Abstract
Monitoring population protective immunity against SARS-CoV-2 variants is critical for risk assessment. We hypothesize that Hong Kong’s explosive Omicron BA.2 outbreak in early 2022 could be ...explained by low herd immunity. Our seroprevalence study using sera collected from January to December 2021 shows a very low prevalence of neutralizing antibodies (NAb) against ancestral virus among older adults. The age group-specific prevalence of NAb generally correlates with the vaccination uptake rate, but older adults have a much lower NAb seropositive rate than vaccination uptake rate. For all age groups, the seroprevalence of NAb against Omicron variant is much lower than that against the ancestral virus. Our study suggests that this BA.2 outbreak and the exceptionally high case-fatality rate in the ≥80 year-old age group (9.2%) could be attributed to the lack of protective immunity in the population, especially among the vulnerable older adults, and that ongoing sero-surveillance is essential.
Aging and aging-related disorders impair the survival and differentiation potential of bone marrow mesenchymal stem cells (MSCs) and limit their therapeutic efficacy. Induced pluripotent stem cells ...(iPSCs) may provide an alternative source of functional MSCs for tissue repair. This study aimed to generate and characterize human iPSC-derived MSCs and to investigate their biological function for the treatment of limb ischemia.
Human iPSCs were induced to MSC differentiation with a clinically compliant protocol. Three monoclonal, karyotypically stable, and functional MSC-like cultures were successfully isolated using a combination of CD24(-) and CD105(+) sorting. They did not express pluripotent-associated markers but displayed MSC surface antigens and differentiated into adipocytes, osteocytes, and chondrocytes. Transplanting iPSC-MSCs into mice significantly attenuated severe hind-limb ischemia and promoted vascular and muscle regeneration. The benefits of iPSC-MSCs on limb ischemia were superior to those of adult bone marrow MSCs. The greater potential of iPSC-MSCs may be attributable to their superior survival and engraftment after transplantation to induce vascular and muscle regeneration via direct de novo differentiation and paracrine mechanisms.
Functional MSCs can be clonally generated, beginning at a single-cell level, from human iPSCs. Patient-specific iPSC-MSCs can be prepared as an "off-the-shelf" format for the treatment of tissue ischemia.
•Hong Kong reported more than 1000 COVID-19 cases between January and May 2020.•The COVID-19 epidemic in Hong Kong was characterized by several waves of imported cases followed by limited local ...transmissions.•A series of public health intervention were implemented in Hong Kong in response to the local and overseas disease situations.•The multi-pronged strategy of border control, social distancing, enhanced surveillance, and contact tracing resulted in the successful prevention of a community-wide outbreak and containment of the epidemic in Hong Kong.
Hong Kong, a Special Administrative Region of China, recorded its first confirmed coronavirus disease 2019 (COVID-19) case on 23 January 2020. We reviewed the case epidemiology and the various public health measures implemented from January to May 2020.
The epidemiological and clinical characteristics of the cases recorded in different phases of the epidemic were described and compared, and the effectiveness of the public health measures implemented were reviewed using the changes in the daily number of confirmed cases and the interval from symptom onset to hospital admission.
Between January and May 2020, 1084 confirmed COVID-19 cases were reported, about 70% of which had a history of travel during the incubation period. The case fatality ratio was 0.4%. The local epidemic progressed through four phases: (1) preparedness and imported infection from mainland China, (2) local transmission, (3) imported infection from overseas countries associated with local transmission, and (4) controlled imported infection with limited local transmission, with an eventual reduction of the daily case number and minimization of the onset-to-admission interval. Various public health measures, including enhanced surveillance, border control, and social distancing, were introduced in phases in response to the prevailing local and global situations.
The overall containment strategy in Hong Kong led to a stabilization of the number of cases and the absence of a community-wide outbreak during the 4.5 m after the first case was reported. This strategy of containment might serve as an example for future planning of preparedness and response against novel infectious agents.
During the investigation of a pet shop outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2) with probable hamster-to-human transmission, the environmental and hamster samples in ...epidemiologically linked pet shops were found positive for SARS-CoV-2 Delta variant AY.127 strains which are phylogenetically closely related to patients and reported European strains. This interspecies' spill-over has triggered transmission in 58 patients epidemiologically linked to three pet shops. Incidentally, three dwarf hamsters imported from the Netherlands and centralized in a warehouse distributing animals to pet shops were positive for SARS-CoV-2 spike variant phylogenetically related to European B.1.258 strains from March 2020. This B.1.258 strain almost disappeared in July 2021. While no hamster-to-human transmission of B.1.258-like strain was found in this outbreak, molecular docking showed that its spike receptor-binding domain (RBD) has a similar binding energy to human ACE2 compared to that of Delta variant AY.127. Therefore, the potential of this B.1.258-related spike variant for interspecies jumping cannot be ignored. The co-circulation of B.1.258-related spike variants with Delta AY.127, which originated in Europe and was not previously found in Hong Kong, suggested that hamsters in our wholesale warehouse and retail pet shops more likely have acquired these viruses in the Netherlands or stopovers during delivery by aviation than locally. The risk of human-to-hamster reverse zoonosis by multiple SARS-CoV-2 variants leading to further adaptive spike mutations with subsequent transmission back to humans cannot be underestimated as an outbreak source of COVID-19. Testing imported pet animals susceptible to SARS-CoV-2 is warranted to prevent future outbreaks.
Recent pre‐clinical and clinical studies have suggested that endogenous cardiospheres (eCS) are potentially safe and effective for cardiac regeneration following myocardial infarction (MI). ...Nevertheless the preparation of autologous eCS requires invasive myocardial biopsy with limited yield. We describe a novel approach to generate induced cardiospheres (iCS) from adult skin fibroblasts via somatic reprogramming. After infection with Sox2, Klf4, and Oct4, iCS were generated from mouse adult skin fibroblasts treated with Gsk3β inhibitor‐(2′Z,3′E)‐ 6‐Bromoindirubin‐3′‐oxime and Oncostatin M. They resembled eCS, but contained a higher percentage of cells expressing Mesp1, Isl1, and Nkx2.5. They were differentiated into functional cardiomyocytes in vitro with similar electrophysiological properties, calcium transient and contractile function to eCS and mouse embryonic stem cell‐derived cardiomyocytes. Transplantation of iCS (1 × 106 cells) into mouse myocardium following MI had similar effects to transplantation of eCS but significantly better than saline or fibroblast in improving left ventricular ejection fraction, increasing anterior/septal ventricular wall thickness and capillary density in the infarcted region 4 weeks after transplantation. No tumor formation was observed. iCS generated from adult skin fibroblasts by somatic reprogramming and a cocktail of Gsk3β inhibitor‐6‐Bromoindirubin‐3′‐oxime and Oncostatin M may represent a novel source for cell therapy in MI. Stem Cells 2016;34:2693–2706
We describe a novel approach to generate induced cardiospheres (iCS) from adult skin fibroblasts via somatic reprogramming. After infection with Sox2, Klf4, and Oct4, iCS were generated from adult skin fibroblasts after treatment with a cocktail of cardiotrophic growth factors: cardiotrophic Gsk3β inhibitor‐(2′Z,3′E)‐ 6‐Bromoindirubin‐3′‐oxime and Oncostatin M, through upregulation of β‐catenin pathway. The iCSs can be differentiated into functional cardiomyocytes in vitro with similar electrophysiological properties, calcium transient and contractile function to endogenous cardiosphere. Transplantation of iCS into mouse myocardium following myocardial infarction had similar effects to transplantation of cardiosphere in improving left ventricular ejection fraction, increasing anterior/septal ventricular wall thickness, and capillary density in the infarcted region.
Abstract
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.
We report a SARS-CoV-2 Delta variant AY.127 outbreak related to a pet store in Hong Kong. Genomic analysis showed that multiple strains were involved. Our study highlighted the possibility of SARS-CoV-2 being transmitted from hamsters to human in the community.
Effectiveness of seasonal influenza vaccine (SIV) varies with the degree of matching with the vaccine and circulating viruses. We continued our SIV effectiveness against medically-attended ...influenza-like illness (ILI) under the Department of Health Hong Kong’s sentinel private medical practitioners (PMP) network, using the test-negative case-control design, for the 2018/19 and 2019/20 season. In addition, we studied the potential interference between SIV and ILI caused by non-influenza respiratory viruses (NIRV) based on data collated from 2017/18 to 2019/20 seasons. 3404 patients were analysed. Across the 2017/18 to 2019/20 seasons, the vaccine effectiveness (VE) of SIV was 44% (95% CI 30–56%) against pan-negative controls, 57% (95%CI. 42–68%) against NIRV controls and 50% (95%CI 38–59%) against both. SIV was moderately effective against medically-attended ILI caused by influenza A/B in both 2018/19 and 2019/20 winter seasons (53.2% (95%CI 36.7–65.5%) and 41.8% (95%CI 6.3–64.1%), respectively). The VE against the main circulating subtype, influenza A(H1), was higher for the 2018/19 season (57.2% (95%CI 39.8–69.9%), compared to 34.6% (95%CI −9.6–61.4%) in the 2019/20 season). When compared to pan negative controls, those with single NIRV infections were similarly likely to have received SIV (OR 1.05 (95%CI 0.72–1.54) within the influenza season; OR 0.97 (95%CI 0.73–1.29) when including non-influenza seasons). Analyses by type of virus showed no increased risk of SIV identified among those with single infections of EV/RV, HMPV and parainfluenza but a 2-fold increased risk was shown for those with single infections of adenovirus and parainfluenza virus (adenovirus: OR 2.54 (95%CI 1.24–5.14) within influenza season and OR 1.78 (95%CI 1.01–3.09) for the whole period; parainfluenza virus: OR 2.01 (95%CI 1.22–3.29) within influenza season and OR 1.89 (95%CI 1.29–2.76) for the whole period). SIV programme and surveillance of influenza and NIRV, including SARS-CoV-2, should continue during the COVID-19 pandemic.
Hong Kong SAR has adopted universal masking, social distancing, testing of all symptomatic and high-risk groups for isolation of confirmed cases in healthcare facilities, and quarantine of contacts ...as epidemiological control measures without city lockdown or border closure. These measures successfully suppressed the community transmission of pre-Omicron SARS-CoV-2 variants or lineages during the first to the fourth wave. No nosocomial SARS-CoV-2 infection was documented among healthcare workers in the first 300 days. The strategy of COVID-19 containment was adopted to provide additional time to achieve population immunity by vaccination. The near-zero COVID-19 situation for about 8 months in 2021 did not enable adequate immunization of the eligible population. A combination of factors was identified, especially population complacency associated with the low local COVID-19 activity, together with vaccine hesitancy. The importation of the highly transmissible Omicron variant kickstarted the fifth wave of COVID-19, which could no longer be controlled by our initial measures. The explosive fifth wave, which was partially contributed by vertical airborne transmission in high-rise residential buildings, resulted in over one million cases of infection. In this review, we summarize the epidemiology of COVID-19 and the infection control and public health measures against the importation and dissemination of SARS-CoV-2 until day 1000.
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