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

Frostbite diagnoses have increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and have been attributed to viral infection and subsequent robust antiviral immune response. As a result, providers managed these cases differently from idiopathic frostbite, which is associated with exposure to cold.

The relationship between pandemic frostbite and SARS-CoV-2 infection, however, remains unclear as most patients do not test positive for PCR or SARS-CoV-2 specific antibodies. To better understand this disconnect, we enrolled pandemic frostbite cases in a study and performed detailed immune profiling of antibody and T-cell responses. Additionally, we compared immunohistochemical staining of pandemic frostbite with prepandemic tissue. Our results do not confirm that SARS-CoV-2 is the cause of the increased incidence of frostbite.

An increased incidence of frostbite has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence for this relationship has been limited, however, as most cases lack molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies.

We recruited a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2-associated rashes (including 21 pandemic frostbite [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined by end-point titration enzyme immunoassay and serum epitope repertoire analysis.

T cell responses to SARS-CoV-2 were assessed by T cell receptor sequencing and SARS-CoV-2 antigen-specific peptide stimulation assays in vitro. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and cared for 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 frostbite; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections.