67 results on '"Perera RAPM"'
Search Results
2. Diversity of dromedary camel coronavirus HKU23 in African camels revealed multiple recombination events among closely related betacoronaviruses of the subgenus Embecovirus
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So, R. T. Y., Chu, D. K. W., Miguel, Eve, Perera, Rapm, Oladipo, J. O., Fassi-Fihri, O., Aylet, G., Ko, R. L. W., Zhou, Z. Q., Cheng, M. S., Kuranga, S. A., Roger, F. L., Chevalier, V., Webby, R. J., Woo, P. C. Y., Poon, L. L. M., and Peiris, M.
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dromedary ,viruses ,coronaviruses ,evolution ,camels ,virus diseases ,betacoronaviruses ,phylogeny ,recombination - Abstract
Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco, and Ethiopia and identified several genomic positions indicative of cross-species virus recombination events among other betacoronaviruses of the subgenus Embecovirus (Glade A beta-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at 8.9-kDa open reading frame 4a at the 3' end of the spike gene. The patterns of recombination differed geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and are also relevant to the emergence and evolution of other betacoronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV). IMPORTANCE Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other Glade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.
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- 2019
3. MERS-CoV in Arabian camels in Africa and Central Asia
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Peiris, JSM, Chevalier, V, Chu, KW, Chan, MS, Poon, LML, Miguel, E, Perera, RAPM, and Roger, F
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viruses ,virus diseases ,respiratory system ,respiratory tract diseases - Abstract
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causing infections in humans is genetically indistinguishable from the virus found in Arabian camels (dromedaries) in the Middle East. Although no primary human case of MERS was reported outside the Arabian Peninsula, camel populations in Africa are known to have high prevalence of antibodies against MERS-CoV. We carried out surveillance for MERS-CoV in dromedaries in Africa and Central Asia. By MERS-CoV spike pseudoparticle neutralization assay we confirmed that camel serum samples from African countries have high prevalence of MERS-CoV antibodies. Using RT-qPCR we detected MERS-CoV positives in camel nasal swabs from all different African countries from which samples were collected. However, dromedary serum and swab samples from Kazakhstan in Central Asia were negative for MERS-CoV by these assays. Phylogenetic analysis of the spike gene revealed that MERS-CoVs from Africa formed a cluster closely related to but distinct from the viruses from the Arabian Peninsula. Results from this study suggest that MERS-CoV is actively circulating in dromedary populations in Africa and the virus in Africa is phylogenetically distinct from that in the Middle East., published_or_final_version
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- 2017
4. Identification of differential pharyngeal cytokine profiles during HIV infection
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Perera RAPM, Tsang PCS, Miller C, Li P, Lee MP, and Samaranayake LP
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lcsh:R ,lcsh:Medicine ,lcsh:Q ,lcsh:Science - Published
- 2011
5. Influenza A(H3N2) Antibody Responses to Standard-Dose Versus Enhanced Influenza Vaccine Immunogenicity in Older Adults and Prior Season's Vaccine Status.
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Zhong S, Ng TWY, Skowronski DM, Iuliano AD, Leung NHL, Perera RAPM, Ho F, Fang VJ, Tam YH, Ip DKM, Havers FG, Fry AM, Aziz-Baumgartner E, Barr IG, Peiris M, Thompson MG, and Cowling BJ
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- Humans, Aged, Aged, 80 and over, Male, Female, Hong Kong epidemiology, Immunogenicity, Vaccine, Vaccination methods, Antibody Formation immunology, Squalene administration & dosage, Squalene immunology, Influenza Vaccines immunology, Influenza Vaccines administration & dosage, Influenza A Virus, H3N2 Subtype immunology, Antibodies, Viral blood, Influenza, Human prevention & control, Influenza, Human immunology, Hemagglutination Inhibition Tests
- Abstract
Background: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses., Methods: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017-2018 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016-2017) standard-dose vaccination., Results: Mean fold rise (MFR) in antibody titers from day 0 to day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017-2018 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) versus without (range, 4.3-14.3) prior 2016-2017 vaccination. MFR was significantly reduced by about one-half to four-fifths for previously vaccinated recipients of standard-dose and all 3 enhanced vaccines (β range, .21-.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR versus standard-dose vaccine by microneutralization assay., Conclusions: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination., Competing Interests: Potential conflicts of interest. B. J. C. has consulted for AstraZeneca, Fosun Pharma, GSK, Haleon, Moderna, Novavax, Pfizer, Roche, and Sanofi Pasteur. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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6. Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.
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Tanneti NS, Patel AK, Tan LH, Marques AD, Perera RAPM, Sherrill-Mix S, Kelly BJ, Renner DM, Collman RG, Rodino K, Lee C, Bushman FD, Cohen NA, and Weiss SR
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- Humans, SARS-CoV-2 genetics, Cell Line, Interferons, COVID-19
- Abstract
The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN-stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper respiratory tract and least favorable in the lower respiratory cell line, and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals., Importance: Comparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern, including Alpha, Beta, Delta, and Omicron, indicated that variants were selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid interface to model upper respiratory infection, Omicron reached the highest titers at early time points, a finding that was confirmed by parallel population sampling studies. While all infections overcame dsRNA-mediated host responses, infections with Omicron induced the strongest interferon and interferon-stimulated gene response. In both primary nasal cultures and lower respiratory cell line, infections by Delta were most damaging to the cells as indicated by syncytia formation, loss of cell barrier integrity, and nasal ciliary function., Competing Interests: The authors declare no conflict of interest.
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- 2024
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7. Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.
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Tanneti NS, Patel AK, Tan LH, Marques AD, Perera RAPM, Sherrill-Mix S, Kelly BJ, Renner DM, Collman RG, Rodino K, Lee C, Bushman FD, Cohen NA, and Weiss SR
- Abstract
The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
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- 2023
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8. Reconstructing household transmission dynamics to estimate the infectiousness of asymptomatic influenza virus infections.
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Tsang TK, Wang C, Fang VJ, Perera RAPM, So HC, Ip DKM, Leung GM, Peiris JSM, Cauchemez S, and Cowling BJ
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- Humans, Bayes Theorem, Disease Outbreaks, Influenza, Human, Influenza A Virus, H1N1 Subtype, COVID-19 epidemiology
- Abstract
There has long been controversy over the potential for asymptomatic cases of the influenza virus to have the capacity for onward transmission, but recognition of asymptomatic transmission of COVID-19 stimulates further research into this topic. Here, we develop a Bayesian methodology to analyze detailed data from a large cohort of 727 households and 2515 individuals in the 2009 pandemic influenza A(H1N1) outbreak in Hong Kong to characterize household transmission dynamics and to estimate the relative infectiousness of asymptomatic versus symptomatic influenza cases. The posterior probability that asymptomatic cases [36% of cases; 95% credible interval (CrI): 32%, 40%] are less infectious than symptomatic cases is 0.82, with estimated relative infectiousness 0.57 (95% CrI: 0.11, 1.54). More data are required to strengthen our understanding of the contribution of asymptomatic cases to the spread of influenza.
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- 2023
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9. Author Correction: Reconstructing antibody dynamics to estimate the risk of influenza virus infection.
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Tsang TK, Perera RAPM, Fang VJ, Wong JY, Shiu EY, So HC, Ip DKM, Malik Peiris JS, Leung GM, Cowling BJ, and Cauchemez S
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- 2023
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10. Impact of host genetic polymorphisms on response to inactivated influenza vaccine in children.
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Tsang TK, Wang C, Tsang NNY, Fang VJ, Perera RAPM, Malik Peiris JS, Leung GM, Cowling BJ, and Ip DKM
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In randomized controlled trials of influenza vaccination, 550 children received trivalent-inactivated influenza vaccine, permitting us to explore relationship between vaccine response and host single nucleotide polymorphisms (SNPs) in 23 candidate genes with adjustment of multiple testing. For host SNPs in TLR7-1817G/T (rs5741880), genotype GT was associated with lower odds (OR: 0.22, 95% CI: 0.09, 0.53) of have post-vaccination hemagglutination-inhibiting (HAI) titers ≥40, compared with genotype GG and TT combined under the over-dominant model. For host SNPs in TLR8-129G/C (rs3764879), genotype GT was associated with lower odds (OR: 0.47; 95% CI: 0.28, 0.80) of have post vaccination HAI titers ≥40 compared with genotype GG and AA combined under the over-dominant model. Our results could contribute to the development of better vaccines that may offer improved protection to all recipients., (© 2023. The Author(s).)
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- 2023
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11. Maternal antibody against influenza neuraminidase in newborns: abridged secondary publication.
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Perera RAPM, Chiu SSS, Au Yeung RSL, and Peiris JSM
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- Humans, Infant, Newborn, Neuraminidase, Antibodies, Viral, Influenza, Human prevention & control, Orthomyxoviridae Infections, Influenza Vaccines
- Published
- 2023
12. Indirect Protection from Vaccinating Children against Influenza A Virus Infection in Households.
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Tsang TK, Wang C, Fang VJ, Perera RAPM, So HC, Ip DKM, Peiris JSM, Leung GM, Cauchemez S, and Cowling BJ
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- Child, Humans, Influenza A Virus, H3N2 Subtype, Vaccination, Influenza, Human epidemiology, Influenza, Human prevention & control, Influenza Vaccines, Influenza A Virus, H1N1 Subtype
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Influenza vaccination is an important intervention to prevent influenza virus infection. Our previous analysis suggested that indirect protection is limited in an influenza B epidemic in Hong Kong. We further analyzed six influenza A epidemics to determine such potential. We applied a statistical model to estimate household transmission dynamics in the 3 influenza A(H3N2) and 3 pandemic influenza A(H1N1) epidemics. Then, we estimated the reduction in infection risk among unvaccinated household members when all children in households are vaccinated, with different assumptions on vaccine efficacy (VE). In the optimal scenario that VE was 70%, the reduction to the total probability of infection was only marginal, with relative probabilities ranged from 0.91-0.94 when all children in households were vaccinated because community was by far the main source of infection during the six epidemics in our study. The proportion of cases attributed to household transmission was 10% (95% CrI: 7%, 13%). Individual influenza vaccination is important even when other household members are vaccinated, given the degree of indirect protection is small.
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- 2022
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13. Biphasic Waning of Hemagglutination Inhibition Antibody Titers After Influenza Vaccination in Children.
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Xiong W, Tsang TK, Perera RAPM, Leung NHL, Fang VJ, Barr IG, Malik Peiris JS, and Cowling BJ
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- Antibodies, Viral, Child, Hemagglutination, Hemagglutination Inhibition Tests, Humans, Influenza A Virus, H3N2 Subtype, Influenza B virus, Vaccination, Vaccines, Inactivated, Influenza Vaccines, Influenza, Human prevention & control
- Abstract
We explored the potential for a biphasic pattern in waning of antibody titers after influenza vaccination. We collected blood samples in a randomized controlled trial of influenza vaccination in children and tested them with hemagglutination inhibition assays for influenza A(H3N2) and influenza B/Victoria lineage. Using piecewise log-linear mixed-effects models, we found evidence for a faster initial waning of antibody titers for the first 1-2 years after vaccination and then slower longer-term declines. Children with higher postvaccination titers had faster antibody decay., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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14. Determining Existing Human Population Immunity as Part of Assessing Influenza Pandemic Risk.
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Cheung JTL, Tsang TK, Yen HL, Perera RAPM, Mok CKP, Lin YP, Cowling BJ, and Peiris M
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- Animals, Hemagglutinins, Humans, Influenza A Virus, H1N2 Subtype, Influenza A Virus, H3N2 Subtype, Reassortant Viruses physiology, Seroepidemiologic Studies, Swine, Zoonoses, Influenza A Virus, H1N1 Subtype, Influenza A virus, Influenza, Human, Orthomyxoviridae Infections, Swine Diseases epidemiology
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Zoonotic influenza infections continue to threaten human health. Ongoing surveillance and risk assessment of animal viruses are needed for pandemic preparedness, and population immunity is an important component of risk assessment. We determined age-stratified hemagglutinin inhibition seroprevalence against 5 swine influenza viruses circulating in Hong Kong and Guangzhou in China. Using hemagglutinin inhibition seroprevalence and titers, we modeled the effect of population immunity on the basic reproduction number (R
0 ) if each virus were to become transmissible among humans. Among 353 individual serum samples, we reported low seroprevalence for triple-reassortant H1N2 and Eurasian avian-like H1N1 influenza viruses, which would reduce R0 by only 18%-20%. The smallest R0 needed to cause a pandemic was 1.22-1.24, meaning existing population immunity would be insufficient to block the spread of these H1N1 or H1N2 variants. For human-origin H3N2, existing population immunity could suppress R0 by 47%, thus reducing pandemic risk.- Published
- 2022
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15. Reconstructing antibody dynamics to estimate the risk of influenza virus infection.
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Tsang TK, Perera RAPM, Fang VJ, Wong JY, Shiu EY, So HC, Ip DKM, Malik Peiris JS, Leung GM, Cowling BJ, and Cauchemez S
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- Adult, Antibodies, Viral, Bayes Theorem, Child, Disease Susceptibility, Hemagglutination Inhibition Tests, Humans, Communicable Diseases, Influenza Vaccines, Influenza, Human, Orthomyxoviridae
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For >70 years, a 4-fold or greater rise in antibody titer has been used to confirm influenza virus infections in paired sera, despite recognition that this heuristic can lack sensitivity. Here we analyze with a novel Bayesian model a large cohort of 2353 individuals followed for up to 5 years in Hong Kong to characterize influenza antibody dynamics and develop an algorithm to improve the identification of influenza virus infections. After infection, we estimate that hemagglutination-inhibiting (HAI) titers were boosted by 16-fold on average and subsequently decrease by 14% per year. In six epidemics, the infection risks for adults were 3%-19% while the infection risks for children were 1.6-4.4 times higher than that of younger adults. Every two-fold increase in pre-epidemic HAI titer was associated with 19%-58% protection against infection. Our inferential framework clarifies the contributions of age and pre-epidemic HAI titers to characterize individual infection risk., (© 2022. The Author(s).)
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- 2022
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16. SARS-CoV-2 Delta Variant (AY.3) in the Feces of a Domestic Cat.
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Lenz OC, Marques AD, Kelly BJ, Rodino KG, Cole SD, Perera RAPM, Weiss SR, Bushman FD, and Lennon EM
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- Animals, COVID-19 transmission, COVID-19 virology, Cats, Female, Genome, Viral genetics, Humans, Phylogeny, RNA, Viral genetics, SARS-CoV-2 classification, United States, Whole Genome Sequencing, COVID-19 veterinary, Feces virology, Pets virology, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species have been scant. Here, we detected and sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples from an 11-year-old domestic house cat previously exposed to an owner who tested positive for SARS-CoV-2. Molecular testing of two fecal samples collected 7 days apart yielded relatively high levels of viral RNA. Sequencing of the feline-derived viral genomes showed the two to be identical, and differing by between 4 and 14 single nucleotide polymorphisms in pairwise comparisons to human-derived lineage AY.3 sequences collected in the same geographic area and time period. However, several mutations unique to the feline samples reveal their divergence from this cohort on phylogenetic analysis. These results demonstrate continued spillover infections of emerging SARS-CoV-2 variants that threaten human and animal health, as well as highlight the importance of collecting fecal samples when testing for SARS-CoV-2 in animals. To the authors' knowledge, this is the first published case of a SARS-CoV-2 delta variant in a domestic cat in the United States.
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- 2022
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17. Detection and Interspecies Comparison of SARS-CoV-2 Delta Variant (AY.3) in Feces from a Domestic Cat and Human Samples.
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Lenz OC, Marques AD, Kelly BJ, Rodino KG, Cole SD, Perera RAPM, Weiss SR, Bushman FD, and Lennon EM
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species has been scant. Here, we detected and sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples from an 11-year-old domestic house cat previously exposed to an owner who tested positive for SARS-CoV-2. Molecular testing of two fecal samples collected 7 days apart yielded relatively high levels of viral RNA. Sequencing of the feline-derived viral genomes showed the two to be identical, and differing by between 4 and 14 single nucleotide polymorphisms in pairwise comparisons to human-derived lineage AY.3 sequences collected in the same geographic area and time period. However, several mutations unique to the feline samples reveal their divergence from this cohort on phylogenetic analysis. These results demonstrate continued spillover infections of emerging SARS-CoV-2 variants that threaten human and animal health, as well as highlight the importance of collecting fecal samples when testing for SARS-CoV-2 in animals. To the authors' knowledge, this is the first published case of a SARS-CoV-2 delta variant in a domestic cat in the United States., Competing Interests: Conflicts of Interest: S.R.W. is on the Scientific Advisory Boards for Ocugen, Inc and Immunome, Inc. O.C.L., A.D.M., B.J.K., K.G.R., S.D.C., R.A.P.M.P., F.D.B., and E.M.L. declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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- 2022
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18. Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018.
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van Doremalen N, Letko M, Fischer RJ, Bushmaker T, Schulz J, Yinda CK, Seifert SN, Kim NJ, Hemida MG, Kayali G, Park WB, Perera RAPM, Tamin A, Thornburg NJ, Tong S, Queen K, van Kerkhove MD, Choi YK, Oh MD, Assiri AM, Peiris M, Gerber SI, and Munster VJ
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- Aerosols, Animals, Camelus, Humans, SARS-CoV-2, Virulence, Zoonoses, COVID-19, Middle East Respiratory Syndrome Coronavirus genetics
- Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.
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- 2021
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19. Tropism of SARS-CoV-2, SARS-CoV, and Influenza Virus in Canine Tissue Explants.
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Bui CHT, Yeung HW, Ho JCW, Leung CYH, Hui KPY, Perera RAPM, Webby RJ, Schultz-Cherry SL, Nicholls JM, Peiris JSM, and Chan MCW
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- Angiotensin-Converting Enzyme 2 metabolism, Animals, COVID-19 metabolism, Dogs, Humans, Influenza, Human metabolism, Influenza, Human virology, Lung metabolism, Nasal Cavity metabolism, Orthomyxoviridae Infections metabolism, Orthomyxoviridae Infections virology, Trachea metabolism, COVID-19 virology, Influenza A virus physiology, Lung virology, Nasal Cavity virology, SARS-CoV-2 physiology, Trachea virology, Viral Tropism physiology
- Abstract
Background: Human spillovers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to dogs and the emergence of a highly contagious avian-origin H3N2 canine influenza virus have raised concerns on the role of dogs in the spread of SARS-CoV-2 and their susceptibility to existing human and avian influenza viruses, which might result in further reassortment., Methods: We systematically studied the replication kinetics of SARS-CoV-2, SARS-CoV, influenza A viruses of H1, H3, H5, H7, and H9 subtypes, and influenza B viruses of Yamagata-like and Victoria-like lineages in ex vivo canine nasal cavity, soft palate, trachea, and lung tissue explant cultures and examined ACE2 and sialic acid (SA) receptor distribution in these tissues., Results: There was limited productive replication of SARS-CoV-2 in canine nasal cavity and SARS-CoV in canine nasal cavity, soft palate, and lung, with unexpectedly high ACE2 levels in canine nasal cavity and soft palate. Canine tissues were susceptible to a wide range of human and avian influenza viruses, which matched with the abundance of both human and avian SA receptors., Conclusions: Existence of suitable receptors and tropism for the same tissue foster virus adaptation and reassortment. Continuous surveillance in dog populations should be conducted given the many chances for spillover during outbreaks., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2021
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20. Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential.
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Zhou Z, Hui KPY, So RTY, Lv H, Perera RAPM, Chu DKW, Gelaye E, Oyas H, Njagi O, Abayneh T, Kuria W, Walelign E, Wanglia R, El Masry I, Von Dobschuetz S, Kalpravidh W, Chevalier V, Miguel E, Fassi-Fihri O, Trarore A, Liang W, Wang Y, Nicholls JM, Zhao J, Chan MCW, Poon LLM, Mok CKP, and Peiris M
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- Africa, Animals, Arabia, Cell Line, Dipeptidyl Peptidase 4 metabolism, Gene Knock-In Techniques, Humans, Kinetics, Middle East Respiratory Syndrome Coronavirus physiology, Phenotype, Phylogeny, Spike Glycoprotein, Coronavirus metabolism, Virus Replication physiology, Middle East Respiratory Syndrome Coronavirus genetics, Zoonoses virology
- Abstract
Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV-infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV., Competing Interests: Competing interest statement: Together with other global opinion leaders, M.P. and K.S. coauthored a perspectives article on optimizing the use of the ferret experimental model for research on influenza [J. A. Belser et al. Emerg. Infect. Dis. 24, 965–971 (2018)]., (Copyright © 2021 the Author(s). Published by PNAS.)
- Published
- 2021
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21. T-cell responses to MERS coronavirus infection in people with occupational exposure to dromedary camels in Nigeria: an observational cohort study.
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Mok CKP, Zhu A, Zhao J, Lau EHY, Wang J, Chen Z, Zhuang Z, Wang Y, Alshukairi AN, Baharoon SA, Wang W, Tan W, Liang W, Oladipo JO, Perera RAPM, Kuranga SA, Peiris M, and Zhao J
- Subjects
- Adolescent, Adult, Aged, Animals, Antibodies, Neutralizing, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Camelus virology, Cohort Studies, Coronavirus Infections transmission, Female, Humans, Leukocytes, Mononuclear immunology, Male, Middle Aged, Nigeria epidemiology, Young Adult, Zoonoses transmission, Zoonoses virology, Camelus immunology, Coronavirus Infections immunology, Coronavirus Infections veterinary, Middle East Respiratory Syndrome Coronavirus immunology, Occupational Exposure statistics & numerical data, T-Lymphocytes immunology, Zoonoses epidemiology, Zoonoses immunology
- Abstract
Background: Middle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV., Methods: Workers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses., Findings: None of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4
+ or CD8+ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01-0·54)., Interpretation: Zoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused., Funding: The National Science and Technology Major Project, National Institutes of Health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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22. Immunogenicity of standard, high-dose, MF59-adjuvanted, and recombinant-HA seasonal influenza vaccination in older adults.
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Li APY, Cohen CA, Leung NHL, Fang VJ, Gangappa S, Sambhara S, Levine MZ, Iuliano AD, Perera RAPM, Ip DKM, Peiris JSM, Thompson MG, Cowling BJ, and Valkenburg SA
- Abstract
The vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use of vaccines with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses of S-IIV versus enhanced vaccines (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), and recombinant-hemagglutinin (HA) (R-eIIV). All vaccines induced comparable H3-HA-specific IgG and elevated antibody-dependent cellular cytotoxicity (ADCC) activity at day 30 post vaccination. H3-HA-specific ADCC responses were greatest following H-eIIV. Only A-eIIV increased H3-HA-IgG avidity, HA-stalk IgG and ADCC activity. eIIVs also increased polyfunctional CD4+ and CD8+ T cell responses, while cellular immune responses were skewed toward single-cytokine-producing T cells among S-IIV subjects. Our study provides further immunological evidence for the preferential use of eIIVs in older adults as each vaccine platform had an advantage over the standard-dose vaccine in terms of NK cell activation, HA-stalk antibodies, and T cell responses.
- Published
- 2021
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23. Evaluation of a SARS-CoV-2 Surrogate Virus Neutralization Test for Detection of Antibody in Human, Canine, Cat, and Hamster Sera.
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Perera RAPM, Ko R, Tsang OTY, Hui DSC, Kwan MYM, Brackman CJ, To EMW, Yen HL, Leung K, Cheng SMS, Chan KH, Chan KCK, Li KC, Saif L, Barrs VR, Wu JT, Sit THC, Poon LLM, and Peiris M
- Subjects
- Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, COVID-19 blood, COVID-19 pathology, Cats, Cricetinae, Cross Reactions, Dogs, Female, Humans, Immune Sera immunology, Male, Neutralization Tests standards, SARS-CoV-2 immunology, Sensitivity and Specificity, COVID-19 diagnosis, COVID-19 Serological Testing methods, Neutralization Tests methods, SARS-CoV-2 isolation & purification
- Abstract
Surrogate neutralization assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be done without biosafety level 3 containment and in multiple species are desirable. We evaluate a recently developed surrogate virus neutralization test (sVNT) in comparison to 90% plaque reduction neutralization tests (PRNT
90 ) in human, canine, cat, and hamster sera. With PRNT90 as the reference, sVNT had sensitivity of 98.9% and specificity of 98.8%. Using a panel of immune sera corresponding to other coronaviruses, we confirm the lack of cross-reactivity to other coronaviruses in SARS-CoV-2 sVNT and PRNT90 , except for cross-reactivity to SARS-CoV-1 in sVNT., (Copyright © 2021 American Society for Microbiology.)- Published
- 2021
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24. Neutralizing antibody titres in SARS-CoV-2 infections.
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Lau EHY, Tsang OTY, Hui DSC, Kwan MYW, Chan WH, Chiu SS, Ko RLW, Chan KH, Cheng SMS, Perera RAPM, Cowling BJ, Poon LLM, and Peiris M
- Subjects
- Adolescent, Adult, Animals, Antibodies, Viral blood, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 Nucleic Acid Testing, COVID-19 Testing, Chlorocebus aethiops, Cohort Studies, Female, Hong Kong epidemiology, Humans, Male, Middle Aged, Neutralization Tests, Pandemics, Vero Cells, Young Adult, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 immunology, SARS-CoV-2 immunology
- Abstract
The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT
90 ) and 50% (PRNT50 ) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT50 titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT50 antibody titres to decrease by half (T1/2 ) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT90 and PRNT50 antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.- Published
- 2021
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25. SARS-CoV-2 in Quarantined Domestic Cats from COVID-19 Households or Close Contacts, Hong Kong, China.
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Barrs VR, Peiris M, Tam KWS, Law PYT, Brackman CJ, To EMW, Yu VYT, Chu DKW, Perera RAPM, and Sit THC
- Subjects
- Animals, COVID-19 transmission, Family Characteristics, Hong Kong, Humans, Pandemics, Quarantine, SARS-CoV-2 genetics, Viral Zoonoses, COVID-19 veterinary, Cats, Pets
- Abstract
We tested 50 cats from coronavirus disease households or close contacts in Hong Kong, China, for severe acute respiratory syndrome coronavirus 2 RNA in respiratory and fecal samples. We found 6 cases of apparent human-to-feline transmission involving healthy cats. Virus genomes sequenced from 1 cat and its owner were identical.
- Published
- 2020
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26. Serologic Responses in Healthy Adult with SARS-CoV-2 Reinfection, Hong Kong, August 2020.
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Chan PKS, Lui G, Hachim A, Ko RLW, Boon SS, Li T, Kavian N, Luk F, Chen Z, Yau EM, Chan KH, Tsang CH, Cheng SMS, Chu DKW, Perera RAPM, Ho WCS, Yeung ACM, Chow C, Poon LLM, Valkenburg SA, Hui DSC, and Peiris M
- Subjects
- Antibody Formation immunology, Hong Kong, Humans, Male, Pandemics, SARS-CoV-2, Young Adult, COVID-19 immunology, Reinfection diagnosis
- Abstract
In March 2020, mild signs and symptoms of coronavirus disease developed in a healthy 33-year-old man in Hong Kong. His first infection did not produce virus neutralizing antibodies. In August, he had asymptomatic reinfection, suggesting that persons without a robust neutralizing antibody response might be at risk for reinfection.
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- 2020
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27. Development and Assessment of a Pooled Serum as Candidate Standard to Measure Influenza A Virus Group 1 Hemagglutinin Stalk-Reactive Antibodies.
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Carreño JM, McDonald JU, Hurst T, Rigsby P, Atkinson E, Charles L, Nachbagauer R, Behzadi MA, Strohmeier S, Coughlan L, Aydillo T, Brandenburg B, García-Sastre A, Kaszas K, Levine MZ, Manenti A, McDermott AB, Montomoli E, Muchene L, Narpala SR, Perera RAPM, Salisch NC, Valkenburg SA, Zhou F, Engelhardt OG, and Krammer F
- Abstract
The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals ( n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and competition ELISAs, using the stalk-reactive monoclonal antibodies KB2 (mouse) and CR9114 (human). A "pooled serum" (PS) consisting of a mixture of selected serum samples was generated. The PS exhibited high levels of stalk-reactive antibodies, had a cH6/1N5-based neutralization titer of 320, and contained high levels of stalk-specific antibodies with ADCC activity. The PS, along with blinded samples of varying anti-stalk antibody titers, was distributed to multiple collaborators worldwide in a pilot collaborative study. The samples were subjected to different assays available in the different laboratories, to measure either binding or functional properties of the stalk-reactive antibodies contained in the serum. Results from binding and neutralization assays were analyzed to determine whether use of the PS as a standard could lead to better agreement between laboratories. The work presented here points the way towards the development of a serum standard for antibodies to the HA stalk domain of phylogenetic group 1.
- Published
- 2020
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28. Variation by lineage in serum antibody responses to influenza B virus infections.
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Lau YC, Perera RAPM, Fang VJ, Luk LH, Chu DKW, Wu P, Barr IG, Peiris JSM, and Cowling BJ
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Humans, Models, Theoretical, Influenza B virus pathogenicity, Influenza, Human virology
- Abstract
Two lineages of influenza B virus currently co-circulate and have distinct antigenicity, termed Victoria and Yamagata after the B/Victoria/2/87 and B/Yamagata/16/88 strains, respectively. We analyzed antibody titer dynamics following PCR-confirmed influenza B virus infection in a longitudinal community-based cohort study conducted in Hong Kong from 2009-2014 to assess patterns in changes in antibody titers to B/Victoria and B/Yamagata viruses following infections with each lineage. Among 62 PCR-confirmed cases, almost half had undetectable hemagglutination inhibition (HAI) antibody titers to the lineage of infection both pre-infection and post-infection. Among those infected with influenza B/Victoria who showed an HAI titer response after infection, we found strong rises to the lineage of infection, positive but smaller cross-lineage HAI titer boosts, a small dependence of HAI titer boosts on pre-infection titers, and a shorter half-life of HAI titers in adults. Our study is limited by the low HAI sensitivity for non-ether-treated IBV antigen and the incapacity of performing other assays with higher sensitivity, as well as the mismatch between the B/Yamagata lineage circulating strain and the assay strain in one of the study seasons., Competing Interests: BJC has received honoraria from Roche and Sanofi. The authors report no other potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2020
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29. SARS-CoV-2 Virus Culture and Subgenomic RNA for Respiratory Specimens from Patients with Mild Coronavirus Disease.
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Perera RAPM, Tso E, Tsang OTY, Tsang DNC, Fung K, Leung YWY, Chin AWH, Chu DKW, Cheng SMS, Poon LLM, Chuang VWM, and Peiris M
- Subjects
- Adult, Aged, COVID-19, Female, Hong Kong, Humans, Male, Middle Aged, Pandemics, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, Betacoronavirus genetics, Coronavirus Infections virology, Pneumonia, Viral virology, RNA, Viral analysis, Respiratory System virology, Severity of Illness Index
- Abstract
We investigated 68 respiratory specimens from 35 coronavirus disease patients in Hong Kong, of whom 32 had mild disease. We found that severe acute respiratory syndrome coronavirus 2 and subgenomic RNA were rarely detectable beyond 8 days after onset of illness. However, virus RNA was detectable for many weeks by reverse transcription PCR.
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- 2020
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30. Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial.
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Cowling BJ, Perera RAPM, Valkenburg SA, Leung NHL, Iuliano AD, Tam YH, Wong JHF, Fang VJ, Li APY, So HC, Ip DKM, Azziz-Baumgartner E, Fry AM, Levine MZ, Gangappa S, Sambhara S, Barr IG, Skowronski DM, Peiris JSM, and Thompson MG
- Subjects
- Adjuvants, Immunologic, Aged, Aged, 80 and over, Antibodies, Viral, Hemagglutination Inhibition Tests, Humans, Immunogenicity, Vaccine, Influenza A Virus, H3N2 Subtype, Squalene, Influenza A Virus, H1N1 Subtype, Influenza Vaccines, Influenza, Human prevention & control
- Abstract
Background: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults., Methods: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group., Results: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses., Conclusions: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients., Clinical Trials Registration: NCT03330132., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)
- Published
- 2020
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31. Maternal Antibodies Against Influenza in Cord Blood and Protection Against Laboratory-Confirmed Influenza in Infants.
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Cowling BJ, Perera RAPM, Fang VJ, Chu DKW, Hui APW, Yeung APC, Peiris JSM, Wong WHS, Chan ELY, and Chiu SS
- Subjects
- Antibodies, Viral, Female, Fetal Blood, Hemagglutination Inhibition Tests, Humans, Infant, Influenza A Virus, H3N2 Subtype, Influenza B virus, Laboratories, Pregnancy, Prospective Studies, Influenza A Virus, H1N1 Subtype, Influenza Vaccines, Influenza, Human prevention & control
- Abstract
Background: Studies that correlate maternal antibodies with protection from influenza A or B virus infection in young infants in areas with prolonged influenza circulation are lacking., Methods: We conducted a prospective, observational study to evaluate the effects of maternally transferred antibodies against influenza A and B viruses against laboratory-confirmed influenza in a cohort born over 24 months. Cord blood samples were retrieved at birth and infants were actively followed for the first 6 months of life. Nasal swabs were collected and tested for influenza A and B by reverse transcriptase-polymerase chain reaction whenever an illness episode was identified. Cord blood samples were tested by the hemagglutination inhibition (HAI) assay to viruses that circulated during the follow-up period., Results: 1162 infants were born to 1140 recruited women: 1092 (94%) infants completed 6 months of follow-up. Proportions of cord blood with HAI antibody titers ≥40 against A(H1N1), A(H3N2), B/Victoria, and B/Yamagata were 31%, 24%, 31%, and 54%, respectively. Only 4% of women had maternal influenza vaccination. Cord blood antigen-specific HAI titers ≥40 were found to correlate with protection from infection only for influenza B/Yamagata. No influenza B virus infection occurred in infants ≤60 days old. Proportional hazards analysis showed that a cord blood HAI titer of 40 was associated with 83% (95% confidence interval, 44-95%) reduction in the risk of influenza B/Yamagata infections compared with a cord blood titer <10., Conclusions: We documented that maternal immunity against influenza B/Yamagata was conferred to infants within the first 6 months of life., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2020
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32. ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection.
- Author
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Hachim A, Kavian N, Cohen CA, Chin AWH, Chu DKW, Mok CKP, Tsang OTY, Yeung YC, Perera RAPM, Poon LLM, Peiris JSM, and Valkenburg SA
- Subjects
- Adult, Aged, Antibodies, Viral immunology, Antigens, Viral immunology, COVID-19, COVID-19 Testing, Coronavirus Infections blood, Coronavirus Infections immunology, Coronavirus Infections virology, Female, Hong Kong, Humans, Male, Middle Aged, Pandemics, Pneumonia, Viral blood, Pneumonia, Viral immunology, Pneumonia, Viral virology, SARS-CoV-2, Sensitivity and Specificity, Time Factors, Antibodies, Viral blood, Betacoronavirus immunology, Clinical Laboratory Techniques methods, Coronavirus Infections diagnosis, Pneumonia, Viral diagnosis, Viral Proteins immunology
- Abstract
The SARS-CoV-2 virus emerged in December 2019 and has caused a worldwide pandemic due to the lack of any pre-existing immunity. Accurate serology testing is urgently needed to help diagnose infection, determine past exposure of populations and assess the response to a future vaccine. The landscape of antibody responses to SARS-CoV-2 is unknown. In this study, we utilized the luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19. We identified new targets of the immune response to SARS-CoV-2 and show that nucleocapsid, open reading frame (ORF)8 and ORF3b elicit the strongest specific antibody responses. ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity. Our findings could be used to develop second-generation diagnostic tests to improve serological assays for COVID-19 and are important in understanding pathogenicity.
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- 2020
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33. Author Correction: ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection.
- Author
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Hachim A, Kavian N, Cohen CA, Chin AWH, Chu DKW, Mok CKP, Tsang OTY, Yeung YC, Perera RAPM, Poon LLM, Peiris JSM, and Valkenburg SA
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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34. Infection of dogs with SARS-CoV-2.
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Sit THC, Brackman CJ, Ip SM, Tam KWS, Law PYT, To EMW, Yu VYT, Sims LD, Tsang DNC, Chu DKW, Perera RAPM, Poon LLM, and Peiris M
- Subjects
- Angiotensin-Converting Enzyme 2, Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Betacoronavirus genetics, COVID-19, Coronavirus Infections epidemiology, Coronavirus Infections virology, Dogs, Female, Hong Kong epidemiology, Humans, Male, Middle Aged, Peptidyl-Dipeptidase A metabolism, Phylogeny, Pneumonia, Viral epidemiology, Pneumonia, Viral virology, Receptors, Virus metabolism, SARS-CoV-2, Time Factors, Betacoronavirus isolation & purification, Coronavirus Infections transmission, Coronavirus Infections veterinary, Dog Diseases transmission, Dog Diseases virology, Pandemics veterinary, Pneumonia, Viral transmission, Pneumonia, Viral veterinary, Zoonoses transmission, Zoonoses virology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019 and caused coronavirus disease 2019 (COVID-19)
1,2 . In 2003, the closely related SARS-CoV had been detected in domestic cats and a dog3 . However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2. Here, using PCR with reverse transcription, serology, sequencing the viral genome and virus isolation, we show that 2 out of 15 dogs from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected with SARS-CoV-2. SARS-CoV-2 RNA was detected in five nasal swabs collected over a 13-day period from a 17-year-old neutered male Pomeranian. A 2.5-year-old male German shepherd was positive for SARS-CoV-2 RNA on two occasions and virus was isolated from nasal and oral swabs. Antibody responses were detected in both dogs using plaque-reduction-neutralization assays. Viral genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases. The dogs remained asymptomatic during quarantine. The evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-2. It is unclear whether infected dogs can transmit the virus to other animals or back to humans.- Published
- 2020
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35. Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults.
- Author
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Cowling BJ, Thompson MG, Ng TWY, Fang VJ, Perera RAPM, Leung NHL, Chen Y, So HC, Ip DKM, and Iuliano AD
- Subjects
- Aged, Aged, 80 and over, Antibodies, Viral blood, Antibodies, Viral immunology, Female, Hemagglutination Inhibition Tests, Hong Kong epidemiology, Humans, Influenza A virus immunology, Influenza Vaccines administration & dosage, Influenza, Human epidemiology, Influenza, Human prevention & control, Betainfluenzavirus immunology, Male, Vaccines, Inactivated administration & dosage, Vaccines, Inactivated adverse effects, Vaccines, Inactivated immunology, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic adverse effects, Vaccines, Synthetic immunology, Influenza Vaccines adverse effects, Influenza Vaccines immunology
- Abstract
Background: We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine., Methods: We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017-2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination., Results: Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01-3.38) for A(H1N1) than in those who did not report feverishness., Conclusions: Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population., Clinical Trials Registration: NCT03330132., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2020
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36. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
- Author
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Arunachalam PS, Wimmers F, Mok CKP, Perera RAPM, Scott M, Hagan T, Sigal N, Feng Y, Bristow L, Tak-Yin Tsang O, Wagh D, Coller J, Pellegrini KL, Kazmin D, Alaaeddine G, Leung WS, Chan JMC, Chik TSH, Choi CYC, Huerta C, Paine McCullough M, Lv H, Anderson E, Edupuganti S, Upadhyay AA, Bosinger SE, Maecker HT, Khatri P, Rouphael N, Peiris M, and Pulendran B
- Subjects
- COVID-19, Cytokines blood, DNA, Bacterial blood, Dendritic Cells immunology, Dendritic Cells metabolism, Female, Flow Cytometry, HLA-DR Antigens analysis, Humans, Immunity, Immunity, Innate, Immunoglobulins blood, Immunoglobulins immunology, Inflammation Mediators blood, Interferon Type I metabolism, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lipopolysaccharides blood, Male, Myeloid Cells immunology, Myeloid Cells metabolism, Pandemics, SARS-CoV-2, Signal Transduction, Single-Cell Analysis, Systems Biology, TOR Serine-Threonine Kinases metabolism, Transcription, Genetic, Transcriptome, Betacoronavirus immunology, Coronavirus Infections immunology, Pneumonia, Viral immunology
- Abstract
Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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- 2020
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37. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters.
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Sia SF, Yan LM, Chin AWH, Fung K, Choy KT, Wong AYL, Kaewpreedee P, Perera RAPM, Poon LLM, Nicholls JM, Peiris M, and Yen HL
- Subjects
- Aerosols, Alveolar Epithelial Cells pathology, Alveolar Epithelial Cells virology, Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antigens, Viral immunology, Antigens, Viral isolation & purification, Antigens, Viral metabolism, Betacoronavirus immunology, Betacoronavirus isolation & purification, Betacoronavirus metabolism, Bronchi pathology, Bronchi virology, COVID-19, Coronavirus Infections immunology, Duodenum virology, Fomites virology, Housing, Animal, Kidney virology, Male, Mesocricetus immunology, Nasal Mucosa virology, Pandemics, Pneumonia, Viral immunology, RNA, Viral analysis, SARS-CoV-2, Viral Load, Weight Loss, Betacoronavirus pathogenicity, Coronavirus Infections transmission, Coronavirus Infections virology, Disease Models, Animal, Lung pathology, Lung virology, Mesocricetus virology, Pneumonia, Viral transmission, Pneumonia, Viral virology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies
1,2 . A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.- Published
- 2020
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38. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures.
- Author
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Hui KPY, Cheung MC, Perera RAPM, Ng KC, Bui CHT, Ho JCW, Ng MMT, Kuok DIT, Shih KC, Tsao SW, Poon LLM, Peiris M, Nicholls JM, and Chan MCW
- Subjects
- Adult, Aged, Aged, 80 and over, Betacoronavirus physiology, COVID-19, Conjunctiva immunology, Conjunctiva physiopathology, Coronavirus Infections physiopathology, Female, Humans, Male, Middle Aged, Pandemics, Pneumonia, Viral physiopathology, Respiratory Mucosa immunology, Respiratory Mucosa physiopathology, Respiratory Mucosa virology, Respiratory System immunology, Respiratory System physiopathology, SARS-CoV-2, Betacoronavirus immunology, Conjunctiva virology, Coronavirus Infections immunology, Immunity, Innate immunology, Pneumonia, Viral immunology, Respiratory System virology, Viral Tropism physiology, Virus Replication physiology
- Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis., Methods: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls., Findings: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV., Interpretation: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens., Funding: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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39. Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections.
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Lv H, Wu NC, Tsang OT, Yuan M, Perera RAPM, Leung WS, So RTY, Chan JMC, Yip GK, Chik TSH, Wang Y, Choi CYC, Lin Y, Ng WW, Zhao J, Poon LLM, Peiris JSM, Wilson IA, and Mok CKP
- Subjects
- Animals, Antibodies, Neutralizing immunology, COVID-19, Chlorocebus aethiops, Coronavirus Infections immunology, Coronavirus Infections prevention & control, Cross Reactions immunology, Enzyme-Linked Immunosorbent Assay, Humans, Male, Mice, Mice, Inbred BALB C, Neutralization Tests, Pandemics prevention & control, Pneumonia, Viral immunology, Pneumonia, Viral prevention & control, Receptors, Virus metabolism, SARS-CoV-2, Severe Acute Respiratory Syndrome immunology, Severe Acute Respiratory Syndrome prevention & control, Sf9 Cells, Vero Cells, Viral Vaccines immunology, Antibodies, Viral immunology, Antigens, Viral immunology, Betacoronavirus immunology, Severe acute respiratory syndrome-related coronavirus immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2020
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40. Harnessing the potential of blood donation archives for influenza surveillance and control.
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Zhang Y, Leung K, Perera RAPM, Lee CK, Peiris JSM, and Wu JT
- Subjects
- Adolescent, Adult, Aged, Antibodies, Viral blood, Antibodies, Viral immunology, Cross-Sectional Studies, Epidemiological Monitoring, Hong Kong epidemiology, Humans, Influenza A Virus, H1N1 Subtype immunology, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza A Virus, H3N2 Subtype immunology, Influenza A Virus, H3N2 Subtype isolation & purification, Influenza, Human immunology, Middle Aged, Young Adult, Blood Banks, Blood Donors, Influenza, Human blood, Influenza, Human epidemiology
- Abstract
Many blood donation services around the globe maintain large archives of serum and/or plasma specimens of blood donations which could potentially be used for serologic surveillance and risk assessment of influenza. Harnessing this potential requires robust evidence that the outcomes of influenza serology in plasma, which is rarely used, is consistent with that in serum, which is the conventional choice of specimens for influenza serology. We harvested EDTA-plasma specimens from the blood donation archives of Hong Kong Red Cross Transfusion Services, where EDTA is the type of anticoagulant used for plasma collection, compared their antibody titers and responses to that in serum. Influenza A/H1N1/California/7/2009 and A/H3N2/Victoria/208/2009 were the test strains. Our results showed that antibody titers in 609 matched serum/EDTA-plasma specimens (i.e. obtained from the same donor at the same time) had good agreement inferred by Intraclass Correlation Coefficient, the value of which was 0.82 (95% CI: 0.77-0.86) for hemagglutination inhibition assay and 0.95 (95% CI: 0.93-0.96) for microneutralization assay; seroconversion rates (based on hemagglutination inhibition titers) during the 2010 and 2011 influenza seasons in Hong Kong inferred from paired EDTA-plasma were similar to that inferred from paired sera. Our study provided the proof-of-concept that blood donation archives could be leveraged as a valuable source of longitudinal blood specimens for the surveillance, control and risk assessment of both pandemic and seasonal influenza., Competing Interests: The authors have declared that no competing interests exist.
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- 2020
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41. Characterizing Emerging Canine H3 Influenza Viruses.
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Martinez-Sobrido L, Blanco-Lobo P, Rodriguez L, Fitzgerald T, Zhang H, Nguyen P, Anderson CS, Holden-Wiltse J, Bandyopadhyay S, Nogales A, DeDiego ML, Wasik BR, Miller BL, Henry C, Wilson PC, Sangster MY, Treanor JJ, Topham DJ, Byrd-Leotis L, Steinhauer DA, Cummings RD, Luczo JM, Tompkins SM, Sakamoto K, Jones CA, Steel J, Lowen AC, Danzy S, Tao H, Fink AL, Klein SL, Wohlgemuth N, Fenstermacher KJ, El Najjar F, Pekosz A, Sauer L, Lewis MK, Shaw-Saliba K, Rothman RE, Liu ZY, Chen KF, Parrish CR, Voorhees IEH, Kawaoka Y, Neumann G, Chiba S, Fan S, Hatta M, Kong H, Zhong G, Wang G, Uccellini MB, García-Sastre A, Perez DR, Ferreri LM, Herfst S, Richard M, Fouchier R, Burke D, Pattinson D, Smith DJ, Meliopoulos V, Freiden P, Livingston B, Sharp B, Cherry S, Dib JC, Yang G, Russell CJ, Barman S, Webby RJ, Krauss S, Danner A, Woodard K, Peiris M, Perera RAPM, Chan MCW, Govorkova EA, Marathe BM, Pascua PNQ, Smith G, Li YT, Thomas PG, and Schultz-Cherry S
- Subjects
- Animals, Communicable Diseases, Emerging transmission, Communicable Diseases, Emerging virology, Dog Diseases transmission, Dogs, Ferrets, Guinea Pigs, Humans, Influenza A Virus, H3N2 Subtype classification, Influenza A Virus, H3N2 Subtype genetics, Influenza A Virus, H3N8 Subtype classification, Influenza A Virus, H3N8 Subtype genetics, Influenza A virus classification, Influenza A virus genetics, Influenza, Human transmission, Influenza, Human virology, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, United States, Zoonoses transmission, Communicable Diseases, Emerging veterinary, Dog Diseases virology, Influenza A Virus, H3N2 Subtype isolation & purification, Influenza A Virus, H3N8 Subtype isolation & purification, Influenza A virus isolation & purification, Zoonoses virology
- Abstract
The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned., Competing Interests: AG-S. is inventor of patents on influenza virus vaccines owned by the Icahn School for Medicine at Mount Sinai and licensed to Medimmune, BI Vetmedica, Vivaldi Biosciences, Zoetis and Avimex.
- Published
- 2020
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42. Influenza A Virus Infections in Dromedary Camels, Nigeria and Ethiopia, 2015-2017.
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Chu DKW, Perera RAPM, Ali A, Oladipo JO, Mamo G, So RTY, Zhou Z, Chor YY, Chan CK, Belay D, Tayachew A, Mengesha M, Regassa F, Lam NT, Poon LLM, and Peiris M
- Subjects
- Animals, Ethiopia epidemiology, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Nigeria epidemiology, Orthomyxoviridae Infections epidemiology, Orthomyxoviridae Infections virology, Camelus virology, Influenza A virus, Orthomyxoviridae Infections veterinary
- Abstract
We examined nasal swabs and serum samples acquired from dromedary camels in Nigeria and Ethiopia during 2015-2017 for evidence of influenza virus infection. We detected antibodies against influenza A(H1N1) and A(H3N2) viruses and isolated an influenza A(H1N1)pdm09-like virus from a camel in Nigeria. Influenza surveillance in dromedary camels is needed.
- Published
- 2020
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43. The Effect of Influenza Vaccination History on Changes in Hemagglutination Inhibition Titers After Receipt of the 2015-2016 Influenza Vaccine in Older Adults in Hong Kong.
- Author
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Ng TWY, Perera RAPM, Fang VJ, Yau EM, Peiris JSM, Tam YH, and Cowling BJ
- Subjects
- Age Factors, Aged, Aged, 80 and over, Female, Hemagglutination, Hong Kong, Humans, Immunization, Secondary, Immunogenicity, Vaccine, Male, Vaccination, Antibodies, Viral blood, Influenza A Virus, H1N1 Subtype immunology, Influenza A Virus, H3N2 Subtype immunology, Influenza B virus immunology, Influenza Vaccines immunology
- Abstract
Background: Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same., Methods: An observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015-2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160., Results: Participants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160., Conclusions: Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2020
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44. Diversity of Dromedary Camel Coronavirus HKU23 in African Camels Revealed Multiple Recombination Events among Closely Related Betacoronaviruses of the Subgenus Embecovirus.
- Author
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So RTY, Chu DKW, Miguel E, Perera RAPM, Oladipo JO, Fassi-Fihri O, Aylet G, Ko RLW, Zhou Z, Cheng MS, Kuranga SA, Roger FL, Chevalier V, Webby RJ, Woo PCY, Poon LLM, and Peiris M
- Subjects
- Animals, Antibodies, Neutralizing, Betacoronavirus classification, Coronavirus classification, Ethiopia, Evolution, Molecular, Genome, Viral, Genotype, Middle East Respiratory Syndrome Coronavirus genetics, Morocco, Nigeria, Open Reading Frames, Phylogeny, Rabbits, Zoonoses virology, Betacoronavirus genetics, Camelus virology, Coronavirus genetics, Coronavirus Infections virology, Genetic Variation, Recombination, Genetic
- Abstract
Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco, and Ethiopia and identified several genomic positions indicative of cross-species virus recombination events among other betacoronaviruses of the subgenus Embecovirus (clade A beta-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at 8.9-kDa open reading frame 4a at the 3' end of the spike gene. The patterns of recombination differed geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and are also relevant to the emergence and evolution of other betacoronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV). IMPORTANCE Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other clade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution., (Copyright © 2019 American Society for Microbiology.)
- Published
- 2019
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45. Transmissibility of MERS-CoV Infection in Closed Setting, Riyadh, Saudi Arabia, 2015.
- Author
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Van Kerkhove MD, Alaswad S, Assiri A, Perera RAPM, Peiris M, El Bushra HE, and BinSaeed AA
- Subjects
- Adult, Air Conditioning, Coronavirus Infections virology, Disease Outbreaks, Female, Housing, Humans, Risk Factors, Saudi Arabia epidemiology, Universities, Coronavirus Infections transmission, Middle East Respiratory Syndrome Coronavirus pathogenicity
- Abstract
To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015-January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%-32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.
- Published
- 2019
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46. Influenza Hemagglutination-inhibition Antibody Titer as a Mediator of Vaccine-induced Protection for Influenza B.
- Author
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Cowling BJ, Lim WW, Perera RAPM, Fang VJ, Leung GM, Peiris JSM, and Tchetgen Tchetgen EJ
- Subjects
- Adolescent, Child, Hemagglutination Inhibition Tests, Humans, Influenza B virus, Influenza Vaccines administration & dosage, Influenza, Human prevention & control, Proportional Hazards Models, Randomized Controlled Trials as Topic, Vaccines, Inactivated administration & dosage, Vaccines, Inactivated immunology, Antibodies, Viral blood, Influenza Vaccines immunology, Influenza, Human immunology, Vaccine Potency
- Abstract
Background: The hemagglutination inhibition (HAI) assay is an established correlate of protection for the inactivated influenza vaccine. However, the proportion of vaccine-induced protection that is mediated by the post-vaccination HAI titer has not been assessed., Methods: We used data from a randomized, placebo-controlled trial of a split-virion inactivated influenza vaccine in children aged 6-17 years. Sera were collected before and 30 days after receipt of vaccination or placebo and tested by the HAI assay against B/Brisbane/60/2008-like (B/Victoria lineage). We fitted Cox proportional hazards models to the time to laboratory-confirmed influenza B. We used causal mediation analysis to estimate the proportion of the total effect of vaccination that was mediated by higher HAI titers., Results: We estimated that vaccine efficacy against confirmed B/Victoria infection was 68% (95% confidence interval, 33%, 88%), and post-vaccination HAI titers explained 57% of the effect of vaccination on protection., Conclusions: The majority of the effect of inactivated influenza vaccination in children is mediated by the increased HAI titer after vaccination; however, other components of the immune response to vaccination may also play a role in protection and should be further explored. Causal mediation analysis provides a framework to quantify the role of various mediators of protection., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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47. Age-specific differences in the dynamics of protective immunity to influenza.
- Author
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Ranjeva S, Subramanian R, Fang VJ, Leung GM, Ip DKM, Perera RAPM, Peiris JSM, Cowling BJ, and Cobey S
- Subjects
- Adolescent, Adult, Age Factors, Aged, Antibodies, Viral immunology, Antigens, Viral immunology, Antigens, Viral isolation & purification, Child, Child, Preschool, Female, Follow-Up Studies, Hemagglutinins immunology, Hong Kong epidemiology, Humans, Incidence, Influenza A Virus, H1N1 Subtype immunology, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza A Virus, H3N2 Subtype immunology, Influenza A Virus, H3N2 Subtype isolation & purification, Influenza Vaccines administration & dosage, Influenza Vaccines immunology, Influenza, Human epidemiology, Influenza, Human prevention & control, Influenza, Human virology, Longitudinal Studies, Male, Middle Aged, Randomized Controlled Trials as Topic, Time Factors, Young Adult, Antibodies, Viral blood, Cross Protection immunology, Immunologic Memory immunology, Influenza, Human immunology, Models, Biological
- Abstract
Influenza A viruses evolve rapidly to escape host immunity, causing reinfection. The form and duration of protection after each influenza virus infection are poorly understood. We quantify the dynamics of protective immunity by fitting individual-level mechanistic models to longitudinal serology from children and adults. We find that most protection in children but not adults correlates with antibody titers to the hemagglutinin surface protein. Protection against circulating strains wanes to half of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that influenza antibody responses shift focus with age from the mutable hemagglutinin head to other epitopes, consistent with the theory of original antigenic sin, and might affect protection. Imprinting, or primary infection with a subtype, has modest to no effect on the risk of non-medically attended infections in adults.
- Published
- 2019
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48. Evidence of equine influenza A (H3N8) activity in horses from Eastern and Central Saudi Arabia: 2013-2015.
- Author
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Hemida MG, Perera RAPM, Chu DKW, Alnaeem AA, and Peiris M
- Subjects
- Animals, Horse Diseases epidemiology, Horses, Orthomyxoviridae Infections blood, Orthomyxoviridae Infections epidemiology, Orthomyxoviridae Infections virology, Saudi Arabia epidemiology, Seroepidemiologic Studies, Antibodies, Viral blood, Horse Diseases virology, Influenza A Virus, H3N8 Subtype, Orthomyxoviridae Infections veterinary
- Abstract
Background: Equine influenza virus (EIV) is one of the main causes of viral respiratory affections in horses. Little is known about the prevalence of EIV in Saudi Arabia especially the H3N8 serotype., Objectives: To assess prevalence of equine influenza in horse populations in Eastern and Central Saudi Arabia., Study Design: Cross-sectional study., Methods: We collected 145 sera, 323 nasal and 323 rectal swabs from horses from six major cities in Eastern and Central regions. None of the horses were vaccinated against EIV. Sera were tested in ELISA assays for influenza A type-specific antibodies and by haemagglutination inhibition (HI) tests using equine H3N8. The swabs were tested by RT-qPCR assay targeting a conserved region of the influenza A matrix gene that detects influenza A viruses of all subtypes., Results: None of the swabs had detectable influenza A virus RNA. Of the 145 serasamples tested by ELISA, 81 (55.9%) were positive and 98 (67.6%) of 145 sera tested by HI tests were positive for equine H3., Main Limitations: Our failure to detect and sequence any EIV prevents identification of the lineage of virus that circulates in the Kingdom of Saudi Arabia., Conclusions: These results confirm that EIV H3N8 is circulating in Saudi Arabia and should be considered as a possible cause when investigating horses with respiratory disease in Saudi Arabia., (© 2018 EVJ Ltd.)
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- 2019
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49. West Nile virus infection in horses in Saudi Arabia (in 2013-2015).
- Author
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Hemida MG, Perera RAPM, Chu DKW, Ko RLW, Alnaeem AA, and Peiris M
- Subjects
- Animals, Antibodies, Neutralizing blood, Culex virology, Enzyme-Linked Immunosorbent Assay, Horse Diseases immunology, Horse Diseases virology, Horses virology, Mosquito Vectors virology, Neutralization Tests, Prevalence, Saudi Arabia epidemiology, Sensitivity and Specificity, West Nile Fever epidemiology, West Nile Fever immunology, West Nile virus, Zoonoses epidemiology, Zoonoses virology, Antibodies, Viral blood, Horse Diseases epidemiology, West Nile Fever veterinary
- Abstract
West Nile virus (WNV) is an important emerging zoonotic arbovirus giving rise to clinical syndromes of varying severity in humans and horses. Culex mosquitoes are the main vector. Although WNV has been reported in many countries in the Middle East and Asia, little is known about its prevalence in equine populations in the Arabian Peninsula. We have carried out a serological study on 200 horses to assess WNV infection in the Eastern and Central regions of Saudi Arabia in 2013-2015. Sera were tested for the presence of WNV antibodies in parallel using a commercial enzyme-linked immunosorbent assay (ELISA) kit and microneutralization (MN) tests. In comparison with the MN assay used as "gold standard," we find the ELISA had a sensitivity of 94.7% and specificity of 80.1%. The prevalence of WNV neutralizing antibody ranged from 5 (17.3%) of 29 sera collected in Riyadh up to 15 (55.6%) of 27 sera collected from Al-Qateef. These findings highlight the need to be aware of the possibility of WNV disease in humans and horses presenting with central nervous system disease in the Kingdom of Saudi Arabia., (© 2018 Blackwell Verlag GmbH.)
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- 2019
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50. Indirect protection from vaccinating children against influenza in households.
- Author
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Tsang TK, Fang VJ, Ip DKM, Perera RAPM, So HC, Leung GM, Peiris JSM, Cowling BJ, and Cauchemez S
- Subjects
- Adolescent, Child, Child, Preschool, Epidemics prevention & control, Hong Kong epidemiology, Humans, Influenza B virus drug effects, Influenza Vaccines administration & dosage, Influenza, Human drug therapy, Influenza, Human epidemiology, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Vaccination methods, Vaccination statistics & numerical data, Family Characteristics, Influenza B virus immunology, Influenza Vaccines immunology, Influenza, Human immunology
- Abstract
Vaccination is an important intervention to prevent influenza virus infection, but indirect protection of household members of vaccinees is not fully known. Here, we analyze a cluster household randomized controlled trial, with one child in each household randomized to receive influenza vaccine or placebo, for an influenza B epidemic in Hong Kong. We apply statistical models to estimate household transmission dynamics and quantify the direct and indirect protection of vaccination. Direct vaccine efficacy was 71%. The infection probability of unvaccinated household members in vaccinated households was only 5% lower than in control households, because only 10% of infections are attributed to household transmission. Even when that proportion rises to 30% and all children are vaccinated, we predict that the infection probability for unvaccinated household members would only be reduced by 20%. This suggests that benefits of individual vaccination remain important even when other household members are vaccinated.
- Published
- 2019
- Full Text
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