COVID-19 induced ischemic stroke and mechanisms of viral entry in brain and clot formation: a systematic review and current update

Abstract

Background: Coronavirus disease 2019, caused by SARS-CoV-2 (SCV-2) was stated as a pandemic on March 11 2020 by World Health Organization (WHO), and since then, it has become a major health issue worldwide. It mainly attacks the respiratory system with various accompanying complications, including cardiac injury, renal failure, encephalitis and Stroke.

Materials and Methods: The current systematic review has been compiled to summarize the available literature on SCV-2 induced ischemic Stroke and its subtypes. Further, the mechanisms by which the virus crosses the blood-brain barrier (BBB) to enter the brain have also been explored. The role of CRP and D-dimer as potent prognostic markers was also explored. The literature search was carried out comprehensively on Google scholar, PubMed, SCOP US, Embase and Cochrane databases by following guidelines.

Results: All the studies were reviewed thoroughly by authors and disagreements were resolved by consensus and help of the senior authors. The most common subtype of the IS was found to be large artery atherosclerosis in SCV-2 induced IS. Hypertension emerged as the most significant risk factor. The mechanism resulting in elevated levels of CRP and D-dimer have also been discussed. However, there is a scarcity of definitive evidence on how SCV-2 enters the human brain. The available literature based on various studies demonstrated that SCV-2 enters through the nasopharyngeal tract via olfactory cells to olfactory neurons, astrocytes and via choroid plexus through endothelial cells. Further, disruption of gut-brain axis has been also discussed.

Conclusion: Data available in the literature is not adequate to come to a conclusion. Therefore, there is a need to carry out further studies to delineate the possible association between SCV-2 induced IS.

Keywords:

• SARS-CoV-2
• Ischemic Stroke
• D-dimer
• Blood-brain barrier

Acknowledgements

Financial assistance from Indian Council of Medical Research (ICMR) New Delhi, Council for Scientific and Industrial Research (CSIR) India and DST-FIST is highly acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Financial support from ICMR, New Delhi (RFC No. (p-64) NCD/Adhoc/139/2020-21), DST-FIST (SR/FST/LS-I/2017/49) and SRF awarded to Mr. Abhilash Ludhiadch (Award No-09/1051(0029)/2 019-EMR-1) from the Council for Scientific and Industrial Research (CSIR) India is acknowledged with thanks.