Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.

COVID-19 can cause neurological symptoms such as fever, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. In this study, we infected two commonly used wild-type mouse lines (C57BL/6J and 129/SvEv) and a 129S calcitonin gene-related peptide (αCGRP) null-line with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including fever, dizziness, and nausea. We then evaluated whether a CGRP receptor antagonist, olcegepant, a "gepant" antagonist used in migraine treatment, could mitigate acute neuroinflammatory and neurological signs of SARS-COV-2 infection. First, we determined whether CGRP receptor antagonism provided protection from permanent weight loss in older (>18 m) C57BL/6J and 129/SvEv mice. We also observed acute fever, dizziness, and nausea in all older mice, regardless of treatment. In both wild-type mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP receptor signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic or endemic coronavirus outbreaks.IMPORTANCECoronavirus disease (COVID-19) can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infection have been hardly assessed in mouse models. In this study, we first infected two commonly used wild-type mouse lines (C57BL/6J and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological symptoms including fever and nausea. Furthermore, we showed that the migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes.

Asymptomatic shedding of HSV-1 in patients undergoing oral surgical procedures and attending for noninvasive treatment.

Oral surgery and stress can trigger and/or increase asymptomatic shedding of herpes simplex virus type-1 (HSV-1) into human saliva. In this investigation we examined the frequency of HSV-1 shedding in 32 patients undergoing an oral surgery procedure compared with 40 control patients attending for noninvasive treatment. Control patients comprised 18 migraine patients and 22 patients with temporomandibular (TMD) joint problems. Nested-PCR was carried out on oral rinses collected from each patient prior to treatment and 7 days post-treatment. Fifty-two of sixty-one seropositive patients were positive for HSV-1 DNA in one or both oral rinses. The frequencies of HSV-1 shedding for the oral surgery and control patients were 84.6% and 85.7% respectively. Seropositive patients who started shedding after treatment were significantly higher in oral surgery patients (46.2%) compared to control patients (34.3%). Shedding of HSV-1 in the oral cavity is not only increased by direct surgical trauma, but also appears to be common in migraine and TMD patients attending for general dental treatment. Thus pain or pain-induced stress as well as anxiety associated with dental treatment may also be a risk factor for asymptomatic shedding in specific seropositive patients attending for dental treatment.