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Das et al. Neuroimmunol Neuroinflammation 2020;7:141-9 I http://dx.doi.org/10.20517/2347-8659.2020.36 Page 147

breathing, but it is unclear which of these three different pathways offer a potential method of invasion
for the virus, and they are not necessarily mutually exclusive. The viral entry of SARS-CoV-2 may be
via circulatory in one patient and via oronasal or peripheral sensory neurons in another. Each of these
pathways warrants further investigation to determine the neurotropism of SARS-CoV-2, and how these
pathways may be exploited to treat patients in the future.

Also, it is evident that one particular approach that is under intense investigation is the development of
potential SARS-CoV-2 treatment using MSCs, which have shown neuro-regenerative properties in several
[46]
brain disorders including traumatic brain injury (TBI) . One of the issues in using MSCs in inflammatory
conditions is that MSCs undergo apoptosis or differentiation due to cytokines being released in those
inflammatory tissues. It has been reported that pretreatment of TBI animals first with an anti-inflammatory
[46]
agent followed by MSC treatments significantly increases the efficacy of MSCs . Whether a similar strategy
would be more successful in COVID-19 remains to be elucidated. Given the pace and expansiveness of the
COVID-19 super pandemic and the fact that the rebound infection may continue for several months to
years or could be a seasonal respiratory virus infection similar to influenza and respiratory syncytial virus,
it may be prudent to test these possibilities.

DECLARATIONS
Authors’ contributions
Wrote the manuscript: Das M, Penn C, Martinez T, Mayilsamy K, McGill A
Made the illustration: Penn C
Reviewed the manuscript: Wiling A, Mohapatra SS, Mohapatra S
Approved the final version of the manuscript: All authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work is partly supported by a University of South Florida Pandemic Response Research Network
funding for COVID-19 and Veterans Affairs Merit Review grant (No. BX002668) to Dr. Subhra Mohapatra,
and Research Career Scientist Awards to Dr. Subhra Mohapatra (No. IK6BX004212) and Dr. Shyam
Mohapatra (No. IK6BX003778). Though this report is based upon work supported, in part, by the
Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development,
the contents of this report do not represent the views of the Department of Veterans Affairs or the United
States Government.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.