Characteristics of the study population and stroke risk factors
The cohort consisted of 265 patients with a mean age of 85.9 ±6.5 years, 43% were male, and the in-hospital mortality rate was 32.1%. Acute stroke was confirmed in 11 patients, which corresponds to an incidence of 4.15% (Figure 1). Mortality was similar between patients with (32.1%) and without stroke (27.3%, p>0.999), and there were no differences regarding age, sex, or length of stay on an acute ward.
Stroke patients had a higher prevalence of active smoking (27.3% vs. 4.8%; p=0.019), as well as history of previous stroke (45.5% vs. 13.8%; p=0.014). On the other hand, tiredness was less frequently reported in the group of stroke patients (9.1% vs. 50.2%; p=0.010) with a trend towards higher “asymptomatic” status at hospital admission (27.3% vs. 7.7%; p=0.056). Interestingly, stroke patients had a lower BMI than those without stroke (20.7 ±3.5 vs. 24.9 ±6.4; p=0.002). While their mean BMI value was within the “normal” range, 45.5% of calculated BMIs were in the underweight range (<20 kg × m−2), while no patient with acute stroke was categorized with obesity (BMI ≥30 kg × m−2) (Figure 2). The trend towards a lower BMI in the stroke group was statistically significant (p=0.038).
There were no differences regarding other cerebrovascular risk factors, except for dyslipidemia, which was more frequent in stroke patients, but with a borderline statistically significant p-value (63.6% vs. 33.2%; p=0.051). Similarly, we did not observe differences in comorbidity burden, functional status, or the prevalence of frailty and the severity of COVID-19 disease course between the two groups (Table 1).
In the univariate logistic regression model of stroke prediction, active smoking and previous stroke remained significant predictors, increasing by more than seven times and by more than five times, respectively, the risk of stroke. Similarly, a higher BMI was protective, as each additional point in BMI reduced the risk of stroke by approximately 14% (Table 2).
Stroke characteristics and prognosis
Of the 11 patients with acute stroke, 81.8% were ischemic (9/11) and 18.2% hemorrhagic (2/11). The stroke events occurred after an average of 15.2 days from COVID-19 diagnosis, and the majority of patients presented stroke during the acute care stay (8/11; 72.7%). Three patients had a simultaneous diagnosis of COVID-19 and acute stroke, whereas another three patients presented a stroke of late occurrence, occurring during the stay on a geriatric rehabilitation ward 25, 45 and 70 days after COVID-19 diagnosis (Supplementary Table S2). An altered state of consciousness and/or delirium were the most frequent clinical manifestation of stroke, reported in 81.8% of cases (9/11). In five patients (45.5%), a focal neurological deficit was present at the time of brain imaging. Thromboembolic risk assessed by the CHA2DS2-VASc score showed a median score of 5 (range, 3-7) in stroke patients, and a HAS-BLED score bleeding risk with a median of 3 (range, 1-5). Among patients with ischemic stroke, 22.2% (2/9) took oral anticoagulant treatment (acenocoumarol or rivaroxaban) for atrial fibrillation by the time of stroke diagnosis, while three patients were under aspirin (acetylsalicylic acid) or clopidogrel medication. The majority of patients with ischemic stroke (55.5%) had no ongoing antithrombotic treatment, while a statin that had been prescribed previously had been maintained in 45.45% of cases.
A large vessel occlusion was reported in 22.2% of ischemic stroke cases (2/9). Furthermore, strokes were mainly limited to one side (5/9 right, 3/9 left) and the middle cerebral artery territory was affected in more than half of all cases (5/9; 55.5%), followed by the posterior cerebral artery (3/9), and vertebrobasilar territories (2/9). One patient had a stroke in the posterior and middle artery junction territory, whereas ischemic lesions in multiple territories were diagnosed in two cases (Supplementary Table S1).
Regarding the etiology of ischemic stroke, a cardioembolic cause was identified in 3 cases (44.5%), followed by artery-to-artery embolization in 2 cases and microangiopathic disease in 1 case. Furthermore, one patient presented a junctional ischemic stroke as a consequence of reduced blood flow and hypoperfusion. Ischemic stroke was classified as cryptogenic in two cases, with no etiology determined in the acute workup.
By the end of the hospital stay, three patients (27.3%) died between 3 and 6 days after the stroke occurrence, whereas four (36.4%) were institutionalized in a nursing home. In-hospital mortality rates were similar between patients with and without acute stroke, as well as institutionalization rates at hospital discharge (21.1% vs 36.4%; p=0.258). All survivors presented moderate to severe disability at discharge according to the MRS (Supplementary Figure S1). Only one patient was eligible for intravenous tissue plasminogen activator treatment, with no complications reported.
Additional features in neuroimaging
There was a high burden of cerebral small vessel disease in patients with stroke, with more than half of patients presenting concomitant lacunes (54.5%). Early confluent to confluent white matter lesions were described in 81.8% of cases and 45.5% of patients had at least one cerebral microbleed, in a classical deep or lobar topography. Additionally, all images were carefully reviewed with no evidence of features of other concomitant neurological complications such as meningitis, encephalitis, or vasculitis.