In line with the other studies [5, 6], we found that ischemic stroke was the commonest type in this study (96.2%). Mathew and his colleagues [5], reported that 97% of patients suffered from ischemic stroke and merely 3% suffered from hemorrhagic stroke [5]. Nannoni and his colleagues [6] also demonstrated relatively similar results as out of 108,571 COVID-19 patients, about 1.4% of them suffered from stroke, 87.4% experienced ischemic stroke and only 11.6% experienced hemorrhagic type [6]. The sole reason of ischemic stroke pathophysiology was the hypercoagulation that occurred in COVID-19 patients. The hypercoagulation state caused by increased inflammation response, including coagulopathy, indicated the high d-dimer level, as demonstrated in this study. The thrombosis also corresponded to the high level of antibodies and antiphospholipid discovered in COVID-19 patients as well [7].

The patients age limit in this study was 55 years which is in line with recent study which indicated that stroke was discovered in patients aged older than 55 years old [1]. This study reported that patients older than 55 years had a significantly worse outcome than patients younger than 55 years. This result was supported by a study conducted by Fridman and his colleagues [8] which found that patients younger than 50 years have a lesser mortality rate compared to patients older than 70 years old [8]. Yanez and his colleagues [9] found that the incidence rate ratio (IRR) of patients 54 years or under was 8.1, indicating that the mortality rate of COVID-19 was 8.1 times higher (95% CI 7.7, 8.5) among patients age between 55 and 64 years, and more than 62 times higher (IRR = 62.1; 95% CI 59.7, 64.7) among those 65 and older [9]. Qureshi and his colleagues [10] also mentioned that in their study, one of the risk factors related to higher mortality in stroke patients with COVID-19 was older age. There were more patients older than 35 years who passed away compared to those younger than 35 years [10]. One of the most possible explanations may be due to the higher chance among older patients to be infected with a more severe type of COVID-19, so that, the outcome was more worse in this group.

This study illustrated that patients with ischemic stroke were prone to have a worse outcome and higher mortality rate compared to patients with hemorrhagic stroke which contradicts a previous cohort study carried out by Syahruland his colleagues [10], where the mortality rate of hemorrhagic stroke patients with COVID-19 was 44.72%, while for the ischemic, 36.23% [11]. This might be due to the small number of patients the study’s sample played a big role as, even though the incidence of hemorrhagic stroke in COVID-19 patients was relatively low. The high mortality rate of ischemic stroke in COVID-19 patients was also demonstrated in a study carried out by Harrison and his colleagues [12] in which 954 patients with ischemic stroke and COVID-19 infection had a higher mortality rate at 60 days compared to non-COVID-19 ischemic stroke patients [12]. This is possibly due to multiorgan failures that occur in COVID-19 patients, therefore the morbidity and mortality chance significantly increased.

Atrial fibrillation was another condition that worsened the outcome of stroke patients with COVID-19 infection. A study conducted by Qureshi and his colleagues [10] indicated that the possibility for COVID-19 patients to experience atrial fibrillation was lower compared to non-COVID-19 patients [10]. That supported this study findings, where only 19.2% of stroke patients with COVID-19 suffered from atrial fibrillation. Furthermore, the patients with atrial fibrillation had a significantly worse outcome and with higher mortality compared to those without such condition (p = 0.036). This could be due to the fact that atrial fibrillation was one of the independent ischemic stroke risk factors [13].

This study also reported that the more severe clinical conditions of COVID-19 infection significantly affected the outcome of stroke patients with the higher mortality rate compared to stroke patients with moderate COVID-19 infection (p: 0.00) as severe or critical COVID-19 conditions increased the patients’ mortality by 40 times (OR: 40, p: 0.00, 95% CI 4.5–350). This is supported by a study conducted by Vidale and his colleagues [14] that the severity of stroke was significantly in line with the severity of COVID-19 infection [14]. Fridman and his colleagues [8] as well discovered that the mortality risk was three times higher compared to other severity levels of COVID-19 infection [8].

Based on a study carried out by Lodigiani and his colleagues [15], the median of d-dimer level for survived patients was 353 ng/mL (μg/L), which increased to 529 ng/mL after 1 week compared to patients who passed away with a higher initial point of d-dimer at 869 ng/mL and 1494 ng/mL at the end of the week [15]. In this study, 98.1% of patients administered an increase in d-dimer, however, a significant cutoff was not identified. This finding differed from the study carried out by Tang and his colleagues [16], which indicated that an increased d-dimer level in COVID-19 patients was closely responsible for poor prognosis and higher mortality rate [16]. This could be due to a lack of samples for better understanding the relationship between an increase in d-dimer level and mortality outcome. The high d-dimer was suspected due to the inflammation in COVID-19 infection, which leads to the coagulation cascade. Therefore, the significance of mortality etiology was still inconclusive.

C-reactive protein or CRP serum was discovered to be an essential marker, which might change significantly in severe COVID-19 patients. CRP was a protein produced by the liver, which had a role as an initial marker of infection and inflammation. In this study, the elevated CRP was observed in 86% of severe COVID-19 patients and more than 60 mg/L of CRP was reported as a cut-off point and thrice tendency for higher mortality (OR: 3.025, 95% CI 0.931–9.827) (p: 0,08). This could be an important finding which differed from other studies considering a meta-analysis study conducted by Yassin and his colleagues [17] which demonstrated that CRP level was not different between stroke patients with COVID-19 and without COVID-19 infection [17].

Fridman and his colleagues [8] stated that comorbidity plays an important role in determining the mortality of stroke patients with COVID-19 infection. This was in line with a finding which stated that hyperlipidemia patients were inclined to a higher mortality rate (p: 1.833, 95% CI 0.574–5.855) [8]. Meanwhile, for the other comorbidities, such as diabetes, this study indicated that there was no significant correlation between diabetes and stroke in COVID-19 patients and the mortality rate. In a study carried out by Jillella and his colleagues [18], it was concluded that, out of 13 stroke patients with COVID-19, 9 patients had diabetes with two of them were being in a prediabetic state [18]. Meanwhile, in a study conducted by Qureshi and his colleagues [10], 58 out of 103 (56.3%) stroke patients with COVID-19 infection, had diabetes, while there was 51.8% of non-COVID-19 stroke patients who had diabetes. Other comorbidities, such as hypertension, CKD, and CAD, did not demonstrate significant results in determining mortality in this study.

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