SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production.

Neurological complications that occur in SARS-CoV-2 infection, such as olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, are thought to contribute to long COVID. However, in autopsies of patients who have died from COVID-19, there is normally no direct evidence that central nervous system damage is due to proliferation of SARS-CoV-2. For this reason, many aspects of the pathogenesis mechanisms of such symptoms remain unknown. Expressing SARS-CoV-2 S1 protein in the nasal cavity of mice was associated with increased apoptosis of the olfactory system and decreased intracerebral acetylcholine production. The decrease in acetylcholine production was associated with brain inflammation, malaise, depressive clinical signs, and decreased expression of the cytokine degrading factor ZFP36. Administering the cholinesterase inhibitor donepezil to the mice improved brain inflammation, malaise and depressive clinical signs. These findings could contribute to the elucidation of the pathogenesis mechanisms of neurological complications associated with COVID-19 and long COVID.

Intensive diagnostic management of coronavirus disease 2019 (COVID-19) in academic settings in Japan: challenge and future.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in Wuhan, China, and has spread globally to most countries. In Japan, the first COVID-19 patient was identified on January 15, 2020. By June 30, the total number of patients diagnosed with COVID-19 reached 18,000. The impact of molecular detection of pathogens is significant in acute-care settings where rapid and accurate diagnostic measures are critical for decisions in patient treatment and outcomes of infectious diseases. Polymerase chain reaction (PCR)-based methods, such as quantitative PCR (qPCR), are the most established gene amplification tools and have a comprehensive range of clinical applications, including detecting a variety of pathogens, even novel agents causing emerging infections. Because SARS-CoV-2 contains a single-stranded RNA genome, reverse-transcription qPCR (RT-qPCR) has been broadly employed for rapid and sensitive quantitative measurements of viral RNA copy numbers. The RT-qPCR method, however, still requires time-consuming reactions with two different enzymes in addition to isolation of RNA from patient samples, limiting the numbers of testing institutions for diagnosing SARS-CoV-2 infection. Japan is known to have performed a relatively small number of PCR tests as well as confirmed cases among developed nations; as of June 30, 2020, approximately 390,000 people in Japan had undergone PCR tests. Given the devastating impact on medical services and the scale of demand for diagnostic testing of COVID-19, it has been proposed that academic settings such as basic research departments in university/college can be engaged in diagnosing, especially in university hospitals or academic medical centers. In collaboration with established diagnostic laboratories, academic facilities can divert their function to detecting virus from patients with suspected COVID-19, adopting existing specialized expertise in virus handling, molecular work, and data analysis. This in-house testing strategy facilitates the rapid diagnosing of thousands of samples per day and reduces sample turnaround time from 1 week to less than 24 h. This review provides an overview of the general principles, diagnostic value, and limitations of COVID-19 diagnosis platforms in Japan, in particular in-house testing at academic settings.