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1.	Title: “Secondary Stabbing Headache Associated with COVID-19”
2.	Key Words: COVID-19, Unilateral ice-pick cephalagia, SARS-CoA-2, Vaccine Sequela, Case report
3.	Abstract:
Although COVID-19 is mainly an acute viral illness, persistent symptoms are common. However, headache is not a frequent sequela of this disease. Furthermore, stabbing/ice-pick cephalalgia has been reported in <10% of cases of COVID-19, and recurrent forms occurring after vaccination against the disease have not been published yet. We present here an unusual short-lasting unilateral stabbing/ice-pick headache with recurrent periodicity over 10 months, which may represent a sequela of COVID-19. The cephalalgia presented in a 55-year-old male with no significant medical problems approximately four months after the acute onset of COVID-19, and recurred twice twelve days after the second dose of Covid-19 vaccination with BNT162b2 (Pfizer). This report represents a contribution to the semiological pattern of COVID-19-related cephalea.
4.	Introduction: 
Meta-analysis reveals an accumulated COVID-19 fatality rate < 1.63% worldwide contributed mostly by individuals with pre-existing conditions, such as diabetes, obesity or lung disease [1].

Although the disease is predominantly an acute viral illness, persistent symptoms such as fatigue, dyspnea, cough, arthralgia and chest pain are common. Headache is reported in < 60% of acute COVID-19 cases and also as a sequela [1].  However, persistent headaches presenting ~ 3-weeks after recovery have been described in < 20% of patients [1].  COVID-19-associated cephalalgias are most frequently chronic, bilateral and tensional-type [2]. Only < 5% show migraine-type phenotype, and ~ 2-10% are stabbing [2].  
Short-lasting unilateral stabbing/ice-pick headache associated with tearing is often idiopathic but can be associated with neoplastic (cerebral or pituitary), inflammatory (vasculitis or encephalitis) or autoimmune disease in patients that may also manifest other types of cephalalgia. Episodic stabbing headache, peaking and disappearing in < 1 minute is not well-characterized as part of COVID-19 symptomatology. 
Secondary effects of the COVID-19 vaccine are often mild, including local pain at injection-site, fatigue and headache [3]. Headaches secondary to the BioNTech (Pfizer) vaccine  have been described in around 50% of the cases [3]. To the best of our knowledge episodic recurrent headaches, as described below, have not been reported in association with COVID-19 or vaccination against it [4].
5.	Patient Information:
-De-identified patient specific information.
55-year old white Hispanic male, blood type O-positive with normal BMI (22 kg/m2).
-Primary concerns and symptoms of the patient.
	     Headache, cough, malaise and bone aches, more pronounced on lower back
                 and legs.
-Medical, family, and psychosocial history including relevant 
genetic information.
                 Not contributory.
-Relevant past interventions and their outcomes.
                 After the second headache episode, the patient received the BioNTech 
                 COVID-19 vaccine (Pfizer).
6.	Clinical Findings:  Unremarkable physical exam at time of consult.
7.	Timeline:  
March 2019: Acute COVID-19 lasting 1 week.
May 2019. Serology confirms COVID-19 infection.  PE unremarkable.
July 2019. Stabbing headache (first episode).
October 2019. Stabbing headache (second episode).
            December 2019.  First dose of BioNTech COVID-19 vaccine (Pfizer).
            January 2020 (twelve days after vaccination). Stabbing headache.
            February 2020. Normal brain MRI.
8.	Diagnostic Assessment.
Antibody testing was performed 19-days after completion of vaccination and was positive for N (15.19 units, Eclisys, Roche) and S (250 units, Eclisys, Roche) proteins. Routine CBC, comprehensive metabolic panel (CHEM20), endocrine panel, lipid panel, sexually transmitted disease panel, iron studies, vitamin B12, vitamin D, immunoglobulins (IgG, IgA and IgM), hemoglobin A1c, C-reactive protein and erythrocyte sedimentation rate were normal. Brain MRI normal.
9.	Therapeutic intervention.  None.
10.	Follow-up and Outcomes. Unremarkable.
11.	Discussion.
 Headaches are alarming and can be associated with various non-infectious and infectious diseases, including COVID-19 or vaccination against SARS-CoA-2 [3].  However, episodic stabbing headaches, mimicking trigeminal autonomic cephalgia (classically unilateral), are rare, incompletely characterized and unassociated with COVID-19 [2].  A unique post-COVID-19 transient severe cephalalgia that recurred after vaccine challenge, and persisted for 10 months is reported.  Diagnostic criteria for short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) are unmet, and he best classification is stabbing headache (International Classification of Headache Disorders/ICHD-3).  Since cephalalgia occurred before and after COVID-19 vaccination, we propose it is due to central nervous system/meningeal/trigeminal irritation related to immune response to SARS-CoA-2.  The severity of COVID-19 may be associated with host genetic factors, such as blood type.  Controversially, milder COVID-19 has been reported in association with O-positive blood type [5], as in our patient.  Further studies to analyze post-COVID-19 headaches according to blood types may be of interest.  Since prior medical history of migraines/chronic headaches, allergies, sinusitis and other predisposing factors were absent, we believe this episodic cephalalgia may represent a sequela of COVID-19, triggered by the immune response to the BioNTech vaccine or the native coronavirus.  Unfortunately, COVID-19 was suspected only retrospectively, and more precise virology/serology cannot be performed.

12.	Patient Perspective.  The patient accepted the diagnosis and is reassured by the negative work-up to rule out other causes of headache.
13.	Informed Consent. The patient consented to the publication of this case report.