Abstract
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.
Immune sera from BNT162b2 and Coronavac recipients had substantially reduced neutralizing antibody titers against the omicron variant. There was no statistically significant difference between the geometric mean neutralization titers against omicron variant strains with or without spike R346K mutation.
Strikingly, however, the breakthrough infection was able to elicit cross-reactive broadly neutralising antibodies (bNAbs) from the unmeasurable level (<1:20) to the mean IC50 value of 1:2929 (range ...588.5–5508) at 9 days post symptoms onset (PSO) in OP1 and from the mean IC50 value of 1:24.3 to 1:854.5 at 12 days PSO in OP2, respectively (Figure 1D). ...the amounts of NAbs in OP1 and OP2 were consistently higher than the mean IC50 values of BNT162b2 vaccinees across all VOCs tested (Figure 1B). In particular, there were 121.41- and 74.89-fold higher IC50 values against beta and omicron in OP1 than those in BNT162b2 vaccinees (Figure 1B). Besides NAbs against the current panel of VOCs, OP1 also displayed enhanced IC50 values of NAbs against 15/16 SARS-CoV-2 variants with individual mutations or deletions, including the E484K mutation, which conferred significant resistance to vaccine-induced NAbs (Figure S1). Spike- and NP-specific CD8 IFN-γ responses were 0.56% and 0.11% in OP1 and 0.10% and 0.08% in OP2, respectively. ...the Spike-specific CD4 and CD8 T-cell responses were relatively higher in OP1 or comparable in OP2 as compared with mean values in BNT162b2 vaccinees (CD4 T: mean 0.19% and CD8 T: mean 0.10%).
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
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.
Using epidemiological and whole viral genome data, we demonstrated a single-source outbreak of Omicron variant sublineage BA.2 with a short doubling time in Hong Kong. This study highlighted the high transmissibility of BA.2 despite stringent prevention measures.
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.
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.
Global dissemination of SARS-CoV-2 Variants of Concern (VOCs) remains a concern. The aim of this study is to describe how mass testing and phylogenetic analysis successfully prevented local ...transmission of SARS-CoV-2 VOC in a densely populated city with low herd immunity for COVID-19.
In this descriptive study, we conducted contact tracing, quarantine, and mass testing of the potentially exposed contacts with the index case. Epidemiological investigation and phylogeographic analysis were performed.
Among 11,818 laboratory confirmed cases of COVID-19 diagnosed till 13th May 2021 in Hong Kong, SARS-CoV-2 VOCs were found in 271 (2.3%) cases. Except for 10 locally acquired secondary cases, all SARS-CoV-2 VOCs were imported or acquired in quarantine hotels. The index case of this SARS-CoV-2 VOC B.1.351 epidemic, an inbound traveler with asymptomatic infection, was diagnosed 9 days after completing 21 days of quarantine. Contact tracing of 163 contacts in household, hotel, and residential building only revealed 1 (0.6%) secondary case. A symptomatic foreign domestic helper (FDH) without apparent epidemiological link but infected by virus with identical genome sequence was subsequently confirmed. Mass testing of 0.34 million FDHs identified two more cases which were phylogenetically linked. A total of 10 secondary cases were identified that were related to two household gatherings. The clinical attack rate of household close contact was significantly higher than non-household exposure during quarantine (7/25, 28% vs 0/2051, 0%; p<0.001).
The rising epidemic of SARS-CoV-2 VOC transmission could be successfully controlled by contact tracing, quarantine, and rapid genome sequencing complemented by mass testing.
Health and Medical Research Fund Commissioned Research on Control of Infectious Disease (see acknowledgments for full list).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Bloodstream infection is a life-threatening clinical condition posing significant morbidities and mortalities. An "Emergency Critical Care Management Program" has been implemented in the ...Emergency Medicine Ward at North Lantau Hospital as a pilot critical care service model in the local emergency medicine wards. Patients with blood stream infection are recruited in the program and managed under pre-defined guideline.
Objectives: We report our experience in managing patients with blood stream infection in the Emergency Medicine Ward and analyzed their clinical outcomes.
Methods: This was a retrospective cohort study including a total of 64 patients with blood stream infection admitted to the Emergency Medicine Ward from 1 March 2015 and 31 March 2018. Patients' characteristics, microbiology, and risk factors associated with adverse outcomes including in-hospital mortality were analyzed.
Results: The most common organism isolated from blood cultures was Escherichia coli (56%). Eight patients were transferred to the tertiary hospital. The overall in-hospital mortality was 7.8% (5/64). From the univariate analysis, advanced age (p < 0.001), higher Sequential Organ Failure Assessment score and quick Sequential Organ Failure Assessment score (p < 0.001), higher Charlson Comorbidity Index (p = 0.003), more organ dysfunction (p < 0.001), preexisting medical history of chronic liver disease (p = 0.001), dysfunction in respiratory system (p = 0.032), cardiovascular system (p = 0.044) and the central nervous system (p < 0.001), presence of septic shock (p = 0.004), and need for higher level of organ support from the use of inotropes (p < 0.001) and mechanical ventilation (p = 0.024) were associated with in-hospital mortality. In the subgroup analysis, the in-hospital mortality rate for the patients with Sequential Organ Failure Assessment score less than 6 was 1.56% (1/64). Among the five in-hospital mortality cases, four of them were managed in the Emergency Medicine W
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective To study the prevalence of fluoroquinolone-resistant (FQ-resistant) and extended-spectrum β-lactamase–producing (ESBL-producing) bacteria in the rectums of patients undergoing transrectal ...ultrasound-guided prostate biopsy (TRUS-Bx), identifying predictive factors for such carriage and to correlate with the microbiology of those who developed postbiopsy infection (PBI). Methods A total of 371 men undergoing TRUS-Bx were prospectively enrolled from August 2011 to March 2012. Rectal swab was obtained before antimicrobial prophylaxis on the day of biopsy and grown in selective media for resistant bacteria. Standard FQ prophylaxis was used without guidance from rectal swab results. Univariate and multivariate analyses were performed to identify predictive factors of either FQ-resistant or ESBL-producing bacteria carriage. Results A total of 199 of 371 patients (53.6%) carried antimicrobial-resistant rectal flora, with 150 (40.4%) and 152 (41.0%) patients having FQ-resistant and ESBL-producing bacteria, respectively. Diabetes mellitus (odds ratio, 2.075; P = .028) and the use of antimicrobials within the prior 5 years (odds ratio, 1.550; P = .047) were independent predictors of rectal carriage of such flora. PBI occurred in 9 patients, of which 7 harbored prebiopsy antimicrobial-resistant bacteria, which completely matched the microbiological data collected during the patients' PBI episodes. Conclusion A high prevalence of FQ-resistant and ESBL-producing rectal flora in Chinese men undergoing TRUS-Bx was found. Diabetes mellitus and prior antimicrobial use within 5 years were significant predictors for resistant bacterial carriage. Despite the high-resistant bacteria prevalence, PBI rate remained low. A targeted approach of antimicrobial prophylaxis using prebiopsy culture swab in areas with high prevalence of resistant bacteria should be further investigated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
International guidelines adopt risk stratification approach to manage patients with low-risk febrile neutropenia patients. We developed this out-patient program using shared-care model with ...professional input and patient empowerment, so as to reduce patients’ psychological burden from hospitalization and to improve the cost-effectiveness of management.
Method
This is a prospective cohort study to compare the efficacy and safeness of the out-patient program when compared with traditional in-patient care. Patients with solid tumors, developed febrile neutropenia with Multinational Association of Supportive Care in Cancer score of at least 21, and good performance status were included. After initial assessment and the first dose of oral antibiotics, patients were observed in the ambulatory center. Stable patients were discharged home after 4 h of observation and nurse counseling. Patients’ condition and clinical progress were regularly reviewed by specialist nurses within the following week by telephone and nurse clinic follow-up. The primary objective of the study is success rate, which defined as the resolution of fever and infection, without hospitalization or any change in antibiotics.
Results
From September 2014 to December 2016, a total of 38 patients were enrolled. Majority were female with breast cancer (97%). Two patients required hospitalization due to persistent fever. The success rate of the out-patient program was not significantly different from the historical in-patient cohort (94.9 versus 97.4%,
p
= 0.053). No mortality was observed. Patients’ compliance to the program was 100%, to telephone follow-up, nurse clinic visits, and daily temperature record.
Conclusion
Out-patient management of patients with low-risk febrile neutropenia is effective and safe through implementation of a structured protocol with joint inputs and engagement from clinicians, oncology nurses, and patients.
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