In COVID-19, CVST may occur in COVID-19 due to virus-associated thrombophilia, virus-mediated hypercoagulable state, or an overzealous host immune response, as suggested by elevated hypercoagulability and inflammatory markers . Extreme elevations of d-dimer levels have been observed in many COVID-19 patients  and marked elevations in d-dimer levels have been reported in COVID-19 patients with ischemic stroke . Two studies by Varga and Ackermann et al. uncovered evidence of endotheliitis with associated intracellular viral particles in tissues of the lungs, heart, kidneys, liver, and small intestine, suggesting that SARS-CoV-2 can induce endothelial dysfunction via direct endothelial invasion. It is postulated that SARS-CoV-2 could infect endothelial cells via the angiotensin-converting enzyme 2 (ACE2) receptors present on the cell surface [9, 10]. Another possible route is through an indirect mechanism. In severe COVID-19 disease, an intense systemic inflammatory response towards the virus could result in a hyperinflammatory state otherwise known as a cytokine storm. In such a hyperinflammatory state, the release of proinflammatory cytokines such as IL-6, IL-1, TNF-α, and interferon leads to deleterious effects, including hypercoagulability, endothelial dysfunction, diffuse alveolar damage, multiorgan failure, and death [11, 12].
Incidence of CVST in COVID-19 is exceedingly rare, estimated at 4.5 per 100,000 cases (0.0045%) . Interestingly, the demographic characteristics of patients with COVID-19-associated CVST differ from non-COVID-19-associated CVST patients, as they tend to be predominantly male (56–70%) and older (42–43 years), compared to non-COVID-19 cases, which predominantly affects women in the third decade of life [13,14,15]. Furthermore, most of the COVID-19 patients affected were relatively young with few comorbidities, and a significant proportion of CVST patients displayed only mild to moderate severity of disease, indicating that COVID-19-associated hypercoagulability may be present even in mild infection .
In this patient, however, SARS-CoV-2 infection is not the sole precipitator of CVST. Hyperthyroidism can induce a hypercoagulable and hypofibrinolytic state and has been implicated as a rare predisposing factor for CVST. Retrospective studies of CVST patients in whom thyroid parameters were available found hyperthyroidism was present in 1.9–7.1% of patients [3, 4]. Previous meta-analyses found that high thyroid hormone levels, both in subclinical and overt hyperthyroidism, were associated with elevations in factors VIII, IX, X, Von Willebrand factor, and fibrinogen. In addition, a hypofibrinolytic state in hyperthyroidism may be caused by reduction of plasmin and plasmin activator, and elevation of plasminogen activator inhibitor-1, 2-antiplasmin, and thrombin activatable fibrinolysis inhibitor [16, 17]. While rare, there have been several reports of thyroid dysfunction in CVST. A previous study of 107 CVST patients in whom thyroid measurements were available found 17.8% had thyroid dysfunction . Another systematic review found 34 cases of venous thrombosis in overt hyperthyroidism, of which CVST composes 73.5% of cases .
As both hyperthyroidism and COVID-19 are capable of inducing inflammatory and hypercoagulable states to certain degrees, we postulate that COVID-19, even in mild disease, could trigger CVST by superimposing endotheliitis and inflammation on the hypercoagulable and hypofibrinolytic state induced by hyperthyroidism. Finally, we recommend that a high index of suspicion must be maintained in evaluating a COVID-19 patient with headache. Headaches account for 37.7% of neurological symptoms in COVID-19 , and are present in 25.2% of all COVID-19 cases . While previous studies found that most headaches in COVID-19 are benign [21, 22] they may also herald a serious underlying etiology, including CVST.