Here, the authors show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, they found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, the authors found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. The authors concluded that their data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.
Krasemann S, Haferkamp U, Pfefferle S, Woo MS, Heinrich F, Schweizer M, Appelt-Menzel A, Cubukova A, Barenberg J, Leu J, Hartmann K, Thies E, Littau JL, Sepulveda-Falla D, Zhang L, Ton K, Liang Y, Matschke J, Ricklefs F, Sauvigny T, Sperhake J, Fitzek A, Gerhartl A, Brachner A, Geiger N, König EM, Bodem J, Franzenburg S, Franke A, Moese S, Müller FJ, Geisslinger G, Claussen C, Kannt A, Zaliani A, Gribbon P, Ondruschka B, Neuhaus W, Friese MA, Glatzel M, Pless O. The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2. Stem Cell Reports. 2022 Jan 3:S2213-6711(21)00650-0.
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Case series/case reports