Functional outcome in patients with stroke and COVID-19.

INTRODUCTION

The coronavirus disease that appeared in China in December 2019, currently a global
pandemic that to date the World Health Organization reports more than 4 million new
cases and 71,000 new deaths per week (1)
Cerebrovascular disease (CVD) represents the second cause of death due to non-
communicable disease in the world and it is one of the pathologies with the highest
burden of disease. (17,18) Cerebral infarction is the most frequent type of CVD,
representing more than 80 % of cases. (19,20)
SARS-Cov-2 binds to ACE2 (angiotensin 2-converting enzyme) receptors, widely
expressed in the Central Nervous System, including endothelial and capillary cells of the
brain as well as due to its expression in the heart, relating SARS-CoV2 infection with
strokes of cardioembolic origin (5, 7-8)
Potential mechanisms by which COVID-19 could increase the risk of stroke have also
been described as hypercoagulability, exaggerated systemic inflammation or a cytokine
storm, which is a marker of severe disease and cardioembolism due to virus-related heart
injury. (11-12)
In patients with stroke, the presence of COVID-19 could be a potential extrinsic factor in
the genesis or worsening, as well as high levels of pro-inflammatory biomarkers
contribute to increasing the risk of stroke, especially in older adults. (13.14)
It has been suggested that COVID-19 could cause or trigger CVD, so further
investigation is required. (16) Growing evidence shows reports of stroke cases in patients
with COVID-19, including a worse prognosis in patients with strokes and COVID-19.
(21) As the disease spreads globally, new evidence emerges, and it is important to know
the factors associated with the functional outcome in patients with stroke and COVID-19.

METHODS
 We conducted a case-control study, where 104 participants were included; the cases were 33
patients with confirmed or probable diagnosis of COVID-19 by chest tomography and rapid
serological test and with the diagnosis of cerebral infarction diagnosed by neuroimaging
(tomography or resonance) who attended the “Instituto Nacional de Ciencias Neurológicas”
in the period of may to december of the year 2020. The controls were 71 patients with a
diagnosis of cerebral infarction without COVID-19, matched by sex and age, those who
received the diagnosis in the period from january to december of the year 2019. A descriptive
analysis was carried out in which the proportions were determined with their respective
confidence intervals, the medians with interquartile ranges and the means with standard
deviation according to the type of variable. In addition, multivariate analysis was performed
to evaluate the association between the functional outcome of the stroke and COVID-19
adjusting by age and score of NIHSS. Data were analyzed using STATA 15.0.

RESULTS

One hundred and four patients were included in the study, the mean age was 64.13 years,
with a discrete predominance of males (55.8%). Of the cases, 9 had PCR positive, 11 had
negative PCR of which 4 have positive IgM and IgG, 2 have positive IgM, 4 have
positive IgG, 1 have no rapid test results. Thirteen have no PCR performed, of which 8
have positive IgG and IgM, 3 only have positive IgG, 2 only have positive IgM.

The median of the illness time was 24 (9-48) hours. The mean of the systolic pressure
was 140.44 mmHg (SD:27.42) and 79.52 mmHg (SD:16.97) for diastolic pressure. The
median of glycosylated hemoglobin was 5.7 mg/dl (IQR:5.4-6.4), the media of LDL
cholesterol 110.5 mg/dl (SD:48.61). The baseline score of the modified Rankin
scale(mRS) was 0, while the median of the score at discharge was 3 (IQR:2-4).

Among the comorbidities, 64 (61.5%) had arterial hypertension, 22 (21.15%) had

diabetes mellitus 2, 18 (17.3%) a history of stroke, 21 (20.19%) had dyslipidemia, as well
as 18 (17.48%) had arrhythmia.

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 Regarding the affected territory, 62 (59.62%) developed a stroke in the anterior cerebral
territory, 36 (34.62%) in the posterior cerebral territory and 6 (5.77%) had a multiple
territory stroke.

There were no differences between the sex, age, education, ilness time, blood pressure.
The cases had a higher level of serum baseline glucose than the controls (133 (IQR:119-
168) versus 118 (102-137) p=0.002). There were no differences in the parameters of lipid
profile. The level of neutrophils was higher in the group of cases ( 7.91 (IQR:6.3-9.3)
versus 5.86 (IQR:4.5-7.8) p=0.002). The cases had a lower count of lymphocytes (1.48
(IQR:1.1-1.8) versus 1.82 (IQR:1.3-2.3) p=0.015). The index of neutrophils/lymphocytes
was higher in the cases (5.38 (IQR:4-8) versus 3.29 (IQR:2.26-5.98) p=0.001). There
were no differences between the comorbidities. The cases had a higher NIHSS score
(14.5 (IQR:9.5-18) vs 7 (IQR:5-11); p=0.000) The cases had a higher mRS at discharge
(4 (IQR:4-5) versus 2 (IQR:1-4) p=0.000). Eight (24.24%) participants died in the group
of cases versus 1 (1.41%) in the controls (p=0.000).

The OR of having an unfavorable outcome (mRS<3) was 3.95 (CI 95%:1.107-14.100,

p=0.034), adjusted for age and NIHSS at admission.

DISCUSIÓN
Durante la pandemia de SARS - CoV -2, de forma temprana se reportaron series de casos sobre
la concomitancia de Distrés respiratorio agudo y eventos cerebro vasculares, la explicación, un
posible mecanismo de daño endotelial que incrementa el riesgo de tromboembolismo, así como
la hipercoagulabilidad, neurotropismo y cardioembolismo.

En las series se reporta que la ocurrencia de Stroke en pacientes con Covid varía de 1 a 5%,
similar a la incidencia de Stroke en pacientes sin Covid (1%), por lo que la incidencia de Stroke
no varía mucho en pacientes con covid con respecto de los no covid (Qureshi) Aunque su
epidemiología no está publicada, es importante reconocer las características clínicas de estos
pacientes para establecer su pronóstico. (Divani),

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Al igual que en una revisión sistemática (Nanoni) encontramos mayor incidencia de Infarto
Cerebral en mayores de 65 años, con una media de 64.9, años no se encontró una asociación
entre un grupo etario sólo un estudio mostró una media menor (50.9 años ) ( Khandewall) sin
embargo la predominancia es a predominio de varones tal y como se refiere en la literatura.
Los factores de riesgo, como la hipertensión arterial, diabetes, arritmia cardiaca y stroke previo
no demostraron tener significancia para la incidencia de stroke en pacientes con covid con
respecto de No covid.

En nuestro trabajo la circulación anterior fue la más afectada, como lo reporta Ntaios y otros
autores, sin embargo estos reportes pertenecen a pacientes cuya etiología demostrada es la
oclusión de grandes vasos.

Se halló que en pacientes con COVID el puntaje NIHSS fue más alto, 14.25 vs 8.29, aunque con
poblaciones étnica distintas, un resultado similar fue reportado por (Cagnazzo) , postulamos que
esto podría atribuirse a la afección frecuente de la circulación anterior.

Aunque la media del valor de glicemia basal (133 mg/dl) en los pacientes en estudio se encuentra
dentro del rango recomendado por la guía de la AHA, (AhA), al igual que lo reportado en otras
series (Bi Fun) se halló que existe también una relación directa entre su valor elevado y un peor
pronóstico funcional en pacientes Con Stroke y Covid, aunque no hay estudios dirigidos. Se ha
demostrado que los pacientes con Covid Moderado a Severo cursan con valores más altos de
glucosa sérica y hemoglobina glicosilada debido a que el Sars Cov 2 en su fisiopatología podría
inducir hiperglicemia. Por lo que es necesario estudios para profundizar este aspecto.

Nuestros hallazgos, demostraron que el tener Covid está directamente relacionado con una
mayor discapacidad al alta y un puntaje mayor al alta medida en la escala de Rankin modificada
I(4 vs 3). Esto se explicaría por el compromiso multisistémico propio de la infección, ademas de
la presencia de marcadores séricos elevados (Quin7- Qreshi)
.
En cuanto a la etiología al igual que lo descrito por (Jillella), el (%) de los pacientes con Stroke y
Covid pertenecen a la categoría de Infarto de causa indeterminada, probablemente a las

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complicaciones propias del cuadro respiratorio y a la dificultad para acceder a distintas carteras
de servicios por las medidas de bioseguridad establecidas para el control de la pandemia.

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