Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have ...developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
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•A postmortem bedside surgical procedure was developed for COVID-19 and control patients•Ciliated cells are the main target cell type for SARS-CoV-2 in the respiratory mucosa•Sustentacular cells (non-neuronal) are the main target cell type in the olfactory mucosa•No evidence for infection of olfactory sensory neurons or olfactory bulb parenchyma
Postmortem samples of respiratory and olfactory mucosa and whole olfactory bulbs are harvested immediately after the death of COVID-19 patients revealing ciliated cells and sustentacular cells but not olfactory sensory neurons as the main target cell types for SARS-CoV-2 infection and replication.
Epidermal nevus syndrome (ENS) comprises a heterogeneous group of neurocutaneous syndromes associated with the presence of epidermal nevi and variable extracutaneous manifestations. Postzygotic ...activating HRAS pathogenic variants were previously identified in nevus sebaceous (NS), keratinocytic epidermal nevus (KEN), and different ENS, including Schimmelpenning–Feuerstein–Mims and cutaneous‐skeletal‐hypophosphatasia syndrome (CSHS). Skeletal involvement in HRAS‐related ENS ranges from localized bone dysplasia in association with KEN to fractures and limb deformities in CSHS. We describe the first association of HRAS‐related ENS and auricular atresia, thereby expanding the disease spectrum with first branchial arch defects if affected by the mosaic variant. In addition, this report illustrates the first concurrent presence of verrucous EN, NS, and nevus comedonicus (NC), indicating the possibility of mosaic HRAS variation as an underlying cause of NC. Overall, this report extends the pleiotropy of conditions associated with mosaic pathogenic variants in HRAS affecting ectodermal and mesodermal progenitor cells.
HRAS‐related epidermal nevus syndromes (ENS): expansion of the spectrum with first branchial arch defects.
Although family physicians (FPs) are community-oriented primary care generalists and should be the entry point for the population’s interaction with the health system, they are underrepresented in ...research on the climate change, migration, and health(care) nexus (hereafter referred to as the nexus). Similarly, FPs can provide valuable insights into building capacity through integrating health-determining sectors for climate-resilient and migration-inclusive health systems, especially in Sub-Saharan Africa (SSA). Here, we explore FPs’ perceptions on the nexus in SSA and on intersectoral capacity building. Three focus groups conducted during the 2019 WONCA-Africa conference in Uganda were transcribed verbatim and analyzed using an inductive thematic approach. Participants’ perceived interactions related to (1) migration and climate change, (2) migration for better health and healthcare, (3) health impacts of climate change and the role of healthcare, and (4) health impacts of migration and the role of healthcare were studied. We coined these complex and reinforcing interactions as continuous feedback loops intertwined with socio-economic, institutional, and demographic context. Participants identified five intersectoral capacity-building opportunities on micro, meso, macro, and supra (international) levels: multi-dimensional and multi-layered governance structures; improving FP training and primary healthcare working conditions; health advocacy in primary healthcare; collaboration between the health sector and civil society; and more responsibilities for high-income countries. This exploratory study presents a unique and novel perspective on the nexus in SSA which contributes to interdisciplinary research agendas and FP policy responses on national, regional, and global levels.
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