Lack of association between pandemic chilblains and SARS-CoV-2 infection
Jeff Gehlhausen, Alicia J. Little, Christine J. Ko, Marc Emmenegger, Carolina Lucas, Patrick Wong, Jon Klein, Peiwen Lu, Tianyang Mao, Jillian R. Jaycox, Eric W. Wang, Yale IMPACT Team, Nelson Ugwu, Cate Muenker, Dilgash Mekael, Rhonda Q. Klein, Robert Patrignelli, Richard J. Antaya, Jennifer M. McNiff, William Damsky, Kathy Kamath, John Shon, Aaron M. Ring, İnci Yıldırım, Saad B. Omer, Albert I. Ko, Adriano Aguzzi, Akiko Iwasaki, Abeer Obaid, Alice Lu-Culligan, Allison Nelson, Anderson F. Brito, Ángela Núñez, Anjelica Martin, Annie Watkins, Bertie Geng, Chaney C. Kalinich, Christina A. Harden, Codruta Todeasa, Cole Jensen, Daniel Kim, David McDonald, Denise Shepard, Edward Courchaine, Elizabeth B. White, Eric Song, Erin Silva, Eriko Kudo, Giuseppe DeIuliis, Harold Rahming, Hong‐Jai Park, Irene Matos, Jessica Nouws, Jordan Valdez, Joseph R. Fauver, Joseph K. Lim, Kadi-Ann Rose, Kelly Anastasio, Kristina Brower, Laura Glick, Lokesh Sharma, Lorenzo R. Sewanan, Lynda Knaggs, Maksym Minasyan, Maria Batsu, Mary E. Petrone, Maxine Kuang, Maura Nakahata, Melissa Campbell, Melissa Linehan, Michael H. Askenase, Michael Simonov, Mikhail Smolgovsky, Nicole Sonnert, Nida Naushad, Pavithra Vijayakumar, Rick Martinello, Rupak Datta, Ryan Handoko, Santos Bermejo, Sarah Prophet, Sean Bickerton, Sofia Velazquez, Tara Alpert, Tyler Rice, William Khoury-Hanold, Xiaohua Peng, Yexin Yang, Yiyun Cao, Yvette Strong
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.