Aim: The aim of this study is to evaluate the role of ultrasonography in diagnosis and treatment of COVID-19, the disease caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), with particular reference to the symptoms that are frequently observed in Neuro-COVID-19, a term that indicates the plethora of short- and long-term neurologic and psychiatric manifestations caused by, or associated with the disease. In a significant percentage of cases, neuro-psychiatric symptoms persist after recovery and long-term sequelae have been reported. SARS-CoV-2 can infect the brain through different routes and the damage can be direct, that is due to the virus itself, or indirect, that is associated with abnormal immune responses, inflammation, and hypoxia. Methods: In this study, the brain was studied by transcranial ultrasonography. Analysis of brain specimens obtained from autopsy demonstrated the presence of the virus in a minority of cases and this leads to hypothesize that SARS-CoV-2 may hide in sanctuary sites in the central nervous system in analogy with what observed for HIV. The existence of sanctuary sites for SARS-CoV-2 has the potential to decrease the efficacy of antiviral therapies or vaccination and may even prevent complete eradication of SARS-CoV-2 from the infected organism. Results: Transcranial ultrasonography demonstrated significant movements of the brain associated with the respiratory cycle. In 2017, a diagnostic and therapeutic procedure was proposed with the goal of identifying and treating pathogens hiding in sanctuaries that elude diagnosis and therapy. This procedure is based on clinical evaluation, diagnostic ultrasonography, therapeutic ultrasounds, and laboratory analyses. Conclusions: Here, it is demonstrated that application of transcranial ultrasonography to Neuro-COVID-19 requires a specific adaptation that takes into account brain movements synchronous with breathing as well as the sensitivity of SARS-CoV-2 to ultrasounds.