Longitudinal Cytokine Profile in Patients With Mild to Critical COVID-19.

The cytokine release syndrome has been proposed as the driver of inflammation in coronavirus disease 2019 (COVID-19). However, studies on longitudinal cytokine profiles in patients across the whole severity spectrum of COVID-19 are lacking. In this prospective observational study on adult COVID-19 patients admitted to two Hong Kong public hospitals, cytokine profiling was performed on blood samples taken during early phase (within 7 days of symptom onset) and late phase (8 to 12 days of symptom onset). The primary objective was to evaluate the difference in early and late cytokine profiles among patient groups with different disease severity. The secondary objective was to assess the associations between cytokines and clinical endpoints in critically ill patients. A total of 40 adult patients (mild = 8, moderate = 15, severe/critical = 17) hospitalized with COVID-19 were included in this study. We found 22 cytokines which were correlated with disease severity, as proinflammatory Th1-related cytokines (interleukin (IL)-18, interferon-induced protein-10 (IP-10), monokine-induced by gamma interferon (MIG), and IL-10) and ARDS-associated cytokines (IL-6, monocyte chemoattractant protein-1 (MCP-1), interleukin-1 receptor antagonist (IL-1RA), and IL-8) were progressively elevated with increasing disease severity. Furthermore, 11 cytokines were consistently different in both early and late phases, including seven (growth-regulated oncogene-alpha (GRO-α), IL-1RA, IL-6, IL-8, IL-10, IP-10, and MIG) that increased and four (FGF-2, IL-5, macrophage-derived chemokine (MDC), and MIP-1α) that decreased from mild to severe/critical patients. IL-8, followed by IP-10 and MDC were the best performing early biomarkers to predict disease severity. Among critically ill patients, MCP-1 predicted the duration of mechanical ventilation, highest norepinephrine dose administered, and length of intensive care stay.

Pearls of experience for safe and efficient hospital practices in otorhinolaryngology-head and neck surgery in Hong Kong during the 2019 novel coronavirus disease (COVID-19) pandemic.

The 2019 novel coronavirus disease (COVID-19) epidemic originated in Wuhan, China and spread rapidly worldwide, leading the World Health Organization to declare an official global COVID-19 pandemic in March 2020. In Hong Kong, clinicians and other healthcare personnel collaborated closely to combat the outbreak of COVID-19 and minimize the cross-transmission of disease among hospital staff members. In the field of otorhinolaryngology-head and neck surgery (OHNS) and its various subspecialties, contingency plans were required for patient bookings in outpatient clinics, surgeries in operating rooms, protocols in wards and other services. Infected patients may shed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) particles into their environments via body secretions. Therefore, otolaryngologists and other healthcare personnel in this specialty face a high risk of contracting COVID-19 and must remain vigilant when performing examinations and procedures involving the nose and throat. In this article, we share our experiences of the planning and logistics undertaken to provide safe and efficient OHNS practices over the last 2 months, during the COVID-19 pandemic. We hope that our experiences will serve as pearls for otolaryngologists and other healthcare personnel working in institutes that serve large numbers of patients every day, particularly with regard to the sharing of clinical and administrative tasks during the COVID-19 pandemic.

Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong.

PURPOSE: Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients. METHODS: Infection control measures implemented in our ophthalmology clinic are discussed. The measures are based on detailed risk assessment by both local ophthalmologists and infection control experts. RESULTS: A three-level hierarchy of control measures was adopted. First, for administrative control, in order to lower patient attendance, text messages with an enquiry phone number were sent to patients to reschedule appointments or arrange drug refill. In order to minimise cross-infection of COVID-19, a triage system was set up to identify patients with fever, respiratory symptoms, acute conjunctivitis or recent travel to outbreak areas and to encourage these individuals to postpone their appointments for at least 14 days. Micro-aerosol generating procedures, such as non-contact tonometry and operations under general anaesthesia were avoided. Nasal endoscopy was avoided as it may provoke sneezing and cause generation of droplets. All elective clinical services were suspended. Infection control training was provided to all clinical staff. Second, for environmental control, to reduce droplet transmission of COVID-19, installation of protective shields on slit lamps, frequent disinfection of equipment, and provision of eye protection to staff were implemented. All staff were advised to measure their own body temperatures before work and promptly report any symptoms of upper respiratory tract infection, vomiting or diarrhoea. Third, universal masking, hand hygiene, and appropriate use of personal protective equipment (PPE) were promoted. CONCLUSION: We hope our initial experience in stepping up infection control measures for COVID-19 infection in ophthalmology can help ophthalmologists globally to prepare for the potential community outbreak or pandemic. In order to minimise transmission of COVID-19, ophthalmologists should work closely with local infection control teams to implement infection control measures that are appropriate for their own clinical settings.

Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-Aspergillus fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of >1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.

Presumed Aggregatibacter aphrophilus endogenous endophthalmitis.

We hereby report a case of endogenous endophthalmitis, presumably caused by a rare culprit-Aggregatibacter aphrophilus. A. aphrophilus is a member of the HACEK group, a group of fastidious Gram-negative bacteria with low pathogenicity and a rare cause of human infections. For ophthalmic infection, it has been reported to cause canaliculitis and exogenous endophthalmitis. A middle-aged gentleman with good past health presented with decreased vision (20/200) in his left eye. Other than fever, he was well on presentation, with no apparent focus of infection. Subsequently, he developed an episode of high fever reaching 39.2 °C, with CRP of 233 mg/L. CT abdomen showed presumed kidney abscess and a rare Gram-negative coccobacillus. A. aphrophilus [formerly Haemophilus aphrophilus (Nørskov-lauritsen and Kilian in Int J Syst Evol Microbiol 56:2135-2146, 2006)] was found in blood culture, Vitreous sample was analysed using 16S ribosomal DNA amplification but failed to identify the organism. After appropriate treatment, his vision improved drastically from 20/200 to 20/30. A. aphrophilus isolated from blood cultures during septicemia in a patient with kidney abscess may be associated with metastatic endophthalmitis, which may appear as a first sign. Our case demonstrates that with prompt diagnosis and appropriate treatment, visual prognosis of A. aphrophilus endophthalmitis can be promising.

Mycobacterium abscessus bacteremia after receipt of intravenous infusate of cytokine-induced killer cell therapy for body beautification and health boosting.

BACKGROUND: We report the first series of Mycobacterium abscessus bacteremia after cytokine-induced killer cell therapy for body beautification and health boosting. METHODS: The clinical manifestations, laboratory and radiological investigations, cytokine/chemokine profiles, and outcomes were described and analyzed. RESULTS: Four patients were admitted, and 3 patients had septic shock. Chest radiographs showed pulmonary infiltrates in all patients. Three patients developed peripheral gangrene, and 1 patient required lower limb and finger amputations. Patient 1 also developed disseminated infection including meningitis and urinary tract infection. Postmortem examination of patient 1 showed focal areas of pulmonary hemorrhage and diffuse alveolar damage, splenic infarct, adrenal necrosis, and hemorrhage, and acid-fast bacilli (AFB) were seen in the lung, liver, kidney, and adrenal gland. Patient 2 developed inguinal granulomatous lymphadenitis about 40 days after onset of lower limb gangrene. Wedge-shaped pulmonary infarcts were found in patient 3, and retinitis and subcutaneous lesions developed in patient 4. Patients in septic shock had dysregulated cytokine/chemokine profiles. Patient 4 with relatively milder presentation had increasing levels of interleukin 17 and cytokines in the interferon-γ/interleukin 12 pathway. All survivors required prolonged intravenous antibiotics. Blood cultures grew M. abscessus for all patients, and admission peripheral blood smear revealed AFB for 3 patients. Mycobacterium abscessus was also isolated from respiratory specimens (2 patients), urine (1 patient), and cerebrospinal fluid (1 patient). Time to initial blood culture positivity (patients 1, 2, and 3: ≤52 hours; patient 4: 83 hours) appeared to correlate with disease severity. CONCLUSIONS: Empirical coverage for rapidly growing mycobacteria should be considered in patients with sepsis following cosmetic procedures.

High mortality associated with Catabacter hongkongensis bacteremia.

Catabacter hongkongensis is a recently described catalase-positive, motile, anaerobic, nonsporulating, Gram-positive coccobacillus that was first isolated from blood cultures of four patients from Hong Kong and Canada. Although DNA sequences representing C. hongkongensis have been detected in environmental sources, only one additional case of human infection has been reported, in France. We describe five cases of C. hongkongensis bacteremia in Hong Kong, two presenting with sepsis, one with acute gangrenous perforated appendicitis, one with acute calculous cholecystitis, and one with infected carcinoma of colon. Three patients, with gastrointestinal malignancy, died during admission. All five isolates were catalase positive, motile, and negative for indole production and nitrate reduction and produced acid from arabinose, glucose, mannose, and xylose. They were unambiguously identified as C. hongkongensis by 16S rRNA gene analysis. Of the total of 10 reported cases of C. hongkongensis bacteremia in the literature and this study, most patients had underlying diseases, while two cases occurred in healthy young individuals with acute appendicitis. Six patients presented with infections associated with either the gastrointestinal or biliary tract, supporting the gastrointestinal tract as the source of bacteremia. C. hongkongensis bacteremia is associated with a poor prognosis, with a high mortality of 50% among reported cases, especially in patients with advanced malignancies. All reported isolates were susceptible to metronidazole. Identification of more C. hongkongensis isolates by 16S rRNA gene sequencing will help better define its epidemiology and pathogenesis.

Prospective evaluation of seropositive occult hepatitis B viral infection in lymphoma patients receiving chemotherapy.

OBJECTIVE. To serially evaluate the viral kinetics of occult hepatitis B virus infection in lymphoma patients and perform a correlation with clinical outcomes. DESIGN. Case series with 1-year follow-up. SETTING. Regional hospital, Hong Kong. PATIENTS. Consecutive patients who were newly diagnosed to have lymphoma in the hospital between 1 April 2007 and 31 March 2008 were tested for hepatitis B (HB) surface (s) antigen (Ag), anti-HBs antibody (Ab) and anti-HB core (c) Ab. Seropositive occult hepatitis B patients as defined by being negative for HBsAg but positive anti-HBsAb and/or anti-HBcAb without a hepatitis B vaccination history were recruited. Serum HBsAg, anti-HBsAb, anti-HBcAb, hepatitis B virus deoxyribonucleic acid (DNA) level, and liver biochemistry were checked at baseline and every 4 weeks during and after chemotherapy until 12 months after the completion of chemotherapy or death. Entecavir was started if patients developed biochemical flare-up of hepatitis B associated with virological rebound. The prevalence and course of hepatitis B virus-related hepatitis, as well as any temporal relationship to viral kinetics and clinical hepatitis, were assessed. RESULTS. Of 47 patients tested, 10 (21%) with lymphoma were seropositive occult hepatitis carriers. Their median baseline hepatitis B virus DNA level was 89 IU/mL (range, <34-807 IU/mL). Virological rebound (as defined by a 10-fold increase in serum hepatitis B virus DNA level from pre-chemotherapy level persisted for 4 weeks) occurred in one of the 10 patients, followed by biochemical reactivation. Whereupon entecavir treatment was started and no liver failure ensued. Regarding the other seropositive occult patients, their serum hepatitis B virus DNA levels fluctuated, but there was no associated biochemical reactivation. CONCLUSION. Detectable baseline serum hepatitis B virus DNA is not uncommon in patients with occult hepatitis B who receive chemotherapy. Transient elevation in serum hepatitis B virus DNA levels does not predict biochemical reactivation, but antiviral treatment might be considered if virological rebound persists.

Inflammatory cytokine profile in children with severe acute respiratory syndrome.

OBJECTIVE: To study the inflammatory cytokine profile in children with severe acute respiratory syndrome (SARS) and to investigate whether monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) could be considered for treatment of these patients. METHODS: Plasma inflammatory cytokine concentrations (interleukin [IL]-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha) were monitored longitudinally on admission, immediately before corticosteroids, and 1 to 2 days and 7 to 10 days after the drug treatment in a cohort of pediatric patients (n = 8) with virologic confirmed SARS-associated coronavirus infection. None of the patients required mechanical ventilation or intensive care treatment. All children except 1 (patient 3) received corticosteroids. RESULTS: Plasma IL-1beta levels (excluding patient 3) were substantially elevated immediately before (range: 7-721 ng/L) and 7 to 10 days after (range: 7-664 ng/L) corticosteroid treatment. In contrast, the plasma concentrations of other key proinflammatory cytokines, including IL-6 and TNF-alpha, were not overtly increased in any of the patients throughout the course of illness. In addition, plasma IL-10 concentration was significantly lower 1 to 2 days and 7 to 10 days after corticosteroid treatment, compared with the immediate pretreatment level. Similarly, plasma IL-6 and IL-8 concentrations were significantly decreased 7 to 10 days after the drug treatment. CONCLUSIONS: Pediatric SARS patients have markedly elevated circulating IL-1beta levels, which suggests selective activation of the caspase-1-dependent pathway. Other key proinflammatory cytokines, IL-6 and TNF-alpha, showed only mildly elevated levels at the initial phase of the illness. The current evidence does not support the use of TNF-alpha monoclonal antibody in this group of children.

Tuberculosis of the nasopharynx: a rare entity revisited.

OBJECTIVES: Tuberculosis of the nasopharynx is uncommon. A large series of 17 cases is reported, and the clinical and pathological features are discussed. STUDY DESIGN: A retrospective review. METHODS: Seventeen archived cases of biopsy-proven nasopharyngeal tuberculosis were reviewed for patient age and sex, presenting complaint and duration, systemic symptoms, cervical lymphadenopathy, and chest x-ray findings. These findings were compared with a compilation of 40 cases reported in the English literature. RESULTS: There was a female predominance (13 women and 4 men), with age range of 20 to 74 years (mean age, 38 y). The most common presentation was enlargement of the cervical lymph nodes (53%), followed by hearing loss (12%), tinnitus, otalgia, nasal obstruction, and postnasal drip (6% each). The duration of the presenting symptoms ranged from 1 week to 1 year (mean duration, 16 wk). Ten patients (59%) had cervical lymphadenopathy, two (12%) had systemic symptoms (fever, weight loss, night sweats), and one patient (6%) had miliary pulmonary tuberculosis. Direct endoscopic examination showed nasopharyngeal mucosal irregularity or mass in the majority of patients (12 patients [70%]). These features were similar to those reported in the literature. CONCLUSIONS: Nasopharyngeal tuberculosis is uncommon, usually occurring without pulmonary or systemic involvement. Cervical lymphadenopathy occurs in more than half of the patients and is the most common presenting complaint; this, together with the nasopharyngeal findings of mass or mucosal irregularity, makes differentiation from carcinoma on clinical examination difficult, necessitating histological evaluation.