COVID-19: Increased mortality rate in concomitant neurological diseases?

A study saw a 13% rate of serious neurological complications in hospitalized COVID-19 patients. Mortality rate was almost 40% higher than in hospitalized COVID-19 patients without neurological complications.

13.5% of hospitalised patients had concomitant neurological diseases

A study1 published in "Neurology" in early October 2020 prospectively surveyed the prevalence of neurological side effects in hospitalised COVID-19 patients. Only severe neurological diseases were recorded, but no "mild" neurological concomitant symptoms such as olfactory or gustatory disorders. The rate of serious neurological complications was 13%. What these concomitant neurological diseases meant for the outcome of the patients is concerning: The mortality rate was almost 40% higher than that of hospitalised COVID-19 patients without neurological complications.

The prospective multicenter observational study1 analysed the course of almost 4,500 patients who were treated in a hospital in New York between March and May for COVID-19 disease. The results showed that 13.5% of the patients developed concomitant neurological diseases. These neurological diagnoses occurred in the median two days after the appearance of COVID-19 symptoms (such as fever, cold symptoms, diarrhoea). The median time to onset after hospital admission was -0.6 days, which means that many patients were already suffering from the neurological symptoms before or at the time of admission.

The most common were toxic or metabolic encephalopathies (6.8% of cases), strokes (1.9%), epileptic seizures (1.6%) and hypoxic brain damage (1.4%). Only neurologically diagnosed serious manifestations were included (encephalopathies, strokes, neuropathies including Guillain-Barré syndrome, myopathies, movement disorders, encephalitis and myelitis), which explains why the rate of concomitant neurological symptoms was relatively low in this study, at 13.5%. Other studies2,3, which also included mild neurological symptoms such as olfactory and gustatory disorders, documented a prevalence of up to 84%, which means that 4 out of 5 patients treated in hospital for COVID-19 have concomitant neurological symptoms.

COVID-19 patients with concomitant neurological disorders have a 38% higher risk of dying in hospital, according to the study

"But a rate of serious neurological complications of 13% is alarmingly high, which ultimately means that every seventh to eighth patient is affected," explains Prof. Peter Berlit, Secretary General of the German Society of Neurology (DGN). "This is a considerable burden for those affected, because the neurological concomitant diseases have a clear implication for the prognosis, as the present study shows" he added.

The authors compared the outcome of patients with concomitant neurological disorders with the outcome of those without neurological manifestations. Compared to these, the neurologically affected patients were older (median 71 vs. 63 years old), more often male (66% vs. 57%) and of white ethnicity (63% vs. 45%). However, even after these and other risk factors were excluded, i.e. adjustment according to age, sex, SOFA score ("Sepsis-related Organ Failure Assessment"), intubation and previous illnesses, COVID-19 patients with neurological concomitant diseases had a 38% higher risk of dying in hospital (p < 0.001) and a 28% lower probability of being discharged home (p < 0.001).

Neurological expertise should be available for intensive care of seriously ill COVID-19 patients

"The neurological manifestations recorded here are an indicator of the severity of COVID-19 disease. With increasing knowledge about the pathogenesis of these mostly secondary neurological disease patterns, a targeted treatment of individual manifestations is possible. For this reason, neurological expertise should be available in the intensive medical care of seriously ill COVID-19 patients," explains Prof. Berlit and refers to the guideline "Neurological Manifestations of COVID-19"4.

The expert derives a further finding from the new study1: Secondary data were collected on the influence of the time of onset of neurological symptoms on mortality. The researchers found that patients who had neurological complaints only after admission to hospital had a much worse prognosis than those who had them before or at the time of admission. "This means that we have to carry out neurological screenings in hospitalised COVID-19 patients so that we can detect and treat a serious neurological complication early on. Especially in critically ill, ventilated patients, such diagnoses can otherwise be overlooked and contribute to the high mortality rate of those affected" Prof. Berlit proposed.

1. Frontera JA, Sabadia S, Lalchan R et al A Prospective Study of Neurologic Disorders in Hospitalized COVID-19 Patients in New York City. Neurology October 5, 2020, DOI:
2. helmets J, Kremer S, Merdji H et al Neurologic Features in Severe SARS-CoV-2 infection. NEJM, April 15, 2020. DOI: 10.1056/NEJMc2008597
3. Liotta E, Batra A, Clark JR et al Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Annals of Clinical and Translational Neurology. First published: 05 October 2020.
4. Berlit P. et al., Neurological manifestations of COVID-19, S1 guideline, 2020, in: Deutsche Gesellschaft für Neurologie (eds.), Guidelines for diagnostics and therapy in neurology.