Danish Neurological Study Shows That Compared To Influenza Or Bacterial Pneumonia, COVID-19 Infections Lead To Higher Risk Of Ischemic Strokes!
: A new study by researchers from Copenhagen University Hospital- Denmark and the University of Copenhagen-Denmark has shown that compared to influenza or bacterial pneumonia, COVID-19 infections lead to higher risk of ischemic strokes!
Ischemic stroke occurs when a blood clot blocks or narrows an artery leading to the brain. A blood clot often forms in arteries damaged by the buildup of plaques (atherosclerosis). It can occur in the carotid artery of the neck as well as other arteries.
Ischemic strokes can lead to brain damage or even death.
Signs and symptoms of stroke include:
-Trouble speaking and understanding what others are saying. You may experience confusion, slur words or have difficulty understanding speech.
-Paralysis or numbness of the face, arm or leg. You may develop sudden numbness, weakness or paralysis in the face, arm or leg. This often affects just one side of the body. Try to raise both your arms over your head at the same time. If one arm begins to fall, you may be having a stroke. Also, one side of your mouth may droop when you try to smile.
-Problems seeing in one or both eyes. You may suddenly have blurred or blackened vision in one or both eyes, or you may see double.
-Headache. A sudden, severe headache, which may be accompanied by vomiting, dizziness or altered consciousness, may indicate that you're having a stroke.
-Trouble walking. You may stumble or lose your balance. You may also have sudden dizziness or a loss of coordination.
It is already known that SARS-CoV-2 infections lead to incidences of specific neurological diseases, however it is unknown if this differs from the risk following other infections.
The COVID-19-Ischemic Strokes
study team characterized the frequency of neurodegenerative, cerebrovascular, and immune-mediated neurological diseases after COVID-19 compared to individuals without COVID-19 and those with other respiratory tract infections.
The population-based cohort study utilized electronic health records covering ~50% of Denmark's population (n = 2,972,192). Between 02/2020 and 11/2021, the study included individuals tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia in hospital-based facilities.
The study team also included individuals tested for influenza in the corresponding pre-pandemic period between 02/ 2018 and 11/2019. We stratified cohorts for in- and outpatient status, age, sex, and comorbidities.
Altogether a total, 919,731 individuals were tested for COVID-19, of whom 43,375 tested positive (35,362 outpatients, 8,013 inpatients).
The study findings showed that compared to COVID-negative outpatients, COVID-19 positive outpatients had an increased RR of Alzheimer's disease (RR = 3.5; 95%CI: 2.2–5.5) and Parkinson's disease (RR = 2.6; 95%CI: 1.7–4.0), ischemic stroke (RR = 2.7; 95%CI: 2.3–3.2) and intracerebral hemorrhage (RR = 4.8; 95%CI: 1.8–12.9).
>Importantly, when comparing to other respiratory tract infections, only the RR for ischemic stroke was increased among inpatients with COVID-19 when comparing to inpatients with influenza (RR = 1.7; 95%CI: 1.2–2.4) and only for those >80 years of age when comparing to inpatients with bacterial pneumonia (RR = 2.7; 95%CI: 1.2–6.2).
The frequencies of multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome and narcolepsy did not differ after COVID-19, influenza and bacterial pneumonia.
The study findings showed that the risk of neurodegenerative and cerebrovascular, but not neuroimmune, disorders was increased among COVID-19 positive outpatients compared to COVID-negative outpatients. However, except for ischemic stroke, most neurological disorders were not more frequent after COVID-19 than after other respiratory infections.
The study findings were published in the peer reviewed journal: Frontiers in Neurology. https://www.frontiersin.org/articles/10.3389/fneur.2022.904796/full
To date, much has been said about the long-term effects of COVID-19 disease, including neurological side effects. This is the only study that has compared the rates of onset of several types of neurological illness, whether degenerative, stroke-related or immunological, after COVID-19 or other respiratory infections.
It has been found that over 80% of COVID-19 patients hospitalized with the diagnosis have reported neurological symptoms, the most common being headache and anosmia. An increased clotting tendency also exists, and strokes have been described to happen as a complication. Some patients have developed neuropathies such as Guillain-Barre syndrome (GBS) or Parkinson’s disease (PD).
Such occurrences have led researchers to question as to whether COVID-19 actually increased the risk of neurodegenerative or post-infectious neurological disease.
The study team examined electronic health records (EHR) for approximately half the population of Denmark, looking for people with a diagnosis of COVID-19 or hospitalized with community-acquired pneumonia, in the period from February 2020 to November 2021. The researchers also included people tested for the flu between February 2018 and November 2019.
It was found that of over 900,000 people with a history of COVID-19 testing, over 43,000 tested positive. During the same period, approximately 1,500 people had bacterial pneumonia. Thirdly, during the study period, over 8,000 had influenza.
Interestingly, the group of individuals with COVID-19, whether hospitalized or not, had higher rates of COVID-19 risk factors, such as high cholesterol levels, type 2 diabetes mellitus and hypertension, than those hospitalized with the flu.
Also, it was found that obesity was more common in COVID-19-positive individuals, or those hospitalized with influenza, and have a history of transient ischemic attacks (TIA).
It was also noted that the latter was more likely among pneumonia inpatients as well, as was smoking, which was also more common among influenza inpatients. Delirium, which is known to be a risk factor for dementia, was more common among COVID-19 patients, at double the frequency among non-COVID-19 patients.
Alarmingly, the risk of hemorrhage into the brain was 5 times higher for outpatients with a history of COVID-19. Against this, it must be remembered that intravenous thrombolysis was seven times more common in this group, at 0.14%. Even after accounting for this risk factor, the risk continued to be over four-fold higher.
The study findings showed that Alzheimer’s disease (AD) risk increased by 3.5 times, up to a year later. This was the case even after excluding cases with delirium and those who were at risk for stroke, both of which are independent risk factors for AD.
The findings also revealed that the risk of Parkinson’s disease and ischemic stroke were almost 3-fold higher at up to 12 months in those with a diagnosis of COVID-19.
This was however brought into perspective when compared with the rates of the same conditions among individuals who had been hospitalized with influenza or bacterial pneumonia, who showed equivalent rates of both AD and PD.
When compared, it was found that the risk of stroke was almost twice as high among COVID-19 outpatients (but not combined in- and out-patients, or inpatients alone), compared to those without COVID-19, once stroke risk factors were compensated for. This risk was not seen at one month, but began to become obvious from 3 months post-COVID-19. The increase in risk was highest among patients aged 40-59 years, younger than the typical at-risk group for ischemic strokes.
Shockingly when compared to those with influenza, COVID-19 inpatients also showed a 70% increase in the stroke risk up to 6 months later, diminishing to 30% at one year. When stroke risk factors were accounted for, the risk was found to be tripled or higher in COVID-19 inpatients, even at one year.
Also, when compared to inpatients with bacterial pneumonia who were over 80 years of age, the risk was almost 3 times higher among COVID-19 inpatients, but no overall increase in risk was found after accounting for the stroke risk factors.
The study findings showed that there was no observable difference in the rates of post-infectious neuropathies or neurodegenerative disease among those with or without a history of any of these infectious conditions.
The study findings indicate a causative role of neuroinflammation, tiredness and negative emotions in COVID-19 patients that may have contributed to the higher incidence of AD and PD at one year from the initial diagnosis. Young patients who died of COVID-19 have been found to have abnormally elevated concentrations of the pathological protein β-amyloid in their brains.
Importantly there was an increased incidence of ischemic stroke among COVID-19 patients compared to those with a history of influenza or bacterial pneumonia. The explanations may include the inflammatory state, the cardiac involvement leading to cardiac embolism, immobilization during the hospital stay, or some unique characteristic of this infection.
Also, the incidence of intracerebral bleeds was more common at one month among COVID-19 outpatients, compared to individuals without COVID-19, but comparable to that found after prior influenza or bacterial pneumonia. Risk factors include anticoagulant therapy, mechanical ventilation, and the use of extracorporeal membrane oxygenation (ECMO).
The study findings showed that even after compensating for thrombolysis, the risk of hemorrhage remained elevated, showing that COVID-19 itself posed a risk factor.
The study findings suggest that patients with a history of respiratory infections should be monitored for neurodegenerative disorders, and that ischemic stroke appears to be a risk peculiar to COVID-19.
It should also be noted that when looking at global excess death figures in the last 24 months, cause of deaths by ischemic strokes comes in second place behind heart failures.
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