In a case series published in the journal Headache, Jyotika Singh, DO, Henry Ford Health System, Department of Neurology, Detroit, Michigan, US, and another colleague, describe 2 instances of women with a history of migraine whose first symptom of coronavirus disease 2019 (COVID-19) was a severe persistent headache.
The first case involves a 31-year-old female, with a history of episodic migraine, whose migraine attacks typically occur once or twice a month, are unilateral, throbbing, moderate-to-severe in intensity, and associated with photophonophobia and nausea. Her headaches generally last from 2-8 hours with treatment.
However, the patient developed a moderate-to-severe daily headache that was characterised as a continuous, pounding, bilateral frontotemporal headache, moderate-to-severe in intensity, and without photophonophobia or nausea. The headache would briefly improve with ibuprofen 400 mg, but recur the next day. One week later, she developed fever, cough, severe myalgias, dyspnea, and diarrhoea, and tested positive for COVID-19.
She switched to acetaminophen without improvement, and was advised to take naproxen 440 mg twice daily as needed, as well as tizanidine 4 mg every 8 hours as needed. She decided not to take tizanidine and only took two doses of naproxen, but saw no improvement and discontinued use. Her classical COVID-19 symptoms and headache resolved 4 days after diagnosis and she did not undergo repeat testing for COVID-19.
The second case centres on a 32-year-old female with a history of chronic migraine who is currently on topiramate 50 mg nightly for prophylaxis, and sumatriptan 50 mg for abortive therapy. Her migraines typically occur 2-3 times per week and are bifrontal, throbbing in quality, severe in intensity, and associated with photophonophobia and nausea, with attacks usually lasting more than 24 hours if left untreated.
In this case, she developed a severe intractable headache one week prior to the onset of typical COVID-19 symptoms. She said the headache was more intense and persistent than usual, and not responsive to abortive therapy with sumatriptan. She took acetaminophen daily without relief.
One week later, she developed low-grade fever, myalgias, nasal congestion, anosmia, and diarrhoea, and tested positive for COVID-19. After two to three days, these symptoms resolved, but her headache persisted. Her topiramate was increased to 100 mg nightly, her sumatriptan was switched to rizatriptan, and she was started on tizanidine 4 mg every 8 hours as needed for breakthrough pain. Two days after starting this regimen, the patient’s headache resolved. Repeat COVID-19 testing via nasopharyngeal swab was performed and was negative, five weeks after initially testing positive.
According to the authors, these two cases demonstrate headache as the first symptom of COVID-19 infection in patients with a history of migraine. They added that the headache preceding typical COVID-19 symptoms was distinct from the patients’ usual migraine, “alluding to the possibility that headache related to COVID-19 is mechanistically different than migraine. It is possible that headache is a manifestation of COVID-19 CNS invasion or cytokine storm, though further data are needed.”
The authors noted that the first patient’s headache resolved with resolution of other COVID-19 symptoms, while the second patient continued to have headaches for two weeks after resolution of typical COVID-19 symptoms. Moreover, the first patient did not have migrainous features with her continuous headache, but the second did.
“Our experience with the above two cases suggests that migraine patients, particularly young healthy women wherein migraine is most prevalent, may be more disabled by COVID-19 infection compared with age-matched cohorts,” the authors said.
The authors also pointed to anecdotal evidence citing worsening of COVID-19 symptoms in young patients who received treatment with NSAIDs early in the disease, “but there is no clinical or population-data that corroborates this risk,” and they called for more study into the safety of commonly used headache treatments.
Another case series published in the Canadian Journal of Ophthalmology looks at a COVID-19 patient that initially presented with keratoconjunctivitis, the first such reported case in North America.
A 29-year-old, otherwise healthy woman presented to the emergency eye clinic with a 1-day history of right eye conjunctivitis, photophobia, and clear watery discharge from the right eye. She had returned from vacation in the Philippines during which time she swam in the ocean and hotel swimming pools. She was feeling well upon arrival back in Canada on February 29, and visited a public swimming pool the day after. Eighteen hours after returning from her trip, she developed rhinorrhea, cough, nasal congestion, and right eye conjunctivitis, and denied having any fever although she had taken over-the-counter antipyretic medication, which may have masked a mild fever.
When she first presented to the ophthalmology service on March 3, she had worsening eye-related symptoms of photophobia, a sore and swollen eyelid, and mucous discharge of the right eye. On examination, she had 20/20 visual acuity in both eyes. Anterior segment examination of the affected eye was remarkable for 1-2+ conjunctival injection, 3+ follicles, 1 small pseudodendrite in the inferior temporal cornea, and 8 small (0.2 mm) subepithelial infiltrates with overlying epithelial defects at the superior temporal limbus. Fundus examinations showed no evidence of inflammation.
The patient was started on oral valacyclovir 500 mg PO TID and moxifloxacin 1 drop QID to the right eye based on a presumed diagnosis of herpetic keratoconjunctivitis. Bloodwork was done, including a complete blood count and electrolytes, which were all within normal limits.
The patient returned to the eye clinic on March 5 due to worsening redness, pain, and irritation. A tender right preauricular node was noted. Visual acuity was measured to be 20/20 in both eyes. On slit-lamp examination, 2+ conjunctival injection was noted along with the development of numerous subepithelial infiltrates with overlying epithelial defects. The patient was continued on oral valacyclovir and moxifloxacin drops, but a presumed diagnosis of epidemic keratoconjunctivitis was given and contact precautions were suggested.
The patient was seen by ophthalmology the next day owing to persistently worsening symptoms and vision decline. Specifically, vision in the right eye was 20/40 pinhole to 20/30. A tender right preauricular lymph node was again noted, as well as cervical lymphadenopathy. Slit-lamp examination of the eye revealed follicular conjunctivitis with 2+ conjunctival injection and over 50 discrete areas of subepithelial infiltrates with overlying epithelial defects spread diffusely through the entire cornea. The patient was continued on valacyclovir. Conjunctival swabs to test for chlamydia, gonorrhea, and bacterial culture came back negative.
A nasopharyngeal swab collected on March 8 was positive for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Retrospective testing of the eye swab originally submitted for gonorrhea/chlamydia two days earlier was found to be weakly positive for the SARS-CoV-2 virus as well.
Marvi Cheema, MD, Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada, and colleagues said initial reports of COVID-19 did not cite ocular transmission as a possibility. However, the authors highlighted “numerous anecdotal reports of a red eye being the initial symptom before the onset of pneumonia… Given this, eye care professionals, most notably ophthalmologists, may be the first point of contact in the healthcare field for patients with possible COVID-19, before the onset of characteristic respiratory symptoms.”
They noted that their case report suggests “the clinical presentation can vary and fluctuate.” For example, the patient in their case study “did not present with conjunctivitis as previously reported for COVID-19 cases, but as keratoconjunctivitis. It was also apparent from the clinical examinations that the epithelial defects varied from one examination to the next and appeared as a pseudodendrite perhaps from a healing epithelial defect or possibly as a progressing subepithelial infiltrate,” they added.
“The case emphasises the importance for eyecare professionals to consider SARS-CoV-2 as the causative agent in patients presenting with viral conjunctivitis, particularly in high-risk patients with travel to areas of active transmission of the virus,” the authors concluded.