The skin is a multi-layered organ equipped with appendages (i.e. follicles and glands) critical for regulating bodily fluid retention and temperature, guarding against external stresses, and mediating touch and pain sensation 1 , 2 . Reconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge 3 – 9 . Here, we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use step-wise modulation of the TGFβ and FGF signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During 4–5 months incubation, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis, and pigmented hair follicles equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking human touch circuitry. Single-cell RNA-sequencing and direct comparison to foetal specimens suggest that skin organoids are equivalent to human facial skin in the second-trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted on nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo . We anticipate skin organoids will be foundational to future studies of human skin development, disease modelling, or reconstructive surgery.

SARS-CoV-2, and its clinical manifestation as COVID-19, is an ongoing global pandemic. Patients with COVID-19 can present with numerous otolaryngologic conditions, such as Bell palsy (BP). Bell palsy is a unilateral peripheral facial nerve palsy of sudden onset. Several case reports and series have described peripheral facial nerve palsies associated with COVID-19. 1 In addition, since the US Food and Drug Administration's (FDA) emergency use authorization of several COVID-19 vaccines, there have been media reports of BP associated with vaccination. 2 Such concerns could erode vaccine confidence and exacerbate public hesitancy to obtain a COVID-19 vaccine. We used data from a large health research network to estimate the incidence of BP in patients with COVID-19 vs individuals vaccinated against the disease.Methods | The institutional review board at Case Western Reserve University deemed this cohort study exempt from review and waived the requirement for patient informed consent because deidentified information, aggregated counts, and statistical summaries of electronic medical records were used. These data were collected from 41 health care organizations worldwide and accessed through TriNetX, a global federated research network. Queries were made on April 7, 2021, to identify patients diagnosed with COVID-19 (January 1, 2020, to December 31, 2020) with or without a diagnosis code of BP within 8 weeks of the COVID-19 diagnosis. Among these patients, we identified those with a history of BP. To account for vaccination, the queries were restricted from January 1, 2021, to March 31, 2021. Using TriNetX to evaluate BP as our outcome, we matched 63 551 non-vaccinated patients with COVID-19 to those who were vaccinated against the disease and had no history of COVID-19 infection.