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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 119; no. 9; pp. 1 - 9
• Main Authors: Gehlhausen, Jeff R., Little, Alicia J., Ko, Christine J., Emmenegger, Marc, Lucas, Carolina, Wong, Patrick, Klein, Jon, Lu, Peiwen, Mao, Tianyang, Jaycox, Jillian, Wang, Eric, Ugwu, Nelson, Muenker, Cate, Mekael, Dilgash, Klein, Rhonda Q., Patrignelli, Robert, Antaya, Richard, McNiff, Jennifer, Damsky, William, Kamath, Kathy, Shon, John, Ring, Aaron M., Yildirim, Inci, Omer, Saad, Ko, Albert I., Aguzzi, Adriano, Iwasaki, Akiko
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01.03.2022
• Subjects: Adult; Antibodies; Antigens; Biological Sciences; Biopsy; Chilblains - epidemiology; Chilblains - immunology; Chilblains - virology; Connecticut - epidemiology; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - epidemiology; Enzyme-linked immunosorbent assay; Epitopes; Female; Humans; Immunohistochemistry; Infections; Lymphocytes; Lymphocytes T; Male; Middle Aged; Pandemics; Respiratory diseases; Retrospective Studies; SARS-CoV-2 - immunology; Serology; Severe acute respiratory syndrome coronavirus 2; T cell receptors; Titration; Viral diseases; Young Adult; Connecticut; covid toe; SARS-CoV-2; pernio; interferon; chilblain
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2122090119

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.