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SARS-CoV-2 viral RNA disseminates to hamster toes and associates with localized IFN-I production: mechanistic footprints of an abortive COVID-19 infection in pandemic-associated pernio

ABSTRACT: SARS-CoV-2 viral RNA disseminates to hamster toes and associates with localized IFN-I production: mechanistic footprints of an abortive COVID-19 infection in pandemic-associated pernio

PROVIDER: PRJNA971244 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24497600_1.fastq.gz	Fastqsanger.gz
	SRR24497600_2.fastq.gz	Fastqsanger.gz
	SRR24497601_1.fastq.gz	Fastqsanger.gz
	SRR24497601_2.fastq.gz	Fastqsanger.gz
	SRR24497602_1.fastq.gz	Fastqsanger.gz

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SARS-CoV-2 viral RNA disseminates to hamster toes and associates with localized IFN-I production: mechanistic footprints of an abortive COVID-19 infection in pandemic-associated pernio

Project description:SARS-CoV-2 infection generates a systemic immune response mediated by type I interferons. Pernio is a rare cutaneous manifestation of disorders characterized by excessive IFN-I signaling. Pernio increased in incidence during the pandemic but lacks direct evidence of SARS-CoV-2. We characterized clinical pernio samples and mechanistic feasibility in a rodent model which phenocopies human SARS-CoV-2 infection. Golden hamsters infected with SARS-CoV-2 experienced rapid dissemination of viral RNA to both lungs and toes. Interferon responses at both sites coincided with detection of viral RNA, which cleared within 10 days post-infection. Live virus could not be detected at acral sites. In two cohorts of clinical biopsies of affected skin, we detected SARS-CoV-2 RNA in 20-30% of cases, plasmacytoid dendritic cell activation, and a robust IFN-I response across all samples. Our data suggest footprints from SARS-CoV-2 exposure in a subset of cases that can produce a sustained localized IFN-I response-- even in the absence of serconversion.

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Project description:Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.

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