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1.
Infect Control Hosp Epidemiol ; 41(11): 1258-1265, 2020 11.
Article Dans Anglais | MEDLINE | ID: covidwho-2096345

Résumé

BACKGROUND: The role of severe respiratory coronavirus virus 2 (SARS-CoV-2)-laden aerosols in the transmission of coronavirus disease 2019 (COVID-19) remains uncertain. Discordant findings of SARS-CoV-2 RNA in air samples were noted in early reports. METHODS: Sampling of air close to 6 asymptomatic and symptomatic COVID-19 patients with and without surgical masks was performed with sampling devices using sterile gelatin filters. Frequently touched environmental surfaces near 21 patients were swabbed before daily environmental disinfection. The correlation between the viral loads of patients' clinical samples and environmental samples was analyzed. RESULTS: All air samples were negative for SARS-CoV-2 RNA in the 6 patients singly isolated inside airborne infection isolation rooms (AIIRs) with 12 air changes per hour. Of 377 environmental samples near 21 patients, 19 (5.0%) were positive by reverse-transcription polymerase chain reaction (RT-PCR) assay, with a median viral load of 9.2 × 102 copies/mL (range, 1.1 × 102 to 9.4 × 104 copies/mL). The contamination rate was highest on patients' mobile phones (6 of 77, 7.8%), followed by bed rails (4 of 74, 5.4%) and toilet door handles (4 of 76, 5.3%). We detected a significant correlation between viral load ranges in clinical samples and positivity rate of environmental samples (P < .001). CONCLUSION: SARS-CoV-2 RNA was not detectable by air samplers, which suggests that the airborne route is not the predominant mode of transmission of SARS-CoV-2. Wearing a surgical mask, appropriate hand hygiene, and thorough environmental disinfection are sufficient infection control measures for COVID-19 patients isolated singly in AIIRs. However, this conclusion may not apply during aerosol-generating procedures or in cohort wards with large numbers of COVID-19 patients.


Sujets)
Microbiologie de l'air , Betacoronavirus/isolement et purification , Infections à coronavirus/transmission , Matières contaminées/virologie , Prévention des infections/méthodes , Chambre de patient , Pneumopathie virale/transmission , Adolescent , Adulte , Aérosols , , Infections à coronavirus/diagnostic , Infections à coronavirus/prévention et contrôle , Femelle , Hospitalisation , Humains , Mâle , Adulte d'âge moyen , Pandémies/prévention et contrôle , Pneumopathie virale/diagnostic , Pneumopathie virale/prévention et contrôle , SARS-CoV-2 , Charge virale
2.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-516989

Résumé

The never-ending emergence of SARS-CoV-2 variations of concern (VOCs) has challenged the whole world for pandemic control. In order to develop effective drugs and vaccines, one needs to efficiently simulate SARS-CoV-2 spike receptor binding domain (RBD) mutations and identify high-risk variants. We pretrain a large protein language model on approximately 408 million protein sequences and construct a high-throughput screening for the prediction of binding affinity and antibody escape. As the first work on SARS-CoV-2 RBD mutation simulation, we successfully identify mutations in the RBD regions of 5 VOCs and can screen millions of potential variants in seconds. Our workflow scales to 4096 NPUs with 96.5% scalability and 493.9 x speedup in mixed precision computing, while achieving a peak performance of 366.8 PFLOPS (reaching 34.9% theoretical peak) on Pengcheng Cloudbrain-II. Our method paves the way for simulating coronavirus evolution in order to prepare for a future pandemic that will inevitably take place.

3.
Journal of infection and public health ; JOUR
Article Dans Anglais | EuropePMC | ID: covidwho-2091864

Résumé

Introduction Influenza infection is characterized by acute viral infection of high transmissibility. Worsening of the case can lead to the need for hospitalization, severe acute respiratory syndrome (SARS) and even death. Method This is a cross-sectional population-based study that used secondary database from the Brazilian Influenza Epidemiological Surveillance Information System. Only cases of adults with diagnosis of influenza by RT-PCR and case evolution recorded were included. Results We identified 2,273 adults with SARS by influenza, 343 of which had death as an outcome. The main risk factors for death were lack of hospitalization, not having cough and age, both with p<0.001. In addition, without asthma, having black skin color, not receiving flu vaccine, having brown skin color and not having a sore throat (p≤ 0.005) were risk factors too. Conclusion Factors associated with death due to SARS caused by influenza in Brazil, risk factors and protective factors to death were identified. It was evident that those who did not receive the flu vaccine presented twice the risk of unfavorable outcome, reinforcing the need to stimulate adherence to vaccination adhering and propose changes in public policies to make influenza vaccines available to the entire population, in order to prevent severe cases and unfavorable outcomes.

4.
Infect Control Hosp Epidemiol ; : 1-4, 2022 Oct 24.
Article Dans Anglais | MEDLINE | ID: covidwho-2087056

Résumé

We obtained 24 air samples in 8 general wards temporarily converted into negative-pressure wards admitting coronavirus disease 2019 (COVID-19) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant BA.2.2 in Hong Kong. SARS-CoV-2 RNA was detected in 19 (79.2%) of 24 samples despite enhanced indoor air dilution. It is difficult to prevent airborne transmission of SARS-CoV-2 in hospitals.

5.
Chinese Journal of Virology ; 37(6):1292-1301, 2021.
Article Dans Chinois | GIM | ID: covidwho-2081015

Résumé

Kashgar is a prefecture in Xinjiang Uygur Autonomous Region. China. Kashgar Prefecture (KP) is a land-cargo port connecting China with central Asian countries and Europe. Frequent transportation of cargo has increased the risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) introduction into China, which has increased the pressure on coronavirus disease-2019 (COVID-19) prevention and control. In November 2020, an imported virus-induced COVID-19 outbreak occurred in KP. To investigate the genetic characterization of SARS-CoV-2 that contaminated the trucks and containers, and the potential of border rapid logistics system to serve as carriers for SARS-CoV-2 transmission, thirty-five SARS-CoV-2-positive nucleic-acid samples collected from KP cross-border trucks and containers from 6-10 November 2020 were subjected into SARS-CoV-2 genomic sequencing and comparative analyses. The results showed that the median (minimum to maximum) Ct value of ORF1ab was 37.64 (28.91-39.81) . and that of the N gene was 36.50 (26.35-39.30), and the median (minimum to maximum) of the reads mapping ratio to SARS-CoV-2 was 51.95% (0.86%-99.31%), which indicated low viral loads in these environmental samples. Eighteen of 35 samples had genomic coverage >70%. According to the Pango nomenclature, 18 SARS-CoV-2 sequences belonged to six lineages (B.1, B.I.1, B.1.9. B.1.1.220, B.1.153 and B.1.465), three of which (B.I. B.1.1 and 8.1.153) were found in case samples from the same period of four China-neighboring countries. Analyses of nucleotide mutations and phylogenetic trees showed that the genome sequences of SARS-CoV-2 collected from the same location were similar. Four of 18 sequences were in a sub-lineage with the representative strain of COVID-19 outbreak in KP, one of which had 1 or 2 differences in nucleotide mutation sites with the strain that caused the COVID-19 outbreak in KP, which indicated high homology in the viral genome. We showed that cross-border trucks and containers were contaminated by various genotypes of SARS-CoV-2 from other countries during the outbreak in KP. and in which contained the parental virus of the KP cases. These trucks and containers served as carriers for SARS-CoV-2 introduction from other countries to cause local transmission. Our results provide important references for COVID-19 prevention-and-control strategies in border ports and tracing of outbreak sources in China.

6.
Cell Rep Med ; 3(10): 100774, 2022 10 18.
Article Dans Anglais | MEDLINE | ID: covidwho-2050073

Résumé

"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Mechanistic assays show that H84T-BanLec targets virus entry. High-speed atomic force microscopy depicts real-time multimolecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modeling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the drug compound's broad-spectrum antiviral activity and the lack of resistant mutants.


Sujets)
, Coronavirus du syndrome respiratoire du Moyen-Orient , Humains , SARS-CoV-2 , Lectines/pharmacologie , Mannose/pharmacologie , , Glycoprotéine de spicule des coronavirus/pharmacologie , Antiviraux/pharmacologie
7.
Clin Transl Med ; 12(9): e1025, 2022 09.
Article Dans Anglais | MEDLINE | ID: covidwho-2027333

Résumé

BACKGROUND: Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. METHODS: We investigated a total of 137 APs infected with SARS-CoV-2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD-, S1-, SSA/Ro- and dsDNA-specific IgG. RESULTS: While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection-induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID-19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. CONCLUSION: Our results reveal an immune mechanism that controls SARS-CoV-2-induced detrimental B cell responses and COVID-19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.


Sujets)
, Vaccins antiviraux , Lymphocytes B , , Cytokines , Humains , Mitochondries , SARS-CoV-2 , Indice de gravité de la maladie , Vaccins antiviraux/pharmacologie
8.
Cell Rep Med ; 3(9): 100743, 2022 09 20.
Article Dans Anglais | MEDLINE | ID: covidwho-2004613

Résumé

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that BA.2 is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of BA.2 remains unclear and is of critical public health significance. Here we investigated the virological features and pathogenicity of BA.2 with in vitro and in vivo models. We show that BA.2 is less dependent on transmembrane protease serine 2 (TMPRSS2) for virus entry in comparison with BA.1 in vitro. In K18-hACE2 mice, BA.2 replicates more efficiently than BA.1 in the nasal turbinates and replicates marginally less efficiently in the lungs, leading to decreased body weight loss and improved survival. Our study indicates that BA.2 is similarly attenuated in lungs compared with BA.1 but is potentially more transmissible because of its better replication at the nasal turbinates.


Sujets)
, SARS-CoV-2 , Animaux , Humains , Souris , SARS-CoV-2/génétique , Sérine , Virulence
9.
The international journal of high performance computing applications ; 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-1999016

Résumé

As a theoretically rigorous and accurate method, FEP-ABFE (Free Energy Perturbation-Absolute Binding Free Energy) calculations showed great potential in drug discovery, but its practical application was difficult due to high computational cost. To rapidly discover antiviral drugs targeting SARS-CoV-2 Mpro and TMPRSS2, we performed FEP-ABFE–based virtual screening for ∼12,000 protein-ligand binding systems on a new generation of Tianhe supercomputer. A task management tool was specifically developed for automating the whole process involving more than 500,000 MD tasks. In further experimental validation, 50 out of 98 tested compounds showed significant inhibitory activity towards Mpro, and one representative inhibitor, dipyridamole, showed remarkable outcomes in subsequent clinical trials. This work not only demonstrates the potential of FEP-ABFE in drug discovery but also provides an excellent starting point for further development of anti-SARS-CoV-2 drugs. Besides, ∼500 TB of data generated in this work will also accelerate the further development of FEP-related methods.

10.
mBio ; 13(4): e0194422, 2022 08 30.
Article Dans Anglais | MEDLINE | ID: covidwho-1986333

Résumé

The human upper respiratory tract, specifically the nasopharyngeal epithelium, is the entry portal and primary infection site of respiratory viruses. Productive infection of SARS-CoV-2 in the nasal epithelium constitutes the cellular basis of viral pathogenesis and transmissibility. Yet a robust and well-characterized in vitro model of the nasal epithelium remained elusive. Here we report an organoid culture system of the nasal epithelium. We derived nasal organoids from easily accessible nasal epithelial cells with a perfect establishment rate. The derived nasal organoids were consecutively passaged for over 6 months. We then established differentiation protocols to generate 3-dimensional differentiated nasal organoids and organoid monolayers of 2-dimensional format that faithfully simulate the nasal epithelium. Moreover, when differentiated under a slightly acidic pH, the nasal organoid monolayers represented the optimal correlate of the native nasal epithelium for modeling the high infectivity of SARS-CoV-2, superior to all existing organoid models. Notably, the differentiated nasal organoid monolayers accurately recapitulated higher infectivity and replicative fitness of the Omicron variant than the prior variants. SARS-CoV-2, especially the more transmissible Delta and Omicron variants, destroyed ciliated cells and disassembled tight junctions, thereby facilitating virus spread and transmission. In conclusion, we establish a robust organoid culture system of the human nasal epithelium for modeling upper respiratory infections and provide a physiologically-relevant model for assessing the infectivity of SARS-CoV-2 emerging variants. IMPORTANCE An in vitro model of the nasal epithelium is imperative for understanding cell biology and virus-host interaction in the human upper respiratory tract. Here we report an organoid culture system of the nasal epithelium. Nasal organoids were derived from readily accessible nasal epithelial cells with perfect efficiency and stably expanded for more than 6 months. The long-term expandable nasal organoids were induced maturation into differentiated nasal organoids that morphologically and functionally simulate the nasal epithelium. The differentiated nasal organoids adequately recapitulated the higher infectivity and replicative fitness of SARS-CoV-2 emerging variants than the ancestral strain and revealed viral pathogenesis such as ciliary damage and tight junction disruption. Overall, we established a human nasal organoid culture system that enables a highly efficient reconstruction and stable expansion of the human nasal epithelium in culture plates, thus providing a facile and robust tool in the toolbox of microbiologists.


Sujets)
, Muqueuse nasale , Organoïdes , SARS-CoV-2 , /virologie , Humains , Muqueuse nasale/virologie , Organoïdes/virologie , SARS-CoV-2/classification , SARS-CoV-2/pathogénicité , SARS-CoV-2/physiologie , Techniques de culture de tissus
11.
Clin Infect Dis ; 2022 Jun 28.
Article Dans Anglais | MEDLINE | ID: covidwho-1985050

Résumé

BACKGROUND: Early antiviral therapy was effective in the treatment of 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 200mg loading on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point 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 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upon follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), 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, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.

12.
Infect Control Hosp Epidemiol ; : 1-6, 2022 Jul 11.
Article Dans Anglais | MEDLINE | ID: covidwho-1977949

Résumé

BACKGROUND: Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown. METHODS: We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed. RESULTS: Of 20 singly isolated patients with median age of 30 months (range, 3 months-15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×103 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×107 copies/mL vs 1.61×105 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×104 copies/mL vs 1.58×103 copies/mL; P = .020). CONCLUSION: Air dispersal of common respiratory viruses may have infection prevention and public health implications.

13.
Signal Transduct Target Ther ; 7(1): 266, 2022 08 03.
Article Dans Anglais | MEDLINE | ID: covidwho-1972575

Résumé

Defective interfering genes (DIGs) are short viral genomes and interfere with wild-type viral replication. Here, we demonstrate that the new designed SARS-CoV-2 DIG (CD3600) can significantly inhibit the replication of SARS-CoV-2 including Alpha, Delta, Kappa and Omicron variants in human HK-2 cells and influenza DIG (PAD4) can significantly inhibit influenza virus replication in human A549 cells. One dose of influenza DIGs prophylactically protects 90% mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral challenge. To further investigate the gene delivery vector in the respiratory tract, a peptidic TAT2-P1&LAH4, which can package genes to form small spherical nanoparticles with high endosomal escape ability, is demonstrated to dramatically increase gene expression in the lung airway. TAT2-P1&LAH4, with the dual-functional TAT2-P1 (gene-delivery and antiviral), can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster lungs. This peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo, which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.


Sujets)
, Sous-type H1N1 du virus de la grippe A , Virus de la grippe A , Grippe humaine , Nanoparticules , Animaux , /génétique , Cricetinae , Humains , Sous-type H1N1 du virus de la grippe A/génétique , Grippe humaine/prévention et contrôle , Souris , Peptides/génétique , Peptides/pharmacologie , SARS-CoV-2/génétique
14.
Viruses ; 14(8)2022 08 04.
Article Dans Anglais | MEDLINE | ID: covidwho-1969516

Résumé

Formulating termination of isolation (de-isolation) policies requires up-to-date knowledge about viral shedding dynamics. However, current de-isolation policies are largely based on viral load data obtained before the emergence of Omicron variant. In this retrospective cohort study involving adult patients hospitalised for COVID-19 between January and February 2022, we sought to determine SARS-CoV-2 viral shedding kinetics and to investigate the risk factors associated with slow viral decline during the 2022 Omicron wave. A total of 104 patients were included. The viral load was highest (Ct value was lowest) on days 1 post-symptom-onset (PSO) and gradually declined. Older age, hypertension, hyperlipidaemia and chronic kidney disease were associated with slow viral decline in the univariate analysis on both day 7 and day 10 PSO, while incomplete or no vaccination was associated with slow viral decline on day 7 PSO only. However, older age was the only risk factor that remained statistically significant in the multivariate analysis. In conclusion, older age is an independent risk factor associated with slow viral decline in this study conducted during the Omicron-dominant 2022 COVID-19 wave. Transmission-based precaution guidelines should take age into consideration when determining the timing of de-isolation.


Sujets)
, Charge virale , Excrétion virale , Adulte , Sujet âgé , /virologie , Humains , Études rétrospectives , Facteurs de risque , SARS-CoV-2
15.
Cell Discov ; 8(1): 57, 2022 Jun 17.
Article Dans Anglais | MEDLINE | ID: covidwho-1967594

Résumé

The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human lung epithelial organoids from lung tissues and developed a 'proximal' differentiation protocol to generate mucociliary airway organoids. However, a respiratory organoid system with bipotential of the airway and alveolar differentiation remains elusive. Here we defined a 'distal' differentiation approach to generate alveolar organoids from the same source for the derivation of airway organoids. The alveolar organoids consisting of type I and type II alveolar epithelial cells (AT1 and AT2, respectively) functionally simulate the alveolar epithelium. AT2 cells maintained in lung organoids serve as progenitor cells from which alveolar organoids derive. Moreover, alveolar organoids sustain a productive SARS-CoV-2 infection, albeit a lower replicative fitness was observed compared to that in airway organoids. We further optimized 2-dimensional (2D) airway organoids. Upon differentiation under a slightly acidic pH, the 2D airway organoids exhibit enhanced viral replication, representing an optimal in vitro correlate of respiratory epithelium for modeling the high infectivity of SARS-CoV-2. Notably, the higher infectivity and replicative fitness of the Omicron variant than an ancestral strain were accurately recapitulated in these optimized airway organoids. In conclusion, we have established a bipotential organoid culture system able to reproducibly expand the entire human respiratory epithelium in vitro for modeling respiratory diseases, including COVID-19.

16.
Emerg Microbes Infect ; 11(1): 2116-2119, 2022 Dec.
Article Dans Anglais | MEDLINE | ID: covidwho-1956544

Résumé

The SARS-CoV-2 Omicron variant has led to a major wave of COVID-19 in Hong Kong between January and May 2022. Here, we used seroprevalence to estimate the combined incidence of vaccination and SARS-CoV-2 infection, including subclinical infection which were not diagnosed at the acute stage. The overall seropositive rate of IgG against receptor binding domain (anti-RBD IgG) increased from 52.2% in December 2021 to 89.3% in May 2022. The level of anti-RBD IgG was lowest in the 0-9 and ≥80 year-old age groups in May 2022. The seropositive rate of antibody against ORF8, which reflects the rate of prior infection, was 23.4% in May 2022. Our data suggest that although most individuals were either vaccinated or infected after the fifth wave, children and older adults remain most vulnerable. Public health measures should target these age groups in order to ameliorate the healthcare consequences of upcoming waves.


Sujets)
, Sujet âgé , Sujet âgé de 80 ans ou plus , Anticorps antiviraux , /épidémiologie , Enfant , Hong Kong/épidémiologie , Humains , Immunoglobuline G , SARS-CoV-2 , Études séroépidémiologiques
17.
Int J Biol Sci ; 18(12): 4781-4791, 2022.
Article Dans Anglais | MEDLINE | ID: covidwho-1954684

Résumé

Rapid development and successful use of vaccines against SARS-CoV-2 might hold the key to curb the ongoing pandemic of COVID-19. Emergence of vaccine-evasive SARS-CoV-2 variants of concern (VOCs) has posed a new challenge to vaccine design and development. One urgent need is to determine what types of variant-specific and bivalent vaccines should be developed. Here, we compared homotypic and heterotypic protection against SARS-CoV-2 infection of hamsters with monovalent and bivalent whole-virion inactivated vaccines derived from representative VOCs. In addition to the ancestral SARS-CoV-2 Wuhan strain, Delta (B.1.617.2; δ) and Theta (P.3; θ) variants were used in vaccine preparation. Additional VOCs including Omicron (B.1.1.529) and Alpha (B.1.1.7) variants were employed in the challenge experiment. Consistent with previous findings, Omicron variant exhibited the highest degree of immune evasion, rendering all different forms of inactivated vaccines substantially less efficacious. Notably, monovalent and bivalent Delta variant-specific inactivated vaccines provided optimal protection against challenge with Delta variant. Yet, some cross-variant protection against Omicron and Alpha variants was seen with all monovalent and bivalent inactivated vaccines tested. Taken together, our findings support the notion that an optimal next-generation inactivated vaccine against SARS-CoV-2 should contain the predominant VOC in circulation. Further investigations are underway to test whether a bivalent vaccine for Delta and Omicron variants can serve this purpose.


Sujets)
, Vaccins antiviraux , Animaux , /prévention et contrôle , , Cricetinae , Humains , SARS-CoV-2 , Vaccins combinés , Vaccins inactivés
18.
Nat Commun ; 13(1): 3618, 2022 Jun 24.
Article Dans Anglais | MEDLINE | ID: covidwho-1908176

Résumé

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.


Sujets)
, SARS-CoV-2 , Sujet âgé , Sujet âgé de 80 ans ou plus , Anticorps neutralisants , Anticorps antiviraux , /épidémiologie , Épidémies de maladies , Hong Kong/épidémiologie , Humains , Études séroépidémiologiques
19.
Cell Discov ; 8(1): 62, 2022 Jun 30.
Article Dans Anglais | MEDLINE | ID: covidwho-1908152

Résumé

The emergence of highly transmissible SARS-CoV-2 variants has led to the waves of the resurgence of COVID-19 cases. Effective antivirals against variants are required. Here we demonstrate that a human-derived peptide 4H30 has broad antiviral activity against the ancestral virus and four Variants of Concern (VOCs) in vitro. Mechanistically, 4H30 can inhibit three distinct steps of the SARS-CoV-2 life cycle. Specifically, 4H30 blocks viral entry by clustering SARS-CoV-2 virions; prevents membrane fusion by inhibiting endosomal acidification; and inhibits the release of virions by cross-linking SARS-CoV-2 with cellular glycosaminoglycans. In vivo studies show that 4H30 significantly reduces the lung viral titers in hamsters, with a more potent reduction for the Omicron variant than the Delta variant. This is likely because the entry of the Omicron variant mainly relies on the endocytic pathway which is targeted by 4H30. Moreover, 4H30 reduces syncytia formation in infected hamster lungs. These findings provide a proof of concept that a single antiviral can inhibit viral entry, fusion, and release.

20.
Build Environ ; 221: 109323, 2022 Aug 01.
Article Dans Anglais | MEDLINE | ID: covidwho-1906829

Résumé

The phenomenon of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-rise residential buildings (HRRBs) is unique in our densely populated cosmopolitan city. The compulsory testing of a whole building under the scheme of restriction-testing declaration (RTD) during the fourth wave (non-Omicron variant) and fifth wave (mostly Omicron variant) of COVID-19 outbreak in Hong Kong allowed us to study the prevalence of this phenomenon, which may represent a form of airborne transmission. From 23 January 2021 to 24 March 2022, 25,450 (5.8%) of 436,397 residents from 223 (63.0%) of 354 HRRBs under RTD were test-positive for SARS-CoV-2. Using the clustering of cases among vertically aligned flats with shared drainage stack and lightwell as a surrogate marker of vertical transmission, the number of vertically aligned flats with positive COVID-19 cases was significantly higher in the fifth wave compared with the fourth wave (14.2%, 6471/45,531 vs 0.24%, 3/1272; p < 0.001; or 2212 vs 1 per-million-flats; p < 0.001). Excluding 22,801 residents from 38 HRRBs who were tested negative outside the 12-week periods selected in fourth and fifth waves, the positive rate among residents was significantly higher among residents during the fifth wave than the fourth wave (6.5%, 25,434/389,700 vs 0.07%, 16/23,896; p < 0.001). Within the flats with COVID-19 cases, the proportion of vertically aligned flats was also significantly higher in the fifth wave than in the fourth wave (95.6%, 6471/6766 vs 30.0%, 3/10, p < 0.001). The proportion of HRRBs with COVID-19 cases was significantly higher during the corresponding 12-week period chosen for comparison (78.2%, 219/280 vs 11.1%, 4/36; p < 0.001). Whole-genome phylogenetic analysis of 332 viral genomes showed that Omicron BA.2 was the predominant strain, supporting the high transmissibility of BA.2 by airborne excreta-aerosol route in HRRBs of Hong Kong.

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