Table 1.
Neurological symptoms and signs of COVID-19 in clinical studies.
| Region | Patients | Median (IQR) age, yr | Gender F (%) | Neurological Symptoms (%) | Other Symptoms (%) | Abnormal lab results (%) | CSF (% of cases) | Results of nervous system imaging or EEG (% of cases) | Ref |
|---|---|---|---|---|---|---|---|---|---|
| Wuhan, China (total 799) | 113 death | 68 (62–77) | 30 (27) | Myalgia (19), headache (10), dizziness (9), impaired consciousness (22) | Fever (92), cough (70), fatigue (57), anorexia (27), dyspnea (62), chest tightness (49), pharyngalgia (4), hemoptysis (4), nausea (7), vomiting (5), abdominal pain (10) | Leukocytosis (50), lymphocytopenia (39); albumin (65) & ↓ K+ (12); ↑ AST (52), ALT (27), K+ (22), Na+ (18), D-dimer (35), LDH (82), CRP (60), IL-1β (9), IL-2R (81), IL-6 (100), IL-8 (28), IL-10 (70), TNF-α (77), pro-BNP (85) & cardiac troponin I (72). Higher ESR, ferritin & PT, and lower TSH in this group. |
NR | NR | (Chen et al., 2020b) |
| 161 recovery | 51 (37–66) | 73 (45) | Myalgia (24), headache (12), dizziness (7), impaired consciousness (1) | Fever (90), cough (66), fatigue (45), anorexia (22), dyspnea (31), chest tightness (30), pharyngalgia (5), hemoptysis (2), nausea (10), vomiting (6), abdominal pain (12) | Leukocytosis (4), lymphocytopenia (5), ↓ albumin (14) & K+ (11), ↑ AST (16), ALT (19), K+ (4), Na+ (2), D-dimer (2), LDH (14), CRP (14), IL-1β (12), IL-2R (37), IL-6 (60), IL-8 (8), IL-10 (19), TNF-α (47), pro-BNP (18) & cardiac troponin I (14). | NR | NR | ||
| Wuhan, China | 214 | Mean (SD) 52.7 (15.5) | 127 (59.3) | Dizziness (16.8), headache (13.1), skeletal muscle injury (10.7), impaired consciousness (7.5), ageusia (5.6), anosmia (5.1), stroke (2.8, ischemic [66.3], hemorrhagic [16.7]), nerve pain (2.3), visual change (1.4), ataxia (0.5), seizure (0.5) | Fever (61.7), cough (50), anorexia (31.8), diarrhea (19.2), throat pain (14.5), abdominal pain (4.7) | Lower lymphocyte & platelets, & higher BUN levels in cases with CNS symptoms; no differences in cases with PNS symptoms; higher CK, CRP, D-dimer & neutrophils with lower lymphocytes in cases with skeletal muscle injury. | NR | NR | (Mao, Jin, 2020) |
| Wuhan, China | 41 | 49 (41–58) | 11 (29) | Headache (8), myalgia or fatigue (44) | Fever (98), cough (76), hemoptysis (5), diarrhea (3), dyspnea (55) | Leukopenia (25), lymphocytopenia (63), thrombocytopenia (5), ↑ AST (37), creatinine (10), CK (33), LDH (73), troponin I (12) & procalcitonin (8); overall ↑ IL-1β, IL-1Rα, IL-7, IL-8, IL-9, IL-10, FGF, GCSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNFα, & VEGF. Higher PT & D-dimer in ICU cases than non-ICU. |
NR | NR | (Huang et al., 2020b) |
| Wuhan, China (total 710) | 52 critical ill | Mean (SD) 59.7 (13.3) | 17 (33) | Headache (6), myalgia (11.5), malaise (35) | Fever (98), cough (77), dyspnea (63.5), rhinorrhea (6), arthralgia (1), chest pain (2), vomiting (4), ARDS (67) | AKI (29), cardiac injury (23), liver dysfunction (29), hyperglycemia (35) | NR | NR | (Yang et al., 2020b) |
| Wuhan, China | 138 | 56 (42–68) | 63 (45.7) | Fatigue (69.6), myalgia (34.8), dizziness (9.4), headache (6.5) | Fever (98.6), cough (59.4), anorexia (39.9), dyspnea (31.2), pharyngalgia (17.4), diarrhea (10.1), nausea (10.1), vomiting (3.6), abdominal pain (2.2), ARDS (19.6) | Acute cardiac injury (7.2), AKI (3.6). Higher WBCs, neutrophils, D-dimer, CK, & creatine in ICU cases than non-ICU. |
NR | NR | Wan et al., 2020; Wang et al., 2020a) |
| Wuhan, China | 99 | Mean (SD) 55.5 (13.1) | 32 (32) | Myalgia (11), confusion (9), headache (8) | Fever (83), cough (82), dyspnea (31), sore throat (5), rhinorrhea (4), chest pain (2), diarrhea (2), nausea/vomiting (1), ARDS (17) | Leukocytosis (24), lymphocytopenia (35), thrombocytosis (4), thrombocytopenia (12), anemia (51), ↓ albumin (98), ↑ neutrophils (38), aPTT (6), PT (5), D-dimer (6), ALT (28), AST (35), BUN (6), CK (13), LDH (76), myoglobin (17), procalcitonin (6), IL-6 (52), ESR (23.4), ferritin (63) & CRP (86); hyperglycemia (51), AKI (3). | NR | NR | (Chen et al., 2020a) |
| Wuhan, China | 452 | 58 (47–67) | 217 (48) | Myalgia (21.4), confusion (0.7), headache (11.4), dizziness (8.1), fatigue (46.4) | Fever (92.6), cough (33.3), hemoptysis (2.6), dyspnea (50.8), rhinorrhea (1.8), pharyngalgia (4.8), anorexia (21), nausea/vomiting (9.2), diarrhea (26.7), abdominal pain (5) | Most cases: lymphocytopenia, ↑ procalcitonin, ESR, ferritin, CRP, TNF-α, IL-2R, & IL-6. ↓ helper T cells (CD3 + CD4+) and suppressor T cells (CD3 + CD8+). | NR | NR | (Qin, Zhou, 2020) |
| Wuhan, China | 140 | Median (range): 57 (25–87) | 69 (49.3) | Fatigue (75) | Fever (91.7), cough (75), chest tightness/dyspnea (36.7), nausea (17.3), diarrhea (12.9), anorexia (12.2), abdominal pain (5.8), belching (5), vomiting (5) | Leukocytosis (12.3), leukopenia (19.6), lymphocytopenia (75.4), ↑ D-dimer (43.2), CRP (91.9), amyloid A (90.2), procalcitonin (34.7) & CK (6.7). | NR | NR | (Zhang et al., 2020b) |
| Wuhan, China (fatal cases) | 85 | Mean (SD): 65.8 (14.2) | 23 (27.1) | Fatigue (58.8), myalgia (16.5), headache (4.7) | Fever (91.8), dyspnea (70.6), anorexia (56.5), cough (22.4), diarrhea (18.8), vomiting (4.7), abdominal pain (3.5), chest pain (2.4), pharyngalgia (2.4), ARDS (74.1) | Leukocytosis (44.7), leukopenia (11.8), ↑ neutrophils (60), neutropenia (12.9), lymphocytopenia (77.6), thrombocytosis (7.1), thrombocytopenia (41.2), ↓ albumin (78.8), ↑ D-dimer (65.9), aPTT (25.9), PT (25.9), fibrinogen (47.1), ALT (16.5), AST (32.9), BUN (49.4), creatinine (18.8), CK (36.5), LDH (82.4), procalcitonin (22.4) & CRP (91.8); hypoglycemia (3.5), hyperglycemia (78.8). | NR | NR | (Du et al., 2020) |
| Wuhan, China | 221 | Median (range): 55 (39–66.5) | 113 (51.1) | Fatigue (70.6), headache (7.7), | Fever (90.5), cough (61.5), anorexia (36.2), dyspnea (29), diarrhea (11.3), pharyngalgia (10), abdominal pain (2.3), ARDS (21.7) | Leukocytosis (10.4), leukopenia (33), lymphocytopenia (17.6), thrombocytosis (5.4), thrombocytopenia (13.4), ↑ procalcitonin (5.9). | NR | NR | (Zhang et al., 2020d) |
| Sichuan, Wuhan & Chongqing in China | 917 | Mean 48.7 (17.1) | 417 (44.8) | Impaired consciousness (2.7), stroke (1.1), muscle cramp (0.2), headache (0.2), occipital neuralgia (0.1), tremor/tic (0.2) | NR | NR | 3 cases: normal | Head CT scan (28 cases): new abnormal findings (32.1) including stroke (25%), brain tumor (3.6) & traumatic brain injury signs (3.5) | (Xiong, Mu, 2020) |
| Zhejiang, China | 645 | NR | 317 (49.1) | Myalgia (11), fatigue (18.3), headache (10.4) | Fever (83.7), cough (65.9), sputum (34.9), hemoptysis (1.7), sore throat (15.04), dyspnea (4). diarrhea (8.2), nausea or vomiting (3.4) | NR | NR | NR | (Zhang et al., 2020e) |
| Zhejiang, China | 91 | 50 (36.5–57) | 54 (59.34) | Fatigue (44), headache (7.7), myalgia (5.5), back discomfort (3.3) | Fever (71.4), cough (60.4), sputum (33), dyspnea (11), anorexia (25.3), diarrhea (23.1), nausea (12.1), vomiting (6.6) | Leukocytosis (4), leukopenia (15.4), lymphopenia (31.8), thrombocytopenia (11), ↑ CRP (53.8), procalcitonin (15.4), fibrinogen (24.2), D-dimer (24.2), ALT (7.7), AST (9.9) | NR | NR | (Qian et al., 2020) |
| Zhejiang, China | 62 | 41 (32–52) | 27 (43.5) | Headache (34), myalgia or fatigue (52) | Fever (77), cough (81), sputum (56), diarrhea (8), hemoptysis (3), dyspnea (3) | Leukopenia (31), lymphocytopenia (42), ↑ AST (16), procalcitonin (11) | NR | NR | (Xu et al., 2020c) |
| Guangdong, China | 90 | Mean (range): 50 (18–86) | 51 (56.7) |
Fatigue/weakness (21), myalgia (28), headache (4) | Fever (78), cough (63), sputum (12), sore throat (26), chills (7), diarrhea (6), nausea (6), vomiting (2) | Leukocytosis (3), leukopenia (21),↑ CRP (42) | NR | NR | (Xu et al., 2020b) |
| Wenzhou, China | 149 | Mean (SD): 45.11 (13.35) | 68 (45.6) | Headache (8.7), myalgia (3.4) | Fever (76.5), cough (58.4), sputum (32.2), dyspnea (1.3), sore throat (14.1), snotty (3.4), chest pain (3.4), chest tightness (10.8), chill (14.1), diarrhea (7.4), nausea or vomiting (1.3) | Leukocytosis (1.34), leukopenia (24.2), neutropenia (28.2), lymphocytopenia (35.6), thrombocytosis (5.4), thrombocytopenia (13.4), ↑ D-dimer (14.1), ALT (12.1), AST (18.1), LDH (30.2), CRP (23) & creatinine (28.9), & prolonged PT (11.4) or aPTT (26.9) | NR | NR | (Yang et al., 2020a) |
| Hubei, China | 137 | Median (range): 57 (20–83) | 76 (55.5) | Myalgia or fatigue (32.1%), headache (9.5) | Fever (81.8), cough (48.2), dyspnea (19), diarrhea (8), palpitation (7.3) | Leukocytosis (19), lymphocytopenia (72.3), ↑ CRP (83.9) | NR | NR | (Liu et al., 2020a) |
| Beijing, China | 13 | 34 (34–48) | 3 (23.1) | Myalgia 3 (23.1), headache (23.1) | Fever (92.3), cough (46.3), upper airway congestion (61.5), diarrhea (7.7), rhinorrhea (7.7) | Lymphocytosis & ↑ CRP (some cases) | NR | NR | (Chang et al., 2020) |
| Beijing, China | 262 | Median (range): 47.5 (1–94) | 216 (82.4) | Fatigue (26.3), headache (6.5), | Fever (82.1), cough (45.8), dyspnea (6.9) | NR | NR | NR | (Tian et al., 2020) |
| China | 1099 | 47 (35–58) | 459 (41.9) | Headache (13.6), fatigue (38.1), myalgia/arthralgia (14.9) | Admission fever (43.8), in-hospital fever (88.7), conjunctival congestion (0.8), nasal congestion (4.8), cough (67.8), sore throat (13.9), hemoptysis (0.9), dyspnea (18.7), nausea/vomiting (5), diarrhea (3.8), chills (11.5), tonsil swelling (2.1), ARDS (3.4) | Leukocytosis (5.9), leukopenia (33.7), lymphocytopenia (83.2), thrombocytopenia (36.2), AKI (0.5), DIC (0.1), rhabdomyolysis (0.2); ↑ CRP (most cases) & ↑ AST, ALT, CK & D-dimer (some cases). | NR | NR | (W-J and Z-Y, 2020) |
| China | 50 | Mean (range): 43.9 (3–85) | 21 (42) | Headache (10), myalgia (16), fatigue (16) | Fever (76), cough (40), sputum (14), sore throat (8), dyspnea (8), diarrhea (2) | Lymphocytopenia (28), ↑ CRP (52) | NR | NR | (Xu et al., 2020d) |
| South Korea | 28 | Mean (range): 42.6 (20–73 | 13 (46.1) | Myalgia (14.3), fatigue (10.7) | Fever (32.1), sore throat (32.1), cough (17.9), chills (17.9) | NR | NR | NR | (2020) |
| New Delhi, India | 21 | Mean (range): 40.3 (16–73) | 7 (33.3) | Headache (14.3) | Fever (42.9), cough (42.9), sore throat (23.8), dyspnea (4.8) | Leukopenia (4.8) | NR | NR | (Gupta et al., 2020) |
| South Iran | 113 | Mean (range): 53.75 (20–99) | 42 (37.2) | Fatigue (66.4), myalgia/arthralgia (61.1), headache (53.1), dizziness/vertigo (39.8), | Fever (59.3), cough (64.6), sputum (21.4), dyspnea (51.3), chest pain (38.1), sore throat (31.9), hemoptysis (6.2), chills (59.3), rhinorrhea (23), abdominal pain (21.2), diarrhea (22.1), nausea (42.5), vomiting (25.7), anorexia (66.4) | Leukocytosis (10.8), leukopenia (9), lymphocytopenia (12.6), thrombocytosis (11), thrombocytopenia (15.6), ↑ CRP (25), ESR (15.9), creatinine (35.5), & prolonged PT (77.9) or aPTT (45.8) | NR | NR | (Shahriarirad et al., 2020) |
| Istanbul, Turkey | 27 cases with brain MRI ⁎ | Median (range): 63 (34–87) | 6 (22) | Not specified | NR | NR | 5 cases: ↑ protein (80), normal WBC, glucose, IgG index & albumin (100), negative RT-PCR for SARS-CoV-2 (100) | Brain MRI: abnormal (44.4); cortical FLAIR signal abnormality (37), increased cortical DWI with corresponding low ADC values (26), subtle leptomeningeal enhancement (18), punctate cortical blooming artifact (11). | (Kandemirli, Dogan, 2020) |
| Strasbourg, France | 58 | 63 | NR | On ICU admission (14); After neuromuscular blockers/sedations hold (67): agitation (69), confusion (65), corticospinal tract signs (hyperreflexia, ankle clonus & Babinski signs) (67), dysexecutive syndrome (36) | Fever (16), ARDS (100) | NR | 7 cases: 0 WBC (100), + oligoclonal band with the same pattern in serum (29), ↑ IgG & protein (14), ↓ albumin (57), negative RT-PCR for SARS-CoV-2 (100) | Brain MRI (13 cases): leptomeningeal enhancement (62), bilateral frontotemporal hypoperfusion (11 cases, 100), ischemic stroke (23). EEG (8 cases): diffuse bifrontal slowing consistent with encephalopathy (12.5) |
(Helms, Kremer, 2020) |
ADC, Apparent diffusion coefficient; AKI, acute kidney injury, ALT, alanine aminotransferase; ARDS, acute respiratory distress syndrome; AST, aspartate aminotransferase; BNP, B-type natriuretic peptide; BUN, blood urea nitrogen; CK, creatine kinase; CNS, central nervous system; CRP, C-reactive protein; DIC, disseminated intravascular coagulation; EEG, electroencephalography; ESR, erythrocyte sedimentation rate; F, female; FGF, fibroblast growth factors; GCSF, granulocyte colony-stimulating factor; GMCSF, granulocyte-macrophage colony-stimulating factor; ICU, intensive care unit; IFN-γ, interferon-γ; IL, interleukin; IP, induced protein; IQR, interquartile range; LDH, lactate dehydrogenase; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; PDGF, platelet derived growth factor; pro-BNP, pro-brain natriuretic peptide; PT, prothrombin time; RANTES, regulated on activation and normally T-cell expressed; SD, standard deviation; TNF-α, tumor necrosis factor-α; TSH, thyroid stimulating hormone; VEGF, vascular endothelial growth factor; WBC, white blood cell.
⁎
This is out of 50 of 235 (21%) ICU patients who developed neurological symptoms.