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

Jeff R GehlhausenAlicia J LittleChristine J KoMarc EmmeneggerCarolina LucasPatrick WongJon KleinPeiwen LuTianyang MaoJillian JaycoxEric Wangnull nullNelson UgwuCate MuenkerDilgash MekaelRhonda Q KleinRobert PatrignelliRichard AntayaJennifer McNiffWilliam DamskyKathy KamathJohn ShonAaron M RingInci YildirimSaad B OmerAlbert I KoAdriano AguzziAkiko Iwasak
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
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.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • coronavirus disease
  • risk factors
  • single molecule
  • flow cytometry