ABSTRACT
Phosphodiesterase 12 (PDE12) is a negative regulator of the type 1 interferon (IFN) response and here we show that PDE12 inhibitors (lead compounds 63 and 17) are associated with increased RNAseL activity, are well tolerated at the therapeutic range and inhibit, both in vitro and in vivo, the replication of several RNA viruses including hepatitis C virus (HCV), dengue virus (DENV), West Nile Virus (WNV) and SARS-CoV-2.
ABSTRACT
BackgroundThe SARS-CoV-2 virus causes a wide spectrum of disease severity. Initial manifestations include fever, dry cough, and constitutional symptoms, which may progress to respiratory disease. There may also be neurological and psychiatric manifestations, involving both the central and peripheral nervous system. MethodsWe performed a literature search of the databases PubMed, EMBASE, The Cochrane Library and Web of Science for observational studies reporting neurological, psychiatric, and neuropsychiatric effects of COVID-19. This was followed by a narrative synthesis to summarise the data and discuss neuropsychiatric associations, symptom severity, management, and recovery. FindingsThe most frequently reported neurological symptoms were ageusia, hyposmia/anosmia, dizziness, headache, and loss of consciousness. Statistically significant relationships were noted between Asian ethnicity and peripheral neuropathy (p=0.0001) and neuro-syndromic symptoms (p=0.001). ITU admission was found to have a statistically significant relationship with male sex (p=0.024). Depression and anxiety were also identified both during and after infection. The most frequent treatments used were intravenous immunoglobulins, followed by antibiotics, antivirals, and hydroxychloroquine; with mean treatment duration of 6 days. InterpretationVarious neuropsychiatric symptoms have been associated with COVID-19 infection. More studies are required to further our knowledge in the management of neurological and psychiatric symptoms during and after COVID-19 infection