“…S10B ), suggesting a potential link between SARS-CoV-2 and brain disease. Moreover, a recent study showed that SARS-CoV-2 was found in olfactory brain areas of rhesus macaques at 7 days post infection ( Beckman et al, 2022 ). Combining all the information together, we thought that SARS-CoV-2 might induce brain disease via its interactome after infection of brain tissue.…”
“…S10B ), suggesting a potential link between SARS-CoV-2 and brain disease. Moreover, a recent study showed that SARS-CoV-2 was found in olfactory brain areas of rhesus macaques at 7 days post infection ( Beckman et al, 2022 ). Combining all the information together, we thought that SARS-CoV-2 might induce brain disease via its interactome after infection of brain tissue.…”
“…Long COVID is becoming a growing concern not only for adults but also for children ( 50 ). Prior studies in adult RMs have demonstrated that SARS-CoV-2 infection, most likely through the olfactory route, invades the brain and may cause neuropathology ( 51 , 52 ). Accordingly, currently ongoing studies are analyzing the brains of the RMs in this study to explore whether the reduced viral replication in the respiratory tract of immunized animals translates into protection against such neuropathology.…”
The U.S. Food and Drug Administration only gave emergency-use-authorization of the BNT162b2 and the mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet, questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3 M-052, a synthetic toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3 M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOC), as well as T cell responses, persisted for 12 months. At one year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched non-vaccinated controls intranasally and intratracheally with a high-dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3 M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. Notably, the observed efficacy of both vaccines one year after vaccination supports the implementation of an early life SARS-CoV-2 vaccine.
“… Route of entry Anatomical site of entry Findings suggesting entry through the route Reference Suggested pathway to ANS invasion Neuronal Olfactory nerve Autopsy of patients with COVID-19 showed viral RNA of SARS-CoV-2 in the olfactory mucosa and olfactory bulb. Spike protein was colocalized with neuronal cells In macaques, SARS-CoV-2 was detected in the olfactory cortex preferentially in neurons Meinhardt et al, 2021 Beckman et al, 2022 Olfactory epithelium → olfactory nerve → olfactory cortex → MFB → brainstem Ocular nerve In patients with COVID-19, SARS-CoV-2 was detected in the retina Patients with COVID-19 had increased retinal nerve fiber layer thickness Casagrande et al, 2020 Burgos-Blasco et al, 2021 Retina → ocular nerve → retinohypothalamic tract → suprachiasmatic nucleus of the hypothalamus Trigeminal nerve Oral mucosa, taste buds, salivary gland, and trigeminal ganglion express ACE-2 receptors and TMPRSS2 Park et al, 2022 Nociceptors in the oral cavity → trigeminal nerve → trigeminal ganglia → trigeminal spinal nucleus caudalis in the medulla Glossopharyngeal and vagus, nerves High expression of ACE-2, NRP1, and TMPRSS2, in the vagus and the glossopharyngeal nerves Vitale-Cross et al, 2022 Taste sensory fibers in oral cavity → glossopharyngeal and vagus nerves → NTS Respiratory tract epithelium → vagus nerve → vagal ganglia → NTS and the nucleus ambiguous Hematogenous BBB Postmortem examination of a COVID-19 patient showed viral-like particles in the capillary endothelium of the frontal lobe Paniz-Mondolfi et al, 2020 Viral hijacked leukocytes or transcellular/paracellular migration across BBB → hypothalamus and brainstem CVOs High expression of ACE-2 in CVOs and PVN Ong et al, 2022 Subfornical zone, organum vasculosum, median eminence, and area postrema → PVN of hypothalamus Fig. 1 Direct invasion of the hypothalamus or the medulla by SARS-CoV-2 through the neuronal or hematogenous routes can induce autonomic dysfunction.…”
Section: Mechanisms Of Autonomic Dysfunction By Sars-cov-2mentioning
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
