Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19

Adrian Scutelnic¹, Anita van de Munckhof², Angel T Miraclin³, Sanjith Aaron³, Sajid Hameed⁴, Mohammad Wasay⁴, Oxana Grosu⁵, Katarzyna Krzywicka², Mayte Sánchez van Kammen², Erik Lindgren^{6

7}, Tiago Moreira^{8

9}, Roberto Acampora¹⁰, Alberto Negro¹⁰, Theodoros Karapanayiotides¹¹, Shadi Yaghi¹², Anna Revert¹³, Elisa Cuadrado Godia¹³, Sebastian Garcia-Madrona¹⁴, Paolino La Spina¹⁵, Francesco Grillo¹⁵, Fabrizio Giammello¹⁵, Thanh N Nguyen^{16

17}, Mohamad Abdalkader¹⁷, Alina Buture¹⁸, Maria Sofia Cotelli¹⁹, Nicolas Raposo²⁰, Georgios Tsivgoulis²¹, Paolo Candelaresi²², Antonio Ciacciarelli^{23

24}, Joshua Mbroh²⁵, Tatiana Batenkova²⁶, Pasquale Scoppettuolo²⁷, Marialuisa Zedde²⁸, Rosario Pascarella²⁹, Kateryna Antonenko¹, Espen S Kristoffersen³⁰, Johanna A Kremer Hovinga³¹, Katarina Jood^{6

7}, Diana Aguiar de Sousa³², Sven Poli^{25

33}, Turgut Tatlisumak^{6

7}, Jukka Putaala³⁴, Jonathan M Coutinho², José M Ferro³⁵, Marcel Arnold¹, Mirjam R Heldner¹

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands.
³ Department of Neurosciences, Christian Medical College Hospital, Vellore, Tamil Nadu, India.
⁴ Aga Khan University, Karachi, Pakistan.
⁵ Institute of Neurology and Neurosurgery "Diomid Gherman," Chisinau, Republic of Moldova.
⁶ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden.
⁸ Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
⁹ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Department of Neurology and Stroke Unit, Ospedale del Mare Hospital, Naples, Italy.
¹¹ 2nd Department of Neurology, Aristotle University of Thessaloniki, School of Medicine, AHEPA University Hospital, Greece.
¹² Department of Neurology, Brown University, Providence, RI, USA.
¹³ Hospital del Mar, Faculty of Medicine and Life Sciences, Pompeu Fabra University Barcelona, Spain.
¹⁴ Department of Neurology and Stroke Center, University Hospital Ramón y Cajal, Madrid, Spain.
¹⁵ Translational Molecular Medicine and Surgery 36th Cycle, Department of BIOMORF, Stroke Unit, Department of Clinical and Experimental Medicine, University Hospital G. Martino, Messina, Italy.
¹⁶ Neurology, Boston Medical Center, MA, USA.
¹⁷ Radiology, Boston Medical Center, MA, USA.
¹⁸ Mater Misericordiae University Hospital, Dublin, Ireland.
¹⁹ Neurology Unit ASST Valcamonica, Esine, Brescia, Italy.
²⁰ Department of Neurology, University Hospital of Toulouse, Toulouse, France.
²¹ Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, "Attikon University Hospital", Athens, Greece.
²² Neurology and Stroke Unit, Cardarelli Hospital, Naples, Italy.
²³ Neurology Division, Santa Maria Goretti Hospital, Latina, Italy.
²⁴ Department of Translation and Precision Medicine, Sapienza University of Rome, Italy.
²⁵ Department of Neurology & Stroke, University Hospital Tuebingen, Eberhard-Karls University, Tuebingen, Germany.
²⁶ Sverdlovsk Regional Clinical Hospital No. 1, Yekaterinburg, Russia.
²⁷ Neurology Department, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCL), Brussels, Belgium.
²⁸ Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
²⁹ Neuroradiology Unit, Azienda Unità Sanitaria-IRCCS di Reggio Emilia, Italy.
³⁰ Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
³¹ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³² Lisbon Central University Hospital and Faculdade de Medicina da Universidade de Lisboa, Portugal.
³³ Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tuebingen, Germany.
³⁴ Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
³⁵ Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

PMID: 38572798
PMCID: PMC11418515
DOI: 10.1177/23969873241241885

Multicenter Study

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19

Adrian Scutelnic et al. Eur Stroke J. 2024 Sep.

. 2024 Sep;9(3):676-686.

doi: 10.1177/23969873241241885. Epub 2024 Apr 4.

Authors

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Department of Neurology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands.
³ Department of Neurosciences, Christian Medical College Hospital, Vellore, Tamil Nadu, India.
⁴ Aga Khan University, Karachi, Pakistan.
⁵ Institute of Neurology and Neurosurgery "Diomid Gherman," Chisinau, Republic of Moldova.
⁶ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden.
⁸ Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
⁹ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Department of Neurology and Stroke Unit, Ospedale del Mare Hospital, Naples, Italy.
¹¹ 2nd Department of Neurology, Aristotle University of Thessaloniki, School of Medicine, AHEPA University Hospital, Greece.
¹² Department of Neurology, Brown University, Providence, RI, USA.
¹³ Hospital del Mar, Faculty of Medicine and Life Sciences, Pompeu Fabra University Barcelona, Spain.
¹⁴ Department of Neurology and Stroke Center, University Hospital Ramón y Cajal, Madrid, Spain.
¹⁵ Translational Molecular Medicine and Surgery 36th Cycle, Department of BIOMORF, Stroke Unit, Department of Clinical and Experimental Medicine, University Hospital G. Martino, Messina, Italy.
¹⁶ Neurology, Boston Medical Center, MA, USA.
¹⁷ Radiology, Boston Medical Center, MA, USA.
¹⁸ Mater Misericordiae University Hospital, Dublin, Ireland.
¹⁹ Neurology Unit ASST Valcamonica, Esine, Brescia, Italy.
²⁰ Department of Neurology, University Hospital of Toulouse, Toulouse, France.
²¹ Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, "Attikon University Hospital", Athens, Greece.
²² Neurology and Stroke Unit, Cardarelli Hospital, Naples, Italy.
²³ Neurology Division, Santa Maria Goretti Hospital, Latina, Italy.
²⁴ Department of Translation and Precision Medicine, Sapienza University of Rome, Italy.
²⁵ Department of Neurology & Stroke, University Hospital Tuebingen, Eberhard-Karls University, Tuebingen, Germany.
²⁶ Sverdlovsk Regional Clinical Hospital No. 1, Yekaterinburg, Russia.
²⁷ Neurology Department, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCL), Brussels, Belgium.
²⁸ Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
²⁹ Neuroradiology Unit, Azienda Unità Sanitaria-IRCCS di Reggio Emilia, Italy.
³⁰ Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
³¹ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³² Lisbon Central University Hospital and Faculdade de Medicina da Universidade de Lisboa, Portugal.
³³ Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tuebingen, Germany.
³⁴ Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
³⁵ Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

PMID: 38572798
PMCID: PMC11418515
DOI: 10.1177/23969873241241885

Abstract

Introduction: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT.

Patients and methods: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex.

Results: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]).

Conclusion: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.

Keywords: COVID-19; Cerebral venous thrombosis; stroke.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AS reports a grant from the Swiss Heart Foundation. MRH reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript. MA reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Medtronic, Novartis, Pfizer, and Amgen. JMC has received grants paid to his institution from Boehringer Ingelheim and Bayer, and payments paid to his institution for data safety monitoring board participation by Bayer. JMF has received personal fees from Boehringer Ingelheim, Bayer, and Daiichi Sankyo as well as grants from Bayer. DAS reports travel support from Boehringer Ingelheim, speaker fees from Bayer, and Advisory Board participation for AstraZeneca. TT has received personal fees from Argenx, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma. NR received consultant fees from Novartis. KJ has received academic grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG 965417) for research on CVT. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). TNN reports advisory board Idorsia, Brainomix. KA reports a grant from Swiss National Science Foundation and Medtronic advisory board participation in 2022, not related to this manuscript. EL has received academic grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG 942851), Swedish Neurologic Society, Elsa and Gustav Lindh’s Foundation, Wennerströms’ Foundation, P-O Ahl’s Foundation and Rune and Ulla Amlöv’s Foundation for research on CVT. All other co-authors report no disclosures.

Figures

**Figure 1.**
Distribution of in-hospital mortality over the years 2020–2023 in patients with cerebral venous thrombosis associated with COVID-19.

**Figure 2.**
Distribution of modified Rankin Scale 0–2 at 6 months over the years 2020–2023 in patients with cerebral venous thrombosis associated with COVID-19.

See this image and copyright information in PMC

References

1. Varga Z, Flammer AJ, Steiger P, et al.. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395: 1417–1418. - PMC - PubMed
1. Al-Mufti F, Amuluru K, Sahni R, et al.. Cerebral venous thrombosis in COVID-19: A New York Metropolitan Cohort Study. AJNR Am J Neuroradiol 2021; 42: 1196–1200. - PMC - PubMed
1. Malentacchi M, Gned D, Angelino V, et al.. Concomitant brain arterial and venous thrombosis in a COVID-19 patient. Eur J Neurol 2020; 27: e38–e39. - PMC - PubMed
1. Beretta S, Da Re F, Francioni V, et al.. Case Report: concomitant massive cerebral venous thrombosis and internal iliac vein thrombosis related to paucisymptomatic COVID-19 infection. Front Neurol 2021; 12: 622130. - PMC - PubMed
1. Taquet M, Husain M, Geddes JR, et al.. Cerebral venous thrombosis and portal vein thrombosis: A retrospective cohort study of 537,913 COVID-19 cases. EClinicalMedicine 2021; 39: 101061. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Atypon
- PubMed Central
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19

Affiliations

Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical