Determining meteorologically-favorable zones for seasonal influenza activity in Hong Kong.

Investigations of simple and accurate meteorology classification systems for influenza epidemics, particularly in subtropical regions, are limited. To assist in preparing for potential upsurges in the demand on healthcare facilities during influenza seasons, our study aims to develop a set of meteorologically-favorable zones for epidemics of influenza A and B, defined as the intervals of meteorological variables with prediction performance optimized. We collected weekly detection rates of laboratory-confirmed influenza cases from four local major hospitals in Hong Kong between 2004 and 2019. Meteorological and air quality records for hospitals were collected from their closest monitoring stations. We employed classification and regression trees to identify zones that optimize the prediction performance of meteorological data in influenza epidemics, defined as a weekly rate > 50th percentile over a year. According to the results, a combination of temperature > 25.1℃ and relative humidity > 79% was favorable to epidemics in hot seasons, whereas either temperature < 16.4℃ or a combination of < 20.4℃ and relative humidity > 76% was favorable to epidemics in cold seasons. The area under the receiver operating characteristic curve (AUC) in model training achieved 0.80 (95% confidence interval [CI], 0.76-0.83) and was kept at 0.71 (95%CI, 0.65-0.77) in validation. The meteorologically-favorable zones for predicting influenza A or A and B epidemics together were similar, but the AUC for predicting influenza B epidemics was comparatively lower. In conclusion, we established meteorologically-favorable zones for influenza A and B epidemics with a satisfactory prediction performance, even though the influenza seasonality in this subtropical setting was weak and type-specific.

Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003.

Importance: Knowledge of the longevity and breath of immune response to coronavirus infection is crucial for the development of next-generation vaccines to control the COVID-19 pandemic. Objectives: To determine the profile of SARS-CoV-2 antibodies among persons infected with the closely related virus, SARS-CoV-1, in 2003 (SARS03 survivors) and to characterize their antibody response soon after the first and second doses of COVID-19 vaccines. Design, Setting, and Participants: This prospective cohort study examined SARS-CoV-2 antibodies among SARS03 survivors compared with sex- and age-matched infection-naive controls. Participants received the COVID-19 vaccines between March 1 and September 30, 2021. Interventions: One of the 2 COVID-19 vaccines (inactivated [CoronaVac] or messenger RNA [BNT162b2]) available in Hong Kong. Two doses were given according to the recommended schedule. The vaccine type administered was known to both participants and observers. Main Outcomes and Measures: SARS-CoV-2 antibodies were measured prevaccination, 7 days after the first dose, and 14 days after the second dose. Results: Eighteen SARS03 adult survivors (15 women and 3 men; median age, 46.5 [IQR, 40.0-54.3] years) underwent prevaccination serologic examination. The vast majority retained a detectable level of antibodies that cross-reacted with SARS-CoV-2 (16 of 18 [88.9%] with nucleocapsid protein antibodies and 17 of 18 [94.4%] with receptor-binding domain of spike protein antibodies); a substantial proportion (11 of 18 [61.1%]) had detectable cross-neutralizing antibodies. Twelve SARS03 adult survivors (10 women and 2 men) underwent postvaccination serologic examination. At 7 days after the first dose of vaccine, SARS03 survivors mounted significantly higher levels of neutralizing antibodies compared with controls (median inhibition: 89.5% [IQR, 77.1%-93.7%] vs 13.9% [IQR, 11.8%-16.1%] for BNT162b2; 64.9% [IQR, 60.8%-69.5%] vs 13.4% [IQR, 9.5%-16.8%] for CoronaVac; P < .001 for both). At 14 days after the second dose, SARS03 survivors generated a broader antibody response with significantly higher levels of neutralizing antibodies against variants of concern compared with controls (eg, median inhibition against Omicron variant, 52.1% [IQR, 35.8%-66.0%] vs 14.7% [IQR, 2.5%-20.7%]; P < .001). Conclusions and Relevance: The findings of this prospective cohort study suggest that infection with SARS-CoV-1 was associated with detectable levels of antibodies that cross-react and cross-neutralize SARS-CoV-2, which belongs to a distinct clade under the same subgenus Sarbecovirus. These findings support the development of broadly protective vaccines to cover sarbecoviruses that caused 2 devastating zoonotic outbreaks in humans over the last 2 decades.

Streptococcus oriscaviae sp. nov. Infection Associated with Guinea Pigs.

Pet bite-related infections are commonly caused by the pet's oral flora transmitted to the animal handlers through the bite wounds. In this study, we isolated a streptococcus, HKU75T, in pure culture from the purulent discharge collected from a guinea pig bite wound in a previously healthy young patient. HKU75T was alpha-hemolytic on sheep blood agar and agglutinated with Lancefield group D and group G antisera. API 20 STREP showed that the most likely identity for HKU75T was S. suis I with 85.4% confidence while Vitek 2 showed that HKU75T was unidentifiable. MALDI-TOF MS identified HKU75T as Streptococcus suis (score of 1.86 only). 16S rRNA gene sequencing showed that HKU75T was most closely related to S. parasuis (98.3% nucleotide identity), whereas partial groEL and rpoB gene sequencing showed that it was most closely related to S. suis (81.8% and 89.8% nucleotide identity respectively). Whole genome sequencing and intergenomic distance determined by ANI revealed that there was <85% identity between the genome of HKU75T and those of all other known Streptococcus species. Genome classification using concatenated sequences of 92 bacterial core genes showed that HKU75T belonged to the Suis group. groEL gene sequences identical to that of HKU75T could be directly amplified from the oral cavities of the two guinea pigs owned by the patient. HKU75T is a novel Streptococcus species, which we propose to be named S. oriscaviae. The oral cavity of guinea pigs is presumably a reservoir of S. oriscaviae. Some of the reported S. suis strains isolated from clinical specimens may be S. oriscaviae. IMPORTANCE We reported the discovery of a novel Streptococcus species, propose to be named Streptococcus oriscaviae, from the pus collected from a guinea pig bite wound in a healthy young patient. The bacterium was initially misidentified as S. suis/S. parasuis by biochemical tests, mass spectrometry. and housekeeping genes sequencing. Its novelty was confirmed by whole genome sequencing. Comparative genomic studies showed that S. oriscaviae belongs to the Suis group. S. oriscaviae sequences were detected in the oral cavities of the two guinea pigs owned by the patient, suggesting that the oral cavity of guinea pigs could be a reservoir of S. oriscaviae. Some of the reported S. suis strains may be S. oriscaviae. Further studies are warranted to refine our knowledge on this novel Streptococcus species.

Hepatitis E Virus Species C Infection in Humans, Hong Kong.

BACKGROUND: Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus species C genotype 1 (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-C1 infections detected in Hong Kong, with an emphasis on outcomes in immunocompromised individuals. METHODS: A surveillance system for detecting human HEV-C1 infections was established in Hong Kong. Epidemiological and clinical characteristics of HEV-C1 cases identified via this system between 1 August 2019 and 31 December 2020 were retrieved. Phylogenetic analysis of HEV-C1 strain sequences was performed. Infection outcomes of immunocompromised individuals with HEV-A and HEV-C1 infections were analyzed. RESULTS: HEV-C1 accounted for 8 of 53 (15.1%) reverse-transcription polymerase chain reaction (RT-PCR)-confirmed HEV infections in Hong Kong during the study period, raising the total number of HEV-C1 infections detected in the city to 16. Two distinct HEV-C1 strain groups caused human infections. Patients were elderly and/or immunocompromised; half tested negative for HEV immunoglobulin M. Cumulatively, HEV-C1 accounted for 9 of 21 (42.9%) cases of hepatitis E recorded in immunocompromised patients in Hong Kong. Immunocompromised HEV-C1 patients progressed to persistent hepatitis at similar rates (7/9 [77.8%]) as HEV-A patients (10/12 [75%]). HEV-C1 patients responded to oral ribavirin, although response to first course was sometimes poor or delayed. CONCLUSIONS: Dedicated RT-PCR-based surveillance detected human HEV-C1 cases that evade conventional hepatitis E diagnostic testing. Immunosuppressed HEV-C1-infected patients frequently progress to persistent HEV-C1 infection, for which ribavirin is a suitable treatment option.

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.

Seroprevalence of Unidentified SARS-CoV-2 Infection in Hong Kong During 3 Pandemic Waves.

Importance: Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic. Objective: To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong. Design, Setting, and Participants: A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ≥18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected. Main Outcomes and Measures: The main outcome was prevalence of SARS-CoV-2 infection. SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein. Results: The study enrolled 4198 participants (2539 [60%] female; median age, 50 years [IQR, 25 years]), including 903 (22%), 1046 (25%), and 2249 (53%) during April 21 to July 7, 2020; during September 29 to November 23, 2020; and during January 15 to April 18, 2021, respectively. The numbers of participants aged 18 to 39 years, 40 to 59 years, and 60 years or older were 1328 (32%), 1645 (39%), and 1225 (29%), respectively. Among the participants, 2444 (58%) stayed in Hong Kong since November 2019 and 2094 (50%) had negative SARS-CoV-2 RNA test results. Only 170 (4%) reported ever having contact with individuals with confirmed cases, and 5% had been isolated or quarantined. Most (2803 [67%]) did not recall any illnesses, whereas 737 (18%), 212 (5%), and 385 (9%) had experienced respiratory symptoms, gastrointestinal symptoms, or both, respectively, before testing. Six participants were confirmed to be positive for anti-SARS-CoV-2 IgG; the adjusted prevalence of unidentified infection was 0.15% (95% CI, 0.06%-0.32%). Extrapolating these findings to the whole population, there were fewer than 1.9 unidentified infections for every recorded confirmed case. The overall prevalence of SARS-CoV-2 infection in Hong Kong before the roll out of vaccination was less than 0.45%. Conclusions and Relevance: In this cross-sectional study of participants from the general public in Hong Kong, the prevalence of unidentified SARS-CoV-2 infection was low after 3 major waves of the pandemic, suggesting the success of the pandemic mitigation by stringent isolation and quarantine policies even without complete city lockdown. More than 99.5% of the general population of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.

Longitudinal Genomic Characterization of Carbapenemase-producing Enterobacteriaceae (CPE) Reveals Changing Pattern of CPE Isolated in Hong Kong Hospitals.

An active, territory-wide, CPE surveillance program implemented from 2011 showed increasing levels of carbapenemase-producing Enterobacteriaceae (CPE) isolates from patients in Hong Kong hospitals. The molecular epidemiology of 567 CPE from patients of three of seven public hospital clusters in Hong Kong are described. During a 7-year period, the incidence of CPE isolation increased from 0.05 to 9.6/100 000 patient-days. The carbapenemase genes identified were polyclonal, including blaKPC, blaNDM and blaIMP, which were mainly associated with hospitalization overseas in previous years. However, increasing CPE isolation from patients without hospitalization overseas occurred in 2015, with blaNDM (52.6%) predominant followed by blaIMP (30.0%). Escherichia coli (46.4%) and Klebsiella spp. (38.3%) were the dominant species. Whole-genome sequencing was performed on 169 representative isolates with a combination of short and long reads using Illumina and Nanopore technology. Two distinct lineages of blaKPC-2-positive Klebsiella pneumoniae (ST11 and ST258) were identified with ST11 carrying yersiniabactin gene ybt-9 on ICEKp3. ST131 E. coli producing IMP-4 was present throughout the study period. The blaNDM and blaIMP genes were mainly carried in IncX3 and IncN-ST7 plasmids, respectively. blaOXA-48-like gene was carried in the IncX3 plasmid in E. coli and in the ColKP3 plasmid in K. pneumoniae. A lineage of K. pneumoniae with blaNDM-1 plus blaOXA-232 in distinct plasmids of IncF1B/IncHI1B was identified and associated with prior hospitalization overseas. This study highlights the threat of multiple types of CPE, with the predominance of blaNDM and blaIMP among CPE in our hospitals. Enhanced containment strategies are needed to mitigate the trend of rapidly rising CPE in healthcare settings.

Viral MicroRNAs Encoded by Nucleocapsid Gene of SARS-CoV-2 Are Detected during Infection, and Targeting Metabolic Pathways in Host Cells.

MicroRNAs (miRNAs) are critical regulators of gene expression that may be used to identify the pathological pathways influenced by disease and cellular interactions. Viral miRNAs (v-miRNAs) encoded by both DNA and RNA viruses induce immune dysregulation, virus production, and disease pathogenesis. Given the absence of effective treatment and the prevalence of highly infective SARS-CoV-2 strains, improved understanding of viral-associated miRNAs could provide novel mechanistic insights into the pathogenesis of COVID-19. In this study, SARS-CoV-2 v-miRNAs were identified by deep sequencing in infected Calu-3 and Vero E6 cell lines. Among the ~0.1% small RNA sequences mapped to the SARS-CoV-2 genome, the top ten SARS-CoV-2 v-miRNAs (including three encoded by the N gene; v-miRNA-N) were selected. After initial screening of conserved v-miRNA-N-28612, which was identified in both SARS-CoV and SARS-CoV-2, its expression was shown to be positively associated with viral load in COVID-19 patients. Further in silico analysis and synthetic-mimic transfection of validated SARS-CoV-2 v-miRNAs revealed novel functional targets and associations with mechanisms of cellular metabolism and biosynthesis. Our findings support the development of v-miRNA-based biomarkers and therapeutic strategies based on improved understanding of the pathophysiology of COVID-19.

A Sensitive and Specific Competitive Enzyme-Linked Immunosorbent Assay for Serodiagnosis of COVID-19 in Animals.

In addition to human cases, cases of COVID-19 in captive animals and pets are increasingly reported. This raises the concern for two-way COVID-19 transmission between humans and animals. Here, we developed a SARS-CoV-2 nucleocapsid protein-based competitive enzyme-linked immunosorbent assay (cELISA) for serodiagnosis of COVID-19 which can theoretically be used in virtually all kinds of animals. We used 187 serum samples from patients with/without COVID-19, laboratory animals immunized with inactive SARS-CoV-2 virions, COVID-19-negative animals, and animals seropositive to other betacoronaviruses. A cut-off percent inhibition value of 22.345% was determined and the analytical sensitivity and specificity were found to be 1:64-1:256 and 93.9%, respectively. Evaluation on its diagnostic performance using 155 serum samples from COVID-19-negative animals and COVID-19 human patients showed a diagnostic sensitivity and specificity of 80.8% and 100%, respectively. The cELISA can be incorporated into routine blood testing of farmed/captive animals for COVID-19 surveillance.

Temporal landscape of human gut RNA and DNA virome in SARS-CoV-2 infection and severity.

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

COVID-19 Viral Load in the Severity of and Recovery From Olfactory and Gustatory Dysfunction.

OBJECTIVES/HYPOTHESIS: This study investigated olfactory and gustatory dysfunction in the 2020 novel coronavirus disease (COVID-19) patients, and their correlations with viral load evaluation. STUDY DESIGN: Prospective cross-sectional cohort study. METHODS: One hundred forty-three symptomatic patients being screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were invited to participate. The clinical data of 83 confirmed COVID-19 subjects were collected, with 60 patients who were symptomatic but negative for COVID-19 recruited as controls. The prevalence and severity of and recovery time for olfactory and gustatory dysfunction, and cycle threshold (Ct) values from a SARS-CoV-2 polymerase chain reaction assay of nasopharyngeal and deep throat swabs were collected. Their correlations with Ct values were reported. RESULTS: Thirty-nine (47.0%) and 36 (43.4%) COVID-19 patients reported olfactory and gustatory dysfunction, respectively. The results of one-way analysis of variance did not show statistically significant relationships between the Ct values and severity of olfactory and gustatory dysfunction (P = .780 and P = .121, respectively). Among the COVID-19 patients who reported smell and taste loss, 28/39 (71.8%) and 30/36 (83.3%) experienced complete recovery, respectively. The mean recovery time was 10.3 ± 8.1 days for olfactory dysfunction and 9.5 ± 6.8 days for gustatory dysfunction. The recovery time was not correlated with the Ct values (Pearson correlation coefficient, smell: -0.008, P = .968; taste: -0.015, P = .940). CONCLUSIONS: There is a high prevalence of olfactory and gustatory dysfunction in COVID-19. However, the severity of and recovery from these symptoms have no correlations with the viral load of SARS-CoV-2. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2680-2685, 2020.

Prospective Study Comparing Deep Throat Saliva With Other Respiratory Tract Specimens in the Diagnosis of Novel Coronavirus Disease 2019.

BACKGROUND: Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. METHODS: We performed a prospective study in 2 regional hospitals in Hong Kong. RESULTS: We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62-0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum. CONCLUSIONS: Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.

Differential Tropism of SARS-CoV and SARS-CoV-2 in Bat Cells.

Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.

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.

Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization.

BACKGROUND & AIMS: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.

Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2.

We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.

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.