Ex vivo detection of SARS CoV 2 spike protein in human hair follicles and potential link to telogen effluvium

Telogen effluvium (TE), a form of hair loss, has emerged in a subset of COVID-19 patients, typically occurring several weeks after infection. TE is characterized by premature entry of hair follicles (HFs) into the telogen phase of the hair cycle. We analyzed the expression of the viral entry factors ACE2 and TMPRSS2 in human scalp specimens. In cryosections of skin biopsies and plucked HFs, both proteins localized to the basal layer of the outer root sheath (ORS), with TMPRSS2 also present in Henle's layer of the inner root sheath (IRS). Ex vivo infection of plucked HFs with SARS-CoV-2 revealed nucleocapsid (NC) protein immunoreactivity in the ORS in two of three donors, corresponding to the K15⁺ epithelial stem/progenitor cell population. These NC⁺ cells co-expressed cleaved caspase3 (CAS3) and TUNEL, indicating apoptosis-related changes. Our findings suggest that SARS-CoV-2 nucleocapsid protein accumulates in ORS cells, potentially triggering local stress responses and apoptosis. This may provide a mechanistic link between SARS-CoV-2 infection and TE and highlights the HF as a potential, yet understudied, target organ in COVID-19.