Last data update: May 28, 2024. (Total: 46864 publications since 2009)
Records 1-30 (of 37 Records) |
Query Trace: Kondor R [original query] |
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An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution
Subissi L , Otieno JR , Worp N , Attar Cohen H , Oude Munnink BB , Abu-Raddad LJ , Alm E , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Ghedin E , Grant R , Haagmans BL , Happi C , Herring BL , Hodcroft EB , Ikejezie J , Katawera V , Kassamali ZA , Leo YS , Leung GM , Kondor RJ , Marklewitz M , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Naindoo D , Oh DY , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Saha S , Shen Y , Siqueira MM , Volz E , Tessema SK , Thiel V , Triki H , van der Werf S , von Eije K , Cunningham J , Koopmans MPG , von Gottberg A , Agrawal A , Van Kerkhove MD . Nat Med 2024 |
Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons
Owuor DC , de Laurent ZR , Nyawanda BO , Emukule GO , Kondor R , Barnes JR , Nokes DJ , Agoti CN , Chaves SS . Sci Rep 2023 13 (1) 22342 Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses of HA protein revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1 through acquisition of additional substitutions. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity declined with an increase in age among children aged < 5 years. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines. |
Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein
Keller MW , Keong LM , Rambo-Martin BL , Hassell N , Lacek KA , Wilson MM , Kirby MK , Liddell J , Owuor DC , Sheth M , Madden J , Lee JS , Kondor RJ , Wentworth DE , Barnes JR . Microbiol Spectr 2023 e0298223 The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection. |
Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution (preprint)
Huddleston J , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Whittaker L , Ermetal B , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Barr I , Subbarao K , Neher RA , Bedford T . bioRxiv 2020 2020.06.12.145151 Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.Competing Interest StatementThe authors have declared no competing interest. |
Bivalent mRNA vaccine improves antibody-mediated neutralization of many SARS-CoV-2 Omicron lineage variants (preprint)
Jiang N , Wang L , Hatta M , Feng C , Currier M , Lin X , Hossain J , Cui D , Mann BR , Kovacs NA , Wang W , Atteberry G , Wilson M , Chau R , Lacek KA , Paden CR , Hassell N , Rambo-Martin B , Barnes JR , Kondor RJ , Self WH , Rhoads JP , Baughman A , Chappell JD , Shapiro NI , Gibbs KW , Hager DN , Lauring AS , Surie D , McMorrow ML , Thornburg NJ , Wentworth DE , Zhou B . bioRxiv 2023 09 The early Omicron lineage variants evolved and gave rise to diverging lineages that fueled the COVID-19 pandemic in 2022. Bivalent mRNA vaccines, designed to broaden protection against circulating and future variants, were authorized by the U.S. Food and Drug Administration (FDA) in August 2022 and recommended by the U.S. Centers for Disease Control and Prevention (CDC) in September 2022. The impact of bivalent vaccination on eliciting neutralizing antibodies against homologous BA.4/BA.5 viruses as well as emerging heterologous viruses needs to be analyzed. In this study, we analyze the neutralizing activity of sera collected after a third dose of vaccination (2-6 weeks post monovalent booster) or a fourth dose of vaccination (2-7 weeks post bivalent booster) against 10 predominant/recent Omicron lineage viruses including BA.1, BA.2, BA.5, BA.2.75, BA.2.75.2, BN.1, BQ.1, BQ.1.1, XBB, and XBB.1. The bivalent booster vaccination enhanced neutralizing antibody titers against all Omicron lineage viruses tested, including a 10-fold increase in neutralization of BQ.1 and BQ.1.1 viruses that predominated in the U.S. during the last two months of 2022. Overall, the data indicate the bivalent vaccine booster strengthens protection against Omicron lineage variants that evolved from BA.5 and BA.2 progenitors. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons (preprint)
Owuor DC , de Laurent ZR , Nyawanda BO , Emukule GO , Kondor R , Barnes JR , Nokes DJ , Agoti CN , Chaves SS . medRxiv 2022 13 Background. Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. Methods. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and determinants of clinical outcome. Results. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity reduced with increase in age among children aged <5 years. Conclusion. Our study highlights the utility of genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on the severity of circulating strains could improve selection of influenza strains for inclusion in vaccines. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Identification of a Novel SARS-CoV-2 Delta-Omicron Recombinant Virus in the United States (preprint)
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Sakaguchi H , Peacock T , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Hassell N , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . bioRxiv 2022 21 Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Genomic surveillance for SARS-CoV-2 variants: Circulation of Omicron lineages - United States, January 2022-May 2023
Ma KC , Shirk P , Lambrou AS , Hassell N , Zheng XY , Payne AB , Ali AR , Batra D , Caravas J , Chau R , Cook PW , Howard D , Kovacs NA , Lacek KA , Lee JS , MacCannell DR , Malapati L , Mathew S , Mittal N , Nagilla RR , Parikh R , Paul P , Rambo-Martin BL , Shepard SS , Sheth M , Wentworth DE , Winn A , Hall AJ , Silk BJ , Thornburg N , Kondor R , Scobie HM , Paden CR . MMWR Morb Mortal Wkly Rep 2023 72 (24) 651-656 CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics. |
Changes in influenza and other respiratory virus activity during the COVID-19 pandemic-United States, 2020-2021.
Olsen SJ , Winn AK , Budd AP , Prill MM , Steel J , Midgley CM , Kniss K , Burns E , Rowe T , Foust A , Jasso G , Merced-Morales A , Davis CT , Jang Y , Jones J , Daly P , Gubareva L , Barnes J , Kondor R , Sessions W , Smith C , Wentworth DE , Garg S , Havers FP , Fry AM , Hall AJ , Brammer L , Silk BJ . Am J Transplant 2021 21 (10) 3481-3486 The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced the transmission of some viral respiratory pathogens.1 In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020,2 and remained low during October 2020–May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1–4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities. |
An early warning system for emerging SARS-CoV-2 variants.
Subissi L , von Gottberg A , Thukral L , Worp N , Oude Munnink BB , Rathore S , Abu-Raddad LJ , Aguilera X , Alm E , Archer BN , Attar Cohen H , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Gaseitsiwe S , Ghedin E , Grant R , Haagmans BL , Herring BL , Iyer SS , Kassamali Z , Kakkar M , Kondor RJ , Leite JA , Leo YS , Leung GM , Marklewitz M , Moyo S , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Oh DY , Pavlin BI , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Sacks J , Shen Y , Siqueira MM , Tessema SK , Volz EM , Thiel V , van der Werf S , Briand S , Perkins MD , Van Kerkhove MD , Koopmans MPG , Agrawal A . Nat Med 2022 28 (6) 1110-1115 Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic. | | In June 2020, the World Health Organization (WHO) SARS-CoV-2 evolution working group was established to track SARS-CoV-2 variants and their specific genetic changes and to monitor viral characteristics and their impact on medical and non-medical countermeasures, including vaccines against COVID-19. In November 2021, this working group transitioned to a formal WHO Technical Advisory Group on Virus Evolution (TAG-VE), with the aim of developing and implementing a global risk-monitoring framework for SARS-CoV-2 variants, based on a multidisciplinary approach that includes in silico, virological, clinical and epidemiological data. |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
Timing of seasonal influenza epidemics for 25 countries in Africa during 2010-19: a retrospective analysis
Igboh LS , Roguski K , Marcenac P , Emukule GO , Charles MD , Tempia S , Herring B , Vandemaele K , Moen A , Olsen SJ , Wentworth DE , Kondor R , Mott JA , Hirve S , Bresee JS , Mangtani P , Nguipdop-Djomo P , Azziz-Baumgartner E . Lancet Glob Health 2023 11 (5) e729-e739 BACKGROUND: Using country-specific surveillance data to describe influenza epidemic activity could inform decisions on the timing of influenza vaccination. We analysed surveillance data from African countries to characterise the timing of seasonal influenza epidemics to inform national vaccination strategies. METHODS: We used publicly available sentinel data from African countries reporting to the WHO Global Influenza Surveillance and Response FluNet platform that had 3-10 years of data collected during 2010-19. We calculated a 3-week moving proportion of samples positive for influenza virus and assessed epidemic timing using an aggregate average method. The start and end of each epidemic were defined as the first week when the proportion of positive samples exceeded or went below the annual mean, respectively, for at least 3 consecutive weeks. We categorised countries into five epidemic patterns: northern hemisphere-dominant, with epidemics occurring in October-March; southern hemisphere-dominant, with epidemics occurring in April-September; primarily northern hemisphere with some epidemic activity in southern hemisphere months; primarily southern hemisphere with some epidemic activity in northern hemisphere months; and year-round influenza transmission without a discernible northern hemisphere or southern hemisphere predominance (no clear pattern). FINDINGS: Of the 34 countries reporting data to FluNet, 25 had at least 3 years of data, representing 46% of the countries in Africa and 89% of Africa's population. Study countries reported RT-PCR respiratory virus results for a total of 503 609 specimens (median 12 971 [IQR 9607-20 960] per country-year), of which 74 001 (15%; median 2078 [IQR 1087-3008] per country-year) were positive for influenza viruses. 248 epidemics occurred across 236 country-years of data (median 10 [range 7-10] per country). Six (24%) countries had a northern hemisphere pattern (Algeria, Burkina Faso, Egypt, Morocco, Niger, and Tunisia). Eight (32%) had a primarily northern hemisphere pattern with some southern hemisphere epidemics (Cameroon, Ethiopia, Mali, Mozambique, Nigeria, Senegal, Tanzania, and Togo). Three (12%) had a primarily southern hemisphere pattern with some northern hemisphere epidemics (Ghana, Kenya, and Uganda). Three (12%) had a southern hemisphere pattern (Central African Republic, South Africa, and Zambia). Five (20%) had no clear pattern (Côte d'Ivoire, DR Congo, Madagascar, Mauritius, and Rwanda). INTERPRETATION: Most countries had identifiable influenza epidemic periods that could be used to inform authorities of non-seasonal and seasonal influenza activity, guide vaccine timing, and promote timely interventions. FUNDING: None. TRANSLATIONS: For the Berber, Luganda, Xhosa, Chewa, Yoruba, Igbo, Hausa and Afan Oromo translations of the abstract see Supplementary Materials section. |
Leveraging International Influenza Surveillance Systems and programs during the COVID-19 pandemic
Marcenac P , McCarron M , Davis W , Igboh LS , Mott JA , Lafond KE , Zhou W , Sorrells M , Charles MD , Gould P , Arriola CS , Veguilla V , Guthrie E , Dugan VG , Kondor R , Gogstad E , Uyeki TM , Olsen SJ , Emukule GO , Saha S , Greene C , Bresee JS , Barnes J , Wentworth DE , Fry AM , Jernigan DB , Azziz-Baumgartner E . Emerg Infect Dis 2022 28 (13) S26-s33 A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential. |
Spike Gene Target Amplification in a Diagnostic Assay as a Marker for Public Health Monitoring of Emerging SARS-CoV-2 Variants - United States, November 2021-January 2023.
Scobie HM , Ali AR , Shirk P , Smith ZR , Paul P , Paden CR , Hassell N , Zheng XY , Lambrou AS , Kondor R , MacCannell D , Thornburg NJ , Miller J , Wentworth D , Silk BJ . MMWR Morb Mortal Wkly Rep 2023 72 (5) 125-127 Monitoring emerging SARS-CoV-2 lineages and their epidemiologic characteristics helps to inform public health decisions regarding vaccine policy, the use of therapeutics, and health care capacity. When the SARS-CoV-2 Alpha variant emerged in late 2020, a spike gene (S-gene) deletion (Δ69-70) in the N-terminal region, which might compensate for immune escape mutations that impair infectivity (1), resulted in reduced or failed S-gene target amplification in certain multitarget reverse transcription-polymerase chain reaction (RT-PCR) assays, a pattern referred to as S-gene target failure (SGTF) (2). The predominant U.S. SARS-CoV-2 lineages have generally alternated between SGTF and S-gene target presence (SGTP), which alongside genomic sequencing, has facilitated early monitoring of emerging variants. During a period when Omicron BA.5-related sublineages (which exhibit SGTF) predominated, an XBB.1.5 sublineage with SGTP has rapidly expanded in the northeastern United States and other regions. |
Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages.
Xia H , Yeung J , Kalveram B , Bills CJ , Chen JY , Kurhade C , Zou J , Widen SG , Mann BR , Kondor R , Todd Davis C , Zhou B , Wentworth DE , Xie X , Shi PY . Emerg Microbes Infect 2023 12 (1) 1-19 The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach. |
An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance
Patel MC , Flanigan D , Feng C , Chesnokov A , Nguyen HT , Elal AA , Steel J , Kondor RJ , Wentworth DE , Gubareva LV , Mishin VP . Antiviral Res 2022 208 105457 Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of virus-infected cells. For convenience, this new assay was named IRINA (Influenza Replication Inhibition Neuraminidase-based Assay). IRINA was successfully validated to assess inhibitory activity of baloxavir on virus replication by testing a large set (>150) of influenza A and B viruses, including drug resistant strains and viruses collected during 2017-2022. To test its versatility, IRINA was utilized to evaluate neutralization activity of a broadly reactive human anti-HA monoclonal antibody, FI6, and post-infection ferret antisera, as well as the inhibition of NA enzyme activity by NA inhibitors. Performance of IRINA was tested in parallel using respective conventional assays. IRINA offers an attractive alternative to current phenotypic assays, while maintaining reproducibility and high throughput capacity. Additionally, the improved turnaround time may prove to be advantageous when conducting time sensitive studies, such as investigating a new virus outbreak. This assay can meet the needs of surveillance laboratories by providing a streamlined and cost-effective approach for virus characterization. |
SARS-CoV-2 Delta-Omicron Recombinant Viruses, United States.
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Hassell N , Sakaguchi H , Peacock T , Groves N , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . Emerg Infect Dis 2022 28 (7) 1442-1445 To detect new and changing SARS-CoV-2 variants, we investigated candidate Delta-Omicron recombinant genomes from Centers for Disease Control and Prevention national genomic surveillance. Laboratory and bioinformatic investigations identified and validated 9 genetically related SARS-CoV-2 viruses with a hybrid Delta-Omicron spike protein. |
Influenza Activity and Composition of the 2022-23 Influenza Vaccine - United States, 2021-22 Season.
Merced-Morales A , Daly P , Abd Elal AI , Ajayi N , Annan E , Budd A , Barnes J , Colon A , Cummings CN , Iuliano AD , DaSilva J , Dempster N , Garg S , Gubareva L , Hawkins D , Howa A , Huang S , Kirby M , Kniss K , Kondor R , Liddell J , Moon S , Nguyen HT , O'Halloran A , Smith C , Stark T , Tastad K , Ujamaa D , Wentworth DE , Fry AM , Dugan VG , Brammer L . MMWR Morb Mortal Wkly Rep 2022 71 (29) 913-919 Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences. |
United States Centers for Disease Control and Prevention support for influenza surveillance, 2013-2021.
McCarron M , Kondor R , Zureick K , Griffin C , Fuster C , Hammond A , Lievre M , Vandemaele K , Bresee J , Xu X , Dugan VG , Weatherspoon V , Williams T , Vance A , Fry AM , Samaan M , Fitzner J , Zhang W , Moen A , Wentworth DE , Azziz-Baumgartner E . Bull World Health Organ 2022 100 (6) 366-374 OBJECTIVE: To assess the stability of improvements in global respiratory virus surveillance in countries supported by the United States Centers for Disease Control and Prevention (CDC) after reductions in CDC funding and with the stress of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We assessed whether national influenza surveillance systems of CDC-funded countries: (i) continued to analyse as many specimens between 2013 and 2021; (ii) participated in activities of the World Health Organization's (WHO) Global Influenza Surveillance and Response System; (iii) tested enough specimens to detect rare events or signals of unusual activity; and (iv) demonstrated stability before and during the COVID-19 pandemic. We used CDC budget records and data from the WHO Global Influenza Surveillance and Response System. FINDINGS: While CDC reduced per-country influenza funding by about 75% over 10 years, the number of specimens tested annually remained stable (mean 2261). Reporting varied substantially by country and transmission zone. Countries funded by CDC accounted for 71% (range 61-75%) of specimens included in WHO consultations on the composition of influenza virus vaccines. In 2019, only eight of the 17 transmission zones sent enough specimens to WHO collaborating centres before the vaccine composition meeting to reliably identify antigenic variants. CONCLUSION: Great progress has been made in the global understanding of influenza trends and seasonality. To optimize surveillance to identify atypical influenza viruses, and to integrate molecular testing, sequencing and reporting of severe acute respiratory syndrome coronavirus 2 into existing systems, funding must continue to support these efforts. |
Interim estimates of 2021-22 seasonal influenza vaccine effectiveness - United States, February 2022
Chung JR , Kim SS , Kondor RJ , Smith C , Budd AP , Tartof SY , Florea A , Talbot HK , Grijalva CG , Wernli KJ , Phillips CH , Monto AS , Martin ET , Belongia EA , McLean HQ , Gaglani M , Reis M , Geffel KM , Nowalk MP , DaSilva J , Keong LM , Stark TJ , Barnes JR , Wentworth DE , Brammer L , Burns E , Fry AM , Patel MM , Flannery B . MMWR Morb Mortal Wkly Rep 2022 71 (10) 365-370 In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season. |
Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (6) 206-211 Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.(†) The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice. |
Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021.
Olsen SJ , Winn AK , Budd AP , Prill MM , Steel J , Midgley CM , Kniss K , Burns E , Rowe T , Foust A , Jasso G , Merced-Morales A , Davis CT , Jang Y , Jones J , Daly P , Gubareva L , Barnes J , Kondor R , Sessions W , Smith C , Wentworth DE , Garg S , Havers FP , Fry AM , Hall AJ , Brammer L , Silk BJ . MMWR Morb Mortal Wkly Rep 2021 70 (29) 1013-1019 The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities. |
Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2.
Shu B , Kirby MK , Davis WG , Warnes C , Liddell J , Liu J , Wu KH , Hassell N , Benitez AJ , Wilson MM , Keller MW , Rambo-Martin BL , Camara Y , Winter J , Kondor RJ , Zhou B , Spies S , Rose LE , Winchell JM , Limbago BM , Wentworth DE , Barnes JR . Emerg Infect Dis 2021 27 (7) 1821-1830 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 10(2.0), influenza B virus at 10(2.2), and SARS-CoV-2 at 10(0.3) 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2. |
Cluster of Oseltamivir-Resistant and Hemagglutinin Antigenically Drifted Influenza A(H1N1)pdm09 Viruses, Texas, USA, January 2020
Mohan T , Nguyen HT , Kniss K , Mishin VP , Merced-Morales AA , Laplante J , St George K , Blevins P , Chesnokov A , De La Cruz JA , Kondor R , Wentworth DE , Gubareva LV . Emerg Infect Dis 2021 27 (7) 1953-1957 Four cases of oseltamivir-resistant influenza A(H1N1)pdm09 virus infection were detected among inhabitants of a border detention center in Texas, USA. Hemagglutinin of these viruses belongs to 6B.1A5A-156K subclade, which may enable viral escape from preexisting immunity. Our finding highlights the necessity to monitor both drug resistance and antigenic drift of circulating viruses. |
Genomic Surveillance for SARS-CoV-2 Variants Circulating in the United States, December 2020-May 2021.
Paul P , France AM , Aoki Y , Batra D , Biggerstaff M , Dugan V , Galloway S , Hall AJ , Johansson MA , Kondor RJ , Halpin AL , Lee B , Lee JS , Limbago B , MacNeil A , MacCannell D , Paden CR , Queen K , Reese HE , Retchless AC , Slayton RB , Steele M , Tong S , Walters MS , Wentworth DE , Silk BJ . MMWR Morb Mortal Wkly Rep 2021 70 (23) 846-850 SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1). Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing. As of May 6, 2021, sequences from 177,044 SARS-CoV-2-positive specimens collected during December 20, 2020-May 6, 2021, from 55 U.S. jurisdictions had been generated by or reported to CDC. These included 3,275 sequences for the 2-week period ending January 2, 2021, compared with 25,000 sequences for the 2-week period ending April 24, 2021 (0.1% and 3.1% of reported positive SARS-CoV-2 tests, respectively). Because sequences might be generated by multiple laboratories and sequence availability varies both geographically and over time, CDC developed statistical weighting and variance estimation methods to generate population-based estimates of the proportions of identified variants among SARS-CoV-2 infections circulating nationwide and in each of the 10 U.S. Department of Health and Human Services (HHS) geographic regions.* During the 2-week period ending April 24, 2021, the B.1.1.7 and P.1 variants represented an estimated 66.0% and 5.0% of U.S. SARS-CoV-2 infections, respectively, demonstrating the rise to predominance of the B.1.1.7 variant of concern(†) (VOC) and emergence of the P.1 VOC in the United States. Using SARS-CoV-2 genomic surveillance methods to analyze surveillance data produces timely population-based estimates of the proportions of variants circulating nationally and regionally. Surveillance findings demonstrate the potential for new variants to emerge and become predominant, and the importance of robust genomic surveillance. Along with efforts to characterize the clinical and public health impact of SARS-CoV-2 variants, surveillance can help guide interventions to control the COVID-19 pandemic in the United States. |
Re-emergence of influenza virus circulation during 2020 in parts of tropical Asia: Implications for other countries
Mott JA , Fry AM , Kondor R , Wentworth DE , Olsen SJ . Influenza Other Respir Viruses 2021 15 (3) 415-418 Global influenza virus circulation declined and has been below traditional seasonal levels during the COVID‐19 pandemic. 1 , 2 , 3 After learning of increased influenza virus circulation in some tropical Asian countries, we reviewed current surveillance data to better ascertain risk for an influenza resurgence during the 2020‐2021 Northern Hemisphere influenza season and subsequent seasons during the COVID‐19 pandemic. |
Effect of antigenic drift on influenza vaccine effectiveness in the United States - 2019-2020.
Tenforde MW , Kondor RJG , Chung JR , Zimmerman RK , Nowalk MP , Jackson ML , Jackson LA , Monto AS , Martin ET , Belongia EA , McLean HQ , Gaglani M , Rao A , Kim SS , Stark TJ , Barnes JR , Wentworth D , Patel MM , Flannery B . Clin Infect Dis 2020 73 (11) e4244-e4250 BACKGROUND: At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses, that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. METHODS: We enrolled outpatients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95%CI: 37-52) against B/Victoria and 30% (95%CI: 21-39) against A(H1N1)pdm09 associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95%CI: -14 to 23%) which predominated after January. CONCLUSIONS: Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed. |
Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020.
Tenforde MW , Talbot HK , Trabue CH , Gaglani M , McNeal TM , Monto AS , Martin ET , Zimmerman RK , Silveira F , Middleton DB , Olson SM , Garten Kondor RJ , Barnes JR , Ferdinands JM , Patel MM . J Infect Dis 2020 224 (5) 813-820 BACKGROUND: Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. METHODS: We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. RESULTS: 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. CONCLUSIONS: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness. |
Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017-2018 influenza season.
Potter BI , Kondor R , Hadfield J , Huddleston J , Barnes J , Rowe T , Guo L , Xu X , Neher RA , Bedford T , Wentworth DE . Virus Evol 2019 5 (2) vez046 The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus's North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70 per cent of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, hemagglutination inhibition assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics. |
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