Two new meta-analyses detail neurologic and psychiatric conditions in COVID-19 patients, one suggesting that symptoms such as fatigue and depression are common even in people with mild illness, and the other showing central and peripheral nervous system involvement in up to 36% of cases that increased the risk of hospitalization.
Brain involvement the norm, rather than exception
In the first study, published yesterday in the Journal of Neurology, Neurosurgery & Psychiatry, a team led by University College London researchers conducted a systematic review and meta-analysis of 215 COVID-19 studies from 30 countries involving 105,638 symptomatic COVID-19 patients from January to July 2020.
The most common symptoms were loss of smell (43%), weakness (40%), fatigue (38%), loss of taste (37%), muscle pain (25%), depression (23%), headache (21%), and anxiety (16%). The researchers also identified major but less common neurologic disorders such as ischemic stroke (1.9%), hemorrhagic stroke (0.4%), and seizures (0.06%).
Among the few nonhospitalized COVID-19 patients with mild illness in the dataset, neurologic and psychiatric symptoms were still common, with 55% reporting fatigue, 52% loss of smell, 47% muscle pain, 45% loss of taste, and 44% headache.
In a University College London news release, lead study author Jonathan Rogers, BChir, said his team had expected neurologic and psychiatric symptoms to be more common in severe COVID-19. "But instead we found that some symptoms appeared to be more common in mild cases," he said. "It appears that COVID-19 affecting mental health and the brain is the norm, rather than the exception."
No clear link to systemic, respiratory symptoms
The researchers posited that brain inflammation, insufficient levels of oxygen delivered to the brain, and psychosocial factors such as isolation may be behind these symptoms.
"Our finding that the most frequently reported neurological symptoms actually occurred more frequently in those with less severe COVID-19 suggests that neurological symptoms are not necessarily correlated with systemic or respiratory symptoms, implying that different mechanisms or timing of mechanisms may be involved," they wrote.
The authors called for more research on symptoms of mental illness, including depression, anxiety, and post-traumatic stress disorder, along with strokes and seizures, in COVID-19 patients.
Co-senior author Alasdair Rooney, MD, PhD, of the University of Edinburgh, said in the release that clinicians should be aware that neurologic and psychiatric symptoms are very common in coronavirus patients. "With millions of people infected globally even the rarer symptoms could affect substantially more people than in usual times," he said. "Mental health services and neurological rehabilitation services should be resourced for an increase in referrals."
Critical conditions tied to severe infection
The second study, published earlier this week in BMC Infectious Diseases, was a meta-analysis of 143 observational and descriptive studies involving 10,723 COVID-19 patients with nervous system involvement. It was led by researchers from Universidad de La Sabana in Colombia.
The researchers identified 119 studies published from December 2019 to June 2020 on the clinical manifestations of neurologic involvement in COVID-19, 62 on neuroimaging findings, 60 on cerebrospinal fluid results, 51 on pathophysiologic mechanisms, 28 on electrophysiologic findings, and 4 on neuropathologic findings.
They found a prevalence of nervous system involvement in coronavirus patients ranging from 22.5% to 36.4%. Neurologic involvement increased the likelihood of hospitalization by roughly 81%. Death rates were not explicitly tied to COVID-19 neurologic involvement but rather to systemic disease.
Fifty-three studies reported 8,129 signs and symptoms of COVID-19 central nervous system involvement, including neuropsychiatric disorders (61.3%), headache (22.2%), dizziness (6.6%), impaired consciousness (5.2%), delirium (4.3%), nausea and vomiting (0.3%), and neck stiffness (0.1%). Loss of smell or taste, brain damage, and stroke were also common. Psychiatric symptoms included anxiety, mood disorders, psychosis, and insomnia, among others.
Focal neurologic conditions among 410 patients, most associated with stroke, were described in 28 studies. They included movement disorders, speech disorders, amnesia, visual field disturbances, and others. Twenty-eight studies reported seizures in 346 patients, about 90% of them new onset.
"Critical neurological events were more frequent among patients with a severe infection than those with mild disease," the researchers said. "Patients with COVID-19 admitted with respiratory compromise only, who developed neurological conditions, tended to progress with a more severe course, with increased intubation and mechanical ventilation requirements."
The authors said that prospective cohort studies are needed to analyze the mid- and long-term complications of nervous system involvement in COVID-19, while randomized clinical trials should assess the effectiveness of treatments for coronavirus-related neurologic conditions.
"International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's central and peripheral neurological involvement and generate therapeutic decision-making strategies," they wrote.