Table 1.
CNS manifestations of COVID-19 patients
| Manifestation | Rate and features | Study type | Location | Author, year |
|---|---|---|---|---|
| Headache | 6.5% of 262 patients | Retrospective | China | Tian et al. (2020) [20] |
| 8% of 41 patients | Retrospective | China | Huang et al. (2020) [21] | |
| 8% of 99 patients | Retrospective | China | Chen et al. (2020) [22] | |
| 11% of 779 patients | Retrospective | China | Chen et al. (2020) [2] | |
| 13.1% of 214 patients | Retrospective | China | Mao et al. (2020) [5] | |
| 13.6% of 1099 patients | Retrospective | China | Guan et al. (2020) [23] | |
| 14.1% of 841 patients | Retrospective | Spain | Romero-Sanchez et al. (2020) [24] | |
| Impaired consciousness | 7.5% of 214 patients | Retrospective | China | Mao et al. (2020) [5] |
| 22% of 113 patients who died; only 1% of the patients who recovered | Retrospective | China | Chen et al. (2020) [2] | |
| 19.6% of 841 patients with COVID-19, mostly in older patients and in severe and advanced stages | Retrospective | Spain | Romero-Sanchez et al. (2020) [24] | |
| 73% of the 37 patients presenting with neurological manifestations with relevant abnormal brain MRI | Retrospective | France | Kremer et al. (2020) [30] | |
| Agitation/delirium | Delirium in the absence of repiratory symptoms or fever | Case report | Saudi Arabia | Alkeridy et al. (2020) [32] |
| Hyperactive ICU delirium | Case report | USA | Sher et al. (2020) [33] | |
| Confusion in 10% of 99 patients | Retrospective | China | Chen et al. (2020) [22] | |
| Agitation in 40 (69%) of 58 ICU patients (patients with ARDS). Of the 40 patients, 26 (65%) experienced delirium | Retrospective | France | Helms et al. (2020) [34] | |
| 19% and 32% of 37 patients presenting with neurological manifestations with relevant abnormal brain MRI experienced agitation and confusion, respectively | Retrospective | France | Kremer et al. (2020) [30] | |
| Hypogeusia/dysgeusia and hyposmia/anosmia | Taste, smell, and chemesthetic function each significantly decreased | Retrospective | Global | Parma et al. (2020) [46] |
| New-onset smell and/or taste disorders were significantly more frequent among COVID-19 patients (39.2%) than in the influenza control group (12.5%) | Case-control | Spain | Beltrán-Corbellini et al. (2020) [42] | |
| Anosmia (4.9%) and dysgeusia (6.2%) occurred early (60% as the initial clinical manifestation) and were commonly found in less severe patients | Retrospective | Spain | Romero-Sanchez et al. (2020) [24] | |
| 5.6% of 214 patients | Retrospective | China | Mao et al. (2020) [5] | |
| 73% of 237 patients prior to COVID-19 diagnosis had anosmia. Anosmia was the initial symptom in 26.6% of the patients | Retrospective | USA | Kaya et al. (2020) [52] | |
| 85.6% with olfactory dysfunction; 88.0% with gustatory dysfunction | Retrospective | Multicenter European study | Lechien et al. (2020) [53] | |
| Smell and taste loss in 20.6% and 11.4% of the 1206 patients, respectively | Retrospective | China | Song et al. (2020) [54] | |
| 98% of the 60 patients with COVID-19 showed some degrees of smell dysfunction | Retrospective | Iran | Moein et al. (2020) [55] | |
| Smell and taste loss in 71% of 59 subjects | Cross-sectional | USA | Yan et al. (2020) [56] | |
| 33.9% of 59 patients with at least one taste or olfactory disorder and 8.6% both disorders | Cross-sectional | Italy | Giacomelli et al. (2020) [49] | |
| 65.03% of 7178 patients | Cohort | UK | Menni et al. (2020) [50] | |
| Five patients with anosmia | Case series | Iran | Gilani et al. (2020) [48] | |
| Sudden and complete olfactory loss function | Case report | France | Eliezer et al. (2020) [43] | |
| Persistent severe anosmia and dysgeusia with a cortical hyperintensity in the right gyrus rectus and a subtle hyperintensity in the olfactory bulbs on FLAIR | Case report | Italy | Politi et al. (2020) [16] | |
| Prefrontal involvement prior anosmia | Case report | France | Le Guennec et al. (2020) [17] | |
| Ageusia and anosmia along with ADEM | Case report | Italy | Novi et al. (2020) [51] | |
| Seizures/electroencepholagrapy (EEG) changes | No new acute symptomatic seizures were seen in 304 patients | Retrospective | China | Lu et al. (2020) [60] |
| 0.5% of 214 patients | Retrospective | China | Mao et al. (2020) [5] | |
| One of 841 patients | Retrospective | Spain | Romero-Sanchez et al. (2020) [24] | |
| Generalized tonic-clonic seizures | Case report | Iran | Karimi et al. (2020) [58] | |
| One-minute transient generalized seizures with MRI changes in the right temporal mesial temporal lobe | Case report | Japan | Moriguchi et al. [59] | |
| Eight out of 22 COVID-19 positive patients had frontal sharp waves | Retrospective | USA | Galanopoulou et al. (2020) [63] | |
| De novo status epilepticus can be the initial presentation in asymptomatic COVID-19 | Retrospective | USA | Somani et al. (2020) [146] | |
| Focal status epilepticus | Case report | Italy | Vollono et al. (2020) [65] | |
| Two COVID-19 patients with right frontocentral/vertex seizure and right more than left frontal seizures | Case report | USA | Hepburn et al. (2020) [64] | |
| An 11-year-old male child with status epilepticus and CSF evidence for encephalitis | Case report | USA | McAbee et al. (2020) [66] | |
| Meningitis/encephalitis | Meningitis/encephalitis with transient generalized seizures. SARS-CoV-2 RNA was isolated from his CSF | Case report | Japan | Moriguchi et al. (2020) [59] |
| Encephalitis | Case report | China | Ye et al. (2020) [72] | |
| Meningoencephalitis | Case report | USA | Duong et al. (2020) [73] | |
| Two cases of meningoencephalitis | Case series | Switzerland | Bernard-Valnet et al. (2020) [74] | |
| Three cases with encephalopathy and encephalitis associated with CSF cytokine changes | Case series | USA | Benameur et al. [76] | |
| One of 841 patients | Retrospective | Spain | Romero-Sanchez et al. (2020) [24] | |
| Myelitis | Acute myelitis | Case report | China | Zhao et al. (2020) [84] |
| Acute transverse myelitis | Case report | Denmark | Sarma et al. (2020) [83] | |
| ADEM | Extensive patchy areas on MRI | Case report | China | Zhang et al. (2020) [86] |
| Scattered hyperintense lesions on FLAIR in deep hemispheric and juxtacortical white matter | Case report | USA | Parsons et al. (2020) [87] | |
| Multiple T1 post-Gd enhancing lesions of the brain associated with a single spinal cord lesion at the T8 level and with enhancement of bilateral optic nerve on MRI | Case report | Italy | Novi et al. (2020) [51] | |
| Vascular and acute disseminated encephalomyelitis like pathology | Case report | USA | Reichard et al. (2020) [88] | |
| Encephalopathy | Diffuse bifrontal slowing in 1 of 8 patients undergoing EEG, confirming encephalopathy | Retrospective | France | Helms et al. (2020) [34] |
| The most common indication for EEG were encephalopathy (68.2% of 22 patients) | Retrospective | USA | Galanopoulou et al. (2020) [63] | |
| Acute necrotizing hemorrhagic encephalopathy | Case report | USA | Poyiadji et al. (2020) [89] | |
| Hypoxic necrotizing leukoencephalopathy | Case report | USA | Radmanesh et al. (2020) [92] | |
| Histopathological examination of brain specimens collected from 18 COVID-19 patients demonstrated acute hypoxic ischemic damage | Case series | USA | Solomon et al. (2020) [81] | |
| Posterior reversible encephalopathy | Case report | Turkey | Kaya et al. (2020) [94] | |
| Posterior reversible leukoencephalopathy | Case series | USA | Kishfiy et al. (2020) [93]. | |
| Diffuse leukoencephalopathy and microhemorrhages | Case report | USA | Sachs et al. (2020) [97] | |
| Diffuse leukoencephalopathy and microhemorrhages | Case series | USA | Radmanesh et al. (2020) [98] | |
| Hypoxic ischemic encephalopathy in 23 (20%) out of 113 deceased patients | Retrospective | China | Chen et al. (2020) [2] | |
| Neurogenic respiratory failure | Possibly due to viral invasion to cranial nerve I, which progresses into rhinencephalon and brainstem respiratory centers | Review | NA | Roman et al. (2020) [126••] |
| Generalized myoclonus | Generalized myoclonus with both positive and negative jerks, predominantly involving the facial, trapezius, sternocleidomastoid, and upper extremities muscle | Case series | Spain | Rábano-Suárez et al. (2020) [99] |
| Strokes | Cerebrovascular diseases were seen in 2.8% of 214 COVID-19 patients. They included 4 ischemic stroke patients and one ICH patient with severe COVID-19, compared to one ischemic stroke patient with non-severe COVID-19 (5.7% vs 0.8%, respectively) | Retrospective | China | Mao et al. (2020) [5] |
| Cerebrovascular disease in 5.1% of 138 patients | Retrospective | China | Wang et al. (2020) [19] | |
| Acute ischemic stroke and ICH in 4.6% and 0.5% of 219 patients, respectively | Retrospective | China | Li et al. (2020) [100] | |
| Cerebrovascular disease in 1.4% of 1099 patients | Retrospective | China | Guan et al. (2020) [23] | |
| Stroke in 1.4% of 143 patients | Retrospective | Italy | Carfi et al. (2020) [101] | |
| Cerebrovascular diseases were seen in 14 (1.7%) of 841 COVID-19 patients including 11 patients with ischemic stroke and 3 patients with ICH | Retrospective | Spain | Romero-Sanchez et al. (2020) [24] | |
| Ischemic stroke in 23% of 13 patients | Retrospective | France | Helms et al. (2020) [34] | |
| Ischemic stroke in three out of 184 ICU patients | Retrospective | The Netherlands | Klok et al. [102] | |
| Multiple arterial thromboses of brain | Case series | China | Zhang et al. [103] | |
| Ischemic stroke in five patients | Case series | USA | Avula et al. (2020) [104] | |
| Low rate of ischemic stroke in hospitalized patients with COVID-19 (0.9%). Most strokes were cryptogenic (65.6%) | Retrospective | USA | Yaghi et al. (2020) [105] | |
| Large-vessel stroke in five patients | Case series | USA | Oxley et al. (2020) [106] | |
| Large vessel occlusion and acute cerebral infarction | Case report | China | Zhao et al. (2020) [107] | |
| Occlusion of the left MCA with a large area of ischemic penumbra | Case report | Italy | Papi et al. (2020) [108] | |
| Massive ICH and SAH | Case report | Iran | Sharifi-Razavi et al. (2020) [109] | |
| Left temporal ICH | Case report | USA | Zahid et al. (2020) [110] | |
| Parenchymal hemorrhages with mass effect and herniation were present in 5 (15.2%) of 33 patients. Among the remaining 28 patients, 7 (25%) experienced punctate hemorrhages, 17 (60.7%) showed small to moderate size hemorrhages, and 4 (14.3%) suffered from a large single hemorrhagic site without herniation | Retrospective | USA | Dogra et al. (2020) [111] | |
| 47 Iranian COVID-19 patients with stroke were studied. 23 patients had ICH and 24 patients had ischemic stroke. Among the COVID-19 patients with ICH, 19 (69.6%) patients had lobar hemorrhage, which was significantly high compared to the number of patients with non-lobar hemorrhage (7 [30.4%]) | Retrospective | Iran | Behzadnia et al. [112] | |
| Hemorrhagic lesions and white matter microhemorrhages in 30% and 24% of 37 COVID-19 patients presenting with neurological manifestations with relevant abnormal brain MRI, respectively | Retrospective | France | Kremer et al. [30] | |
| Bilateral basal ganglia hemorrhage | Case report | Iran | Haddai et al. (2020) [113] | |
| Immune thrombocytopenic purpura—SAH | Case report | France | Zulfiqar et al. (2020) [114] | |
| Vasculitis | Case report | France | Hanafi et al. (2020) [115] | |
| Cerebral venous sinus thrombosis | Case report | UK | Hughes et al. (2020) [116] | |
| Cerebral venous thrombosis | Case report | USA | Klein et al. [117] | |
| Venus thromboembolism was seen in 36% and ischemic stroke in 2.5% of 388 patients | Retrospective | Italy | Lodigiani et al. [118] | |
| Silent hypoxemia | Attributable to the brain infection and subsequent dysfunction of breathe controlling centers in cortical regions rather than subcortical structures and the brain stem | Commentary | NA | Coen et al. (2020) [120] |
| White matter and globus pallidum inflammatory lesions | CT scan of the brain demonstrated hypodense lesions involving supratentorial white matter and pallidum bilaterally. MRI showed bilateral but asymmetrical lesions with periventricular and deep white matter involvement | Case report | France | Brun et al. (2020) [147] |
| Neuroleptic malignant syndrome | Haloperidol decanoate use 3 weeks prior to admission | Case report | USA | Kajani et al. (2020) [127] |
| Steroid responsive encephalitis | High dose of corticosteroid was useful | Case report | Italy | Oilotto et al. (2020) [82] |
| Kawasaki syndrome | A 6-month-old infant with presentations of classic Kawasaki syndrome | Case report | USA | Jones et al. (2020) [131] |
| 22% of 58 patients | Case series | UK | Whittaker et al. (2020) [132] | |
| Of 21 children with Kawasaki syndrome, 19 (90%) had COVID-19 | Retrospective | France | Toubiana et al. (2020) [133] |