Login / Signup

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.

Daniel ButlerChristopher MozsaryCem MeydanJonathan FooxJoel RosieneAlon ShaiberDavid DankoEbrahim AfshinnekooMatthew MacKayFritz J SedlazeckNikolay A IvanovMaria SierraDiana PohleMichael ZietzUndina GisladottirVijendra RamlallEvan T SholleEdward J SchenckCraig D WestoverCiaran HassanKrista RyonBenjamin YoungChandrima BhattacharyaDianna L NgAndrea C GranadosYale A SantosVenice ServellitaScot FedermanPhyllis RuggieroArkarachai FungtammasanChen-Shan ChinNathaniel M PearsonBradley W LanghorstNathan A TannerYoungmi KimJason W ReevesTyler D HetherSarah E WarrenMichael BaileyJustyna GawrysDmitry MeleshkoDong XuMara Couto-RodriguezDorottya Nagy-SzakalJoseph BarrowsHeather WellsNiamh B O'HaraJeffrey A RosenfeldYing ChenPeter A D SteelAmos J ShemeshJenny XiangJean Thierry-MiegDanielle Thierry-MiegAngelika IftnerDaniela BezdanElizabeth SanchezThomas R CampionJohn SipleyLin CongArryn CraneyPriya VeluAri M MelnickSagi D ShapiraIman HajirasoulihaAlain C BorczukThomas IftnerMirella SalvatoreMassimo LodaLars F WestbladeMelissa CushingShixiu WuShawn E LevyCharles Y ChiuRobert E SchwartzNicholas P TatonettiHanna RennertMarcin ImielinskiChristopher E Mason
Published in: Nature communications (2021)
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.
Keyphrases