ABSTRACT
In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.
Subject(s)
COVID-19/genetics , COVID-19/virology , SARS-CoV-2/genetics , Adult , Aged , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antiviral Agents/pharmacology , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , Drug Interactions , Female , Gene Expression Profiling , Genome, Viral , HLA Antigens/genetics , Host Microbial Interactions/drug effects , Host Microbial Interactions/genetics , Humans , Male , Middle Aged , Molecular Diagnostic Techniques , New York City/epidemiology , Nucleic Acid Amplification Techniques , Pandemics , RNA-Seq , SARS-CoV-2/classification , SARS-CoV-2/drug effects , COVID-19 Drug TreatmentABSTRACT
The rapid global spread of the novel coronavirus SARS-CoV-2 has strained healthcare and testing resources, making the identification and prioritization of individuals most at-risk a critical challenge. Recent evidence suggests blood type may affect risk of severe COVID-19. Here, we use observational healthcare data on 14,112 individuals tested for SARS-CoV-2 with known blood type in the New York Presbyterian (NYP) hospital system to assess the association between ABO and Rh blood types and infection, intubation, and death. We find slightly increased infection prevalence among non-O types. Risk of intubation was decreased among A and increased among AB and B types, compared with type O, while risk of death was increased for type AB and decreased for types A and B. We estimate Rh-negative blood type to have a protective effect for all three outcomes. Our results add to the growing body of evidence suggesting blood type may play a role in COVID-19.
Subject(s)
ABO Blood-Group System , Betacoronavirus , Coronavirus Infections/blood , Pneumonia, Viral/blood , Rh-Hr Blood-Group System , Adult , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Humans , Intubation, Intratracheal , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Prevalence , Risk Factors , SARS-CoV-2 , Survival AnalysisABSTRACT
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.