Impact of the COVID‐19 pandemic on acute stroke care: An analysis of the 24‐month data from a comprehensive stroke center in Shanghai, China

Abstract Introduction Whether the coronavirus disease‐2019 (COVID‐19) pandemic is associated with a long‐term negative impact on acute stroke care remains uncertain. This study aims to compare the timing of key aspects of stroke codes between patients before and after the COVID‐19 pandemic. Methods This retrospective cohort study was conducted at an academic hospital in Shanghai, China and included all adult patients with acute ischemic stroke hospitalized via the emergency department (ED) stroke pathway during the 24 months since the COVID‐19 outbreak (COVID‐19: January 1, 2020–December 31, 2021). The comparison cohort included patients with ED stroke pathway visits and hospitalizations during the same period (pre‐COVID‐19: January 1, 2018–December 31, 2019). We compared critical time points of prehospital and intrahospital acute stroke care between patients during the COVID‐19 era and patients during the pre‐COVID‐19 era using t test, χ2, and Mann–Whitney U test where appropriate. Results A total of 1194 acute ischemic stroke cases were enrolled, including 606 patients in COVID‐19 and 588 patients in pre‐COVID‐19. During the COVID‐19 pandemic, the median onset‐to‐hospital time was about 108 min longer compared with the same period of pre‐COVID‐19 (300 vs 192 min, p = 0.01). Accordingly, the median onset‐to‐needle time was 169 min in COVID‐19 and 113 min in pre‐COVID‐19 (p = 0.0001), and the proportion of patients with onset‐to‐hospital time within 4.5 h was lower (292/606 [48.2%] vs 328/558 [58.8%], p = 0.0003) during the pandemic period. Furthermore, the median door‐to‐inpatient admission and door‐to‐inpatient rehabilitation times increased from 28 to 37 h and from 3 to 4 days (p = 0.014 and 0.0001). Conclusions During the 24 months of COVID‐19, a prolongation of stroke onset to hospital arrival and to intravenous rt‐PA administration times were noted. Meanwhile, acute stroke patients needed to stay in the ED for a longer time before hospitalization. Educational system support and process optimization should be pursued in order to acquire timely delivery of stroke care during the pandemic.


| INTRODUC TI ON
Ischemic stroke is a devastating cerebrovascular disease with serious adult disability and mortality worldwide. Acute ischemic stroke (AIS) management relies on timely delivery. The evaluation of a patient and a decision to treatment, that is, within different time windows after acute stroke onset, need to be made effectively. [1][2][3][4] The coronavirus disease 2019 (COVID-19) outbreak has affected several aspects of acute stroke care since its emergence in December 2019 in China, including declines in the number of stroke patients, delays in stroke onset to hospital arrival time. [5][6][7][8][9] Since the first case of COVID-19 was confirmed in Shanghai on January 20, 2020, strict measures were taken to prevent and control the spread of COVID-19. 10 During the period of lockdown in Shanghai (January 24 to March 24, 2020), the number of outpatient and emergency department visits was dropped dramatically compared with the same period of 2019. 11,12 Different from western countries, China has implemented the normalized epidemic prevention and control and zero-COVID policy since the COVID-19 outbreak. In terms of hospital admission during the pandemic, official guidelines were launched in Shanghai that it is mandatory to perform epidemiological investigation, COVID-19 nucleic acid detection, and Chest CT before in-hospital management. 10 Several studies showed that during the early lockdown phase of the pandemic, the COVID-19 outbreak impacted stroke care significantly in China, including a prolongation in stroke onset to hospital arrival time, a significant drop in admissions, thrombolysis, and thrombectomy. 7,9,12 However, it remains not clear whether the pandemic has a long-term effect on the timing of key aspects of the in-hospital stroke pathway. In the present study, we, therefore, compared the onset to hospital arrival (onset-

| Design
This single-center retrospective cohort study was conducted at the Southern Campus of the Shanghai General Hospital, which is one of the 46 large hospitals in Shanghai with over 2000 beds and is also the sole academic tertiary hospital with a comprehensive stroke center to the population of 2,000,000. 13 One group of the study population comprised consecutive patients 18 years or older who had confirmation of acute ischemic stroke (AIS) by a panel of attending neurologists and had an acute stroke pathway visit in emergency department (ED) and hospitalization from January 1, 2020 to Available data were retrieved from the Shanghai General Hospital stroke registry, which is approved by the local institutional review board and waived the requirement for informed consent.

| Measurements
The acute stroke pathway comprises a stroke multidisciplinary team that enrolls patients presenting to the ED within 24 h of stroke onset, including all acute stroke patients transferred by ambulance, coming to the hospital by themselves, or transferred from outpatient service. The diagnosis of AIS was confirmed by a panel of attending neurologists. Exclusion criteria were the following: any stroke code that after initial evaluation from the ED stroke pathway was determined not to be a stroke, any stroke patients admitted to Shanghai General Hospital without going through the acute stroke pathway, any stroke transferred to the hospital when the stroke presenting >24 h after symptoms onset. Stroke onset was defined as the last time the patient was observed without deficit or last seen well time.
We used electronic data capture and manual abstraction to collect information from our clinical research database, including demographics, vascular risk factors, onset-to-door time (ODT), onset-to-needle time (ONT), door-to-needle time (DNT), door-toinpatient admission time (DAT), door-to-inpatient rehabilitation time (DRT), and details of AIS treatment.
Stroke onset-to-door time was defined as the duration between stroke onset to ED arrival; onset-to-needle time was the duration between stroke onset to administration of IV rt-PA (intravenous recombinant tissue-type plasminogen activator); door-to-needle time was the duration between ED arrival to the administration of IV rt-PA; doorto-inpatient admission time was the duration between ED arrival to admitted to the inpatient setting, whereas door-to-inpatient rehabilitation time was the time between ED arrival to initiation of rehabilitation.

| Analysis
We analyzed baseline demographics, vascular risk factors, and critical time points between AIS patients during COVID-19 and those Educational system support and process optimization should be pursued in order to acquire timely delivery of stroke care during the pandemic.   (Table 1). When the lockdown measures were progressively eased from March 24, 2020, the number of cases gradually returned and even exceeded the previous level ( Figure 2).

K E Y W O R D S
During the COVID-19 period, 38.9% of the patients (n = 236) had diabetes, while 31.7% of the patients (n = 177) had diabetes during the pre-COVID-19 period (p = 0.01). Patients with atrial fibrillation were 30 (5.0%) in the COVID-19 group and 44 (8.2%) in the pre-COVID-19 group (p = 0.02). NIHSS scores were greater in the pre-COVID-19 group than that in the COVID-19 group. No significant differences were noted in age, sex, and vascular risk factors between the two groups ( Table 2).  Table 2).

| DISCUSS ION
In this retrospective cohort study, our findings suggest the possi-   pandemic.
For acute ischemic stroke, it is widely accepted that the wise strategy is to obtain earlier reperfusion, which is associated with better clinical outcomes. 20 A decision to treatment should be made timely, including tissue plasminogen activator (t-PA) that can only be given in the first 4.5 h after symptom onset and mechanical thrombectomy to be performed within 24 h of acute ischemic stroke. 4,[20][21][22] Any delays in seeking those treatments may exert a negative impact on stroke outcomes, including the short-term functional recovery and the long-term outcomes of death and recurrent ischemic  26 Since the pandemic has been going on for a long period of time, focusing on the early stages is insufficient for a comprehensive presentation. There is still a necessary demand for research with a longer study period and larger sample sizes to reflect the impact of COVID-19 on stroke onset-to-door time as a whole.
Based on our data (Figure 3), the extension of onset-to-door time has lasted 2 years since the outbreak of the pandemic. We believe that there are several reasons for the prolongation of the time from onset to arrival at the hospital. On the one hand, during the pandemic, in the acute phase of stroke patients may be reluctant to come to the hospital due to fear of the virus. 9 Under the "dynamic zero-COVID policy," people in China had a higher level of anxiety, compared with that of people living in Western countries. 27 In a retrospective observational cohort study performed in Shanghai, there was nearly a 30% drop in the total number of primary care general practice consultation visits in the early stage of the COVID-19 pandemic from January to June 2020, compared to the same period in 2019. 11 On the other hand, in Shanghai, during the COVID-19 period, some primary stroke centers were closed or unable to treat stroke patients for several months due to the need of pandemic prevention. 28 In an observational study in China, a survey distributed to the leaders of stroke centers in 280 hospitals, indicated that during the COVID-19 outbreak in 2020, 70% of hospitals reduced their emergency stroke capacity, and over 4% of stroke centers were closed. 12 As a regional medical center with no change in stroke capacity, our hospital admitted more stroke patients (8.6% increase) during the pandemic.
Additionally, at the early stage of the COVID-19 outbreak, patient transportation was limited due to the lockdown. Thereafter, under the "dynamic zero-COVID policy," some hospitals with stroke centers were closed for several days or a few months without warning due to COVID-19-positive patients detected in these institutions.
Thus, the passive adjustment of medical transfer system may lead to the reduction of transportation efficiency and the prolongation of onset to hospital arrival.
Previous studies indicated that patients who were treated with tPA and had door-to-needle times of longer than 60 min, had significantly higher all-cause mortality, higher symptomatic intracranial hemorrhage, and lower odds of independent ambulation, compared with those treated within 60 min. 29,30 Since the COVID-19 pandemic   33 In addition, with the change in pandemic situation and the emergence of new COVID variants, the prevention and control policies are also changing, which will also affect the patient's medical behavior.

| CON CLUS IONS
The

CO N FLI C T O F I NTER E S T S TATEM ENT
The authors declare that they have no conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.

PATI ENT CO N S ENT S TATEM ENT
Informed consent was not sought for the present study because the manuscript does not contain patient data.

PE R M I SS I O N TO R E PRO D U CE M ATE R I A L FRO M OTH E R S O U RCE S
Not Applicable.

CLI N I C A L TR I A L R EG I S TR ATI O N
Not Applicable.

RO LE O F TH E FU N D E R /S P O N S O R
The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.