RESUMEN
Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.
Asunto(s)
Líquido del Lavado Bronquioalveolar/microbiología , COVID-19/terapia , Respiración Artificial , SARS-CoV-2/patogenicidad , Inmunidad Adaptativa , Adulto , Anciano , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Carga Bacteriana , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/virología , COVID-19/inmunología , COVID-19/microbiología , COVID-19/mortalidad , Enfermedad Crítica , Femenino , Hospitalización , Humanos , Inmunidad Innata , Masculino , Microbiota , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Estudios Prospectivos , Sistema Respiratorio/inmunología , Sistema Respiratorio/microbiología , Sistema Respiratorio/virología , SARS-CoV-2/inmunología , Carga ViralRESUMEN
Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.
Asunto(s)
COVID-19 , Genoma Viral , Pandemias , Filogenia , SARS-CoV-2/genética , Secuenciación Completa del Genoma , COVID-19/epidemiología , COVID-19/genética , COVID-19/transmisión , Femenino , Humanos , Masculino , Ciudad de Nueva YorkRESUMEN
Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.