ABSTRACT
Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the {beta} strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon {lambda}1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and -synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and {beta}-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS.
ABSTRACT
The retrospective analysis of clinical data of patients suffering from COVID-19 has indicated that statin therapy, used to lower plasma cholesterol levels, is associated with a better clinical outcome. We therefore investigated the effect of statins on SARS-CoV-2 infection and found that selective statins reduced SARS-CoV-2 cell entry and inhibited high and low pathogenic coronavirus infection in human cells. A retrospective study on hospitalized patients with COVID-19 implies that reduced high density lipoprotein levels, which are typically counteracted by statin therapy, are associated with aggravated disease outcome. These results suggest that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that some statins may have a mild beneficial effect on COVID-19 outcome. Placebo controlled trials are required to clarify the role of statins in COVID-19 infected patients.
