Acute intracranial hemorrhage in 76 COVID-19 patients during the first and second pandemic waves

Biljana  Georgievski Brkić; Marjana Vukićević; Vladimir Debeljković; Ljubica  Nikčević-Krivokapić; Nataša Stanisavljević; Dejan Kostić; Filip Vitošević; Verica Jovanović; Slobodan Marinković

doi:10.2298/VSP230905065G

Biljana Georgievski Brkić Special Hospital for Cerebrovascular Diseases “Sveti Sava”, *Department of Neuroradiology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia
Marjana Vukićević University of Belgrade, Faculty of Medicine, Belgrade, Serbia; University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Vladimir Debeljković Special Hospital for Cerebrovascular Diseases “Sveti Sava”, Department of Neuroradiology, Belgrade, Serbia
Ljubica Nikčević-Krivokapić Special Hospital for Cerebrovascular Diseases “Sveti Sava”, Department of Neuroradiology, Department of Physical Therapy, Belgrade, Serbia
Nataša Stanisavljević University Hospital Medical Center “Bežanijska kosa”, Department of Hematology, Belgrade, Serbia
Dejan Kostić Military Medical Academy, Insitute of Radiology, Belgrade, Serbia; University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Filip Vitošević Special Hospital for Cerebrovascular Diseases “Sveti Sava”, Department of Neurointervetion Radiology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia
Verica Jovanović University of Belgrade, Faculty of Medicine, Institute of Public Health of Serbia “Dr. Milan Jovanović Batut”, Belgrade, Serbia
Slobodan Marinković University of Belgrade, Faculty of Medicine, Institute of Public Health of Serbia “Dr. Milan Jovanović Batut”, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP230905065G

Keywords: covid-19;, fibrin fragment d;, intracranial hemorrhage;, mortality;, risk factors;, serbia;, tomography, x-ray computed

Abstract

Background/Aim. There is limited data on the frequency of intracranial hemorrhage (ICrH) in the first wave [beta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and second wave (delta variant of SARS-CoV-2) coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to analyze the appearance of ICrH in COVID-19 patients (CP). Methods. Among 505 CP treated at the Special Hospital for Cerebrovascular Diseases “Sveti Sava” intermittently during the 2020–2021 period, ICrH was diagnosed in 76 (15.1%) patients. The available information from the medical records regarding clinical, demographic, as well as radiological data (multislice computed tomography examination of the endocranium) was collected and analyzed. Results. In the first wave, out of 308 CP, 63 (20.5%) were diagnosed with ICrH. In the second wave, out of 197 CP, ICrH was diagnosed in 13 (6.6%) patients, which was a statistically significant difference (p < 0.002). There was no statistically significant difference for the presence of hypertension (p = 0.271), diabetes mellitus (p = 0.558), and chronic obstructive pulmonary disease (p = 0.794) among CP with ICrH comparing the two waves of the pandemic. However, a statistically significant difference was proven in the frequency of patients with atrial fibrillation and anticoagulant drug therapy (p = 0.021 each). There was no statistically significant difference in the frequency of patients with fever (p = 0.637), fatigue (p = 0.587), hemiparesis (p = 0.831), respiratory symptoms (p = 0.289), and loss of consciousness (p = 0.247). D-dimer values in the second pandemic wave were statistically significantly lower (p = 0.003). The combination of ischemic stroke and ICrH was six times more common in the second wave (p = 0.003). However, cerebral parenchymal hemorrhage was two times less frequent (p = 0.001) in the second wave but with statistically higher frequencies of multifocal (23.1%) and diffuse type (36.4%) of ICrH (p = 0.007). Combined hemorrhages, as well as subarachnoid and subdural subtypes, were more common in the second wave (23.1% each). Fatal outcomes occurred in 38.1% of patients in the first wave compared to 69.2% in the second wave (p = 0.039). Conclusion. In the first pandemic wave of COVID-19, ICrH in CP was significantly more frequent and D-dimer was singled out in laboratory analyses, the values of which were statistically significantly higher in comparison with second wave. In the second wave of COVID-19, parenchymal ICrH was less frequent and multifocal and diffuse ICrH were more common in CP with ICrH. The mortality rate was very high in the second wave.

References

Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune path-ogenesis and diagnosis of COVID-19. J Pharmaceut Anal 2020; 10(2): 102–8.

Kirschenbaum D, Imbach LL, Rushing EJ, Frauenknecht KBM, Gascho D, Ineichen BV, et al. Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19. Neuropathol Appl Neurobiol 2021; 47(3): 454–9.

Thakur V, Bhola S, Thakur P, Patel SKS, Kulshrestha S, Ratho RK, et al. Waves and variants of SARS CoV 2: understanding the causes and effect of the COVID-19 catastrophe. Infection 2022; 50(2): 309–25. Erratum in: Infection 2022; 50(2): 327.

Aghagoli G, Gallo Marin B, Katchur NJ, Chaves-Sell F, Asaad WF, Murphy SA. Neurological involvement in COVID-19 and potential mechanisms: A review. Neurocrit Care 2021; 34(3): 1062–71.

Baig AM, Sanders EC. Potential neuroinvasive pathways of SARS-CoV-2: Deciphering the spectrum of neurological defi-cit seen in coronavirus disease-2019 (COVID-19). J Med Vi-rol 2020; 92(10): 1845–57.

Nannoni S, de Groot R, Bell S, Markus HS. Stroke in COVID-19: A systematic review and meta-analysis. Int J Stroke 2021; 16(2): 137–49.

Daly SR, Nguyen AV, Zhang Y, Feng D, Huang JH. The rela-tionship between COVID-19 infection and intracranial hem-orrhage: A systematic review. Brain Hemorrhages 2021; 2(4): 141–50.

Fabbri VP, Riefolo M, Lazzarotto T, Gabrielli L, Cenacchi G, Gallo C, et al. COVID-19 and the brain: The neuropathologi-cal Italian experience on 33 adult autopsies. Biomolecules 2022; 12(5): 629.

Leasure AC, Khan YM, Iyer R, Elkind MSV, Sansing LH, Fal-cone GJ, et al. Intracerebral hemorrhage in patients with COVID-19: An analysis from the COVID-19 cardiovascular disease registry. Stroke 2021; 52(7): e321–3.

Beyrouti R, Best JG, Chandratheva A, Perry RJ, Werring DJ. Characteristics of intracerebral hemorrhage associated with COVID-19: a systematic review and pooled analysis of indi-vidual patient and aggregate data. J Neurol 2021; 268(9): 3105–15.

Margos NP, Meintanopoulos AS, Filioglou D, Ellul J. Intracerebral hemorrhage in COVID-19: A narrative review. J Clin Neuro-sci 2021; 89: 271–8.

Qureshi AI, Baskett WI, Huang W, Myers D, Lobanova I, Ishfaq MF, et al. Intracerebral hemorrhage and coronavirus disease 2019 in a cohort of 282,718 hospitalized patients. Neurocrit Care 2022; 36(1): 259–65.

Qureshi AI, Baskett WI, Huang W, Shyu D, Myers D, Lobanova I, et al. Subarachnoid hemorrhage and COVID-19: An analysis of 282,718 patients. World Neurosurg 2021; 151: e615–20.

Cezar-Junior AB, Faquini IV, Silva JLJ, de Carvalho Junior EV, Lemos LEAS, Freire Filho JBM, et al. Subarachnoid hemor-rhage and COVID-19. Association or coincidence? Medicine (Baltimore) 2020; 99(51): e23862.

Ladopoulos T, Zand R, Shahjouei S, Chang JJ, Motte J, Charles James J, et al. COVID-19: neuroimaging features of a pandem-ic. J Neuroimaging 2021; 31(2): 228–43.

Beretta S, Iannuzzi F, Diamanti S, Bianchi E, D'Urbano L, Elisa C, et al. Neurovascular and infectious disease phenotype of acute stroke patients with and without COVID-19. Neurol Sci 2022; 43(8): 4619–25.

Ravindra VM, Grandhi R, Delic A, Hohmann S, Shippey E, Tirschwell D, et al. Impact of COVID-19 on the hospitaliza-tion, treatment, and outcomes of intracerebral and subarach-noid hemorrhage in the United States. PLoS One 2021; 16(4): e0248728.

Freeman A, Watson A, O’Regan P, Wysocki O, Burke H, Freitas A, et al. Wave comparisons of clinical characteristics and out-comes of COVID-19 admissions - Exploring the impact of treatment and strain dynamics. J Clin Virol 2022; 146: 105031.

Rahman FI, Ether SA, Islam R. The “Delta Plus” COVID-19 variant has evolved to become the next potential variant of concern: mutation history and measures of prevention. J Basic Clin Physiol Pharmacol 2022; 33(1): 109–12.

Altschul DJ, Unda SR, de La Garza Ramos R, Zampolin R, Ben-ton J, Holland R, et al. Hemorrhagic presentations of COVID-19: Risk factors for mortality. Clin Neurol Neurosurg 2020; 198: 106112.

Dhamoon MS, Thaler A, Gururangan K, Kohli A, Sisniega D, Wheelwright D, et al. Acute cerebrovascular events with COVID-19 infection. Stroke 2021; 52(1): 48–56.

Pavlov V, Beylerli O, Gareev I, Torres Solis LF, Solís Herrera A, Aliev G. COVID-19-related intracerebral hemorrhage. Front Aging Neurosci 2020; 12: 600172.

Siegler JE, Cardona P, Arenillas JF, Talavera B, Guillen AN, Chavarría-Miranda A, et al. Cerebrovascular events and out-comes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry. Int J Stroke 2021; 16(4): 437–47.

Greenway MRF, Erben Y, Huang JF, Siegel JL, Lamb CJ, Badi MK, et al. Yield of head imaging in ambulatory and hospital-ized patients with SARS-CoV-2: A multi-center study of 8675 patients. Neurohospitalist 2021; 11(3): 221–8.

Sangalli D, Martinelli-Boneschi F, Versino M, Colombo I, Ciccone A, Beretta S, et al. Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy. J Neurol Sci 2021; 426: 117479.

Cucchiara B. Invited commentary on intracerebral hemorrhage in COVID-19 patients with pulmonary failure: A propensity Score-Matched Registry Study. Neurocrit Care 2021; 34(3): 720–1.

Shakil SS, Emmons-Bell S, Rutan C, Walchok J, Navi B, Sharma R, et al. Stroke among patients hospitalized with COVID-19: Results from the American Heart Association COVID-19 Cardiovascular Disease Registry. Stroke 2022; 53(3): 800–7.

Shahjouei S, Naderi S, Li J, Khan A, Chaudhary D, Farahmand G, et al. Risk of stroke in hospitalized SARS-CoV-2 infected pa-tients: A multinational study. EBioMedicine 2020; 59: 102939.

Cheruiyot I, Sehmi P, Ominde B, Bundi P, Mislani M, Ngure B, et al. Intracranial hemorrhage in coronavirus disease 2019 (COVID-19) patients. Neurol Sci 2021; 42(1): 25–33.

Kvernland A, Kumar A, Yaghi S, Raz E, Frontera J, Lewis A, et al. Anticoagulation use and hemorrhagic stroke in SARS-CoV-2 patients treated at a New York Healthcare System. Neu-rocrit Care 2021; 34(3): 748–59.

Hernández-Fernández F, Sandoval Valencia H, Barbella-Aponte RA, Collado-Jiménez R, Ayo-Martín Ó, Barrena C, et al. Cere-brovascular disease in patients with COVID-19: neuroimag-ing, histological and clinical description. Brain 2020; 143(10): 3089–103.

Fuentes B, Alonso de Leciñana M, Rigual R, García-Madrona S, Díaz-Otero F, Aguirre C, et al. Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network. Eur J Neurol 2021; 28(12): 4078–89.

Jassat W, Mudara C, Ozougwu L, Tempia S, Blumberg L, Davies MA, et al. Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study. Lancet Glob Health 2021; 9(9): e1216–25.

Richter D, Eyding J, Weber R, Bartig D, Grau A, Hacke W, et al. A full year of the COVID-19 pandemic with two infection waves and its impact on ischemic stroke patient care in Ger-many. Eur J Neurol 2022; 29(1): 105–13.

Yamagami H, Ohara N, Imamura H, Sakai N, Hirano T, Hash-imoto Y, et al. Abstract TMP23: Impact of Covid-19 on num-ber of acute stroke patients in Japan: A nationwide survey in primary stroke centers. Stroke 2022; 53(Suppl 1): ATMP23.

Abbas R, Naamani KE, Sweid A, Schaefer JW, Bekelis K, Sourour N, et al. Intracranial hemorrhage in patients with Coronavirus Disease 2019 (COVID-19): A case series. World Neurosurg 2021; 154: e473–80.

Melmed KR, Cao M, Dogra S, Zhang R, Yaghi S, Lewis A, et al. Risk factors for intracerebral hemorrhage in patients with COVID-19. J Thromb Thrombolysis 2021; 51(4): 953–60.

Benger M, Williams O, Siddiqui J, Sztriha L. Intracerebral haemorrhage and COVID-19: Clinical characteristics from a case series. Brain Behav Immun 2020; 88: 940–4.

Berikol G, Berikol GB, Dogan H. Retrospective analysis of in-tracranial hemorrhages in the COVID-19 pandemic. Turk Neurosurg 2021; 31(5): 763–70.

Dong S, Liu P, Luo Y, Cui Y, Song L, Chen Y. Pathophysiology of SARS-Cov-2 infection in patients with intracerebral hem-orrhage. Aging (Albany NY) 2020; 12(13): 13791–802.

Motoie R, Akai M, Kitahara T, Imamura H, Tanabe T, Sarazawa K, et al. Coronavirus disease 2019 complicated by multiple simultaneous intracerebral hemorrhages. Intern Med 2020; 59(20): 2597–600.

Wang H, Tang X, Fan H, Luo Y, Song Y, Xu Y, et al. Potential mechanisms of hemorrhagic stroke in elderly COVID-19 pa-tients. Aging (Albany NY) 2020; 12(11): 10022–34.

Daci R, Kennelly M, Ferris A, Azeem MU, Johnson MD, Hamzei-Sichani F, et al. Bilateral basal ganglia hemorrhage in a patient with confirmed COVID-19. AJNR Am J Neuroradiol 2020; 41(10): 1797–9.

Flores G, Kumar JI, Pressman E, Sack J, Alikhani P. Spontane-ous brainstem hemorrhagic stroke in the setting of novel coronavirus disease 2019 – A case report. Cureus 2020; 12(10): e10809.

Brunssen A, Rücker V, Heuschmann P, Held J, Hermanek P, Berlis A, et al. Stroke care during the COVID-19 pandemic: Case numbers, treatments, and mortality in two large German stroke registries. Front Neurol 2022; 13: 924271.

Yoshimoto T, Yamagami H, Sakai N, Toyoda K, Hashimoto Y, Hirano T, et al. Impact of COVID-19 on the volume of acute stroke admissions: A nationwide survey in Japan. Neurol Med Chir (Tokyo) 2022; 62(8): 369–76.

Nguyen TN, Qureshi MM, Klein P, Yamagami H, Mikulik R, Etminan N, et al. Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up. J Neu-rol Neurosurg Psychiat 2022; 93(10): 1028–38.

Nawabi J, Morotti A, Wildgruber M, Boulouis G, Kraehling H, Schlunk F, et al. Clinical and imaging characteristics in patients with SARS-CoV-2 infection and acute intracranial hemor-rhage. J Clin Med 2020; 9(8): 2543.

Fan H, Tang X, Song Y, Liu P, Chen Y. Influence of COVID-19 on cerebrovascular disease and its possible mechanism. Neuropsychiatr Dis Treat 2020; 16: 1359–67.

Yang W, Shaman J. COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant and implications for vaccina-tion. J R Soc Interface 2022; 19(191): 20210900.