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BACKGROUND: The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses. METHODS: We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies - one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models. RESULTS: Among children, the overall effectiveness of the 10-µg primary vaccine series against infection with the omicron variant was 25.7% (95% confidence interval [CI], 10.0 to 38.6). Effectiveness was highest (49.6%; 95% CI, 28.5 to 64.5) right after receipt of the second dose but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI, 21.5 to 63.3) among children 5 to 7 years of age and 16.6% (95% CI, -4.2 to 33.2) among those 8 to 11 years of age. Among adolescents, the overall effectiveness of the 30-µg primary vaccine series against infection with the omicron variant was 30.6% (95% CI, 26.9 to 34.1), but many adolescents had been vaccinated months earlier. Effectiveness waned over time since receipt of the second dose. Effectiveness was 35.6% (95% CI, 31.2 to 39.6) among adolescents 12 to 14 years of age and 20.9% (95% CI, 13.8 to 27.4) among those 15 to 17 years of age. In the pre-omicron study, the overall effectiveness of the 30-µg primary vaccine series against SARS-CoV-2 infection among adolescents was 87.6% (95% CI, 84.0 to 90.4) and waned relatively slowly after receipt of the second dose. CONCLUSIONS: Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna BNT162 , COVID-19 , Eficacia de las Vacunas , Adolescente , Niño , Humanos , Vacuna BNT162/administración & dosificación , Vacuna BNT162/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/uso terapéutico , Qatar/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Preescolar , Eficacia de las Vacunas/estadística & datos numéricosRESUMEN
BACKGROUND: The protection conferred by natural immunity, vaccination, and both against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the BA.1 or BA.2 sublineages of the omicron (B.1.1.529) variant is unclear. METHODS: We conducted a national, matched, test-negative, case-control study in Qatar from December 23, 2021, through February 21, 2022, to evaluate the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), natural immunity due to previous infection with variants other than omicron, and hybrid immunity (previous infection and vaccination) against symptomatic omicron infection and against severe, critical, or fatal coronavirus disease 2019 (Covid-19). RESULTS: The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). The effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible (-1.1%; 95% CI, -7.1 to 4.6), but nearly all persons had received their second dose more than 6 months earlier. The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9). The effectiveness of previous infection and two doses of BNT162b2 was 55.1% (95% CI, 50.9 to 58.9), and the effectiveness of previous infection and three doses of BNT162b2 was 77.3% (95% CI, 72.4 to 81.4). Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection. Similar results were observed in analyses of effectiveness against BA.1 infection and of vaccination with mRNA-1273. CONCLUSIONS: No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , COVID-19 , Inmunidad Innata , Inmunización , SARS-CoV-2 , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/uso terapéutico , Vacuna BNT162/inmunología , Vacuna BNT162/uso terapéutico , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Estudios de Casos y Controles , Humanos , Inmunidad Innata/inmunología , Inmunización Secundaria , Recurrencia , SARS-CoV-2/inmunología , VacunaciónRESUMEN
BACKGROUND: Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear. METHODS: We conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19-related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022. The association of booster status with infection was estimated with the use of Cox proportional-hazards regression models. RESULTS: In a population of 2,239,193 persons who had received at least two doses of BNT162b2 or mRNA-1273 vaccine, those who had also received a booster were matched with persons who had not received a booster. Among the BNT162b2-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 2.4% (95% confidence interval [CI], 2.3 to 2.5) in the booster cohort and 4.5% (95% CI, 4.3 to 4.6) in the nonbooster cohort after 35 days of follow-up. Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19-related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1). Among the mRNA-1273-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 1.0% (95% CI, 0.9 to 1.2) in the booster cohort and 1.9% (95% CI, 1.8 to 2.1) in the nonbooster cohort after 35 days; booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273-vaccinated cohorts. CONCLUSIONS: The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19-related hospitalization and death. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna BNT162/inmunología , COVID-19 , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios de Cohortes , Humanos , Inmunización Secundaria , Inmunogenicidad Vacunal , Qatar/epidemiología , ARN Mensajero , Estudios Retrospectivos , SARS-CoV-2 , Eficacia de las Vacunas , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
BACKGROUND: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear. METHODS: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021. RESULTS: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months. CONCLUSIONS: BNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.).
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Vacuna BNT162/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Eficacia de las Vacunas , Vacuna nCoV-2019 mRNA-1273 , Adulto , Anciano , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/mortalidad , Vacunas contra la COVID-19 , Estudios de Casos y Controles , Femenino , Humanos , Inmunización Secundaria , Masculino , Persona de Mediana Edad , Qatar/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , Vacuna BNT162 , SARS-CoV-2 , Sueroterapia para COVID-19 , Anticuerpos Neutralizantes , Citotoxicidad Celular Dependiente de Anticuerpos , Anticuerpos Antivirales , VacunaciónRESUMEN
The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection ($P{E}_S$) by novel SARS-CoV-2 variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case-control study design to derive $P{E}_S$. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for $P{E}_S$ and true value of $P{E}_S$ was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of $P{E}_S$ and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated $P{E}_S$, but the underestimate was considerable only when >50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated $P{E}_S$. The test-negative design was applied to national-level testing data in Qatar to estimate $P{E}_S$ for SARS-CoV-2. $P{E}_S$ against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI: 93.6-98.6) and 85.5% (95% CI: 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.
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BACKGROUND: We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to used rotavirus vaccines. METHODS: Rotavirus-positive samples (n = 231) were collected and analyzed. The VP7 and VP4 genes were sequenced and analyzed against the rotavirus vaccine strains. Antigenic variations were illustrated on the three-dimensional models of surface proteins. RESULTS: In all, 59.7% of the hospitalized children were vaccinated, of which only 57.2% received two doses. There were no significant differences between the vaccinated and non-vaccinated groups in terms of clinical outcome. The G3 was the dominant genotype (40%) regardless of vaccination status. Several amino acid changes were identified in the VP7 and VP4 antigenic epitopes compared to the licensed vaccines. The highest variability was seen in the G3 (6 substitutions) and P[4] (11 substitutions) genotypes in comparison to RotaTeq®. In comparison to Rotarix®, G1 strains possessed three amino acid changes in 7-1a and 7-2 epitopes while P[8] strains possessed five amino acid changes in 8-1 and 8-3 epitopes. CONCLUSIONS: The current use of Rotarix® vaccine might not be effective in preventing the infection due to the higher numbers of G3-associated cases. The wide range of mutations in the antigenic epitopes compared to vaccine strains may compromise the vaccine's effectiveness. IMPACT: The reduced rotavirus vaccine effectiveness necessitate regular evaluation of the vaccine content to ensure optimal protection. We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to the Rotarix vaccine strain that is used in Qatar. The study highlight the importance for regular monitoring of emerging rotavirus variants and their impact on vaccine effectiveness in young children.
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Infecciones por Rotavirus , Rotavirus , Humanos , Niño , Lactante , Preescolar , Rotavirus/genética , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Qatar , Antígenos Virales/genética , Antígenos Virales/química , Proteínas de la Cápside/genética , Genotipo , Epítopos/genéticaRESUMEN
SHORT SUMMARY: Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to <18 years also have less severe disease than those <6 years old. BACKGROUND: There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant. METHODS: We identified children and adolescents <18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta and propensity score-matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. Primary outcome was disease severity, determined by hospital admission, admission to the intensive care unit (ICU), or mechanical ventilation within 14 days of diagnosis, or death within 28 days. RESULTS: Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score-matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P < .001). Omicron variant infection (vs Delta) was associated with significantly lower odds of moderate or severe/critical disease (adjusted odds ratio [AOR], 0.12; 95% confidence interval [CI], .07-.18). Those aged 6-11 and 12 to <18 years had lower odds of developing moderate or severe/critical disease compared with those younger than age 6 years (aOR, 0.47; 95% CI, .33-.66 for 6-11 year olds; aOR, 0.45; 95% CI, .21-.94 for 12 to <18 year olds). CONCLUSIONS: Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to <18 years of age also have less severe disease than those <6 years old.
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COVID-19 , Adolescente , Niño , Humanos , Respiración Artificial , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Beta (B.1.351)-variant coronavirus disease 2019 (COVID-19) disease was investigated in Qatar. Compared with the Alpha (B.1.1.7) variant, odds (95% confidence interval) of progressing to severe disease, critical disease, and COVID-19-related death were 1.24-fold (1.11-1.39), 1.49-fold (1.13-1.97), and 1.57-fold (1.03-2.43) higher, respectively, for the Beta variant.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genéticaRESUMEN
Importance: The effect of prior SARS-CoV-2 infection on vaccine protection remains poorly understood. Objective: To assess protection from SARS-CoV-2 breakthrough infection after mRNA vaccination among persons with vs without prior SARS-CoV-2 infection. Design, Setting, and Participants: Matched-cohort studies in Qatar for the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines. A total of 1 531 736 individuals vaccinated with either vaccine between December 21, 2020, and September 19, 2021, were followed up beginning 14 days after receiving the second dose until September 19, 2021. Exposures: Prior SARS-CoV-2 infection and COVID-19 vaccination. Main Outcomes and Measures: Incident SARS-CoV-2 infection, defined as a polymerase chain reaction (PCR)-positive nasopharyngeal swab regardless of reason for PCR testing or presence of symptoms. Cumulative incidence was calculated using the Kaplan-Meier estimator method. Results: The BNT162b2-vaccinated cohort comprised 99 226 individuals with and 290 432 matched individuals without prior PCR-confirmed infection (median age, 37 years; 68% male). The mRNA-1273-vaccinated cohort comprised 58 096 individuals with and 169 514 matched individuals without prior PCR-confirmed infection (median age, 36 years; 73% male). Among BNT162b2-vaccinated persons, 159 reinfections occurred in those with and 2509 in those without prior infection 14 days or more after dose 2. Among mRNA-1273-vaccinated persons, 43 reinfections occurred in those with and 368 infections in those without prior infection. Cumulative infection incidence among BNT162b2-vaccinated individuals was an estimated 0.15% (95% CI, 0.12%-0.18%) in those with and 0.83% (95% CI, 0.79%-0.87%) in those without prior infection at 120 days of follow-up (adjusted hazard ratio for breakthrough infection with prior infection, 0.18 [95% CI, 0.15-0.21]; P < .001). Cumulative infection incidence among mRNA-1273-vaccinated individuals was an estimated 0.11% (95% CI, 0.08%-0.15%) in those with and 0.35% (95% CI, 0.32%-0.40%) in those without prior infection at 120 days of follow-up (adjusted hazard ratio, 0.35 [95% CI, 0.25-0.48]; P < .001). Vaccinated individuals with prior infection 6 months or more before dose 1 had statistically significantly lower risk for breakthrough infection than those vaccinated less than 6 months before dose 1 (adjusted hazard ratio, 0.62 [95% CI, 0.42-0.92]; P = .02 for BNT162b2 and 0.40 [95% CI, 0.18-0.91]; P = .03 for mRNA-1273 vaccination). Conclusions and Relevance: Prior SARS-CoV-2 infection was associated with a statistically significantly lower risk for breakthrough infection among individuals receiving the BNT162b2 or mRNA-1273 vaccines in Qatar between December 21, 2020, and September 19, 2021. The observational study design precludes direct comparisons of infection risk between the 2 vaccines.
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Vacunas contra la COVID-19 , COVID-19/complicaciones , Vacuna nCoV-2019 mRNA-1273 , Adulto , Anciano , Vacuna BNT162 , COVID-19/diagnóstico , COVID-19/prevención & control , Prueba de Ácido Nucleico para COVID-19 , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , QatarRESUMEN
BACKGROUND: Influenza surveillance is necessary for detection of emerging variants of epidemiologic and clinical significance. This study describes the epidemiology of influenza types A and B, and molecular characteristics of surface glycoproteins (hemagglutinin [HA] and neuraminidase [NA]) of influenza A subtypes: pH1N1 and H3N2 circulated in Arabian Gulf, Levant and North Africa regions during 2009-2017. METHODS: Analysis of phylogenetics and evolution of HA and NA genes was done using full HA and NA sequences (n = 1229) downloaded from Influenza Research Database (IRD). RESULTS: In total, 130,354 influenza positive cases were reported to WHO during study period. Of these, 50.8% were pH1N1 positive, 15.9% were H3N2 positives and 17.2% were influenza B positive. With few exceptions, all three regions were showing the typical seasonal influenza peak similar to that reported in Northern hemisphere (December-March). However, influenza activity started earlier (October) in both Gulf and North Africa while commenced later during November in Levant countries. The molecular analysis of the HA genes (influenza A subtypes) revealed similar mutations to those reported worldwide. Generally, amino acid substitutions were most frequently found in head domain in H1N1 pandemic viruses, while localized mainly in the stem region in H3N2 viruses. Expectedly, seasons with high pH1N1 influenza activity was associated with a relatively higher number of substitutions in the head domain of the HA in pH1N1 subtype. Furthermore, nucleotide variations were lower at the antigenic sites of pH1N1 viruses compared to H3N2 viruses, which experienced higher variability at the antigenic sites, reflecting the increased immunological pressure because of longer circulation and continuous vaccine changes. Analysis of NA gene of pH1N1 viruses revealed sporadic detections of oseltamivir-resistance mutation, H275Y, in 4% of reported sequences, however, none of NAI resistance mutations were found in the NA of H3N2 viruses. CONCLUSIONS: Molecular characterization of H1N1 and H3N2 viruses over 9 years revealed significant differences with regard to position and function of characterized substitutions. While pH1N1 virus substitutions were mainly found in HA head domain, H3N2 virus substitutions were mostly found in HA stem domain. Additionally, more fixed substitutions were encountered in H3N2 virus compared to larger number of non-fixed substitutions in pH1N1.
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Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Mutación , África del Norte/epidemiología , Sustitución de Aminoácidos , Evolución Molecular , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/virología , Medio Oriente/epidemiología , Neuraminidasa/genética , Filogenia , Estaciones del AñoRESUMEN
The emergence of swine-origin pandemic H1N1 (pH1N1) in 2009 invigorated extensive surveillance programs worldwide which have resulted in the deposition of large numbers of H1N1 sequences to Genbank. In the present study, we report on global evolution and dynamics of the pandemic H1N1 influenza Hemagglutinin (HA) protein in viruses isolated from three different continents (North America, Europe and Asia) during the period between April 2009 until April 2017. Close to 2000 HA full protein sequences were downloaded from the Influenza Research Database of the NCBI and analyzed using DNAStar to run an alignment, the web-based NetNglyc to predict N-Glycosylation sites and finally, the BEAST software package to calculate evolution and substitution rates. Our analysis improves upon other published papers in that we report on frequencies, dynamics and impact of HA mutations in pH1N1 viruses isolated from three continents during the past decade, as well as the evolution rate and site-specific selection pressures. Sequence based analysis demonstrated substantial changes in the HA protein over the last decade. Results showed that the HA gene is under negative selection (P value; HA= -2.253). The evolution rates varied among the three continents ranging from 2.36 × 10-3 in Europe to 3.18 × 10-3 in Asia. Mutations were detected at higher frequency and faster rate at the antigenic sites surrounding the receptor-binding domain (RBD), in particular, in the Sa and Sb sites. Mutations were either gradually accumulated to become fixed in currently circulating strains (D114N, S179N, S202T, S220T, I233T, K300E and E391K) or dynamic in terms of appearance and disappearance, both spatially and temporally (A203T, N458K and E508G). Some of the reported mutations have been shown to increase infection severity (D239G/N; globular head), enhance HA binding affinity to its receptor (S200P and S202T; RBD), or have deleterious effect on HA function (N458K and E508G; stem region). The continuous accumulation of mutations at the Sa site led to the gradual acquisition of glycosylation at residue 179 starting from 2015, which became a dominant feature in all strains isolated in the following years. In addition to sharing common amino acid substitutions (e.g. S179N in HA head and E516K in HA stem) with previous seasonal strains, the pattern of glycosylation acquisition/loss at 177 and 179 positions on the globular head, which are prominent features of immune escape, implicate that pH1N1 might follow a similar evolution trend as the SC1918 pandemic virus.
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Evolución Molecular , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , Infecciones por Orthomyxoviridae/veterinaria , Enfermedades de los Porcinos/virología , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Glicosilación , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Subtipo H1N1 del Virus de la Influenza A/química , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Mutación , Infecciones por Orthomyxoviridae/virología , Filogenia , PorcinosRESUMEN
Coronavirus Disease 2019 (COVID-19) manifestations range from mild to severe life-threatening symptoms, including death. COVID-19 susceptibility has been associated with various factors, but studies in Qatar are limited. The objective of this study was to investigate the correlation between COVID-19 susceptibility and various sociodemographic and lifestyle factors, including age, gender, body mass index, smoking status, education level, dietary patterns, supplement usage, physical activity, a history of bariatric surgery, diabetes, and hypertension. We utilized logistic regression to analyze these associations, using the data of 10,000 adult participants, aged from 18 to 79, from Qatar Biobank. In total, 10.5% (n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR] = 0.55; 95% CI: 0.44-0.68 and OR = 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction in the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥ 30 kg/m2), a history of bariatric surgery, and higher adherence to the modern dietary pattern-characterized by the consumption of foods high in saturated fat and refined carbohydrates-were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.
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Bancos de Muestras Biológicas , COVID-19 , Adulto , Humanos , COVID-19/epidemiología , Qatar/epidemiología , Estilo de Vida , Suplementos DietéticosRESUMEN
Human monkeypox is a rare viral zoonosis that was first identified in 1970; since then, this infectious disease has been marked as endemic in central and western Africa. The disease has always been considered rare and self-limiting; however, recent worldwide reports of several cases suggest otherwise. Especially with monkeypox being recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era, its spread across the globe marks a new epidemic. Currently, there is no proven treatment for human monkeypox, and questions about the necessity of developing a vaccine persist. Notably, if we are to take lessons from the COVID-19 pandemic, developing a nanomedicine-based preventative strategy might be prudent, particularly with the rapid growth of the use of nanotechnology and nanomaterials in medical research. Unfortunately, the collected data in this area is limited, dispersed, and often incomplete. Therefore, this review aims to trace all reported nanomedicine approaches made in the monkeypox area and to suggest possible directions that could be further investigated to develop a counteractive strategy against emerging and existing viruses that could diminish this epidemic and prevent it from becoming a potential pandemic, especially with the world still recovering from the COVID-19 pandemic.
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The diet-microbiome-immunity axis is one among the many arms that draw up the "we are what we intake" proclamation. As such, studies on the effect of food and beverage intake on the gut environment and microbiome and on modulating immunological responses and the host's susceptibility to pathogens are on the rise. A typical accompaniment in different sustenance we consume on daily basis is the trimethylxanthine alkaloid caffeine. Being a chief component in our regular aliment, a better understanding of the effect of caffeine containing food and beverages on our gut-microbiome-immunity axis and henceforth on our health is much needed. In this study, we shed more light on the effect of oral consumption of caffeine supplemented sugar diet on the gut environment, specifically on the gut microbiota, innate immunity and host susceptibility to pathogens using the Drosophila melanogaster model organism. Our findings reveal that the oral intake of a dose-specific caffeine containing sucrose/agarose sugar diet causes a significant alteration within the fly gut milieu demarcated by microbial dysbiosis and an elevation in the production of reactive oxygen species and expression of immune-deficiency (Imd) pathway-dependent antimicrobial peptide genes. The oral intake of caffeine containing sucrose/agarose sugar diet also renders the flies more susceptible to bacterial infection and shortens their lifespan in both infection and non-infection settings. Our findings set forth additional insight into the potentiality of diet to alter the gut milieu and highlight the importance of dietary control on health.
Asunto(s)
Drosophila melanogaster , Microbioma Gastrointestinal , Animales , Drosophila melanogaster/microbiología , Cafeína/farmacología , Longevidad , Sefarosa , SacarosaRESUMEN
BACKGROUND: Long-term effectiveness of COVID-19 mRNA boosters in populations with different previous infection histories and clinical vulnerability profiles is inadequately understood. We aimed to investigate the effectiveness of a booster (third dose) vaccination against SARS-CoV-2 infection and against severe, critical, or fatal COVID-19, relative to that of primary-series (two-dose) vaccination over a follow-up duration of 1 year. METHODS: This observational, matched, retrospective, cohort study was done on the population of Qatar in people with different immune histories and different clinical vulnerability to infection. The source of data are Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation, and death. Associations were estimated using inverse-probability-weighted Cox proportional-hazards regression models. The primary outcome of the study is the effectiveness of COVID-19 mRNA boosters against infection and against severe COVID-19. FINDINGS: Data were obtained for 2 228 686 people who had received at least two vaccine doses starting from Jan 5, 2021, of whom 658 947 (29·6%) went on to receive a third dose before data cutoff on Oct 12, 2022. There were 20 528 incident infections in the three-dose cohort and 30 771 infections in the two-dose cohort. Booster effectiveness relative to primary series was 26·2% (95% CI 23·6-28·6) against infection and 75·1% (40·2-89·6) against severe, critical, or fatal COVID-19, during 1-year follow-up after the booster. Among people clinically vulnerable to severe COVID-19, effectiveness was 34·2% (27·0-40·6) against infection and 76·6% (34·5-91·7) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 61·4% (60·2-62·6) in the first month after the booster but waned thereafter and was modest at only 15·5% (8·3-22·2) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2·75* subvariant incidence, effectiveness was progressively negative albeit with wide CIs. Similar patterns of protection were observed irrespective of previous infection status, clinical vulnerability, or type of vaccine (BNT162b2 vs mRNA-1273). INTERPRETATION: Protection against omicron infection waned after the booster, and eventually suggested a possibility for negative immune imprinting. However, boosters substantially reduced infection and severe COVID-19, particularly among individuals who were clinically vulnerable, affirming the public health value of booster vaccination. FUNDING: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core (both at Weill Cornell Medicine-Qatar), Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, and Qatar University Biomedical Research Center.