Головные боли, ассоциированные с COVID-19

Головная боль как является частым симптомом острого периода COVID-19, так и нередко персистирует длительное время после перенесенной инфекции. Среди всех неврологических проявлений COVID-19 головная боль является ведущим симптомом, а примерно у пятой части пациентов она может быть тяжелым дезадаптирующим расстройством. У пациента с COVID-19 может возникать новый тип головной боли или усугубляться паттерн имеющейся первичной цефалгии. В острый период инфекции у большинства пациентов цефалгия может рассматриваться как головная боль, связанная с острой вирусной инфекцией. Однако нередко рассматриваются и иные формы, такие как кашлевая головная боль, головная боль при физической активности и др. В этих случаях цефалгические проявления коррелируют  с другими симптомами COVID-19. Длительно персистирующие головные боли как один из наиболее частых и стойких симптомов постковидного синдрома чаще протекают по типу головной боли напряжения и мигрени и существенно чаще выявляются у лиц с предшествующим анамнезом цефалгии. Многообразие фенотипов головных болей при COVID-19 требует привлечения универсальных стратегий их лечения. Нестероидные противовоспалительные препараты (НПВП) являются наиболее изученными и часто используемыми в клинической практике средствами для облегчения боли, а также лихорадки и других симптомов инфекции. Длительный опыт применения НПВП в клинической практике, наличие клинических данных и результатов специальных исследований обусловливают возможность их применения у пациентов с COVID-19 и жалобами на головные боли. Тем не менее для эффективного и безопасного применения НПВП у этой категории пациентов требуется тщательный анализ современных данных их применения.

1. Liguori C., Pierantozzi M., Spanetta M., Sarmati L., Cesta N., Iannetta M. et al. Subjective neurological symptoms frequently occur in patients with SARSCoV2 infection. Brain Behav Immun. 2020;88:11–16. https://doi.org/10.1016/j.bbi.2020.05.037.

2. Sampaio Rocha-Filho P.A., Albuquerque P.M., Carvalho L.C.L.S., Dandara Pereira Gama M., Magalhães J.E. Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study. J Headache Pain. 2022;23(1):2. https://doi.org/10.1186/s10194-021-01367-8.

3. Islam M.A., Alam S.S., Kundu S., Hossan T., Kamal M.A., Cavestro C. Prevalence of Headache in Patients With Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of 14,275 Patients. Front Neurol. 2020;11:562634. https://doi.org/10.3389/fneur.2020.562634.

4. García-Azorín D., Sierra Á., Trigo J., Alberdi A., Blanco M., Calcerrada I. et al. Frequency and phenotype of headache in COVID-19: a study of 2194 patients. Sci Rep. 2021;11(1):14674. https://doi.org/10.1038/s41598-021-94220-6.

5. Bolay H., Gül A., Baykan B. COVID-19 is a Real Headache! Headache. 2020;60(7):1415–1421. https://doi.org/10.1111/head.13856.

6. Tostmann A., Bradley J., Bousema T., Yiek W.K., Holwerda M., Bleeker-Rovers C. et al. Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020. Euro Surveill. 2020;25(16):2000508. https://doi.org/10.2807/1560-7917.ES.2020.25.16.2000508.

7. Rocha-Filho P.A.S., Magalhães J.E. Headache associated with COVID-19: Frequency, characteristics and association with anosmia and ageusia. Cephalalgia. 2020;40(13):1443–1451. https://doi.org/10.1177/0333102420966770.

8. Orrù G., Bertelloni D., Diolaiuti F., Mucci F., Di Giuseppe M., Biella M. et al. Long-COVID Syndrome? A Study on the Persistence of Neurological, Psychological and Physiological Symptoms. Healthcare (Basel). 2021;9(5):575. https://doi.org/10.3390/healthcare9050575.

9. Fernández-de-Las-Peñas C., Navarro-Santana M., Gómez-Mayordomo V., Cuadrado M.L., García-Azorín D., Arendt-Nielsen L., Plaza-Manzano G. Headache as an acute and post-COVID-19 symptom in COVID-19 survivors: A meta-analysis of the current literature. Eur J Neurol. 2021;28(11):3820–3825. https://doi.org/10.1111/ene.15040.

10. Trigo J., García-Azorín D., Planchuelo-Gómez Á., Martínez-Pías E., Talavera B., Hernández-Pérez I. et al. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study. J Headache Pain. 2020;21(1):94. https://doi.org/10.1186/s10194-020-01165-8.

11. De Marinis M., Welch K.M. Headache associated with non-cephalic infections: classification and mechanisms. Cephalalgia. 1992;12(4):197–201. https://doi.org/10.1046/j.1468-2982.1992.1204197.x.

12. Amanat M., Rezaei N., Roozbeh M., Shojaei M., Tafakhori A., Zoghi A. et al. Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study. BMC Neurol. 2021;21(1):116. https://doi.org/10.1186/s12883-021-02152-5.

13. Toptan T., Aktan Ç., Başarı A., Bolay H. Case Series of Headache Characteristics in COVID-19: Headache Can Be an Isolated Symptom. Headache. 2020;60(8):1788–1792. https://doi.org/10.1111/head.13940.

14. Porta-Etessam J., Matías-Guiu J.A., González-García N., Gómez Iglesias P., Santos-Bueso E., Arriola-Villalobos P. et al. Spectrum of Headaches Associated With SARS-CoV-2 Infection: Study of Healthcare Professionals. Headache. 2020;60(8):1697–1704. https://doi.org/10.1111/head.13902.

15. López J.T., García-Azorín D., Planchuelo-Gómez Á., García-Iglesias C., Dueñas-Gutiérrez C., Guerrero Á.L. Phenotypic characterization of acute headache attributed to SARS-CoV-2: An ICHD-3 validation study on 106 hospitalized patients. Cephalalgia. 2020;40(13):1432–1442. https://doi.org/10.1177/0333102420965146.

16. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd ed. Cephalalgia. 2018;38(1):1–211. https://doi.org/10.1177/0333102417738202.

17. Caronna E., Ballvé A., Llauradó A., Gallardo V.J., Ariton D.M., Lallana S. et al. Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution. Cephalalgia. 2020;40(13):1410–1421. https://doi.org/10.1177/0333102420965157.

18. Sampaio Rocha-Filho P.A. Headache associated with COVID-19: Epidemiology, characteristics, pathophysiology, and management. Headache. 2022;62(6):650–656. https://doi.org/10.1111/head.14319.

19. Goërtz Y.M.J., Van Herck M., Delbressine J.M., Vaes A.W., Meys R., Machado F.V.C. et al. Persistent symptoms 3 months after a SARSCoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020;6(4):00542–2020. https://doi.org/10.1183/23120541.00542-2020.

20. Huang C., Huang L., Wang Y., Li X., Ren L., Gu X. et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220–232. https://doi.org/10.1016/S01406736(20)32656-8.

21. Fernández-de-Las-Peñas C., Navarro-Santana M., Gómez-Mayordomo V., Cuadrado M.L., García-Azorín D., Arendt-Nielsen L., Plaza-Manzano G. Headache as an acute and post-COVID-19 symptom in COVID-19 survivors: A meta-analysis of the current literature. Eur J Neurol. 2021;28(11):3820–3825. https://doi.org/10.1111/ene.15040.

22. Garcia-Azorin D., Layos-Romero A., Porta-Etessam J., Membrilla J.A., Caronna E., Gonzalez-Martinez A. et al. Post-COVID-19 persistent headache: A multicentric 9-months follow-up study of 905 patients. Cephalalgia. 2022;42(8):804–809. https://doi.org/10.1177/03331024211068074.

23. Fernández-de-Las-Peñas C., Gómez-Mayordomo V., Cuadrado M.L., Palacios-Ceña D., Florencio L.L., Guerrero A.L. et al. The presence of headache at onset in SARS-CoV-2 infection is associated with longterm post-COVID headache and fatigue: A case-control study. Cephalalgia. 2021;41(13):1332–1341. https://doi.org/10.1177/03331024211020404.

24. Al-Hashel J.Y., Abokalawa F., Alenzi M., Alroughani R., Ahmed S.F. Coronavirus disease-19 and headache; impact on pre-existing and characteristics of de novo: a cross-sectional study. J Headache Pain. 2021;22(1):97. https://doi.org/10.1186/s10194-021-01314-7.

25. Caronna E., Alpuente A., Torres-Ferrus M., Pozo-Rosich P. Toward a better understanding of persistent headache after mild COVID-19: Three migraine-like yet distinct scenarios. Headache. 2021;61(8):1277–1280. https://doi.org/10.1111/head.14197.

26. Szperka C.L., Ailani J., Barmherzig R., Klein B.C., Minen M.T., Halker Singh R.B., Shapiro R.E. Migraine Care in the Era of COVID-19: Clinical Pearls and Plea to Insurers. Headache. 2020;60(5):833–842. https://doi.org/10.1111/head.13810.

27. Al-Hashel J.Y., Ismail I.I. Impact of coronavirus disease 2019 (COVID-19) pandemic on patients with migraine: a web-based survey study. J Headache Pain. 2020;21(1):115. https://doi.org/10.1186/s10194-020-01183-6.

28. Magdy R., Hussein M., Ragaie C., Abdel-Hamid H.M., Khallaf A., Rizk H.I., Dahshan A. Characteristics of headache attributed to COVID-19 infection and predictors of its frequency and intensity: A cross sectional study. Cephalalgia. 2020;40(13):1422–1431. https://doi.org/10.1177/0333102420965140.

29. Li C., Li Y., Ma M., Zhang Y., Bao J., Ge W. et al. The impact of COVID-19 pandemic on headache symptoms and drug withdrawal among patients with medication overuse headache: a cross-sectional study. J Headache Pain. 2021;22(1):41. https://doi.org/10.1186/s10194-021-01256-0.

30. Straburzyński M., Nowaczewska M., Budrewicz S., Waliszewska-Prosół M. COVID-19-related headache and sinonasal inflammation: A longitudinal study analysing the role of acute rhinosinusitis and ICHD-3 classification difficulties in SARS-CoV-2 infection. Cephalalgia. 2022;42(3):218–228. https://doi.org/10.1177/03331024211040753.

31. Bolay H., Karadas Ö., Oztürk B., Sonkaya R., Tasdelen B., Bulut T.D.S. et al. HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism. J Headache Pain. 2021;22(1):94. https://doi.org/10.1186/s10194-021-01306-7.

32. Trigo J., García-Azorín D., Sierra-Mencía Á., Tamayo-Velasco Á., Martínez-Paz P., Tamayo E. et al. Cytokine and interleukin profile in patients with headache and COVID-19: A pilot, CASE-control, study on 104 patients. J Headache Pain. 2021;22(1):51. https://doi.org/10.1186/s10194-021-01268-w.

33. Messlinger K., Neuhuber W., May A. Activation of the trigeminal system as a likely target of SARS-CoV-2 may contribute to anosmia in COVID-19. Cephalalgia. 2022;42(2):176–180. https://doi.org/10.1177/03331024211036665.

34. Bergmann C.C., Lane T.E., Stohlman S.A. Coronavirus infection of the central nervous system: host-virus stand-off. Nat Rev Microbiol. 2006;4(2):121–132. https://doi.org/10.1038/nrmicro1343.

35. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052.

36. Meinhardt J., Radke J., Dittmayer C., Franz J., Thomas C., Mothes R. et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021;24(2):168–175. https://doi.org/10.1038/s41593-020-00758-5.

37. Brann D.H., Tsukahara T., Weinreb C., Lipovsek M., Van den Berge K., Gong B. et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020;6(31):eabc5801. https://doi.org/10.1126/sciadv.abc5801.

38. Schulte L.H., May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(Pt 7):1987–1993. https://doi.org/10.1093/brain/aww097.

39. Yan J., Melemedjian O.K., Price T.J., Dussor G. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6). Mol Pain. 2012;8:6. https://doi.org/10.1186/1744-8069-8-6.

40. Goadsby P.J., Edvinsson L., Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28(2):183–187. https://doi.org/10.1002/ana.410280213.

41. Boldrini M., Canoll P.D., Klein R.S. How COVID-19 Affects the Brain. JAMA Psychiatry. 2021;78(6):682–683. https://doi.org/10.1001/jamapsychiatry.2021.0500.

42. Maassen Van Den Brink A., de Vries T., Danser A.H.J. Headache medication and the COVID-19 pandemic. J Headache Pain. 2020;21(1):38. https://doi.org/10.1186/s10194-020-01106-5.

43. Arca K.N., Smith J.H., Chiang C.C., Starling A.J., Robertson C.E., Halker Singh R.B. et al. COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use. Headache. 2020;60(8):1558–1568. https://doi.org/10.1111/head.13903.

44. Gupta R., Misra A. Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infection with reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc.). Diabetes Metab Syndr. 2020;14(3):251–254. https://doi.org/10.1016/j.dsx.2020.03.012.

45. Caronna E., José Gallardo V., Alpuente A., Torres-Ferrus M., Sánchez-Mateo N.M., Viguera-Romero J. et al. Safety of anti-CGRP monoclonal antibodies in patients with migraine during the COVID-19 pandemic: Present and future implications. Neurologia (Engl Ed). 2021;36(8):611–617. https://doi.org/10.1016/j.nrl.2021.03.003.

46. Bailey E., Worthington H., Coulthard P. Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth, a Cochrane systematic review. Br Dent J. 2014;216(8):451–455. https://doi.org/10.1038/sj.bdj.2014.330.

47. Moore R.A., Derry S., Aldington D., Wiffen P.J. Single dose oral analgesics for acute postoperative pain in adults – an overview of Cochrane reviews. Cochrane Database Syst Rev. 2015;(9):CD008659. https://doi.org/10.1002/14651858.CD008659.pub3.

48. Moore R.A., Wiffen P.J., Derry S., Maguire T., Roy Y.M., Tyrrell L. Nonprescription (OTC) oral analgesics for acute pain – an overview of Cochrane reviews. Cochrane Database Syst Rev. 2015;(11):CD010794. https://doi.org/10.1002/14651858.CD010794.pub2.

49. Little P. Non-steroidal anti-inflammatory drugs and COVID-19. BMJ. 2020;368:m1185. https://doi.org/10.1136/bmj.m1185.

50. Amponsah S.K., Tagoe B., Adams I., Bugyei K.A. Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review. Front Pharmacol. 2022;13:1063246. https://doi.org/10.3389/fphar.2022.1063246.

51. Winther B., Mygind N. Potential benefits of ibuprofen in the treatment of viral respiratory infections. Inflammopharmacology. 2003;11(4):445–452. https://doi.org/10.1163/156856003322699627.

52. Rinott E., Kozer E., Shapira Y., Bar-Haim A., Youngster I. Ibuprofen use and clinical outcomes in COVID-19 patients. Clin Microbiol Infect. 2020;26(9):1259.e5–1259.e7. https://doi.org/10.1016/j.cmi.2020.06.003.

53. Lund L.C., Kristensen K.B., Reilev M., Christensen S., Thomsen R.W., Christiansen C.F. et al. Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study. PLoS Med. 2020;17(9):e1003308. https://doi.org/10.1371/journal.pmed.1003308.

54. Chandan J.S., Zemedikun D.T., Thayakaran R., Byne N., Dhalla S., Acosta-Mena D. et al. Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19. Arthritis Rheumatol. 2021;73(5):731–739. https://doi.org/10.1002/art.41593.

55. Abu Esba L.C., Alqahtani R.A., Thomas A., Shamas N., Alswaidan L., Mardawi G. Ibuprofen and NSAID Use in COVID-19 Infected Patients Is Not Associated with Worse Outcomes: A Prospective Cohort Study. Infect Dis Ther. 2021;10(1):253–268. https://doi.org/10.1007/s40121-020-00363-w.

56. Kelleni M.T. Early use of non-steroidal anti-inflammatory drugs in COVID-19 might reverse pathogenesis, prevent complications and improve clinical outcomes. Biomed Pharmacother. 2021;133:110982. https://doi.org/10.1016/j.biopha.2020.110982.

57. Kelleni M.T. Nitazoxanide/azithromycin combination for COVID-19: A suggested new protocol for early management. Pharmacol Res. 2020;157:104874. https://doi.org/10.1016/j.phrs.2020.104874.

58. Moore N., Bosco-Levy P., Thurin N., Blin P., Droz-Perroteau C. NSAIDs and COVID-19: A Systematic Review and Meta-analysis. Drug Saf. 2021;44(9):929–938. https://doi.org/10.1007/s40264-021-01089-5.