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The global spread of the 2019 coronavirus disease pandemic (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has sparked intense interest in the different manifestations of the infection, including its neurological characteristics. A compact synthesis by UK researchers of what is currently known about this facet of the disease is presented in a new article, published on the medRxiv * pre-print server.
Many previous reports were small and retrospective, reflecting the need for early information in the face of a rapidly spreading viral infection. These were followed by larger multicenter prospective studies which are currently underway.
This document details the team’s goal of setting up a new platform that will assess and review this area of pandemic disease in real time. As of May 2020, researchers reviewed all kinds of relevant scientific publications dealing with neurological symptoms, associated clinical features, and potential pathogenic mechanisms in the form of a weekly blog.
This blog is titled “The Neurology and Neuropsychiatry of COVID-19” and appears on the Journal of Neurology, Neurosurgery and Psychiatry website. Taking their work a little later, the researchers compiled the evidence in the form of a systematic review and meta-analysis, dubbed “Systematically Analyzing and Reviewing COVID-19 Neurology and Neuropsychiatry Studies” (SARS- COVNeuro).
Methodology of ancient literature in this field
The most common type of study was case series. When classified at the start of data collection, they found that 65 and 115 studies were “early” and “late”. These started collecting data between December 2019 and February 2020, and between March 2020 and July 2020, respectively.
Of the early studies, 57% were case series, but only 35% of later studies. Most are single-center studies and involve inpatients in more than half and two-thirds of the early and late studies, respectively.
There were 18 studies with a thousand or more participants. In total, there were over 1,000,000 participants. High-quality studies made up only 11% of the total, with 46% of medium quality and 44% of low quality.
The first cohort study emerged at least two months after the initial SARS-CoV-2 outbreak in Wuhan, China. Overall, the studies come from China, the United States, Italy and France, with China being the biggest contributor by far.
Early prevalence of neurological complications in COVID-19
The meta-analysis included at least 20 neurological or related manifestations described by at least three studies. In total, this included 147 studies, with almost 1,00,000 patients.
The most commonly studied symptoms included headache, muscle pain, fatigue, anosmia, and dysgeusia, all mentioned in 52 to 84 studies. The most common reported the symptoms were similar.
However, the order of prevalence was, in decreasing order, anosmia, weakness, fatigue, dysgeusia and muscle pain. These would be present in 43% of patients, for anosmia, up to 25% for myalgia.
The inter-study variability ranged from very high (over 90%) for 13 of these symptoms to less than 50% for five manifestations. Many studies have simply recorded the presence or absence of these symptoms.
Depression and anxiety were reported in 23% and 16%, respectively, indicating their high prevalence. Strokes and seizures were much less common, at 2.3% and 006%, respectively.
Among the subgroups, the researchers found that headache, myalgia, anosmia, and dysgeusia were reported at much higher rates in prospective studies than in retrospective studies. When analyzed by clinical severity, the study reports a higher prevalence of headache, myalgia, dysgeusia and anosmia in the less severe patient groups.
What are the implications?
In this largest of all available systematic reviews of the neurological manifestations of COVID-19, researchers found that most symptoms were nonspecific, indicating the systemic nature of the disease. Specific symptoms related to the nervous system, such as seizures, altered mental status, depression and anxiety, and sleep disturbances, have not been studied as frequently.
Although depression and anxiety have been less studied, their prevalence was high. Organic diseases, such as strokes and seizures, were much less common.
The researchers say the study design, as well as the severity of the disease and the country where the study was performed, affects how often a symptom is reported. Especially for nonspecific symptoms, including anosmia and dysgeusia, the prevalence is much higher in prospective studies.
Retrospective studies can help capture associations but lead to an underestimation of symptom prevalence, especially with symptoms like those in the current study. Thus, even in emergency conditions, it is necessary to bring out prospective studies at a much faster pace than what has been achieved with the current pandemic.
Care should also be taken to reduce unnecessary and potentially burdensome regulations governing such studies, especially in pandemic situations and when the studies are not interventionally designed. This would help to conduct research quickly, when the results are available within a timeframe that allows their application to current policy-making.
Outpatient investigations are also needed and more attention should be paid to the more severe symptoms, contrary to what was found in this review. “A rebalancing would be welcome with more attention given to major neurological and neuropsychiatric disorders. “
There were few high-quality studies, which limited the quality of the evidence. The long-term impact of COVID-19 on neuropsychiatric health is also an open question, which can only be addressed through prospective cohort studies.
If there is a real increase in the incidence of these complications, services and structures must be put in place to anticipate the increase in neuropsychiatric cases, especially if they become chronic. This care must begin in the acute phase, since non-specific features are so common that they suggest neurological and neuropsychiatric manifestations are the norm in COVID-19.
And finally, “Although long-term evidence from this early literature has been scarce, it gives an initial indication that the symptoms described in the “ long COVID ” may be a continuation of some of those experienced in the acute phase of the disease.. “
*Important Notice
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or be treated as established information.
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