![of potential mechanisms involved in the pathogenesis of neurological symptoms in the spectrum of long COVID. Neurological symptoms in long COVID may be attributed to two main mechanisms: viral neuro-invasion and persistent neuroinflammation. The SARS-CoV-2 virus interacts with angiotensin-converting enzyme 2 (ACE2) receptors present not only in the lungs but also in neural cells. One potential route for the virus to enter the central nervous system is through endothelial transcytosis. Notably, the brainstem harbors a significant number of ACE2 receptors, which may account for autonomic dysregulation observed in long COVID patients [46]. Furthermore, patients with neurological symptoms who have recovered from COVID-19 exhibit structural and metabolic brain abnormalities [47–49]. These findings suggest that persistent neuroactivation is a consequence of immunological overactivation triggered by upregulated expression of proinflammatory cytokines such as IFN-β, IFN-λ1, IFN-γ, IL-2, IL-6, IL-17, CXCL8, CXCL9, and CXC10. This immune response activates non-classical and intermediate monocytes, fibroblasts, and myeloid cells while also inducing a dysfunctional TH2 cytokine pool that produces CCL11. These pathways collectively result in microglia activation, leading to subcortical white matter demyelination by damaging oligodendrocytes and their precursors, as well as diminished hippocampal neurogenesis. Additionally, T-cell dysfunction and monocyte expansion may contribute to chronic inflammation and disruption of the blood-brain barrier [43]](https://www.researchgate.net/publication/376519520/figure/fig4/AS:11431281212421946@1702610520874/of-potential-mechanisms-involved-in-the-pathogenesis-of-neurological-symptoms-in-the_Q320.jpg)
December 2023
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179 Reads
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7 Citations
BMC Infectious Diseases
Background Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache syndromes. Methods We conducted a cross-sectional study in Latin America to characterize individuals with persistent headache after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify factors associated with NDPH. Participants over 18 years old who tested positive for SARS-CoV-2 infection and reported persistent headache among their symptoms completed an online survey that included demographics, past medical history, persistent headache clinical characteristics, and COVID-19 vaccination status. Based on participants’ responses, NDPH diagnostic criteria were used to group participants into NDPH and non-NDPH groups. Participant data was summarized by descriptive statistics. Student’s t and Mann–Whitney U tests were used according to the distribution of quantitative variables. For categorical variables, Pearson’s chi-square and Fisher’s exact tests were used according to the size of expected frequencies. Binomial logistic regression using the backward stepwise selection method was performed to identify factors associated with NDPH. Results Four hundred and twenty-one participants from 11 Latin American countries met the inclusion criteria. One in four participants met the NDPH diagnostic criteria. The mean age was 40 years, with most participants being female (82%). Over 90% of the participants reported having had mild/moderate COVID-19. Most participants had a history of headache before developing COVID-19 (58%), mainly migraine type (32%). The most predominant clinical characteristics in the NDPH group were occipital location, severe/unbearable intensity, burning character, and radiating pain (p < 0.05). A higher proportion of anxiety symptoms, sleep problems, myalgia, mental fog, paresthesia, nausea, sweating of the face or forehead, and ageusia or hypogeusia as concomitant symptoms were reported in participants with NDPH (p < 0.05). Palpebral edema as a concomitant symptom during the acute phase of COVID-19, occipital location, and burning character of the headache were risk factors associated with NDPH. Conclusion This is the first study in Latin America that explored the clinical spectrum of NDPH after SARS-CoV-2 infection and its associated factors. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH.