The Relationship of Headache with Inflammatory Serum Parameters and Disease Severity in COVID-19 Patients

Year 2020, Volume: 22 Issue: Special Issue, 44 - 50, 30.11.2020

Nuray Bilge , Fatma Kesmez Can Handan Alay

https://doi.org/10.18678/dtfd.776731

Abstract

Aim: Most of the coronavirus disease 2019 (COVID-19) patients have respiratory symptoms; however, various neurological symptoms, such as headache, can be seen. The pathophysiological mechanism of headache in COVID-19 is unknown completely. In our study, we aimed to investigate the relationship between headache and inflammatory markers and disease severity in COVID-19 patients.
Material and Methods: Two hundred and three hospitalized patients with a polymerase chain reaction (PCR)-confirmed COVID-19 diagnosis between 15 March and 01 June 2020 were retrospectively investigated. A total of 62 patients with headache symptoms (n=31) and without headache symptoms (n=31), who were age and gender-matched, were included in the study. The demographic characteristics, inflammatory serum parameters, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP)/albumin ratio (CAR), hospitalization times, and disease severity were determined.
Results: Of the 203 COVID-19 patients, 36 (17.7%) had a headache, and it was the fourth most common symptom. Headache accompanied other symptoms in all patients. Of the patients with headache, 14 (45.2%) were female, 17 (54.8%) were male, and the mean age was 37.74±16.65 years. In our COVID-19 patients, the neutrophil count, NLR, CRP, CAR were significantly higher, and hospital stay was longer in patients with headache than those without headache (p=0.023, p=0.041, p=0.034, p=0,048 and p=0.049, respectively).
Conclusion: As a result, the increased inflammatory response may play a role in the pathogenesis of headache in COVID-19 patients. Our study is the first study that evaluated the relationship between headache symptom and inflammation in COVID-19 patients. Further research is needed on this subject.

Keywords

COVID-19, headache, neutrophil-lymphocyte ratio, C-reactive protein, albumin

Supporting Institution

NO SUPPORTING INSTITUTION

COVID-19 Hastalarında Başağrısının Enflamatuvar Serum Parametreleri ve Hastalık Şiddeti ile İlişkisi

Abstract

Amaç: Koronavirüs hastalığı 2019 (coronavirüs disease 2019, COVID-19) hastalarının çoğunun solunum semptomları vardır; ancak baş ağrısı gibi çeşitli nörolojik semptomlar da görülebilir. COVID-19'daki baş ağrısının patofizyolojik mekanizması tam olarak bilinmemektedir. Çalışmamızda COVID-19 hastalarında baş ağrısının enflamatuvar belirteçler ve hastalık şiddeti ile olan ilişkisini araştırmayı amaçladık.
Gereç ve Yöntemler: 15 Mart ve 01 Haziran 2020 tarihleri arasında polimeraz zincir reaksiyonu (polymerase chain reaction, (PCR) ile doğrulanmış COVID-19 tanısıyla hastaneye yatırılan 203 hasta retrospektif olarak incelendi. Baş ağrısı semptomu olan (n=31) ve baş ağrısı semptomu olmayan (n=31) yaş ve cinsiyet eşleştirilmiş toplam 62 hasta çalışmaya dahil edildi. Hastaların demografik özellikleri, enflamatuar serum parametreleri, nötrofil/lenfosit oranı (neutrophil-lymphocyte ratio, NLR), C-reaktif protein (C-reactive protein, CRP)/albümin oranı (CRP-albumin ratio, CAR), hastanede yatış süreleri ve hastalık şiddeti belirlendi.
Bulgular: İki yüz üç COVID-19 hastasının 36 (%17,7)'sında baş ağrısı semptomu vardı ve en sık dördüncü semptomdu. Baş ağrısı, hastaların tümünde diğer semptomlara eşlik ediyordu. Baş ağrısı olan hastaların 14 (%45,2)'ü kadın, 17 (%54,8)'si erkekti ve yaş ortalamaları 37,74±16,65 yıl idi. COVID-19 hastalarımızda baş ağrısı olanlarda baş ağrısı olmayanlara göre nötrofil sayısı, NLR, CRP, CAR anlamlı düzeyde yüksekti ve hastane yatış süreleri daha uzundu (sırasıyla, p=0,023; p=0,041; p=0,034; p=0,048 ve p=0,049).
Sonuç: Sonuç olarak, COVID-19 hastalarında baş ağrısı patogenezinde artmış enflamatuvar yanıtın rolü olabilir. Çalışmamız, COVID-19 hastalarında baş ağrısı semptomu ile inflamasyon arasındaki ilişkiyi değerlendiren ilk çalışmadır. Bu konuda daha fazla araştırmaya ihtiyaç vardır.

Keywords

COVID-19, başağrısı, nötrofil-lenfosit oranı, C-reaktif protein, albumin

References

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
• Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020;202(5):756-9.
• Rabaan AA, Al-Ahmed SH, Sah R, Tiwari R, Yatoo MI, Patel SK, et al. SARS-CoV-2/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic. Ann Clin Microbiol Antimicrob. 2020;19:40.
• Machhi J, Herskovitz J, Senan AM, Dutta D, Nath B, Oleynikov MD, et al. The natural history, pathobiology, and clinical manifestations of SARS-CoV-2 infections. J Neuroimmune Pharmacol. 2020;15(3):359-86.
• Imai Y, Kuba K, Ohto-Nakanishi T, Penninger JM. Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. Circ J. 2010;74(3):405-10.
• Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-7.
• McIntosh K, Anderson LJ. Coronaviruses, including severe acute respiratory distress syndrome (SARS)-associated coronavirus. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005. p.1990-7.
• Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20.
• Tsivgoulis G, Palaiodimou L, Katsanos AH, Caso V, Köhrmann M, Molina C, et al. Neurological manifestations and implications of COVID-19 pandemic. Ther Adv Neurol Disord. 2020;13:1756286420932036.
• Tian S, Hu N, Lou J, Chen K, Kang X, Xiang Z, et al. Characteristics of COVID-19 infection in Beijing. J Infect. 2020;80(4):401-6.
• Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J Med Virol. 2020;[Epub ahead of print]. doi: 10.1002/jmv.25781.
• Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382(23):2268-70.
• Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-90.
• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
• Borges do Nascimento IJ, Cacic N, Abdulazeem HM, von Groote TC, Jayarajah U, Weerasekara I, et al. Novel coronavirus infection (COVID-19) in humans: A scoping review and meta-analysis. J Clin Med. 2020;9(4):941.
• Zhang X, Cai H, Hu J, Lian J, Gu J, Zhang S, et al. Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings. Int J Infect Dis. 2020;94:81-7.
• Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-CoV-2) outside of Wuhan, China: Retrospective case series. BMJ. 2020;368:m606.
• Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci. 2018;12:386.
• Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
• Ear T, McDonald PP. Cytokine generation, promoter activation, and oxidant-independent NF-kappaB activation in a transfectable human neutrophilic cellular model. BMC Immunol. 2008;9:14.
• Robertson CM, Coopersmith CM. The systemic inflammatory response syndrome. Microbes Infect. 2006;8(5):1382-9.
• Ucar Karabulut K, Egercioglu TU, Uyar M, Ucar Y. The change of neutrophils/lymphocytes ratio in migraine attacks: a case-controlled study. Ann Med Surg (Lond). 2016;10:52-6.
• Yang AP, Liu JP, Tao WQ, Li HM. The diagnostic and predictive role of NLR, d-NLR, and PLR in COVID-19 patients. Int Immunopharmacol. 2020;84:106504.
• Luan YY, Yao YM. The clinical significance and potential role of C-reactive protein in chronic inflammatory and neurodegenerative diseases. Front Immunol. 2018;9:1302.
• Vanmolkot FH, de Hoon JH. Increased C-reactive protein in young adult patients with migraine. Cephalalgia. 2007;27(7):843-6.
• Kaplan M, Ates I, Akpinar MY, Yuksel M, Kuzu UB, Kacar S, et al. Predictive value of C-reactive protein/albumin ratio in acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2017;16(4):424-30.
• Yazar HO, Yazar T, Aygün A, Kaygisiz Ş, Kirbaş D. Evaluation of simple inflammatory blood parameters in patients with migraine. Ir J Med Sci. 2020;189(2):677-83.
• Bobker SM, Robbins MS. COVID-19 and headache: a primer for trainees. Headache. 2020;60(8):1806-11.
• Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med. 2002;8(2):136-42.
• Bolay H, Gül A, Baykan B. COVID-19 is a Real Headache! Headache. 2020;60(7):1415-21.
• Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
• Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL, Lazartigues E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R373-81.
• Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264-75.
• Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92(6):552-5.
• Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11(7):995-8.
• Manji H, Carr AS, Brownlee WJ, Lunn PM. Neurology in the time of COVID-19. J Neurol Neurosurg Psychiatry. 2020;91(6):568-70.
• Eliezer M, Hautefort C, Hamel AL, Verillaud B, Herman P, Houdart E, et al. Sudden and complete olfactory loss function as a possible symptoms of COVID-19. JAMA Otolaryngol Head Neck Surg. 2020;146(7):674-5.
• Hopkins C, Surda P, Kumar N. Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology. 2020;58(3):295-8.
• St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ. Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J Virol. 2004;78(16):8824-34.
• Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: Imaging features. Radiology, 2020;296(2):E119-20.
• Filatov A, Sharma P, Hindi F, Espinosa PS. Neurological complications of coronavirus disease (COVID-19): encephalopathy. Cureus. 2020;12(3):e7352.
• Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58(7):1116-20.
• Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-9.
• Cavalcanti DD, Raz E, Shapiro M, Dehkharghani S, Yaghi S, Lillemoe K, et al. Cerebral venous thrombosis associated with COVID-19. AJNR Am J Neuroradiol. 2020;41(8):1370-6.
• Al Saiegh F, Ghosh R, Leibold A, Avery MB, Schmidt RF, Theofanis T, et al. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. J Neurol Neurosurg Psychiatry. 2020;91(8):846-8.