key: cord-1024791-xw5xpubg authors: Richter, Daniel; Eyding, Jens; Weber, Ralph; Bartig, Dirk; Grau, Armin; Hacke, Werner; Krogias, Christos title: A full year of the COVID‐19 pandemic with two infection waves and its impact on ischemic stroke patient care in Germany date: 2021-08-22 journal: Eur J Neurol DOI: 10.1111/ene.15057 sha: 0982955fb22dc6cb6f2261c507da193d7cf29588 doc_id: 1024791 cord_uid: xw5xpubg BACKGROUND AND PURPOSE: Many countries worldwide, including Germany, reported that the first wave of the coronavirus disease 2019 (COVID‐19) pandemic in early 2020 influenced the care of acute ischemic stroke (AIS) patients, but data are lacking for further pandemic wave periods. METHODS: We conducted a nationwide, retrospective, cross‐sectional study of all hospitalized patients with the main diagnosis of AIS in 2019 and 2020. Primary outcomes were the number of hospitalizations for AIS, the application of stroke unit care, intravenous thrombolysis (IVT), and mechanical thrombectomy (MT), as well as the in‐hospital mortality during the different pandemic periods in 2020 compared to the corresponding periods in 2019. Secondarily, we analyzed differences in outcomes between patients with and without concurrent COVID‐19. RESULTS: We included 429,841 cases with AIS, of which 1268 had concurrent COVID‐19. Hospitalizations for AIS declined during both pandemic wave periods in 2020 (first wave: −10.9%, second wave: −4.6%). MT rates were consistently higher throughout 2020 compared to 2019, whereas the IVT rate dropped during the second wave period (16.0% vs. 17.0%, p < 0.001). AIS patients with concurrent COVID‐19 frequently received recanalization treatments, with an overall MT rate of 8.4% and IVT rate of 15.9%. The in‐hospital mortality was high (22.8% vs. 7.5% in noninfected AIS patients, p < 0.001). CONCLUSIONS: These findings demonstrate a smaller decline in hospitalizations for AIS in the more severe second wave of the COVID‐19 pandemic. AIS patients with and without concurrent COVID‐19 who did seek acute care continued to receive recanalization treatments in Germany. The year 2020 was dominated by the coronavirus disease 2019 pandemic, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Several neurological manifestations and complications have been reported, including acute ischemic stroke (AIS), that might be mainly caused by an inflammation-induced prothrombotic state, but also by angiotensin-converting enzyme-2 receptor dysregulation or COVID-19-associated cardiac injury [1] . in AIS patients is associated with substantially higher mortality [2, 3] and a frequent appearance of large vessel occlusions (LVOs) [4] . In addition to direct disease-related complications, the first wave of the COVID-19 pandemic influenced AIS care on a global level, with a strong decline in the number of AIS patient hospitalizations [5] . A similar decrease was observed for Germany during the first wave of the pandemic in spring 2020 [6] . The decline was attributed to lockdown measures and fear of attending hospitals. However, during the first pandemic wave period, the acute recanalization therapy rates remained at high levels in Germany. As the COVID-19 pandemic is still ongoing, most countries have gone through the second wave of this pandemic, including Germany, where the second wave started in October 2020. This second wave was even worse, with a massive increase in the numbers of new infections with SARS-CoV-2 and a substantial rise in COVID-19-related deaths [7, 8] . This development also unsettled the stroke community. To date, it is unknown to which extend this more severe second pandemic wave might have influenced the acute stroke care and the in-hospital mortality of AIS patients in Germany. Therefore, we sought to investigate and compare the number of patients hospitalized for AIS, treatment rates with intravenous thrombolysis (IVT) and mechanical thrombectomy (MT), and the in-hospital mortality rate among AIS patients during the COVID-19 pandemic in 2020, including both infection waves, using the full-year nationwide data of Germany. Secondarily, we aimed to analyze differences in acute care and in-hospital mortality of AIS patients with and without concurrent COVID-19. This study followed the reporting STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline. This is a German nationwide retrospective cross-sectional study using the administrative diagnosis-related group database (data transmission according to §21 KHEntgG and §24 para. 2 KHG; official data on file, source: Institut für das Entgeltsystem im Krankenhaus, www. g-drg.de). In Germany, all inpatient stroke cases are encoded according to the German version of the 10th International Classification of Diseases (ICD-10-GM) and operating and procedure (OPS) keys issued by the Federal Institute for Drugs and Medical Devices. We included all hospitalized patients in Germany with the ICD-10 main diagnosis I63 (ischemic stroke, n = 429,841) from 1 January 2019 to 31 December 2020. AIS patients being transferred once or multiple times from one hospital to another for acute stroke therapy and/ or early rehabilitation were censored to avoid double and multiple counting cases with main diagnosis I63 (excluding "discharge key 06"). Case numbers with the main diagnosis of I63 were aggregated at the level of the 3-digit ICD code. Primary outcomes were the number of AIS hospital admissions, application of acute recanalization procedures (IVT, MT), stroke unit care (SUC), and in-hospital mortality among AIS patients during the following predefined periods of interest: 1 January to 29 February 2020 (pre-first wave), 1 March to 31 May 2020 (first wave), 1 June to 30 September 2020 (pre-second wave), 1 October to 31 December 2020 (second wave; Figure S1 in the online supplement). The number of AIS recanalization therapies was assessed using the corresponding OPS key for IVT (OPS code 8-020.8) and MT (OPS 8-836.80) in combination with the main diagnosis ICD I63. The following OPS codes combined with the I63 main diagnosis were analyzed to assess SUC: 8-981.x (complex treatment of acute stroke) and 8-98b.*0/*1 (other complex treatment of acute stroke without/with teleconsultation). In-hospital mortality was assessed using discharge key 07 (death during hospital stay). Secondary outcomes were the acute care and in-hospital mortality of AIS patients depending on the copresence of COVID-19. Comorbid COVID-19 was assessed by the concurrent coding of ICD U07.1 (laboratory-confirmed COVID-19). Rates are given for categorical variables, and means and SDs for continuous variables. Absolute and relative changes in hospitalizations, treatment rates, and in-hospital mortality rates in AIS patients between the different periods of interest are given in numbers and percent. We used the chi-squared test for categorical variables and t-test for continuous variables to compare each period of interest's data with the corresponding previous year period. Additionally, differences between the periods of interest of 2020 versus 2019 were investigated using odds ratio (OR) estimates. ORs and 95% confidence intervals were calculated for the predefined outcomes under the random effects model (DerSimonian-Laird). Within and in-between differences were analyzed with the Cochran test for heterogeneity and I 2 statistics. The same approach was used to investigate statistical differences in outcome measures in AIS patients with concurrent COVID-19 (AIS pos ) compared to noninfected AIS patients. Two-sided p < 0.05 was set as the level of statistical significance. Before the first wave, the number of hospitalized AIS patients slightly increased by 1.0% as compared to the corresponding period in 2019. During the first and second waves of the COVID-19 pandemic, there was a marked decline in patients hospitalized for AIS, with −10.9% during the first and −4.6% during the second pandemic wave period. In between, case numbers increased again, with only a mild decline (−1.5%) in hospitalized AIS patients compared to the previous year period ( Figure 1 ). The age of hospitalized AIS patients in 2020 did not differ from the previous year (Table 1) . During both the first and second pandemic wave, we observed a greater decline in hospital admissions of female as compared to male AIS patients (first wave: −11.8% vs. −10.1%, second wave: −6.1% vs. −3.1%). This difference was statistically significant for the second pandemic wave (Table 1 ). The proportion of AIS patients who received stroke unit care was higher before the first wave (73.9% vs. 72.1%, p < 0.001), during the first wave (76.7% vs. 74.2%, p < 0.001), and after the first wave (75.9% vs. 75.1%, p < 0.001) of the pandemic as compared to the 2019 periods. During the second wave, the proportion of SUC decreased to 74.1%, which was significantly lower as compared to the corresponding period in 2019 (76.4%, p < 0.001; Table 1 ). The use of IVT in AIS patients was significantly lower during the second wave (16.0% vs. 17.0%, p < 0.001) but did not differ in any other period as compared to 2019. The MT rate was consistently higher in 2020 as compared to 2019, with the most remarkable difference during the first wave of the pandemic (8.1% vs. 6.8%, p < 0.001; Table 1 ). The proportion of AIS patients who died during the hospital stay was significantly higher during the first wave period in 2020 as compared to the corresponding period in 2019 (8.0% vs. 7.5%, p = 0.021), whereas there was no statistical difference in any other time period (Table 1) . Log OR estimates for all outcomes are displayed in Figure 2 . Throughout the year 2020, a total of 1268 hospitalized AIS patients were coded with a concurrent COVID-19 diagnosis in Germany. The number of these AIS pos patients peaked during the first and second wave of the COVID-19 pandemic, with the highest number during the second wave period (n = 909, 1.9% of all AIS patients in this period; Table 2 ). The mean age of the AIS pos patients was 76.6 years, and 50.1% were male. The overall SUC, IVT, and MT rates were Table 2 ). The proportion of AIS pos patients receiving MT increased from the first wave (6.7%) to the second wave period (8.5%, p = 0.337). There was no significant difference in the use of MT in AIS pos patients compared to AIS patients without COVID-19 (first wave: 8.1%, second wave: 7.9%, p > 0.05 for both comparisons). The highest MT rate in AIS pos patients was found during the pre-second wave period (14.8% vs. 7.8% in noninfected AIS patients, p = 0.066). Overall, 289 of 1268 AIS pos patients (22.8%) died during hospital stay compared to 15,619 of 208,986 noninfected AIS patients (7.5%, p < 0.001). The in-hospital mortality rate in AIS pos patients was 20.6% during the first pandemic wave, 10.2% in the pre-second wave period, and finally increased to 24.6% in the second pandemic wave period (Table 2 ). There was a substantial decline in patients hospitalized for AIS in 2020, with the most pronounced decline during the first wave period of the COVID-19 pandemic in Germany. Although the number of COVID-19 patients was much higher during the second pandemic wave, the decrease in AIS patient hospitalizations was only approximately half of that compared to the first wave period. A significant decrease in stroke admissions has also been noted in other European countries, such as Greece. Data from three representative tertiary care hospitals showed that the decline in stroke admissions and acute coronary syndromes was almost similar between the first two pandemic wave periods, although the number of new infections with SARS-CoV-2 was also higher in Greece during the second wave period [9, 10] . For Germany, we also found differences in German citizens' mobility between the two wave periods. The national analysis of mobile communication data in Germany revealed an average mobility reduction of −20% during the first and only −9% during the second wave period as compared to the corresponding periods in 2019 [11]. The decline in German citizens' mobility during these periods was probably a consequence of the national lockdowns. The probable lower obedience to the second lockdown that the difference of the mobility reduction between the first and second wave period might reflect indicates a change in behavior of German citizens. During the first pandemic wave, there was a great fear of acquiring a SARS-CoV-2 infection during a hospital stay [12] . Although specula- In-hospital mortality rate 22.2% (7.4%) 20.6% c (7.9%) 10.2% (7.1%) 24.6% c (7.7%) Note: Age is given as mean ± standard deviation, and rates are shown in percent. Pandemic periods in 2020 are defined as pre-first wave: January to February, first wave: March to May, pre-second wave: June to September, and second wave: October to December 2020. The corresponding data of patients without concurrent COVID-19 is given in parentheses. Abbreviations: AIS, acute ischemic stroke; IVT, intravenous thrombolysis; MT, mechanical thrombectomy; SUC, stroke unit care. a p <0.05 for comparing pre-first and pre-second wave periods. Furthermore, there was no change in the German coding system nor a revision of the ICD version during the analyzed periods that could have affected the coding quality. Despite these common limitations, administrative data have been considered appropriate for investigating such dynamics over the years [25] . A substantial decline in AIS hospitalizations characterized the first pandemic wave in spring 2020. Although the number of patients with COVID-19 was much higher during the second wave period in fall/winter 2020, the decline in AIS hospitalizations was substantially lower compared to the first wave period. This was most likely attributable to reduced fear of infection, routine implementation of hygiene concepts, and improvements in hospital infrastructure for effective clinical management of COVID-19 patients. Irrespective of comorbid COVID-19, acute AIS therapies remained at high levels in Germany during the first and second pandemic wave period, including recanalization treatments and SUC. Nevertheless, AIS and concurrent COVID-19 were associated with very high in-hospital mortality. Open access funding enabled and organized by Projekt DEAL. WOA Institution: Ruhr-Universitat Bochum Blended DEAL: Projekt DEAL. None. This study represents a secondary data analysis of data from the German Federal Statistical Office, complying with the German data protection regulations. No informed consent or ethical approval was required. The data that support the findings of this study are available from the corresponding author upon reasonable request. Ralph Weber https://orcid.org/0000-0002-5486-7027 Christos Krogias https://orcid.org/0000-0003-2965-4051 COVID-19 and cerebrovascular diseases: a comprehensive overview Letter to the editor: Comparison of stroke care parameters in acute ischemic stroke patients with and without concurrent Covid-19. 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Additional supporting information may be found online in the Supporting Information section.