Strokes Typically Are The First Symptoms Of COVID-19 In Younger Asymptomatic Patients According To A New Canadian Study

Strokes-COVID-19: According to a new study led by Canadian researchers from Western University -Ontario, strokes may be the first presenting symptom of COVID-19 in younger patients who are typically asymptomatic.


 
The new study findings were published in the peer reviewed journal: Neurology, the medical journal of the American Academy of Neurology. https://n.neurology.org/content/early/2020/09/15/WNL.0000000000010851 or
https://n.neurology.org/content/neurology/early/2020/09/15/WNL.0000000000010851.full.pdf
 
This could be a worrisome trend as in many countries; doctors and healthcare professionals are still ignorant and do not seem to identify COVID-19 with a sudden surge of younger adults manifesting strokes.
 
The study found that patients less than 50 years of age with any stroke or ischemic stroke were the ones with the lowest prevalence of hypertension and atrial fibrillation compared to other age groups. Young patients with stroke of any type also had the lowest prevalence of coronary artery disease. Interestingly, ≈50% of patients aged less than 50 years experienced their strokes before the onset of COVID-19 respiratory symptoms, and  this was significantly more frequent than in other age groups. This finding may imply that, in the COVID-19 era, younger patients presenting to the Emergency Department with acute stroke would need to be tested for SARS-COV-2 even in the absence of specific symptoms or regardless of having passed a COVID-19 screen.
 
The researchers carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.
 
However although younger patients had the highest risk of stroke, the highest risk of death was in patients who were older, had other chronic conditions, and had more severe COVID-19-associated respiratory symptoms.
 
Lead author Dr Luciano Sposato, MD, MBA, Associate Professor and chair in stroke research, Schulich School of Medicine and Dentistry, Western University, Ontario, Canada told Thailand Medical News, "One of the most eye-opening findings of this study is that for patients under 50 years old, many were totally asymptomatic when they had a stroke related to COVID-19, which means that, for these patients, the stroke was their first symptom of the disease.
 
Dr Sposato added, "In early April of 2020, we realized that COVID-19 was a highly thrombogenic disease. Almost in parallel, I started to see anecdotal reports in social media of strokes occurring in patients with COVID-19, and there were also very few case reports."
 
The study team "thought it would be a good idea to put all the data together in one paper," he said, and began by conducting a systematic review of 10 published studies of COVID-19 and stroke (n = 125 patients), which were then pooled with 35 unpublished cases from Canada, the United States, and Iran for a total of 160 cases.
 
The study analysis examined in-hospital mortality rates of patients with stroke and COVID-19.
 
The study team also further conducted a second review of 150 papers, encompassing a final cohort of 3306 COVID-19 patients with stroke of any type and 5322 with ischemic stroke.
 
Dr Sposato explained, "Some research reported data for only ischemic stroke, and some reported data for all strokes considered together, which resulted in a different number of patients on each meta-analysis, with a lower number of 'any stroke' cases’. This review looked at the number of patients who developed a stroke during admission and included thousands of patients."
 
He noted that the first review was conducted on single case reports and small case series "to understand the clinical characteristics of strokes in patients with COVID-19 on an individual patient level," since "large studies, including hundreds of thousands of patients, usually do not provide the level of detail for a descriptive analysis of the clinical characteristics of a disease."
 
Detailed cluster analyses were used to "identify specific clinical phenotypes and their relationship with death."
 
All patients were stratified into 3 age groups: <50, 50-70, and >70 years ("young," "middle-aged," and "older," respectively). The median (IQR) age was 65 years (54.0 - 76.3) and 43% were female.
 
The study showed that 1.8% (95% CI, 0.9% - 3.7%) of patients experienced a new stroke, while 1.5% (0.8% - 2.8%) of these experienced an ischemic stroke.
 
Dr Sposato commented, "These numbers are higher than historical data for other infectious diseases, for example, 0.75% in SARS-CoV-1, 0.78% in sepsis, and 0.2% in influenza."
 
He warned, “Moreover, this number may be an underestimate, given that many patients die without a confirmed diagnosis and that some patients did not come to the emergency department when experiencing mild symptoms during the first months of the pandemic.”
 
On the study of 160 patients, the team described in-hospital mortality for strokes of all types and for ischemic strokes alone as "remarkably high" (34.4% [95% CI, 27.2% - 42.4%] and 35.7% [95% CI, 27.5% - 44.8%], respectively), with most deaths occurring among ischemic stroke patients.
 
Dr Sposato cautioned, "This high mortality rate is higher than the [roughly] 15% to 30% reported for stroke patients without COVID-19 admitted to intensive care units."
 
It was found that many "young" COVID-19 patients (under age 50) who had a stroke (42.9%) had no previous risk factors or comorbidities. Moreover, in almost half of these patients (48.3%), stroke was more likely to occur before the onset of any COVID-19 respiratory symptoms.
 
Also, younger patients showed the highest frequency of elevated cardiac troponin compared with middle-aged and older patients (71.4%, vs 48.4% and 27.8%, respectively). On the other hand, mortality was 67% lower in younger vs older patients (OR, 0.33; 95% CI, 0.12 - 0.94; P = .039).
 
It was also noted that the proportion of ischemic stroke patients with large vessel occlusion was "higher than previously reported" for patients with stroke without COVID-19 (47% compared with 29%, respectively).
 
Dr Sposato suggested, "We should consider COVID-19 as a new cause or risk factor for stroke. At least, patients with stroke should probably be tested for SARS-CoV-2 infection if they are young and present with a large vessel occlusion, even in the absence of typical COVID-19 respiratory symptoms.”
 
The study team identified a "high-risk phenotype" for death for all types of stroke considered together: older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms. Patients with all three characteristics had the highest in-hospital mortality rate (58.6%) and a threefold risk of death, compared with the rest of the cohort (OR, 3.52; 95% CI, 1.53 - 8.09; P = .003).
 
Dr Sposato  added, "Several potential mechanisms can explain the increased risk of stroke among COVID-19 patients, but perhaps the most important one is increased thrombogenesis secondary to an exaggerated inflammatory response.”
 
The study team acknowledged that the study was small and that there "can be problems associated with a systematic review of case reports, such as publication bias, lack of completeness of data, etc, so more research is needed."
 
Medical experts commenting on the study said, "consistent with and underscore public health messaging emphasizing that COVID-19 does not only affect the elderly and those with underlying health conditions, but can have serious and even fatal consequences at any age. Adherence to public health recommendations is critical to begin to reduce the rising incidence in younger adults."
 
In conclusion, the study team found that the frequency of stroke occurrence is high among hospitalized COVID19 patients. In-hospital mortality is also exceedingly higher than previously reported in non-COVID 19 patients with stroke. LVO is twice as frequent as previously reported and its prevalence is high across all age groups, even in the absence of risk factors or comorbidities, suggesting the role of COVID-19-related hypercoagulability. Specific clinical phenotypes characterized by the interplay of older age, a higher burden of cardiovascular comorbidities, and severe COVID-19 respiratory symptoms were associated with a substantial increase in the risk of death. COVID-19 severity seems to be the major determinant of death.
 
The study findings should serve as information for guiding prognostication, resource allocation, and counseling of patients and their families
 
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