optimal cutoff of blood eosinophil percentage for exacerbation prediction was 2.8%. Conclusion: Blood eosinophilia was associated with higher exacerbation risk in COPD patients. Further studies are required to elucidate the mechanism of eosinophilic inflammation in COPD and determine the optimal treatment strategy to reduce exacerbations.

Heterogeneous Associations Between Obesity and Reproductive-Related Factors and Specific Breast Cancer Subtypes Among Hong Kong Chinese Women.

Previous studies reported heterogeneous associations between obesity and reproductive-related breast cancer risk factors and breast cancer intrinsic subtypes; however, few studies have been conducted in Asian populations. Here, we aimed to examine whether risks associated with established breast cancer risk factors varied by breast cancer subtypes in Chinese women. We conducted a hospital-based case-control study in Hong Kong, including a total of 2169 Chinese women. Unconditional polytomous logistic regression models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals(95%CIs) to estimate relative risks associated with examined risk factors in case-control analyses and to test for heterogeneity across breast cancer subtypes in case-case analyses. In case-case analyses, compared with luminal A patients, luminal B (AOR = 1.76, 95% CI = 1.07-2.88), HER2 overexpressing (AOR = 3.40, 95% CI = 1.56-7.39), and triple negative (TNBC, AOR = 2.39, 95% CI = 1.18-4.82) patients were more likely to be postmenopausal. In case-control analyses, reduced risks associated with parity and younger age at first birth were only seen for luminal A and B cases especially among postmenopausal women, whereas having ≥ 3 children was associated with increased risk for HER2 overexpressing and TNBC among premenopausal women. Obesity was associated with increased risk for all subtypes. We found heterogeneous associations between parity-related risk factors by menopausal status and breast cancer subtypes among Chinese patients, which is similar to those observed in Western populations. Interestingly, obesity was associated with increased breast cancer risk regardless of menopausal status or subtypes, except for premenopausal luminal patients, which appears to be unique in Asian populations.

Endobronchial one-way valve for persistent air leak and lung volume reduction.

There are randomized controlled study data showing that endobronchial one-way valves (EBV) are useful for bronchoscopic lung volume reduction (BLVR). There is also case series data showing EBV to be effective in stopping persistent air leaks complicating pneumothoraces. We describe a 66-year-old man with severe chronic obstructive pulmonary disease (COPD) who failed assessments for BLVR because of the inability to perform the carbon monoxide diffusion test but subsequently had EBV deployed to his right upper lobe bronchi for persistent air leak complicating a spontaneous pneumothorax. Afterwards, there was subjective improvement in breathlessness, exercise capacity, and reduced frequency of exacerbations requiring hospitalization. Lung function parameters showed marked improvement. This case suggests that patients with compatible spirometric lung volume and computed tomography findings should proceed with BLVR. In addition, one should be aware of the possibility of improved lung function in patients with pulmonary emphysema following implantation of EBV for persistent air leak.

Associations between Coffee Products and Breast Cancer Risk: a Case-Control study in Hong Kong Chinese Women.

Coffee contains caffeine and diterpenes that were associated with decreased breast cancer risk, but results remained inconsistent. The study purpose was to investigate the associations between coffee products and breast cancer risk among Hong Kong Chinese women. We conducted a hospital-based case-control study in three public hospitals. 2169 Chinese women aged 24-84 years old were interviewed using a standardized questionnaire with questions asking types, cups and duration on coffee drinking. We used unconditional multivariate logistic regression to calculate the adjusted odds ratio (AOR) and 95% confidence interval (95% CI) for breast cancer risk with different coffee products. 238 (20.6%) cases and 179 (17.7%) controls are habitual coffee drinkers. No association was found between overall coffee drinking and breast cancer risk. Compared to the non-habitual coffee drinkers, women who consumed instant coffee (AOR = 1.50, 95% CI = 1.10-2.03) were significantly associated with an increased breast cancer risk. Women who drank brewed coffee (AOR = 0.48, 95% CI = 0.28-0.82) were negatively associated with breast cancer risk. A positive association between instant coffee and breast cancer risk was observed, contradicted to the outcomes of drinking brewed coffee. Larger studies are warranted to ascertain the role of different types of coffee products in breast cancer risk.

Spirometry is underused in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD).

Spirometry is important in the diagnosis and management of chronic obstructive pulmonary disease (COPD), yet it is a common clinical observation that it is underused though the extent is unclear. This survey aims to examine the use of spirometry in the diagnosis and management of COPD patients in a district in Hong Kong. It is a cross-sectional survey involving four clinic settings: hospital-based respiratory specialist clinic, hospital-based mixed medical specialist clinic, general outpatient clinic (primary care), and tuberculosis and chest clinic. Thirty physician-diagnosed COPD patients were randomly selected from each of the four clinic groups. All of them had a forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio less than 0.70 and had been followed up at the participating clinic for at least 6 months for COPD treatment. Of 126 patients who underwent spirometry, six (4.8%) did not have COPD. Of the 120 COPD patients, there were 111 males and mean post-bronchodilator FEV1 was 46.2% predicted. Only 22 patients (18.3%) had spirometry done during diagnostic workup, and 64 patients (53.3%) had spirometry done ever. The only independent factor predicting spirometry done ever was absence of old pulmonary tuberculosis and follow-up at respiratory specialist clinic. Age, sex, smoking status, comorbidities, duration of COPD, percentage predicted FEV1, body mass index, 6-minute walking distance, and Medical Research Council dyspnea score were not predictive. We conclude that spirometry is underused in general but especially by nonrespiratory physicians and family physicians in the management of COPD patients. More effort at educating the medical community is urgently needed.

Use of endobronchial one-way valves reveals questions on etiology of spontaneous pneumothorax: report of three cases.

Spontaneous pneumothoraces are believed to arise when air from the supplying airway exit via a ruptured visceral pleural bleb into the pleural cavity. Endobronchial one-way valves (EBVs) allow air exit (but not entry) from individual segmental airways. Systematic deployment of EBVs was applied to three patients with secondary spontaneous pneumothoraces and persistent airleak. In all cases, balloon-catheter occlusion of the upper lobe bronchus stopped the airleak. EBVs applied to individual upper lobe segmental airways failed to terminate the airleak, which only stopped after placements of multiple EBVs to occlude all upper lobe segments. The observation questions the traditional belief of 'one-airway-one-bleb-one-leak' in spontaneous pneumothorax.