Introduction {#sec0001}
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During the coronavirus disease 2019 (COVID-19) pandemic the use of health care systems changed suddenly. Hospitals were overwhelmed as a result of the staggering COVID-19 patient numbers[@bib0001] and/or modified their daily routine due to prophylactic allocation of resources.[@bib0002] Public lockdowns with strict containment recommendations for the community have been announced around the world.[@bib0003] Emergency Medical Services (EMS) and dispatch centers were confronted with increasing numbers of patients/calls and reorganization of the dispatch system including Code Stroke patient referral.[@bib0004], [@bib0005], [@bib0006] Though COVID-19 disease is associated with vascular thrombotic events,[@bib0007] several studies suggest a decline of patients with vascular diseases and strokes presenting to hospitals since the beginning of the pandemic.[@bib0008], [@bib0009], [@bib0010], [@bib0011], [@bib0012], [@bib0013], [@bib0014], [@bib0015] Probably, less severely affected stroke patients avoided emergent medical evaluation.[@bib0013] ^,^ [@bib0016] It was speculated that patients changed their health care utilization patterns during the pandemic and its lockdowns.[@bib0017] So far, it is unclear how EMS and their Code Stroke patient referral system were affected during the pandemic. Mostly, stroke patients are admitted to hospitals by EMS as Code Stroke patients.[@bib0018] A sufficient maintenance of the interplay between EMS and stroke units during a pandemic and public lockdown is crucial to provide appropriate stroke care. In the present study, we analyzed numbers and patterns of Code Stroke patients dispatched by EMS during the COVID-19 pandemic at a German Comprehensive Stroke Center, which is located at one of the pandemic hotspots in Germany.

Methods {#sec0002}
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Study design {#sec0003}
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We retrospectively analyzed all consecutive patients with an activated Code Stroke by the EMS following prehospital triage and who were directly referred to our stroke unit between 1^st^ January 2020 and 19^th^ April 2020 using the electronic database *IVENA eHealth* of the Munich EMS dispatch. The time period 1^st^ January 2020 to 20^th^ March 2020 was defined as *pre-lockdown* and the time period during the Bavarian public lockdown between 21^st^ March 2020 and 19^th^ April 2020 as *lockdown* ([Fig. 1](#fig0001){ref-type="fig"} ). We extracted EMS admission patterns and analyzed patient data regarding age, sex, stroke severity as measured by the National Institute of Health Stroke Scale (NIHSS), diagnosis of discharge and mode of treatment in case of ischemic strokes. Based on the diagnosis of discharge, patients were categorized as stroke (ischemic stroke, hemorrhagic stroke, transient ischemic attack) or stroke mimic, respectively. Given the retrospective and anonymous design, approval by the local ethics committee and a need for written consent was waived based on the Bayerisches Krankenhausgesetz (Section 27, paragraph 4). The study conforms with World Medical Association Declaration of Helsinki. Data that support the findings of this study are available from the corresponding author upon reasonable request.Fig. 1Number of SARS-CoV-2 infections in Bavaria. Public lockdown came into force the 21^st^ of March.Fig 1

Local COVID-19 measures and patient referral {#sec0004}
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In Bavaria the first COVID-19 patient was recorded the 27^th^ of January 2020. To prevent further infections, among others, a public lockdown came into force between the 21^st^ of March ([Fig. 1](#fig0001){ref-type="fig"}) and all hospitals were obliged to allocate resources for expected COVID-19 patients.[@bib0019] For all patients admitted to our hospital strict hygienic measures were applied.[@bib0020] The standard procedure to refer patients to stroke units directly via EMS was continued during the pandemic. The referral is organized and monitored by the *Integrierte Rettungsleitstelle München*, which is the EMS dispatch center for Munich metropolitan area in Upper Bavaria.

Statistical analysis {#sec0005}
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Analysis were performed using GraphPad Prism version 7.04 (GraphPad). Quantitative differences between groups were analyzed using Student\'s t-test or the non-parametric Mann-Whitney U test (two-tailed tests) depending on whether or not values followed a Gaussian distribution. Categorical differences were evaluated using bivariate analysis with Fisher\'s exact test. Association between Stroke Unit availability and referral patterns were evaluate using Pearson correlation. The statistical significance threshold was p\<0.05. Values are provided as mean ±standard deviation (SD) if normally distributed, otherwise as median (25%--75% interquartile range (IQR)).

Results {#sec0006}
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During the lockdown, daily availability of our stroke unit to admit Code Stroke patients by EMS increased from 51% (12 ± 7 h) to 86% (20 ± 4 h; *p* \<0.001). During the study period, 246 direct Code Stroke referrals to our stroke unit were identified. Five patients were excluded from analysis, as they were transferred from other hospitals for thrombectomy with activated Code Stroke. This resulted in a study population of 241 patients. Mean age was 73.0 ± 16 years. 117 patients (48.5%) were female.

A total of 171 patients was referred to us during pre-lockdown and 70 patients during lockdown ([Fig. 2](#fig0002){ref-type="fig"} A). There were no differences in EMS-based daily referral of Code Stroke patients between pre-lockdown and lockdown ([Fig. 2](#fig0002){ref-type="fig"}B). Comparable portions of daily referred patients were categorized as stroke mimic during pre-lockdown (50% (IQR 13-100)) and lockdown (50% (IQR 31-67)). There were no differences in daily referral numbers of ischemic strokes, hemorrhagic stroke, and transient ischemic attacks between both periods (data not shown). By trend, we found a weak association between daily availability of our Stroke Unit and daily admission numbers (Pearson *r* = 0.16, *p* = 0.10).Fig. 2Code Stroke patient referral. A, Absolute daily number of all referred patients. B, median daily number of all referred patients.Fig 2

Age between patients before and during the lockdown did not differ (73.8 ± 16 versus 71.0 ± 16 years; *p* = n.s.). The rate of female patients decreased significantly during lockdown ([Fig. 3](#fig0003){ref-type="fig"} A). NIHSS scales of stroke at admission patients increased from 3 (IQR 0--7) to 6 (IQR 1--15.5) points during the lockdown ([Fig. 3](#fig0003){ref-type="fig"}B). The portion of patients receiving invasive stroke treatment between both time periods did not change ([Fig. 3](#fig0003){ref-type="fig"}C). No associations between daily Stroke Unit availability and stroke severity or sex were detected (data not shown).Fig. 3Patients' characteristics. A; fraction of female patients. B, Median NIHSS (National Institutes of Health Stroke Scale) values. C, fraction of thrombolysis/thrombectomy in patients with ischemic stroke. \* indicates p values \<0.05.Fig 3

Discussion {#sec0007}
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In the present study, we present data about the interaction of EMS and a Comprehensive Stroke Center during the public COVID-19 pandemic lockdown. Our data suggest that EMS services operate stable and reliable during a lockdown, but patients' health care utilization of the EMS may alter within a public lockdown.

We did not observe a clear change of daily referrals to our stroke unit during the lockdown. This suggests a sufficient maintenance of out- and inpatient care providers and EMS organization during the COVID-19 pandemic lockdown, which is in line to a recent Canadian study.[@bib0021] As we did not study all hospitalized patients, but analyzed Code Stroke patients referred by EMS only, our finding is not contradicting previous observations of an overall decline of hospitalized stroke patients.[@bib0008], [@bib0009], [@bib0010], [@bib0011], [@bib0012], [@bib0013], [@bib0014], [@bib0015] Importantly, among admitted Code Stroke patients the proportion of patients with stroke and stroke mimics remained stable, indicating, that the prehospital management including triage of EMS is resilient during this current stress test. This is line to studies from Spain and France, displaying stable rates of stroke mimics during the COVID-19 pandemic.[@bib0022] ^,^ [@bib0023] As none of the prior studies discussed this important point furtherly, we feel the need to highlight this particularly.

The increased availability of our stroke unit within the public lockdown is most likely explained by the legal measures to stop routine out- and inpatient visits, resulting in vast capacities in German hospitals. As we found a weak and non-significant association of daily referral numbers and availability of our stroke unit, we cannot rule out that this issue may affect our observations. In addition to first examples showing that in hospital stroke care can be upheld sufficiently during this crisis,[@bib0024] our data suggest that strict containment measures do not necessarily disrupt the interplay of stroke units and EMS.

Since we detected a shift to male and more severely affected stroke patients during the lockdown, our data suggest a change in patients' behavior and subsequent health care utilization. This fits well to prior studies.[@bib0013] ^,^ [@bib0016] Possibly, patients avoid calling EMS and inpatient hospital care in fear of being infected with SARS-CoV-2.[@bib0017] As such patients may benefit from therapy similarly, this aspect should be analyzed in detail during future studies. Providing stroke care to those patient subgroups during future pandemics will be crucial. Intense public education might be required prior to further lockdowns.

Our study has several limitations. Besides the retrospective data collection, our study is monocentric and does not address referral patterns in bigger areas. Multicenter studies covering whole districts are necessary to minimize the risk of skewed datasets. It should be noted that most actions to fight the pandemic were taken in a prophylactic manner and not as consequence of a health care system collapse in Germany. Thus, our findings might not be easily transferred to other regions in the world. However, since our hospital is located within a COVID-19 hotspot in Germany and treated more than 200 patients with COVID-19 till June 2020, our monocentric data provide important notes for coordination units and EMS to prepare for future lockdowns.

Declaration of Competing Interest {#sec0008}
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BH reports personal fees from Desitin, personal fees from Novartis, personal fees from AllergyCare, personal fees from TG Therapeutics, grants from Regeneron, outside the submitted work. BK reports grants from Novartis, during the conduct of the study; other from Novartis, grants from German Federal Ministry of Education and Research, grants from Technical University of Munich, School of medicine, outside the submitted work. BI, MD, KGK and SW have nothing to disclose.

Grant support {#sec0009}
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None.

Acknowledgments {#sec0010}
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None.

Sources of funding {#sec0011}
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No sources of funding were utilized for this project.

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[^4]: Contributed equally

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