4.8 Article

Lack of association between pandemic chilblains and SARS-CoV-2 infection

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2122090119

Keywords

chilblain; interferon; pernio; covid toe; SARS-CoV-2

Funding

  1. Yale COVID-19 Research Resource Fund
  2. Yale Dermatology T32 Award [5T32AR007016-46]
  3. University of Zurich
  4. University Hospital of Zurich
  5. Swiss Personalized Health Network Driver Grant [2017DRI17]
  6. NOMIS Foundation
  7. European Research Council Grant ERC Prion2020 [670958]
  8. University Hospital Zurich
  9. HHMI
  10. European Research Council (ERC) [670958] Funding Source: European Research Council (ERC)

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An increased incidence of chilblains during the SARS-CoV-2 pandemic has been observed, but there is limited direct evidence linking it with viral infection. This study found that the percentage of prior SARS-CoV-2 infection in patients diagnosed with COVID toes was similar to the background seroprevalence at that time.
An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence of this relationship has been limited, however, as most cases do not have molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies. We enrolled a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2-associated skin eruptions (including 21 pandemic chilblains [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined through endpoint titration enzyme-linked immunosorbent assay and serum epitope repertoire analysis. T cell responses to SARSCoV-2 were assessed by T cell receptor sequencing and in vitro SARS-CoV-2 antigen-specific peptide stimulation assays. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and managed as covid toes during the pandemic, we find a percentage of prior SARS-CoV-2 infection (9.5%) that approximates background seroprevalence (8.5%) at the time. Immunohistochemistry studies suggest that SARS-CoV-2 staining in PC biopsies may not be from SARS-CoV-2. Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV2 seronegative abortive infections.

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