Abstract
COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.
Significance Statement
COVID-19 can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have not been assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 – and demonstrated neurological signs that including motion-related dizziness. Further, we show that CGRP signaling blockade can reduce IL-6 release and reverse long-term weight loss associated with SARS-CoV-2 infection, without rescuing either fever and/or dizziness. These findings suggest that CGRP signaling blockade can be protective in acute SARS-CoV-2 infections, and raise the possibility that it may also impact long-term outcomes of infection.
Full Text Availability
The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.