By Alexander E. Merkler, MD

Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College, and Assistant Attending Neurologist, NewYork-Presbyterian Hospital

Dr. Merkler reports he receives grant/research support from the American Heart Association and is a consultant for Medicolegal.

SYNOPSIS: Neurological symptoms and impairments have been found in one-third of hospitalized patients with COVID-19 from countries that have reported these observations so far. This is a rapidly evolving consequence of SARS-CoV-2 infection.

SOURCE: Mao L, Jin H, Wang M, et al. Neurological manifestations of hospitalized patients with coronarvirus disease 2019 in Wuhan, China. JAMA Neurol 2020; April 10. doi: 10.1001/jamaneurol.2020/1127. [Online ahead of print].

The world currently is under siege by coronavirus disease 2019 (COVID-19). Since December 2019, COVID-19 has affected more than 4 million people and caused more than 300,000 deaths worldwide. Although the most common manifestations of COVID-19 include fever, cough, and shortness of breath, this study by Mao et al is the first to report the frequency of neurological symptoms in hospitalized patients with COVID-19. In this retrospective, observational study performed at three centers in Wuhan, China, the authors studied the frequency and characteristics of neurological symptoms in hospitalized patients with COVID-19 infection between Jan. 16 and Feb. 19, 2020. For each subject, neurological symptoms were reviewed and confirmed by two trained neurologists, with a third resolving any disagreements.

The authors categorized neurological symptoms of COVID-19 into three categories: central nervous system (dizziness, headache, impaired consciousness, stroke, ataxia, seizures), peripheral nervous system (taste or olfactory impairment, vision impairment, and nerve pain), and skeletal muscular injury. Among 214 hospitalized patients, 78 (36.4%) had neurological symptoms; 53 (24.8%) originated from the central nervous system, 19 (8.9%) from the peripheral nervous system, and 23 (10.7%) were skeletal muscular injury. Dizziness (16.8%) and headache (13.1%) were the most common neurological symptoms. Taste and olfactory impairment occurred in 5.6% and 5.1%, respectively. Most neurological symptoms occurred early in the illness (median time one to two days). Neurological symptoms were more common in patients who had severe respiratory disease vs. non-severe respiratory disease (45.5% vs. 30.2%) and in those with lower lymphocyte and platelet counts. Six (2.8%) patients had a stroke. Stroke was the initial presenting complaint in two of the six patients with stroke, and these patients had an absence of typical respiratory manifestations of COVID-19 (fever, cough, diarrhea), although they had typical computed tomography chest findings of COVID-19.

COMMENTARY

Neurological symptoms appear to be common in patients with COVID-19, occurring in more than one-third of hospitalized patients. Taste and olfactory loss occurred in 5% of patients, and other reports suggest that impairments in these modalities are common and often seen in milder cases of COVID-19 disease that do not require hospitalization.¹ Stroke occurred in 2.8% of hospitalized patients with COVID-19 and, interestingly, consistent with another report, often was the initial presenting symptom of COVID-19.² Stroke mainly occurred in patients with severe COVID-19 infection, which is consistent with another study that found evidence of stroke in 3/13, or 13% of patients with severe COVID-19 infection.³

The mechanisms underpinning these neurological symptoms remain unclear. As with other viral infections (such as influenza) inflammation, hypercoagulability, and endothelial injury likely increase the risk of stroke. In addition, many patients hospitalized with severe COVID-19 infection are systemically ill, often requiring mechanical ventilation and developing other risk factors for stroke, such as atrial fibrillation. Loss of olfaction may suggest that the olfactory epithelium could serve as a nose-brain entrance path for the virus, but this remains to be confirmed, and most patients with decreased sense of smell do not develop severe neurological consequences, such as stroke.⁴

Taken together, the neurological symptoms among hospitalized patients with COVID-19 not only are common but may be the sole presenting feature in the disease. The rate of neurological symptoms among people who do not require hospitalization with COVID-19 is uncertain, but clinicians should consider COVID-19 as an etiology of new neurological symptoms, especially in patients with acute onset loss of taste or smell.

REFERENCES

1. Yan CH, Faraji F, Prajapati DP, et al. Self-reported olfactory loss associates with outpatient clinical course in COVID-19. Int Forum Allergy Rhinol 2020; April 14. doi: 10.1002/alr.22592. [Online ahead of print].
2. Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020;382:e60.
3. Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020; April 15. doi: 10.1056/NEJMc2008597. [Online ahead of print].
4. Marinosci A, Landis BN, Calmy A. Possible link between anosmia and COVID-19: Sniffing out the truth. Eur Arch Otorhinolaryngol 2020; April 17. doi: 10.1007/s00405-020-05966-0. [Online ahead of print].