No 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.

The pandemic from the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) led to hundreds of thousands of deaths, including >15,000 in New York City (NYC). This pandemic highlighted a pressing clinical and public health need for rapid, scalable diagnostics that can detect SARS-CoV-2 infection, interrogate strain evolution, and map host response in patients. To address these challenges, we designed a fast (30 minute) colorimetric test to identify SARS-CoV-2 infection and simultaneously developed a large-scale shotgun metatranscriptomic profiling platform for nasopharyngeal swabs. Both technologies were used to profile 338 clinical specimens tested for SARS-CoV-2 and 86 NYC subway samples, creating a broad molecular picture of the COVID-19 epidemic in NYC. Our results nominate a novel, NYC-enriched SARS-CoV-2 subclade, reveal specific host responses in ACE pathways, and find medication risks associated with SARS-CoV-2 infection and ACE inhibitors. Our findings have immediate applications to SARS-CoV-2 diagnostics, public health monitoring, and therapeutic development.