Scientists confirm the strong link between COVID-19 and stroke risk, highlighting the urgent need for further research into prevention and treatment strategies.

Test: Association between SARS-CoV-2 and stroke: perspectives from the metaumbrella review. Photo credit: Kateryna Kon / Shutterstock

*Necessary note: medRxiv publishes preliminary scientific reports that are usually not peer-reviewed and due to this fact mustn’t be considered conclusive, guide clinical practice/health-related behavior, or be relied upon as established information.

In a recent research paper submitted to the positioning medRxiv preprint* researchers conducted a metaumbral review of 34 systematic reviews and 70 primary studies to elucidate risk associations between SARS-CoV-2 infections and stroke.

Equivalent odds ratio (eOR) evaluation showed a powerful association between the severity of COVID-19 infection and the following risk of stroke (eOR = 2.48), with the very best risk being hemorrhagic stroke (eOR = 3.86) and ischemic stroke (eOR = 2.48). . Nevertheless, considerable heterogeneity was observed in lots of studies, suggesting variability in results (in some cases I² values ​​> 50%), requiring careful interpretation of those relationships.

Moreover, it was observed that patients with concomitant cerebrovascular diseases or a history of stroke had a better risk of stroke-related death (eOR = 2.48 and 6.08, respectively). Collectively, these findings establish a major link between SARS-CoV-2 and stroke.

Despite these findings, the strength of evidence for some associations, equivalent to stroke mortality and risk of ischemic stroke, was considered weak as a consequence of small sample size and potential publication bias (identified by Egger’s test). Unfortunately, despite extensive work on this area, methodological shortcomings in much of the work highlight the necessity for extra research into the mechanisms underlying these risk associations.

Background

Strokes, commonly called “brain attacks” and in medicine “cerebrovascular accidents (CVA),” are conditions wherein the blood supply to the brain is stopped. The brain needs a continuing supply of oxygenated blood to operate properly. In consequence, even a brief reduction in oxygen access can lead to everlasting brain damage, disability, and sometimes even death.

Alarmingly, despite many years of research, stroke stays the second leading explanation for human mortality (roughly 5.5 million deaths) and the third leading explanation for disability worldwide, necessitating a greater understanding of the danger aspects and mechanisms underlying its manifestation.

Stroke is a multifactorial condition consisting of mixtures of environmental, modifiable and non-modifiable risk aspects that influence its incidence and outcomes. Recent research suggests that the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, the pathogen causing severe acute respiratory syndrome 2 (SARS-CoV-2), may increase the danger of stroke.

Although SARS-CoV-2 is primarily recognized as a respiratory pathogen, it’s increasingly causing systemic inflammation, immunological complications, and damage to the nervous system, which can increase the danger and severity of stroke. Unfortunately, the connection between COVID-19 and stroke risk stays confusing.

Concerning the study

The current study used a metaumbrella review approach to look at associations between SARS-CoV-2 and subsequent stroke risk. Umbrella reviews are large-scale, exhaustive studies of primary publications, systematic reviews, and meta-analyses designed to handle a selected query or topic.

A vital limitation of this study is the overlap between studies, where some primary research papers were counted greater than once across multiple reviews, potentially affecting overall conclusions. This paper searched 4 online scientific repositories (PubMed/MEDLINE, Scopus, Web of Science, and LILACS) for any studies published between March 2020 and March 2023 examining the association between COVID-19 and any stroke subtype ( ischemic or hemorrhagic). Non-clinical assessments, letters, reports, opinion articles, and book chapters were excluded from the dataset.

Two independent reviewers assessed the study in two stages – title and abstract and full text. Cohen’s Kappa was used to measure the consistency of reviewers’ selections. Covidence software was used to calculate Cohen’s Kappa and generate the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart.

The ROBIS tool was used to evaluate the methodological correctness of the included studies, including the danger of bias. Two study participants (“COVID-19 and stroke mortality” and “COVID-19 and risk of ischemic stroke”) showed evidence of excess significance bias (ESB), where the variety of positive results exceeded what would normally be expected. Pooled effect sizes for aspects assessed across multiple studies were estimated using a random-effects meta-analysis. These effect sizes were then used to calculate equivalent odds ratios (eORs).

Finally, heterogeneity between studies was assessed using the I² index, and the strength of evidence from each study was assessed on a 4-class rating scale. Of the five study sites, only two showed low heterogeneity (I² < 50%), indicating greater consistency, while three others showed greater variability, reducing the arrogance in the outcomes.

Research results

Initial database search results identified 2,490 studies relevant to the present metaumbrella review. Title and abstract screening excluded 1,430 studies, and full-text screening excluded a further 1,026 studies, leaving 34 eligible studies for inclusion in the present work. Summary statistics of the included studies showed a mean age of 61.2 years (high stroke risk population) and a predominantly male population (59.9%). The geographic scope of the included studies was large and included america (US), Italy, India, Spain, Brazil and, to the best extent, China.

The ROBIS risk of bias assessment revealed that the majority studies showed minimal risk of bias by way of study identification, eligibility, and selection. Nevertheless, some studies showed a high or uncertain risk of bias, particularly in study selection and synthesis of results, further emphasizing the necessity for caution when interpreting pooled results.

Metaumbrella analyzes showed that the incidence of stroke in COVID-19 survivors was significantly higher than in individuals who never contracted SARS-CoV-2 infection, establishing a pathological link between SARS-CoV-2 and stroke predisposition. . Amongst stroke subtypes, hemorrhagic (eOR = 3.86) and ischemic (eOR = 2.48) stroke were most affected by previous vaccination against Covid-19.

Moreover, the overlap between some key studies across multiple reviews, equivalent to Qureshi and Merkler’s, suggests that this work played a key role in influencing the ultimate conclusions.

Although the mechanisms underlying these associations require more work to be elucidated, this study suggests that SARS-CoV-2 infections may cause hypercoagulability in patients, increasing the danger of blood clotting in blood vessels supplying oxygen to the brain, which in turn causes stroke.

Conclusions

This review uses the relatively latest methodological approach of metaumbrella to elucidate potential associations between COVID-19 and subsequent stroke risk. The study results showed that SARS-CoV-2 infections significantly increase the danger of stroke, especially its hemorrhagic and ischemic subtypes.

Nevertheless, the strength of the evidence for some associations was rated as weak, especially for stroke mortality and ischemic stroke risk, as a consequence of small sample size and potential publication bias. It further suggests that SARS-CoV-2 may influence stroke risk by causing a hypercoagulable state in patients, triggering a cascade that culminates in stroke events.

“Future, prospective, multicenter studies are mandatory to further explore the mechanisms underlying the association between Covid-19 and stroke, develop comprehensive clinical guidelines for the management of patients with Covid-19 and stroke risk, and evaluate the effectiveness of prevention. interventions equivalent to anticoagulation to scale back the incidence of stroke in patients with Covid-19.”

Cövid needs to be considered a brand new risk of coronary heart disease, new-onset hypertension, diabetes, pulmonary embolism and… Yes, stroke.

We do not connect the dots

Regards, Mon Ami @ejustin46 ���� https://t.co/2RgisLK5Xs

— David Joffe MB BS (Hons), PhD, FRACP ���� (@DavidJoffe64) October 5, 2024

*Necessary note: medRxiv publishes preliminary scientific reports that are usually not peer-reviewed and due to this fact mustn’t be considered conclusive, guide clinical practice/health-related behavior, or be relied upon as established information.