Would a SARS-CoV-2 infection disrupt the blood-brain barrier, leaving the brain more vulnerable to drugs taken simultaneously with the infection?

Question

According to some studies[1], there is some evidence that the virus could cross the BBB. Is that is the case, does that mean that it would weaken the barrier allowing potentially neurotoxic drugs to enter the brain. Could this happen for example if the virus downregulates p-glycoprotein which prevents the uptake of drugs?

An example of this concern is with the drug ivermectin which has gained some recent notoriety as a possible prophylactic and treatment of the infection. There is some evidence for the neurotoxicity of this drug in dogs.[2]

[1] Rhea, E. M., Logsdon, A. F., Hansen, K. M., Williams, L. M., Reed, M. J., Baumann, K. K., ... & Erickson, M. A. (2021). The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice. Nature neuroscience, 24(3), 368-378. https://doi.org/10.1038/s41593-020-00771-8 [Open Access]

[2] Merola, V. A., Khan, S., & Gwaltney-Brant, S. (2009). Ivermectin toxicosis in dogs: a retrospective study. Journal of the American Animal Hospital Association, 45(3), 106-111. https://doi.org/10.5326/0450106
Free copy at http://jcore-reference.highwire.org/content/45/3/106

Answer 1

The Rhea et al. article on SARS-CoV-2 suggests that the S1 protein crosses the BBB by a specific mechanism (general albumin protein does not cross at the same time), so no general disruption of the BBB is indicated (See Fig. 1 in paper). The authors also note "Based on experiments with the glycoprotein WGA, we found that brain entry of I-S1 likely involves the vesicular-dependent mechanism of adsorptive transcytosis."

Even without general BBB disruption, ivermectin can cause serious neurological issues in humans.