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1.
Nat Commun ; 11(1): 2750, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: covidwho-680538

RESUMEN

Influenza viruses annually kill 290,000-650,000 people worldwide. Antivirals can reduce death tolls. Baloxavir, the recently approved influenza antiviral, inhibits initiation of viral mRNA synthesis, whereas oseltamivir, an older drug, inhibits release of virus progeny. Baloxavir blocks virus replication more rapidly and completely than oseltamivir, reducing the duration of infectiousness. Hence, early baloxavir treatment may indirectly prevent transmission. Here, we estimate impacts of ramping up and accelerating baloxavir treatment on population-level incidence using a new model that links viral load dynamics from clinical trial data to between-host transmission. We estimate that ~22 million infections and >6,000 deaths would have been averted in the 2017-2018 epidemic season by administering baloxavir to 30% of infected cases within 48 h after symptom onset. Treatment within 24 h would almost double the impact. Consequently, scaling up early baloxavir treatment would substantially reduce influenza morbidity and mortality every year. The development of antivirals against the SARS-CoV2 virus that function like baloxavir might similarly curtail transmission and save lives.


Asunto(s)
Antivirales/uso terapéutico , Epidemias , Gripe Humana/tratamiento farmacológico , Orthomyxoviridae/efectos de los fármacos , Oxazinas/uso terapéutico , Piridinas/uso terapéutico , Tiepinas/uso terapéutico , Triazinas/uso terapéutico , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , COVID-19 , Proliferación Celular , Infecciones por Coronavirus/tratamiento farmacológico , Dibenzotiepinas , Humanos , Gripe Humana/virología , Morfolinas , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Oxazinas/farmacología , Pandemias , Neumonía Viral/tratamiento farmacológico , Salud Pública , Piridinas/farmacología , Piridonas , ARN Mensajero/metabolismo , SARS-CoV-2 , Estaciones del Año , Tiepinas/farmacología , Triazinas/farmacología , Carga Viral , Replicación Viral/efectos de los fármacos
2.
EClinicalMedicine ; 26: 100479, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-710599

RESUMEN

BACKGROUND: Pandemic SARS-CoV-2 was first reported in Wuhan, China on December 31, 2019. Twenty-one days later, the US identified its first case--a man who had traveled from Wuhan to the state of Washington. Recent studies in the Wuhan and Seattle metropolitan areas retrospectively tested samples taken from patients with COVID-like symptoms. In the Wuhan study, there were 4 SARS-CoV-2 positives and 7 influenza positives out of 26 adults outpatients who sought care for influenza-like-illness at two central hospitals prior to January 12, 2020. The Seattle study reported 25 SARS-CoV-2 positives and 442 influenza positives out of 2353 children and adults who reported acute respiratory illness prior to March 9, 2020. Here, we use these findings to extrapolate the early prevalence of symptomatic COVID-19 in Wuhan and Seattle. METHODS: For each city, we estimate the ratio of COVID-19 to influenza infections from the retrospective testing data and estimate the age-specific prevalence of influenza from surveillance reports during the same time period. Combining these, we approximate the total number of symptomatic COVID-19 infections. FINDINGS: In Wuhan, there were an estimated 1386 [95% CrI: 420-3793] symptomatic cases over 30 of COVID-19 between December 30, 2019 and January 12, 2020. In Seattle, we estimate that 2268 [95% CrI: 498, 6069] children under 18 and 4367 [95% CrI: 2776, 6526] adults were symptomatically infected between February 24 and March 9, 2020. We also find that the initial pandemic wave in Wuhan likely originated with a single infected case who developed symptoms sometime between October 26 and December 13, 2019; in Seattle, the seeding likely occurred between December 25, 2019 and January 15, 2020. INTERPRETATION: The spread of COVID-19 in Wuhan and Seattle was far more extensive than initially reported. The virus likely spread for months in Wuhan before the lockdown. Given that COVID-19 appears to be overwhelmingly mild in children, our high estimate for symptomatic pediatric cases in Seattle suggests that there may have been thousands more mild cases at the time.

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