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1.
Theranostics ; 12(12): 5317-5329, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35910807

RESUMEN

Human pluripotent stem cell derived brain organoids offer an unprecedented opportunity for various applications as in vitro model. Currently, human brain organoids as models have been used to understand virus-induced neurotoxicity. Methods: The brain organoids were separately challenged by multiple viruses including influenza viruses (H1N1-WSN and H3N2-HKT68), Enteroviruses (EV68 and EV71) and Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) to investigate the impaired effect of these viruses on human brain development. Results: The brain organoids challenged by influenza viruses had decreased overall organoid size, while enteroviruses infected brain organoids displayed the opposite result. Then, we found WSN preferentially infected MAP2+ neurons compared to SOX2+ neural stem cells (NSCs) and GFAP+ astrocytes in brain organoids, and induced apoptosis of NSCs and neurons, and released inflammatory factors (TNF-α, INF-γ, and IL-6), facilitating brain damage. Furthermore, transcriptional profiling revealed several co-upregulated genes (CSAG3 and OAS2) and co-downregulated genes (CDC20B, KCNJ13, OTX2-AS1) after WSN infection for 24 hpi and 96 hpi, implicating target for antiviral drugs development. Finally, we explored compound PYC-12 could significantly suppress virus infection, apoptosis, and inflammatory responses. Conclusions: Collectively, we established a tractable experimental model to investigate the impact and mechanism of virus infection on human brain development.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Antivirales/farmacología , Encéfalo , Humanos , Subtipo H3N2 del Virus de la Influenza A , Organoides
2.
BMC Health Serv Res ; 22(1): 982, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35915483

RESUMEN

BACKGROUND: Considering the importance of intention to receive COVID-19 vaccine among healthcare workers and its role in maintaining their health and inhibiting the epidemic spread of Covid-19, the present study was done to identify the changes in intention to receive COVID-19 vaccine rate in two different time points and it's determinants based on the dimensions of the health belief model among healthcare workers in Iran. METHODS: Two cross-sectional surveys performed to investigate COVID-19 vaccination intent and associated factors based on the health belief model. The first conducted on 1244 participants from August 18 to 23, 2020, and the second on 1514 participants from February 5 to April 29, 2021, both using a questionnaire of intent to accept COVID-19 vaccination. The questionnaire distribution platform in both surveys was similarly, WhatsApp and Telegram social and working virtual groups of HCWs. Data were analyzed with SPSS-16 software for descriptive and analytical statistics. RESULTS: In the first survey, 58.4% (95% CI: 0.55-0.61%) of healthcare workers intended to receive the COVID-19 vaccine, the rate dropped to 45.7% (95% CI: 0.43-0.48%) in the second survey (P < 0.001). The regression analysis indicated six factors that were significantly associated with higher intention to receive COVID-19 vaccine: being a female (OR = 1.84, 95% CI (1.11-3.03)), history of Covid-19 infection (OR = 1.54, 95% CI (1.09-2.18), perceptions of Covid-19 disease (OR = 1.13, 95% CI (1.01-1.28)), perceived benefits of COVID-19 vaccine (OR = 1.34, 95% CI (1.22-1.47)), prosocial norms for COVID-19 vaccination (OR = 1.25, 95% CI (1.21-1.29)), and COVID-19 vaccine safety/cost concerns (OR = 1.25, 95% CI (1.17-1.33)). CONCLUSIONS: Present study showed an undesirable rate of intention to receive COVID-19 vaccine among healthcare workers, especially decreasing over the time, emphasize the need of interventions to promote healthcare workers' intention to receive the vaccine and reduce the spread of COVID-19 disease.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Transversales , Femenino , Personal de Salud , Humanos , Gripe Humana/prevención & control , Intención , Encuestas y Cuestionarios , Vacunación
3.
Signal Transduct Target Ther ; 7(1): 266, 2022 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-35922403

RESUMEN

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


Asunto(s)
COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Nanopartículas , Animales , COVID-19/genética , Cricetinae , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/prevención & control , Ratones , Péptidos/genética , Péptidos/farmacología , SARS-CoV-2/genética
4.
Washington, D.C.; PAHO; 2022-08-04.
en Inglés, Español | PAHO-IRIS | ID: phr-56217

RESUMEN

[WEEKLY SUMMARY]. North America: Overall, influenza activity decreased in the subregion while SARS-CoV-2 continued elevated. In Mexico, influenza activity with A(H3N2) virus predominance decreased, while SARS-CoV-2 positivity continued to increase. SARI activity remained at moderate-intensity levels, whereas ILI activity rose to high-intensity levels, driven by the SARS-CoV-2 circulation. In the United States, influenza activity was low, with influenza A(H3N2) viruses predominance. In addition, RSV activity remained stable compared to previous weeks, while SARS-CoV-2 activity increased with higher COVID-19-associated hospitalizations. Caribbean: Influenza activity remained low, with the predominance of the influenza A(H3N2) virus. Belize and the Dominican Republic, reported increased SARS-CoV-2 activity, with increased SARI cases, although below the epidemic thresholds, except in Haiti, with levels above average for this time of year. In the Dominican Republic, RSV activity remained elevated at levels seen in the pre-pandemic period with SARS-CoV-2 cocirculation. Central America: Influenza activity continued to decrease in the subregion, with influenza A(H3N2) virus predominance. In Nicaragua, influenza activity increased to moderate-intensity levels, with the A(H3N2) virus predominance. SARS-CoV-2 activity rose across the subregion, with increased levels in Costa Rica, Honduras and Guatemala. Influenza and SARS-CoV-2-associated ILI counts remained at moderate levels in Guatemala. Andean Countries: Influenza activity remained low with A(H3N2) predominance, except in Bolivia and Peru where circulation increased above epidemic levels.SARS-CoV-2 activity continued to increase in Bolivia, Colombia, and Peru. Brazil and Southern Cone: Overall, influenza activity remained at low levels with influenza A(H3N2) predominance and driven by its circulation in Chile and Uruguay. SARS-CoV-2 activity continued to increase throughout the subregion. Chile, Paraguay, and Uruguay reported SARI activity elevated above epidemic levels for the period, with RSV and SARS-CoV-2 predominance in Chile and Uruguay, while SARS-CoV-2 predominated in Paraguay.


[RESUMEN SEMANAL]. América del Norte: en general, la actividad de la influenza disminuyó en la subregión, mientras que el SARS-CoV-2 continuó elevado. En México disminuyó la actividad de influenza con predominio del virus A(H3N2) mientras que la positividad del SARS-CoV-2 siguió aumentando. La actividad de la ETI se mantuvo en niveles de intensidad moderada mientras que la actividad de la IRAG ascendió a niveles de intensidad altos, en ambos casos a expensas de la circulación de SARS-CoV-2. En los Estados Unidos, la actividad de la influenza fue baja, predominando los virus influenza A(H3N2). La actividad del VRS se mantuvo estable respecto a las semanas previas mientras que la actividad del SARS-CoV-2 continuó en aumento con un mayor número de hospitalizaciones asociadas a la COVID-19. Caribe: la actividad de la influenza se mantuvo muy baja, con predominio del virus influenza A(H3N2). Belice y la República Dominicana notificaron un aumento de la actividad del SARS-CoV-2, con un aumento de los casos de IRAG, sin superar los umbrales epidémicos, excepto en Haití donde los niveles se sitúan por encima del promedio para esta época del año. En la República Dominicana, la actividad del VRS se mantuvo elevada en niveles observados en el período previo a la pandemia con circulación concurrente de SARS-CoV-2. América Central: la actividad de la influenza continuó en descenso en la subregión, con predominio de influenza A(H3N2). En Nicaragua la actividad de la influenza ascendió en niveles de intensidad moderados con predominio del virus A(H3N2). La actividad del SARS CoV-2 continuó en aumento en toda la subregión con niveles elevados en Costa Rica, Honduras y Guatemala. Los recuentos de casos de ETI asociados con influenza y SARS-CoV-2 se mantuvieron en niveles moderados en Guatemala. Países Andinos: la actividad de la influenza se mantuvo baja con predominio de A(H3N2), excepto en Bolivia y Perú donde la circulación aumentó por encima de los niveles epidémicos. La actividad del SARS-CoV-2 siguió aumentando en Bolivia, Colombia y Perú, Brasil y Cono Sur: en general, la actividad de la influenza se mantuvo en niveles bajos con predominio de influenza A(H3N2) y a expensas de la circulación en Chile y Uruguay. La actividad del SARS-CoV‑2 siguió en aumento en niveles moderados en toda la subregión. Chile, Paraguay y Uruguay reportaron actividad de la IRAG elevada sobre los niveles epidémicos para el periodo, con predominio de VRS y SARS-CoV-2 en Chile y Uruguay, mientras que predominó el SARS-CoV-2 en Paraguay.


Asunto(s)
Gripe Humana , COVID-19 , SARS-CoV-2 , Betacoronavirus , Reglamento Sanitario Internacional , Américas , Región del Caribe , Gripe Humana , Reglamento Sanitario Internacional , Américas , Región del Caribe
5.
PLoS One ; 17(8): e0270469, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35921608

RESUMEN

Shortly after the implementation of community mitigation measures in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), sharp declines in respiratory syncytial virus and influenza circulation were noted; post-mitigation circulation of other respiratory pathogens has gone unexplored. We retrospectively analyzed all records of a provider-ordered multiplex test between April 1, 2018, and July 31, 2021, in Nashville, Tennessee, and we noted disrupted historical seasonal patterns for common respiratory pathogens during the SARS-CoV-2 pandemic.


Asunto(s)
COVID-19 , Gripe Humana , COVID-19/epidemiología , Humanos , Gripe Humana/epidemiología , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Tennessee/epidemiología
6.
Proc Natl Acad Sci U S A ; 119(32): e2205797119, 2022 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-35914171

RESUMEN

Narcolepsy type 1 (NT1), a disorder caused by hypocretin/orexin (HCRT) cell loss, is associated with human leukocyte antigen (HLA)-DQ0602 (98%) and T cell receptor (TCR) polymorphisms. Increased CD4+ T cell reactivity to HCRT, especially DQ0602-presented amidated C-terminal HCRT (HCRTNH2), has been reported, and homology with pHA273-287 flu antigens from pandemic 2009 H1N1, an established trigger of the disease, suggests molecular mimicry. In this work, we extended DQ0602 tetramer and dextramer data to 77 cases and 44 controls, replicating our prior finding and testing 709 TCRs in Jurkat 76 T cells for functional activation. We found that fewer TCRs isolated with HCRTNH2 (∼11%) versus pHA273-287 or NP17-31 antigens (∼50%) were activated by their ligand. Single-cell characterization did not reveal phenotype differences in influenza versus HCRTNH2-reactive T cells, and analysis of TCR CDR3αß sequences showed TCR clustering by responses to antigens but no cross-peptide class reactivity. Our results do not support the existence of molecular mimicry between HCRT and pHA273-287 or NP17-31.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Narcolepsia , Humanos , Orexinas/metabolismo , Receptores de Antígenos de Linfocitos T/genética
7.
JAMA Netw Open ; 5(8): e2224657, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35917125

RESUMEN

Importance: Despite the high 3-dose vaccination rate among health care workers (HCWs) in Israel, a high rate of SARS-CoV-2 breakthrough infections in this group was observed during the Omicron wave. As a result, the Israeli Ministry of Health decided to recommend a fourth vaccine dose to medical staff. Objective: To evaluate the benefit of a fourth BNT162b2 vaccine dose on the breakthrough infection rate among HCWs. Design, Setting, and Participants: This multicenter cohort study was performed in January 2022, the first month of the 4-dose vaccination campaign, during a surge of the Omicron variant wave. All health care workers at 11 general hospitals in Israel who had been vaccinated with 3 doses up to September 30, 2021, and had not contracted COVID-19 before the vaccination campaign were included. Exposures: Vaccination with a fourth dose of the BNT162b2 vaccine during January 2022. Main Outcomes and Measures: Breakthrough COVID-19 infections in 4-dose recipients vs 3-dose recipients measured by a polymerase chain reaction test result positive for SARS-CoV-2. Health care workers were tested based on symptoms or exposure. Results: A total of 29 611 Israeli HCWs (19 381 [65%] female; mean [SD] age, 44 [12] years) had received 3 vaccine doses between August and September 2021; of these, 5331 (18%) received the fourth dose in January 2022 and were not infected by the first week after vaccination. Overall breakthrough infection rates were 368 of 5331 (7%) in the 4-dose group and 4802 of 24280 (20%) in the 3-dose group (relative risk, 0.35; 95% CI, 0.32-0.39). Similar reductions were found in a matched analysis by the exact day of receiving the third vaccine (relative risk, 0.61; 95% CI, 0.54-0.71) and in a time-dependent Cox proportional hazards regression model (adjusted hazard ratio, 0.56; 95% CI, 0.50-0.63). In both groups, no severe disease or death occurred. Conclusions and Relevance: In this cohort study, the fourth BNT162b2 vaccine dose resulted in a reduced breakthrough infection rate among hospital staff. This reduction was lower than that observed after the third dose; nevertheless, considering the high infectivity of the Omicron variant, which led to critical medical staff shortages, a fourth vaccine dose should be considered to mitigate the infection rate among HCWs.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Actitud del Personal de Salud , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Niño , Estudios de Cohortes , Femenino , Humanos , Gripe Humana/prevención & control , Israel/epidemiología , Masculino , Personal de Hospital , SARS-CoV-2 , Encuestas y Cuestionarios
8.
Proc Natl Acad Sci U S A ; 119(32): e2116818119, 2022 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-35917349

RESUMEN

How does the COVID-19 pandemic affect interpersonal trust? Most evidence shows that natural disasters reinforce trust and cooperation, but the COVID-19 virus differs from other calamities, since it spreads through contact with people, potentially increasing suspicion and distrust, as, according to contemporaneous writers' accounts, seems to have been the case with the Black Death, the London plague, and the Spanish influenza. We investigate the link between interpersonal trust and individuals exposed to COVID-19, either vicariously through their community or networks or directly by becoming infected. We rely on an original panel survey, including a survey experiment, with a representative sample of adults in Italy, one of the countries hardest struck by the pandemic. Our experimental findings reveal that priming people about the risk that the pandemic poses to their health leads to a substantial increase in their trust in strangers. Our panel data analysis of within-individual effects shows that those who become infected trust strangers more than those who are not infected. Our findings could be explained by people observing higher than expected altruistic behavior or becoming more dependent on other people's support, consistent with the "emancipation theory of trust." When people recover from COVID-19, however, they drop to trusting strangers as much as those who were not directly exposed to the virus, an indication that the positive effects on trust during the pandemic have an emotional source. Nonetheless, the evidence suggests that, in the aggregate, there has been a small but significant increase in trust among the general population relative to prepandemic levels.


Asunto(s)
COVID-19 , Gripe Humana , Adulto , COVID-19/epidemiología , Humanos , Gripe Humana/epidemiología , Pandemias , SARS-CoV-2 , Confianza/psicología
9.
Arch. argent. pediatr ; 120(4): 269-273, Agosto 2022. tab, ilus
Artículo en Inglés, Español | LILACS, BINACIS | ID: biblio-1372375

RESUMEN

Introducción. Durante la pandemia de COVID-19, disminuyeron las notificaciones de infecciones respiratorias. El objetivo fue estimar la prevalencia de virus sincicial respiratorio (VSR) e influenza en niños escolarizados asistidos en un hospital pediátrico durante el retorno a la presencialidad. Métodos. Estudio transversal de casos sospechosos de COVID-19, de 3-18 años, con prueba negativa para SARSCoV-2, entre agosto y octubre de 2021. Se estratificó por nivel educativo. Se utilizó PCR para detectar VSR e influenza. Resultados. Se incluyeron 619 niños: 234 del nivel inicial, 224 del primario y 161 del secundario; 25,5 % (158) fueron positivos para VSR (36,3 % del nivel inicial versus 21 % del primario y 16 % del secundario); en adolescentes se asoció la infección al contacto escolar con caso sintomático (OR 2,5; IC95%: 1-6,80; p = 0,04). No se aisló virus influenza. Conclusión. VSR se aisló en un cuarto de la población estudiada, con mayor frecuencia en el nivel inicial; en adolescentes, se asoció con contacto escolar sintomático. No se detectaron casos de influenza


Introduction. Reporting of respiratory infections reduced during the COVID-19 pandemic. The objective was to estimate the prevalence of respiratory syncytial virus (RSV) and influenza in schoolchildren seen at a children's hospital during the return to school. Methods. Cross-sectional study of patients aged 3­18 years suspected of COVID-19 with a negative test for SARS-CoV-2 between August and October 2021. Participants were stratified by level of education. PCR was used to detect RSV and influenza. Results. A total of 619 children were included: 234 in preschool, 224 in primary and 161 in secondary school; 25.5% (158) tested positive for RS (36.3% in the pre-school level versus 21% in primary and 16% in secondary school). Infection among adolescents was associated with school contact with symptomatic cases (OR 2.5; 95%CI 1­6.80; p = 0.04). No case of influenza was detected. Conclusion. RSV was isolated in one fourth of the study population, with a higher frequency in pre-school; among adolescents, it was associated with school contact with symptomatic cases. No case of influenza was detected.


Asunto(s)
Humanos , Preescolar , Niño , Adolescente , Virus Sincitial Respiratorio Humano , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , COVID-19 , Estudios Transversales , Pandemias , SARS-CoV-2 , Hospitales Pediátricos
10.
Front Immunol ; 13: 867753, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812426

RESUMEN

Background: Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled and excessive inflammation leading to high mortality. Aetiology of HLH can be primarily due to genetic causes or secondarily due to infections or rheumatological illness. However, rarely T-cell deficiencies like severe combined immunodeficiency (SCID) can develop HLH. Objective: To describe clinical and laboratory features of SCID cases who developed HLH. Methods: We collected clinical, laboratory, and molecular details of patients with SCID who developed HLH at our center at Chandigarh, North India. Results: Of the 94 cases with SCID, 6 were noted to have developed HLH-like manifestations. Male-female ratio was 5:1. Median (inter-quartile range) age of onset of clinical symptoms was 4.25 months (2-5 months). Median (inter-quartile range) delay in diagnosis was 1 month (1-3.5 months). Family history of deaths was seen in 4 cases. Molecular defects in IL2RG were seen in 5 out of 6 cases. Documented infections include disseminated bacillus calmette-guerin (BCG) infection (n=2), blood stream infections (n=3) with Staphylococcal aureus (n=1), Klebsiella pneumonia (n=1), and Pseudomonas aeruginosa (n=1), pneumonia (influenza H1N1 strain, and K. pneumoniae (n=1). Conclusion: Children with SCID can present with HLH-like manifestations secondary to fulminant infections. A high index of suspicion of SCID is needed in infants who present with HLH who have an associated infection or a suggestive family history. Occurrence of HLH-like manifestations in SCID suggests that T-lymphocytes may not have a significant role in immunopathogenesis of HLH.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Linfohistiocitosis Hemofagocítica , Inmunodeficiencia Combinada Grave , Niño , Femenino , Humanos , Lactante , Gripe Humana/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Masculino , Inmunodeficiencia Combinada Grave/complicaciones , Inmunodeficiencia Combinada Grave/diagnóstico , Linfocitos T/patología
11.
Front Public Health ; 10: 921855, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812517

RESUMEN

An efficient and safe vaccine is expected to allow people to return to normal life as soon as possible. However, vaccines for new diseases are likely to be in short supply during the initial deployment due to narrow production capacity and logistics. There is an urgent need to optimize the allocation of limited vaccines to improve the population effectiveness of vaccination. Existing studies mostly address a single epidemiological landscape. The robustness of the effectiveness of other proposed strategies is difficult to guarantee under other landscapes. In this study, a novel vaccination allocation model based on spatio-temporal heterogeneity of epidemiological landscapes is proposed. This model was combined with optimization algorithms to determine the near-optimal spatio-temporal allocation for vaccines with different effectiveness and coverage. We fully simulated the epidemiological landscapes during vaccination, and then minimized objective functions independently under various epidemiological landscapes and degrees of viral transmission. We find that if all subregions are in the middle or late stages of the pandemic, the difference between the effectiveness of the near-optimal and pro-rata strategies is very small in most cases. In contrast, under other epidemiological landscapes, when minimizing deaths, the optimizer tends to allocate the remaining doses to sub-regions with relatively higher risk and expected coverage after covering the elderly. While to minimize symptomatic infections, allocating vaccines first to the higher-risk sub-regions is near-optimal. This means that the pro-rata allocation is a good option when the subregions are all in the middle to late stages of the pandemic. Moreover, we suggest that if all subregions are in the period of rapid virus transmission, vaccines should be administered to older adults in all subregions simultaneously, while when the epidemiological dynamics of the subregions are significantly different, priority can be given to older adults in subregions that are still in the early stages of the pandemic. After covering the elderly in the region, high-risk sub-regions can be prioritized.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Anciano , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Gripe Humana/epidemiología , Vacunación
12.
PLoS Pathog ; 18(7): e1010698, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35830486

RESUMEN

Baloxavir marboxil (BXM) is approved for treating uncomplicated influenza. The active metabolite baloxavir acid (BXA) inhibits cap-dependent endonuclease activity of the influenza virus polymerase acidic protein (PA), which is necessary for viral transcription. Treatment-emergent E23G or E23K (E23G/K) PA substitutions have been implicated in reduced BXA susceptibility, but their effect on virus fitness and transmissibility, their synergism with other BXA resistance markers, and the mechanisms of resistance have been insufficiently studied. Accordingly, we generated point mutants of circulating seasonal influenza A(H1N1)pdm09 and A(H3N2) viruses carrying E23G/K substitutions. Both substitutions caused 2- to 13-fold increases in the BXA EC50. EC50s were higher with E23K than with E23G and increased dramatically (138- to 446-fold) when these substitutions were combined with PA I38T, the dominant BXA resistance marker. E23G/K-substituted viruses exhibited slightly impaired replication in MDCK and Calu-3 cells, which was more pronounced with E23K. In ferret transmission experiments, all viruses transmitted to direct-contact and airborne-transmission animals, with only E23K+I38T viruses failing to infect 100% of animals by airborne transmission. E23G/K genotypes were predominantly stable during transmission events and through five passages in vitro. Thermostable PA-BXA interactions were weakened by E23G/K substitutions and further weakened when combined with I38T. In silico modeling indicated this was caused by E23G/K altering the placement of functionally important Tyr24 in the endonuclease domain, potentially decreasing BXA binding but at some cost to the virus. These data implicate E23G/K, alone or combined with I38T, as important markers of reduced BXM susceptibility, and such mutants could emerge and/or transmit among humans.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Tiepinas , Sustitución de Aminoácidos , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Dibenzotiepinas , Farmacorresistencia Viral/genética , Endonucleasas/metabolismo , Hurones , Humanos , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/metabolismo , Virus de la Influenza A/genética , Virus de la Influenza A/metabolismo , Morfolinas , Oxazinas/farmacología , Piridinas/farmacología , Piridonas/farmacología , Tiepinas/farmacología , Triazinas , Proteínas Virales/metabolismo
13.
Neurol India ; 70(3): 1203-1206, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35864666

RESUMEN

Influenza A viruses, known etiological agents of seasonal outbreaks, epidemics, and pandemics, are RNA viruses of the Orthomyxoviridae family. They can manifest with a wide range of neurological complications. Influenza related encephalitis is rarely reported and poorly characterized in adults. Its diagnosis is hampered by significant variation in clinical presentation and difficulties in virus detection in the cerebrospinal fluid. Diffuse brain edema, symmetric involvement of thalamus, brain stem, and cerebellum, or normal findings in the acute phase followed by the appearance of diffuse low attenuation and mild brain atrophy are reported cranial magnetic resonance imaging findings, but unilateral temporal lobe involvement has not been observed before. Here we describe an unusual adult case who presented with new-onset epileptic seizures and unilateral temporal lobe lesion mimicking herpes simplex encephalitis but a polymerase chain reaction of cerebrospinal fluid confirmed influenza type A associated encephalitis.


Asunto(s)
Encefalitis por Herpes Simple , Epilepsia , Virus de la Influenza A , Gripe Humana , Adulto , Epilepsia/complicaciones , Humanos , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/patología , Imagen por Resonancia Magnética , Convulsiones/complicaciones , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología
14.
Comput Math Methods Med ; 2022: 6322350, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35866038

RESUMEN

Objective: The autoregressive integrated moving average (ARIMA) model has been widely used to predict the trend of infectious diseases. This paper is aimed at analyzing the application of the ARIMA model in the prediction of the incidence trend of influenza-like illness (ILI) in Wuhan and providing a scientific basis for the prediction and prevention of influenza. Methods: The weekly ILI data of two influenza surveillance sentinel hospitals in Wuhan City published on the website of the National Influenza Center of China were collected, and the ARIMA model was used to model the data from 2014 to 2020, to predict and verify the ILI data in 2021. Results: The optimal model for the incidence trend of ILI in Wuhan was ARIMA (1, 1, 1), the residuals were in line with the white noise sequence (0.018 < Ljung-Box Q < 30.695, P > 0.05), and the relative error between the predicted value and the actual value was small, which all proved the model was practical. Conclusion: ARIMA (1, 1, 1) can effectively simulate the short-term incidence trend of ILI in Wuhan.


Asunto(s)
Gripe Humana , Virosis , China/epidemiología , Predicción , Humanos , Incidencia , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Modelos Estadísticos
15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(7): 1023-1026, 2022 Jul 06.
Artículo en Chino | MEDLINE | ID: mdl-35899359

RESUMEN

This article uses the analysis framework of the macro model of the health system to analyze the influenza vaccine policy documents issued by the state and governments at all levels from three perspectives: structure, process and results, and provides a scientific basis for improving the application strategy of influenza vaccine. It is suggested that on the basis of continuing to strengthen publicity, mobilization and organizational guarantee, measures to promote the application of influenza vaccine in China by exploring multi-channel financing mechanisms, combining the experience of new crown vaccination to improve the convenience of influenza vaccination, and scientifically setting vaccination rate targets, improve preparedness for an influenza pandemic.


Asunto(s)
Vacunas contra la Influenza , Gripe Humana , China , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias/prevención & control , Políticas , Vacunación
16.
BMC Health Serv Res ; 22(1): 896, 2022 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-35820916

RESUMEN

BACKGROUND: The emergency primary care (EPC) services in Norway have been at the frontline of the COVID-19 pandemic. Knowledge about the EPC services' management of the COVID-19 outbreak can be used to prepare for future outbreaks and improve patient management. The objectives of this study were to identify pandemic preparedness and management strategies in EPC centres in Norway during the COVID-19 outbreak. METHODS: Questions regarding patient management of the COVID-19 outbreak were included in data collection for the National Out-Of-Hours Services Registry. The data collection was web-based, and an invitation was sent by email to the managers of all EPC services in Norway in June 2020. The EPC services were asked questions about pre-pandemic preparedness, access to personal protective equipment (PPE), organizational measures taken, and how staffing was organized during the onset of the pandemic. RESULTS: There were 169 municipal and inter-municipal EPC services in Norway in 2020, and all responded to the questionnaire. Among the EPC services, 66.7% (n = 112) had a pandemic plan, but only 4.2% had performed training for pandemic preparedness. Further, fewer than half of the EPC centres (47.5%) had access to supplies of PPE, and 92.8% answered that they needed extra supplies of PPE. 75.3% of the EPC services established one or more respiratory clinics. Staffing with other personnel than usual was done in 44.6% (n = 74) of the EPC services. All EPC services except one implemented new strategies for assessing patients, while about half of the wards implemented new strategies for responding to emergency calls. None of the largest EPC services experienced that their pandemic plan was adequate, while 13.3% of the medium-sized EPC services and 48.9% of the small EPC services reported having an adequate pandemic plan. CONCLUSIONS: Even though the EPC services lacked well-tested plans and had insufficient supplies of PPE at the outbreak of the COVID-19 pandemic, most services adapted to the pandemic by altering the ways they worked and by hiring health care professionals from other disciplines. These observations may help decision makers plan for future pandemics.


Asunto(s)
COVID-19 , Gripe Humana , COVID-19/epidemiología , COVID-19/terapia , Brotes de Enfermedades/prevención & control , Humanos , Gripe Humana/epidemiología , Pandemias , Atención Primaria de Salud , Encuestas y Cuestionarios
17.
Nat Commun ; 13(1): 4054, 2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35831293

RESUMEN

Establishment of zoonotic viruses, causing pandemics like the Spanish flu and Covid-19, requires adaptation to human receptors. Pandemic influenza A viruses (IAV) that crossed the avian-human species barrier switched from binding avian-type α2-3-linked sialic acid (2-3Sia) to human-type 2-6Sia receptors. Here, we show that this specificity switch is however less dichotomous as generally assumed. Binding and entry specificity were compared using mixed synthetic glycan gradients of 2-3Sia and 2-6Sia and by employing a genetically remodeled Sia repertoire on the surface of a Sia-free cell line and on a sialoglycoprotein secreted from these cells. Expression of a range of (mixed) 2-3Sia and 2-6Sia densities shows that non-binding human-type receptors efficiently enhanced avian IAV binding and entry provided the presence of a low density of high affinity avian-type receptors, and vice versa. Considering the heterogeneity of sialoglycan receptors encountered in vivo, hetero-multivalent binding is physiologically relevant and will impact evolutionary pathways leading to host adaptation.


Asunto(s)
COVID-19 , Virus de la Influenza A , Influenza Pandémica, 1918-1919 , Gripe Humana , Animales , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Virus de la Influenza A/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores Virales/metabolismo
18.
Sci Rep ; 12(1): 12026, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35835833

RESUMEN

We analysed 2006-2016 national influenza surveillance data in Japan with regards to age-, sex-, and predominant virus-related epidemic patterns and the prevalence of serum influenza virus antibodies. We found a significant increase in influenza prevalence in both children (≤ 19 years old) and adults (≥ 20 years old) over time. The influenza prevalence was higher in children (0.33 [95% CI 0.26-0.40]) than in adults (0.09 [95% CI 0.07-0.11]). Additionally, the mean prevalence of antibodies for A(H1N1)pdm09 and A(H3N2) was significantly higher in children than in adults, whereas the mean prevalence of antibodies for B lineages was relatively low in both children and adults. There was a biennial cycle of the epidemic peak in children, which was associated with a relatively higher prevalence of B lineages. The female-to-male ratios of the influenza prevalence were significantly different in children (≤ 19 years old; 1.10 [95% CI:1.08-1.13]), adults (20-59 years old; 0.79 [95% CI 0.75-0.82]), and older adults (≥ 60 years old; 1.01 [95% CI 0.97-1.04]). The significant increase in influenza prevalence throughout the study period suggests a change of immunity to influenza infection. Long-term surveillance is important for developing a strategy to monitor, prevent and control for influenza epidemics.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Adulto , Anciano , Anticuerpos Antivirales , Niño , Femenino , Humanos , Subtipo H3N2 del Virus de la Influenza A , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estaciones del Año , Adulto Joven
20.
Methods Mol Biol ; 2511: 53-65, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35838951

RESUMEN

COVID-19 disease caused by the novel SARS-CoV-2 virus represents a new challenge for healthcare systems. The molecular confirmation of infection is crucial to guide public health decision-making. This task could be made more difficult during the next influenza season. Thus, a rapid and user-friendly diagnostic test to discriminate SARS-CoV-2 from influenza viruses is urgently needed. Here, we present a multiplex quantitative polymerase chain reaction (qPCR) assay capable of distinguishing SARS-CoV-2 from influenza A and B cases. This assay benefits from the use of an inhibitor tolerant PCR mix which obviates the need for the rate-limiting extraction step, allowing for a more rapid and accurate analysis.


Asunto(s)
COVID-19 , Herpesvirus Cercopitecino 1 , Virus de la Influenza A , Gripe Humana , COVID-19/diagnóstico , Pruebas Diagnósticas de Rutina , Humanos , Virus de la Influenza A/genética , Virus de la Influenza B , Gripe Humana/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2/genética , Sensibilidad y Especificidad
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