COVID-associated pernio: Mechanistic insights to an abortive, seronegative SARS-CoV-2 infection
Pediatric Dermatology
; 40(Supplement 1):30, 2023.
Artigo
em Inglês
| EMBASE | ID: covidwho-20232566
ABSTRACT
Introduction:
SARS-CoV-2 replicates primarily in the airways but generates a systemic immune response mediated by Type I interferons (IFN-I). Pernio is a rare skin manifestation of disorders characterized by excessive IFN-I signalling. Although pernio increased in incidence during the pandemic, the relationship to SARS-CoV-2 remains controversial. Because of the pivotal nature of interferons in COVID-19 outcomes, pernio offers a window to investigate the biology underlying host resiliency to SARS-CoV-2 infection. Method(s) To further assess COVID-associated pernio, we characterized clinical samples from affected patients across 4 waves of the pandemic and investigated mechanistic feasibility in a rodent model. Patients were followed longitudinally with banking of blood and tissue. Golden hamsters were mock-treated or intra-nasally infected with SARS-CoV-2 and harvested at 3-and 30-days post-infection. Result(s) In affected tissue, immunophenotyping utilizing multiplex immunohistochemistry profiled a robust IFN-1 signature characterized by plasmacytoid dendritic cell activation. Viral RNA was detectable in a subset of cases using in situ hybridization for the SARS-CoV-2 S gene transcript. Profiling of the systemic immune response did not reveal a durable type 1 interferon signature. Consistent with previous literature, antibody and T-cell specific responses to SARS-CoV-2 were not detected. Nasopharyngeal SARS-CoV-2 inoculation in hamsters resulted in rapid dissemination of viral RNA and the generation of an IFN-I response that were both detectable in the paws of infected animals. Conclusion(s) Our data support a durable local IFN signature, with direct evidence of viral SARS-CoV-2 RNA in acral skin and suggest that COVID-associated pernio results from an abortive, seronegative SARS-CoV-2 infection.
adult; animal experiment; animal model; animal tissue; cell activation; chilblain; conference abstract; controlled study; coronavirus disease 2019; feasibility study; female; genetic transcription; histopathology; human; immune response; immunohistochemistry; immunophenotyping; in situ hybridization; inoculation; male; nonhuman; pandemic; paw; plasmacytoid dendritic cell; protein fingerprinting; rodent model; Severe acute respiratory syndrome coronavirus 2; skin; Syrian hamster; T lymphocyte; endogenous compound; interferon; virus RNA
Texto completo:
Disponível
Coleções:
Bases de dados de organismos internacionais
Base de dados:
EMBASE
Tipo de estudo:
Estudo observacional
/
Estudo prognóstico
Idioma:
Inglês
Revista:
Pediatric Dermatology
Ano de publicação:
2023
Tipo de documento:
Artigo
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