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

Proc Natl Acad Sci U S A. 2022 Mar 1;119(9):e2122090119. doi: 10.1073/pnas.2122090119.

Abstract

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 SARS-CoV-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-CoV-2 seronegative abortive infections.

Keywords: SARS-CoV-2; chilblain; covid toe; interferon; pernio.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • COVID-19 / complications*
  • COVID-19 / epidemiology
  • Chilblains / epidemiology
  • Chilblains / immunology*
  • Chilblains / virology
  • Connecticut / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • SARS-CoV-2 / immunology
  • Young Adult