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Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.

ABSTRACT: Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy.

SUBMITTER: Lin QXX

PROVIDER: S-EPMC10796319 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.

Lin Quy Xiao Xuan QXX Rajagopalan Deepa D Gamage Akshamal M AM Tan Le Min LM Venkatesh Prasanna Nori PN Chan Wharton O Y WOY Kumar Dilip D Agrawal Ragini R Chen Yao Y Fong Siew-Wai SW Singh Amit A Sun Louisa J LJ Tan Seow-Yen SY Chai Louis Yi Ann LYA Somani Jyoti J Lee Bernett B Renia Laurent L Ng Lisa F P LFP Ramanathan Kollengode K Wang Lin-Fa LF Young Barnaby B Lye David D Singhal Amit A Prabhakar Shyam S

Nature communications 20240118 1

Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated g ...[more]

PMID: 38238298

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Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.

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Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.

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