key: cord-1049311-60x2gflg
authors: Cougo, Pedro; Bessen, Bruno; Bezerra, Daniel; Moreira, Rodrigo de Carvalho; Brandão, Carlos Eduardo; Salgueiro, Emmanuel; Balduino, Alex; Pontes-Neto, Octávio; Cravo, Victor
title: Social distancing, stroke admissions and stroke mortality during the COVID-19 pandemic: a multicenter, longitudinal study
date: 2022-02-21
journal: J Stroke Cerebrovasc Dis
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106405
sha: d94501f5f5195e861634b236f72851b679b31681
doc_id: 1049311
cord_uid: 60x2gflg

Objectives. We aimed to evaluate the relationship between social distancing, stroke admissions and stroke mortality during the COVID-19 pandemic, while accounting for the rate of COVID-19 admissions. Methods. We performed a longitudinal analysis of a multicenter, prospective, hospital-based registry of intensive care units from 19 hospitals from Brazil, comprising a 14-month period of the COVID-19 pandemic. We investigated whether the daily rate of admissions (DRA(stroke)) and daily mortality rate for stroke were associated with the social distancing index (SDI), taking into account the daily rate of admissions for COVID-19 (DRA(COVID)) in univariate and multivariate regression models. We also compared the clinical characteristics of patients with stroke admitted before and during the pandemic. Results. We found that DRA(stroke) decreased significantly in association with a strong rise in the SDI during the early months of the pandemic. However, in the latter period of the pandemic, only minor changes were observed in the SDI, and still, DRA(stroke) was inversely associated with the DRA(COVID). Throughout the pandemic, higher SDI and DRA(COVID) were associated with higher in-hospital mortality for stroke. Conclusions. The severity of surges of the COVID-19 pandemic were independently and persistently associated with declines in stroke admissions, even during periods when social distancing policies were not intensified.

rate of COVID-19 admissions. Methods. We performed a longitudinal analysis of a multicenter, prospective, hospital-based registry of intensive care units from 19 hospitals from Brazil, comprising a 14-month period of the COVID-19 pandemic. We investigated whether the daily rate of admissions (DRA stroke ) and daily mortality rate for stroke were associated with the social distancing index (SDI), taking into account the daily rate of admissions for COVID-19 (DRA COVID ) in univariate and multivariate regression models. We also compared the clinical characteristics of patients with stroke admitted before and during the pandemic. Results. We found that DRA stroke decreased significantly in association with a strong rise in the SDI during the early months of the pandemic.

However, in the latter period of the pandemic, only minor changes were observed in the SDI, and still, DRA stroke was inversely associated with the DRA COVID . Throughout the pandemic, higher SDI and DRA COVID were associated with higher in-hospital mortality for stroke. Conclusions. The severity of surges of the COVID-19 pandemic were independently and persistently associated with declines in stroke admissions, even during periods when social distancing policies were not intensified. Keywords: acute stroke; epidemiology; systems of care; COVID-19.

A relationship between COVID-19 and stroke has been speculated since the beginning of the pandemic, following initial case series of stroke as a presenting symptom of COVID- 19 , and given that COVID-19 is currently well known for its high risk of arterial and venous thromboembolic complications. (1, 2) Many studies have addressed the rate of cerebrovascular events in patients admitted with COVID-19. (3) (4) (5) Stroke is the second most common neurological complication among COVID-19 patients, after encephalopathy, and the rate of stroke among hospitalized patients with COVID-19 has been reported as 1-3%. (6) (7) (8) (9) On the other hand, it has been hypothesized that social distancing, lockdown policies and the overwhelming burden of hospital admissions for COVID-19 could negatively influence the concern for stroke symptoms, the search for emergency care, and actual access to hospital care.(10-12) Indeed, it has been shown that in the first months of the pandemic and during periods of intense social distancing, hospital admissions for stroke, use of stroke imaging and of reperfusion therapies dropped significantly. (12) (13) (14) (15) (16) (17) (18) (19) However, a long-term, longitudinal, quantitative assessment of a concurrent association between stroke admissions, stroke outcomes and social distancing has not been reported.

We therefore aimed to evaluate whether social distancing indexes had any association with the rate of stroke admissions and in-hospital mortality, taking into account the rate of intensive care unit (ICU) admissions for COVID-19, during a fourteen-month period of the ongoing pandemic in Brazil, using a large, prospective, hospital-based, ICU registry. We also aimed to compare the profile of stroke patients and their final hospital outcome between the pandemic and pre-pandemic periods.

We performed a retrospective analysis of a prospective, multicenter, hospital-based registry oriented to clinical and administrative purposes. 

In this registry, consecutive patients are recruited once admitted to the ICU, and are followed up daily until hospital discharge. Registry data are extracted from local electronic medical records and are entered daily by trained nurses during working days. We selected patients from January 1 st , 2019 to May 31 st , 2021, and included patients with the following database codes for ICU admission: "Ischemic stroke", "Transient ischemic attack" "Intraparenchymal hemorrhage", "Intraparenchymal hemorrhage surgery", "Subarachnoid hemorrhage", "Cerebral venous thrombosis" and "COVID-19". We extracted admission variables, including demographics, comorbidities, cause of admission, and final hospital outcome (discharged alive or not).

We obtained social distancing indexes (SDI) during the pandemic period from the cities where the hospitals of the network are located from data made publicly available by the Health Secretariat of the State of São Paulo.(23) SDI is derived from cell phone data shared by the main phone companies in Brazil with the Health Secretariat. Adherence to social distancing is determined whenever the phone location during the day was maintained during the day within 200 meters from its location between 10:00 PM and 02:00 AM. The SDI is updated daily and is represented as a percentage of identifiable cell phones adherent to the aforementioned criterion. (24) Mean SDI across the nine cities was used for statistical analysis.

Rate of admissions were reported as daily rate of admissions (DRA). Daily rates of inhospital stroke mortality (DRM stroke ) were calculated as the ratio between the 14-day moving average of stroke-related deaths and the 14-day moving average of stroke admissions.

Other variables were reported as either a mean value ± standard deviation, a median value with an interquartile range (IQR), or as absolute frequencies and proportions.

Pandemic and pre-pandemic characteristics of stroke patients were compared in univariate analysis using using Student's t-test or Wilcoxon two-sample rank sum test for quantitative variables and Fisher's exact test for binary variables, as appropriate.

Independent predictors of mortality were assessed using multivariable logistic regression, with inclusion of variables associated with outcome in univariate analysis, and exclusion by stepwise, backward selection of variables.

To investigate the relationship between the daily rate of stroke admissions (DRA stroke ), DRM stroke , SDI and the daily rate of COVID-19 admissions (DRA COVID ), we built univariate and multivariate generalized linear models having DRA stroke or DRM stroke as the dependent variable, using the Poisson method or linear regression, respectively. This analysis was performed for the whole pandemic period and also separately for each of the pandemic periods of acceleration and descent ("waves") of admissions. P-values below 0.01 were considered statistically significant. Statistical analysis were performed using R (version 21.04).

The proportion of ischemic strokes. Overall, the daily rate of admissions for stroke and for all stroke subtypes was lower during the pandemic period ( Table 1) . Stroke in-hospital mortality had higher peaks at the early beginning of the pandemic and during the two later surges of COVID-19 admissions (Figure 1) . In multivariable analysis, admission during the pandemic period was independently associated with hospital mortality (OR = 1.040; 95% Using the nadir of MA COVID as a divisor of the two periods of the pandemic, we found that social distancing showed distinct behaviors during the two main periods of COVID-19 acceleration (Figure 1) . In the first period, there was a sharp and early increase in the SDI and a gradual decrease during the following six months. This contrasted with the second period, when observed responses in the SDI due to the worsening of the pandemic were small. The pattern of SDI variation during the pandemic was similar across the cities (Figure 2) . When analyzing the whole pandemic period, both DRA COVID and SDI were inversely associated with DRA stroke . During the first period, DRA stroke suffered a sharp decline inversely associated with SDI, while no association with DRA COVID was observed.

On the other hand, during the second period, DRA stroke was inversely associated with DRA COVID , when SDI showed minor variations that were unrelated to DRA stroke ( Table 2 ).

In this study, the pandemic of COVID-19 was associated with reduced ICU admissions for stroke, with periods of acceleration of the pandemic timely correlated with declining rates of stroke admissions, and an overall lower rate of stroke admissions when compared to 2019. While social distancing was also associated with reduced admissions for stroke, specially during the early phase of the pandemic, stroke admissions were still strongly affected by surges of COVID-19 even when social distancing responses to the pandemic were minor. All stroke subtypes were negatively affected by the rate of COVID-19

admissions, with approximately one less admission per day for every stroke subtype.

Furthermore, patients admitted with stroke during the pandemic had higher mortality.

These data provide an alarming picture that supports the need for continuing public policies aiming at sustaining stroke awareness and stroke network preparedness during the pandemic. In our study, stroke in-hospital mortality was not only higher during the pandemic, but was associated with periods of more intense social distancing and of higher admissions for COVID-19. We believe that this association may reflect two phenomena. First, that the increase in social distancing and the high demand for COVID-19 admissions promoted a selection of more severe patients with stroke for hospital admission. Second, that the burdensome pressure on systems of care imposed by COVID-19 surges might have impacted performance of stroke care. Indeed, some studies have shown that performance of stroke care declined during the pandemic, with increases in door-to-needle and door-togroin times, and a reduction of intravenous thrombolysis and endovascular therapy procedures. (18, (26) (27) (28) (29) In one study, delays in stroke therapy were related to increased time from symptom detection to hospital arrival.(30) These findings underline the hypothesis that the drop in stroke admissions probably reflect increased barriers to stroke care. As our study suggests, however, these barriers cannot be solely attributed to social distancing policies, but rather derive to the severity of the pandemic itself, with the ensuing overwhelming of systems of care.

Global economic disparities could play an important role in the negative impact of the pandemic on stroke care. Shahjouei et al reported that stroke patients with COVID-19 from countries with lower health expenditure had higher NIHSS scores at admission and lower rate of mechanical thrombectomy, which suggests that the negative impact of the COVID-19 pandemic on healthcare access is probably more severe in developing countries. (4) In our study setting, we have found stroke admissions to be still negatively impacted by the fluctuating course of the pandemic even 14 months after the first admission for COVID-19.

Thus, the COVID-19 pandemic is still a developing scenario that could possibly increase the already significant global gap in stroke care. Title. Social distancing indexes in the nine cities included in the registry. Atrial fibrillation 134 (7) 128 (7) Chronic renal disease 123 (7) 122 (7) Days (7) 283 (12) 37 (2) 1398 (68) 235 (11) 188 (9) 187 (9) 34 (2) In-hospital mortality* 236 (10) 295 (14) Daily rate of admissions* 

Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19 : An updated analysis

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

COVID-19-related strokes are associated with increased mortality and morbidity: A multicenter comparative study from Bengaluru, South India

SARS-CoV-2 and Stroke Characteristics: A Report from the Multinational COVID-19 Stroke Study Group

SARS-CoV-2 and Stroke in a New York Healthcare System

Neurologic manifestations associated with COVID-19: a multicentre registry

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease

Acute Cerebrovascular Events in Hospitalized COVID-19 Patients

COVID-19 and Stroke: Incidence and Etiological Description in a High-Volume Center

Acute Stroke in Times of the COVID-19 Pandemic

Impact of COVID-19 on hospital admission of acute stroke patients in Bangladesh

Hospitalizations for Stroke in France during the COVID-19 Pandemic Before, During, and after the National Lockdown

Collateral Effect of Covid-19 on Stroke Evaluation in the United States

Impact of COVID-19 outbreak on ischemic stroke admissions and in-hospital mortality in North-West Spain

Global impact of COVID-19 on stroke care

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore

Impact of COVID-19 pandemic on acute stroke care: facing an epidemiological paradox with a paradigm shift

Impact of the COVID-19 Epidemic on Stroke and Potential Solutions

COVID-19 Lockdown Effects on Acute Stroke Care in Latin America

The Epimed Monitor ICU Database®: a cloud-based national registry for adult intensive care unit patients in Brazil. Rev Bras Ter Intensiva

COVID-19 Brazil Portal. COVID-19 BRAZIL

Adherence to social distancing, Government of São Paulo

Challenges and Strategies for Information Systems in the Decision-Making Process to Face the COVID-19 Pandemic: The São Paulo Case

Decline in mild stroke presentations and intravenous thrombolysis during the COVID-19 pandemic: The Society of Vascular and Interventional Neurology Multicenter Collaboration

Effect of the COVID-19 pandemic and the lockdown measures on the local stroke network

Effect of lockdown on the management of ischemic stroke: an Italian experience from a COVID hospital

Acute Stroke Management during the COVID-19 Pandemic: Does Confinement Impact Eligibility for Endovascular Therapy?

Influence of the COVID-19 Pandemic on Treatment Times for Acute Ischemic Stroke: The Society of Vascular and Interventional Neurology Multicenter Collaboration

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain