ABSTRACT
Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.
ABSTRACT
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.
Subject(s)
Autopsy/methods , COVID-19/mortality , COVID-19/virology , Olfactory Bulb/virology , Olfactory Mucosa/virology , Respiratory Mucosa/virology , Aged , Anosmia , COVID-19/physiopathology , Endoscopy/methods , Female , Glucuronosyltransferase/biosynthesis , Humans , Immunohistochemistry , In Situ Hybridization , Male , Microscopy, Fluorescence , Middle Aged , Olfaction Disorders , Olfactory Receptor Neurons/metabolism , Respiratory System , SARS-CoV-2 , SmellSubject(s)
COVID-19 , RNA, Viral/isolation & purification , SARS-CoV-2 , Transplants , Biopsy/methods , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/virology , Humans , In Situ Hybridization, Fluorescence/methods , Lung Transplantation , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Time Factors , Transplants/pathology , Transplants/virologyABSTRACT
On March 11, 2020 the World Health Organization declared COVID-19 pandemic, leading to a subsequent impact on the entire world and health care system. Since the causing Severe Acute Respiratory Syndrome Coronavirus 2 houses in the aerodigestive tract, activities in the gastrointestinal outpatient clinic and endoscopy unit should be limited to emergencies only. Health care professionals are faced with the need to perform endoscopic or endoluminal emergency procedures in patients with a confirmed positive or unknown COVID-19 status. With this report, we aim to provide recommendations and practical relevant information for gastroenterologists based on the limited amount of available data and local experience, to guarantee a high-quality patient care and adequate infection prevention in the gastroenterology clinic.