Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.

Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses.

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.

Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron.

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population1. Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies2-10, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.

Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants.

The high transmissibility of SARS-CoV-2 Omicron subvariants was generally ascribed to immune escape. It remained unclear whether the emerging variants have gradually acquired replicative fitness in human respiratory epithelial cells. We sought to evaluate the replicative fitness of BA.5 and earlier variants in physiologically active respiratory organoids. BA.5 exhibited a dramatically increased replicative capacity and infectivity than B.1.1.529 and an ancestral strain wildtype (WT) in human nasal and airway organoids. BA.5 spike pseudovirus showed a significantly higher entry efficiency than that carrying WT or B.1.1.529 spike. Notably, we observed prominent syncytium formation in BA.5-infected nasal and airway organoids, albeit elusive in WT- and B.1.1.529-infected organoids. BA.5 spike-triggered syncytium formation was verified by lentiviral overexpression of spike in nasal organoids. Moreover, BA.5 replicated modestly in alveolar organoids, with a significantly lower titer than B.1.1.529 and WT. Collectively, the higher entry efficiency and fusogenic activity of BA.5 spike potentiated viral spread through syncytium formation in the human airway epithelium, leading to enhanced replicative fitness and immune evasion, whereas the attenuated replicative capacity of BA.5 in the alveolar organoids may account for its benign clinical manifestation.

Development and Evaluation of an In-House Real-Time RT-PCR Targeting nsp10 Gene for SARS-CoV-2 Detection.

The emergence of SARS-CoV-2 mutations poses significant challenges to diagnostic tests, as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, the nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had a limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to the ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using a LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were found to be 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman's ρ = 0.968; p < 0.0001). In conclusion, nsp10 is a suitable target for a SARS-CoV-2 RT-PCR assay.

Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial.

BACKGROUND: Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. CLINICAL TRIALS REGISTRATION: NCT04647695.

Autoantibodies against angiotensin-converting enzyme 2 (ACE2) after COVID-19 infection or vaccination.

Autoantibodies against angiotensin-converting enzyme 2 (ACE2) are frequently reported in patients during coronavirus disease 2019 (COVID-19) with evidence for a pathogenic role in severe infection. However, little is known of the prevalence or clinical significance of ACE2 autoantibodies in late convalescence or following COVID-19 vaccination. In this study, we measured ACE2 autoantibodies in a cohort of 182 COVID-19 convalescent patients, 186 COVID-19 vaccine recipients, and 43 adolescents with post-mRNA vaccine myopericarditis using two ACE2 enzymatic immunoassays (EIAs). ACE2 IgM autoantibody EIA median optical densities (ODs) were lower in convalescent patients than pre-COVID-19 control samples with only 2/182 (1.1%) convalescents testing positive. Similarly, only 3/182 (1.6%) convalescent patients tested positive for ACE2 IgG, but patients with history of moderate-severe COVID-19 tended to have significantly higher median ODs than controls and mild COVID-19 patients. In contrast, ACE2 IgG antibodies were detected in 10/186 (5.4%) COVID-19 vaccine recipients after two doses of vaccination. Median ACE2 IgG EIA ODs of vaccine recipients were higher than controls irrespective of the vaccine platform used (inactivated or mRNA). ACE2 IgG ODs were not correlated with surrogate neutralizing antibody levels in vaccine recipients. ACE2 IgG levels peaked at day 56 post-first dose and declined within 12 months to baseline levels in vaccine recipients. Presence of ACE2 antibodies was not associated with adverse events following immunization including myopericarditis. One convalescent patient with ACE2 IgG developed Guillain-Barre syndrome, but causality was not established. ACE2 autoantibodies are observed in COVID-19 vaccine recipients and convalescent patients, but are likely innocuous.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

COVID-19 Vaccine Allergy Safety Track (VAS-Track) pathway: real-world outcomes on vaccination rates and antibody protection.

BACKGROUND: Misdiagnosed vaccine-related "allergies" lead to unnecessary vaccine deferrals and incomplete vaccinations, leaving patients unprotected against COVID-19. To overcome limitations and queues for Allergist assessment, the "VAS-Track" pathway was developed to evaluate patients via a multi-disciplinary triage model including nurses, non-specialists, and Allergists. OBJECTIVE: We assessed the effectiveness and safety of VAS-Track and evaluate its real-world impact in terms of vaccination rates and COVID-19 protection. METHODS: Patients referred to VAS-Track between September 2021 and March 2022 were recruited. Subgroup analysis was performed with prospective pre- and post-clinic antibody levels. RESULTS: Nurse-assisted screening identified 10,412 (76%) referrals as inappropriate. 369 patients were assessed by VAS-Track. Overall, 100% of patients were recommended to complete vaccination and 332 (90%) completed their primary series. No patients reported any significant allergic reactions following subsequent vaccination. Vaccination completion rates between patients seen by non-specialists and additional Allergist review were similar (90% vs. 89%, p = 0.617). Vaccination rates were higher among patients with prior history of immediate-type reactions (odds ratio: 2.43, p = 0.025). Subgroup analysis revealed that only 20% (56/284) of patients had seropositive COVID-19 neutralizing antibody levels (≥ 15 AU/mL) prior to VAS-Track, which increased to 92% after vaccine completion (pre-clinic antibody level 6.0 ± 13.5 AU/mL vs. post-clinic antibody level 778.8 ± 337.4 AU/mL, p > 0.001). CONCLUSIONS: A multi-disciplinary allergy team was able to streamline our COVID-19 VAS services, enabling almost all patients to complete their primary series, significantly boosting antibody levels and real-world COVID-19 protection. We propose similar multidisciplinary models to be further utilized, especially in the settings with limited allergy services.

Coronavirus Disease 2019 Messenger RNA Vaccines Associated With Delayed Onset of Breakthrough Infections and Fewer Radiographic Abnormalities.

This retrospective study of incoming travelers with coronavirus disease 2019 showed that individuals immunized by messenger RNA vaccines had significantly longer postvaccination intervals (median, 30.5 days) to breakthrough infection, lower white blood cell counts and lactate dehydrogenase levels on admission, and fewer radiographic abnormalities than those immunized by inactivated virus vaccine, who paradoxically had lower respiratory viral load.

Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model.

BACKGROUND: Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown. METHODS: We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control. RESULTS: Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1-2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1ß, interferon (IFN)-ß, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal. CONCLUSIONS: This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Subvariant BA.2 in a Single-Source Community Outbreak.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.2 sublineage has increased rapidly in Europe and Asia since January 2022. Here, we report the epidemiological and genomic analysis of a large single-source BA.2 outbreak in a housing estate. METHODS: We analyzed the epidemiological information on a community outbreak of BA.2 (STY outbreak). We performed whole viral genome sequencing using the Oxford Nanopore MinION device. We calculated the doubling time of the outbreak within a housing estate. RESULTS: The STY outbreak involved a total of 768 individuals as of 5 February 2022, including 432 residents, visitors, or staff (56.3%) from a single housing estate (KC Estate). The outbreak at the KC Estate had a short doubling time of 1.28 days (95% confidence interval: .560-1.935). The outbreak was promptly controlled with the lockdown of 3 buildings within the housing estate. Whole-genome sequencing was performed for 133 patients in the STY outbreak, including 106 residents of the KC Estate. All 133 sequences from the STY outbreak belonged to the BA.2 sublineage, and phylogenetic analysis showed that these sequences cluster together. All individuals in the STY cluster had the unique mutation C12525T. CONCLUSIONS: Our study highlights the exceptionally high transmissibility of the Omicron variant BA.2 sublineage in Hong Kong, where stringent measures are implemented as part of the elimination strategy. Continual genomic surveillance is crucial in monitoring the emergence of epidemiologically important Omicron sublineages.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage.

BACKGROUND: The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pathogenesis of testicular damage is uncertain. METHODS: We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by wild-type SARS-CoV-2 and its variants with intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. RESULTS: Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, serum testosterone and inhibin B at 4-7 days after infection; and chronic reduction in testicular size and weight, and serum sex hormone at 42-120 days after infection. Acute histopathological damage with worsening degree of testicular inflammation, hemorrhage, necrosis, degeneration of seminiferous tubules, and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and death of Sertoli and Leydig cells were found. Although viral loads and SARS-CoV-2 nucleocapsid protein expression were markedly lower in testicular than in lung tissues, direct intratesticular injection of SARS-CoV-2 demonstrated nucleocapsid expressing interstitial cells and epididymal epithelial cells, While intranasal or intratesticular challenge by A(H1N1)pdm09 control showed no testicular infection or damage. From 7 to 120 days after infection, degeneration and apoptosis of seminiferous tubules, immune complex deposition, and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. This testicular damage can be prevented by vaccination. CONCLUSIONS: SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent coronavirus disease 2019 in men.

False Coronavirus Disease 2019 Cases due to Contamination by Inactivated Virus Vaccine.

A false-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction result can lead to unnecessary public health measures. We report 2 individuals whose respiratory specimens were contaminated by an inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises. Incidentally, whole genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination.

BACKGROUND: Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (VOIs). Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively. METHODS: The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay. RESULTS: The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding. CONCLUSIONS: P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and "nonvariant" strains.

Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant by Sera From BNT162b2 or CoronaVac Vaccine Recipients.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment. METHODS: Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay. RESULTS: The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K. CONCLUSIONS: Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.

Probable Animal-to-Human Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Variant AY.127 Causing a Pet Shop-Related Coronavirus Disease 2019 (COVID-19) Outbreak in Hong Kong.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human and other mammals, including hamsters. Syrian (Mesocricetus auratus) and dwarf (Phodopus sp.) hamsters are susceptible to SARS-CoV-2 infection in the laboratory setting. However, pet shop-related Coronavirus Disease 2019 (COVID-19) outbreaks have not been reported. METHODS: We conducted an investigation of a pet shop-related COVID-19 outbreak due to Delta variant AY.127 involving at least 3 patients in Hong Kong. We tested samples collected from the patients, environment, and hamsters linked to this outbreak and performed whole genome sequencing analysis of the reverse transcription polymerase chain reaction (RT-PCR)-positive samples. RESULTS: The patients included a pet shop keeper (Patient 1), a female customer of the pet shop (Patient 2), and the husband of Patient 2 (Patient 3). Investigation showed that 17.2% (5/29) and 25.5% (13/51) environmental specimens collected from the pet shop and its related warehouse, respectively, tested positive for SARS-CoV-2 RNA by RT-PCR. Among euthanized hamsters randomly collected from the storehouse, 3% (3/100) tested positive for SARS-CoV-2 RNA by RT-PCR and seropositive for anti-SARS-CoV-2 antibody by enzyme immunoassay. Whole genome analysis showed that although all genomes from the outbreak belonged to the Delta variant AY.127, there were at least 3 nucleotide differences among the genomes from different patients and the hamster cages. Genomic analysis suggests that multiple strains have emerged within the hamster population, and these different strains have likely transmitted to human either via direct contact or via the environment. CONCLUSIONS: Our study demonstrated probable hamster-to-human transmission of SARS-CoV-2. As pet trading is common around the world, this can represent a route of international spread of this pandemic virus.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination.

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Comprehensive investigation of antibiotic resistance gene content in cfiA-harboring Bacteroides fragilis isolates of human and animal origins by whole genome sequencing.

INTRODUCTION: The emergence of multidrug resistance in Bacteroides fragilis, especially the phylogenetic lineage carrying the carbapenemase gene cfiA, represents an increasing threat to human health. However, knowledge on the diversity of the multidrug-resistant strains and the genetic elements carrying the antibiotic resistance genes (ARGs) remains limited. AIM: The objective of the study was to describe the resistome in cfiA-positive B. fragilis. METHODS: A collection of cfiA-positive B. fragilis from diverse human (8 bacteremias, 15 wound infections) and animal (2 chickens, 2 pigs, 6 dogs, 3 cats) sources in Hong Kong, 2015-2017 was analysed by whole genome sequencing. RESULTS: In the 36 isolates, 13 distinct ARGs (total number 83, median 2, range 0-7 per isolate) other than cfiA were detected. ARGs encoding resistance to aminoglycosides, ß-lactams, macrolides, sulphonamides and tetracyclines were carried by CTn341-like, CTnHyb-like, Tn5220-like, Tn4555-like and Tn613-like transposons and were detected in phylogenetically diverse isolates of different host sources. Only few ARGs encoding resistance to metronidazole and tetracyclines were localized on plasmids. In two chicken isolates, a novel transposon (designated as Tn6994) was found to be involved in the dissemination of multiple ARGs mediating resistance to multiple antibiotics, including metronidazole and linezolid that are critically important for treatment of anaerobic infections. In mating experiments, Tn6994 and the associated phenotypic resistance could be transferred to Bacteroides nordii recipient. CONCLUSION: This study illustrates the importance of transposons in the dissemination of ARGs in the cfiA-positive division of B. fragilis. One Health approach is necessary to track the dissemination of ARGs.