Neurological Manifestations and Complications of the Central Nervous System as Risk Factors and Predictors of Mortality in Patients Hospitalized with COVID-19: A Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants and Procedures
- -
- At admission: headache and vomiting.
- -
- At hospital: delirium, hallucinations, altered state of consciousness (drowsiness and stupor), language disorders (dysarthria and aphasia), motor deficits (hemiparesis, hemiplegia and quadriparesis), anisocoria, and seizures.
- -
- At hospital: ischemic stroke (left and right middle cerebral artery; right and left carotid artery), hemorrhagic stroke, subarachnoid hemorrhage, encephalitis, de novo epilepsy, and ataxia (uncoordinated movements).
2.2. Statistical Analysis
3. Results
3.1. Risk Factors Associated with Hospital CNS Manifestations and Complications in Patients with COVID-19
3.2. Mortality Predictors Associated with Hospital CNS Manifestations and Complications in Patients with COVID-19
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study Variables | All Patients (n = 991) | Without Neurological Complications in the CNS n = 895 (90.3%) | Neurological Complications in the CNS n = 96 (9.7%) |
---|---|---|---|
Neurological manifestations in the central nervous system (CNS) on admission | |||
Headache, n (%) | 392 (39.6) | 350 (39.1) | 42 (43.8) |
Vomiting, n (%) | 31/641 (4.87) | 25/553 (4.5) | 6/88 (6.8) |
Neurological manifestations in the central nervous system (CNS) while in hospital | |||
Delirium, n (%) | 63 (6.4) | - | 63 (65.6) |
Hallucinations, n (%) | 4 (0.4) | - | 4 (4.2) |
Drowsiness, n (%) | 32/990 (3.2) | - | 32 (33.3) |
Stupor, n (%) | 21 (2.1) | - | 21 (21.9) |
Dysarthria, n (%) | 5 (0.5) | - | 5 (5.2) |
Aphasia, n (%) | 5 (0.5) | - | 5 (5.2) |
Hemiparesis, n (%) | 9 (0.9) | - | 9 (9.4) |
Hemiplegia, n (%) | 4 (0.4) | - | 4 (4.2) |
Quadriparesis, n (%) | 3 (0.3) | 3 (3.1) | |
Anisocoria, n (%) | 4 (0.4) | - | 4 (4.2) |
Seizures, n (%) | 9/990 (0.9) | - | 9 (9.4) |
Hospital neurological complications in the central nervous system (CNS) while in hospital | |||
Stroke, n (%) | 19 (1.9) | - | 19 (19.8) |
Ischemic stroke, n (%) | 14 (1.4) | - | 14 (14.6) |
Ischemic in the left middle cerebral artery, n (%) | 7 (0.7) | - | 7 (7.3) |
Ischemic in right middle cerebral artery, n (%) | 5 (0.5) | - | 5 (5.2) |
Left carotid ischemic stroke, n (%) | 1 (0.1) | - | 1 (1.0) |
Right carotid ischemic stroke, n (%) | 1 (0.1) | - | 1 (1.0) |
Hemorrhagic stroke, n (%) | 5 (0.5) | - | 5 (5.2) |
Subarachnoid hemorrhage, n (%) | 4 (0.4) | - | 4 (4.2) |
Encephalitis, n (%) | 3 (0.3) | - | 3 (3.1) |
Epilepsy NOVO, n (%) | 9 (0.9) | - | 9 (9.4) |
Ataxia, n (%) | 7 (0.7) | - | 7 (7.3) |
Neurological manifestations in the peripheral nervous system (PNS) on admission | |||
Myalgias, n (%) | 185 (18.7) | 168 (18.8) | 17 (17.7) |
Anosmia, n (%) | 82 (8.3) | 75 (8.4) | 7 (7.3) |
Dysgeusia, n (%) | 94 (9.5) | 86 (9.6) | 8 (8.3) |
Hospital neurological complications in the peripheral nervous system (PNS) while in hospital | |||
Cranial neuropathy, n (%) | 7 (0.7) | 7 (7.3) | - |
Guillain Barré syndrome de novo, n (%) | 1 (0.10) | 1 (0.11) | - |
Myopathy, n (%) | 7 (0.7) | 5 (0.6) | 2 (2.1) |
Demographic Characteristics and Risk Factors | All Patients n = 991 | Without De Novo CNS Disorders n = 895 (90.3%) | With De Novo CNS Disorders n = 96 (9.7%) | OR | CI 95% | p |
---|---|---|---|---|---|---|
Age years, median (IQR) (range) | 62 (50–71) | 60 (49–70), (20–95) | 70 (62–76.8), (19–91) | 0.000 | ||
≥64 years, n (%) | 453 (45.7) | 389 (43.5) | 64 (66.7) | 2.60 | 1.67–4.06 | 0.000 |
Male gender, n (%) | 614 (62.0) | 557 (62.2) | 57 (59.4) | 0.583 | ||
Unvaccinated patients, n (%) | 752/771 (97.5) | 679/695 (97.7) | 73/76 (96.1) | 0.422 | ||
Comorbidities | ||||||
Hypertension, n (%) | 549 (55.4) | 482 (53.9) | 67 (69.8) | 1.98 | 1.26–3.12 | 0.003 |
Diabetes mellitus, n (%) | 412 (41.6) | 360 (40.2) | 52 (54.2) | 1.76 | 1.15–2.68 | 0.008 |
Obesity, n (%) | 396/814 (48.6) | 366/735 (49.8) | 30/79 (38.0) | - | ||
Smoking, n (%) | 221/982 (22.5) | 195/886 (22.0) | 26/96 (27.1) | 0.258 | ||
Chronic kidney disease, n (%) | 100 (10.1) | 86 (9.6) | 14 (14.6) | 0.124 | ||
Any pulmonary history, n (%) | 76 (7.7) | 65 (7.3) | 11 (11.5) | 0.142 | ||
Chronic obstructive pulmonary disease, n (%) | 50 (5.0) | 41 (4.6) | 9 (9.4) | 2.15 | 1.01–4.58 | 0.041 |
Asthma, n (%) | 26 (2.6) | 24 (2.7) | 2 (2.1) | 1.000 | ||
History of coronary disease, n (%) | 55 (5.5) | 51 (5.7) | 4 (4.2) | 0.813 | ||
History of heart failure, n (%) | 28 (2.8) | 21 (2.3) | 7 (7.3) | 3.27 | 1.35–7.91 | 0.005 |
History of peripheral vascular event, n (%) | 15 (1.5) | 12 (1.3) | 3 (3.1) | 0.171 | ||
Malignancy, n (%) | 30 (3.0) | 25 (2.8) | 5 (5.2) | 0.202 | ||
Any neurological history, n (%) | 30 (3.0) | 20 (2.2) | 10 (10.4) | 5.09 | 2.31–11.22 | 0.000 |
History of cerebrovascular disease, n (%) | 22 (2.2) | 16 (1.8) | 6 (6.3) | 3.66 | 1.40–9.59 | 0. 005 |
History of epilepsy, n (%) | 6 (0.6) | 3 (0.3) | 3 (3.1) | 9.59 | 1.91–48.20 | 0.014 |
Multiple sclerosis, n (%) | 2 (0.2) | 1 (0.1) | 1 (1.0) | 0.184 | ||
Chronic steroid use, n (%) | 23/842 (2.7) | 19/754 (2.5) | 4/88 (4.5) | 0.289 | ||
Chronic liver disease, n (%) | 11 (1.1) | 7 (0.8) | 4 (4.2) | 5.52 | 1.58–19.20 | 0.016 |
Kidney transplant, (%) | 17 (1.7) | 17 (1.9) | - | - | ||
HIV infection, n (%) | 5 (0.5) | 4 (0.4) | 1 (1.0) | 0.400 | ||
Clinical and laboratory findings | ||||||
Headache | 392 (39.6) | 350 (39.1) | 42 (43.8) | 0.377 | ||
Vomiting | 31/641 (4.8) | 25/553 (4.5) | 6/88 (6.8) | 0.351 | ||
Lymphopenia ≤ 0.900 cells (103/µL), n (%) | 386/978 (39.5) | 335/883 (37.9) | 51/95 (53.7) | 1.90 | 1.24–2.90 | 0.003 |
Platelets ≤ 150 cells (103/µL), n (%) | 137/982 (14.0) | 109/887 (12.3) | 28/95 (29.5) | 2.98 | 1.84–4.84 | 0.000 |
D-dimer ≥ 1000 ng/mL, n (%) | 361/912 (39.6) | 303/828 (36.6) | 58/84 (69.0) | 3.87 | 2.38–6.27 | 0.000 |
Troponin ng/mL, median (IQR) | 12.4 (2.9–36.7) | 11.4 (2.6–32.4) | 27.5 (11.3–27.5) | 0.000 | ||
BNP pg/mL, median (IQR) | 635 (195–2304) | 561 (176–1940) | 1858 (410–6216) | 0.000 |
Covariates | All Patients n = 991 | Without De Novo CNS Disorders n = 895 (90.3%) | With De Novo CNS Disorders n = 96 (9.7%) | OR | CI 95% | p |
---|---|---|---|---|---|---|
Onset of symptoms at hospital admission (days) median (IQR) (range) | 7 (5–11) | 7 (5–11) (1–41) | 7 (4–10.3) (1–53) | 0.172 | ||
Severity of illness on admission associated with neurological complications | ||||||
CORADS 6, n (%) | 141/803 (17.6) | 111/725 (15.3) | 30/78 (38.5) | 3.46 | 2.10–5.69 | 0.000 |
Severe ARDS, n (%) on admission | 301/902 (33.4) | 256/810 (31.6) | 45/92 (48.9) | 2.07 | 1.34–3.20 | 0.001 |
CURB-65, median (IQR) | 1 (0–2) | 1 (0–2) | 2 (1–3) | 0.000 | ||
qSOFA, median (IQR) | 1 (1–1) | 1 (1–1) | 2 (1–3) | 0.000 | ||
SOFA ≥5, n (%) | 191/702 (27.2) | 149/635 (23.5) | 42/67 (62.7) | 5.48 | 3.23–9.29 | 0.000 |
NEWS2 score ≥8, n (%) | 313/874 (35.8) | 267/793 (33.7) | 46/81 (56.8) | 2.59 | 1.63–4.12 | 0.000 |
Days from hospital admission to discharge (days) median (IQR) | 10 (6–17) | 10 (3–17) (1–94) | 11 (7–18) (1–75) | 0.324 | ||
Extraneurological complications associated with complications in the central nervous system (CNS) in patients with COVID-19 | ||||||
Cardiovascular manifestations de novo, n (%) | 43 (4.3) | 31 (3.5) | 12 (12.5) | 3.98 | 1.97–8.04 | 0.000 |
Congestive heart failure de novo, n (%) | 20 (2.0) | 13 (1.5) | 7 (7.3) | 5.34 | 2.08–13.72 | 0.000 |
Pulmonary thromboembolism de novo, n (%) | 8 (0.8) | 5 (0.6) | 3 (3.1) | 5.74 | 1.35–24.41 | 0.034 |
Deep venous thrombosis de novo, n (%) | 11 (1.1) | 5 (0.6) | 6 (6.3) | 11.87 | 3.55–39.65 | 0.000 |
Outcomes | ||||||
Invasive mechanical ventilation (IMV), n (%) | 310/989 (31.3) | 265/893 (29.7) | 45/96 (46.9) | 2.09 | 1.36–3.20 | 0.001 |
Admission to intensive care unit (ICU), n (%) | 146/889 (16.4) | 136/801 (17.0) | 10/88 (11.4) | 0.177 | ||
Septic shock, n (%) | 277 (28.0) | 230 (25.7) | 47 (49.0) | 2.77 | 1.80–4.25 | 0.000 |
Death, n (%) | 433 (43.7) | 359 (40.1) | 74 (77.1) | 5.02 | 3.06–8.23 | 0.000 |
Demographic Characteristics and Risk Factors | All Patients n = 991 | No Deaths n = 558/991 (56.3%) | Deaths n = 433/991 (43.7%) | CI 95% | p | aOR (95%CI) | p |
---|---|---|---|---|---|---|---|
≥64 years, n (%) | 453 (45.7) | 184 (33.0) | 269 (62.1) | 3.33 (2.57–4.33) | 0.000 | 2.87 (2.02–4.08) | 0.000 |
Male gender, n (%) | 614 (62.0) | 328 (58.8) | 286 (66.1) | 1.36 (1.05–1.77) | 0.019 | ||
Hypertension, n (%) | 549 (55.4) | 269 (48.2) | 280 (64.7) | 1.97 (1.52–2.54) | 0.000 | ||
Diabetes mellitus, n (%) | 412 (41.6) | 205 (36.7) | 207 (47.8) | 1.58 (1.22–2.04) | 0.000 | ||
Chronic kidney disease, n (%) | 100 (10.1) | 43 (7.7) | 57 (13.2) | 1.82 (1.20–2.76) | 0.005 | ||
Any pulmonary history, n (%) | 76 (7.7) | 28 (5.0) | 48 (11.1) | 2.36 (1.45–3.83) | 0.000 | ||
COPD, n (%) | 50 (5.0) | 11 (2.0) | 39 (9.0) | 4.92 (2.49–9.73) | 0.000 | ||
History of heart failure, n (%) | 28 (2.8) | 9 (1.6) | 19 (4.4) | 2.80 (1.25–6.25) | 0.009 | ||
General neurological (CNS + PNS) manifestations and complications, n (%) | 202 (20.3) | 97 (17.4) | 105 (24.2) | 1.52 (1.12–2.08) | 0.008 | ||
De novo CNS manifestations and complications while in hospital, n (%) | 96 (9.7) | 22 (3.9) | 74 (17.1) | 5.0 (3.06–8.23) | 0.000 | 3.05 (1.39–6.72) | 0.006 |
CNS manifestations | |||||||
Delirium, (%) | 63 (6.4) | 15 (2.7) | 48 (11.1) | 4.51 (2.49–8.18) | 0.000 | ||
Altered consciousness, n (%) | 50 (5.0) | 6 (1.1) | 44 (10.2) | 10.41 (4.39–24.66) | 0.000 | ||
Drowsiness, n (%) | 32/990 (3.2) | 7 (1.3) | 25/432 (5.8) | 4.84 (2.07–11.29) | 0.000 | ||
Stupor, n (%) | 21 (2.1) | 3 (0.5) | 18 (4.2) | 8.02 (2.35–27.42) | 0.000 | ||
Seizures, n (%) | 9 (0.9) | 4 (0.7) | 5 (1.2) | 0.515 | |||
Hemiplegia, n (%) | 4 (0.4) | 1 (0.2) | 3 (0.7) | 0.324 | |||
Dysarthria, n (%) | 5 (0.5) | 1 (0.2) | 4 (0.9) | 0.174 | |||
Aphasia, n (%) | 5 (0.5) | 0 (0.0) | 5 (1.2) | - | |||
Anisocoria, n (%) | 4 (0.4) | 0 (0.0) | 4 (0.9) | - | |||
Hallucinations, n (%) | 4 (0.4) | 1 (0.2) | 3 (0.7) | 0.324 | |||
CNS syndrome or complications | |||||||
Stroke, n (%) | 19 (1.9) | 3 (0.5) | 16 (3.7) | 7.09 (2.06–24.52) | 0.001 | ||
Ischemic stroke, n (%) | 14 (1.4) | 3 (0.5) | 11 (2.5) | 4.82 (1.34–17.39) | 0.012 | ||
Ischemic in the left middle cerebral artery, n (%) | 7 (0.7) | 2 (0.4) | 5 (1.2) | 0.250 | |||
Ischemic in right middle cerebral artery, n (%) | 5 (0.5) | 1 (0.2) | 4 (0.9) | 0.174 | |||
Left carotid ischemic stroke, n (%) | 1 (0.1) | 0 (0.0) | 1 (0.2) | - | |||
Right carotid ischemic stroke, n (%) | 1 (0.1) | 0 (0.0) | 1 (0.2) | - | |||
Hemorrhagic stroke, n (%) | 5 (0.5) | 1 (0.2) | 4 (0.9) | 0.174 | |||
Subarachnoid hemorrhage | 4 (0.4) | 0 (0.0) | 4 (0.9) | - | |||
Epilepsy de novo, n (%) | 9 (0.9) | 4 (0.7) | 5 (1.2) | 0.515 | |||
Ataxia, n (%) | 7 (0.7) | 1 (0.2) | 6 (1.4) | - | |||
Encephalitis, n (%) | 3 (0.3) | 2 (0.4) | 1 (0.2) | 1.000 | |||
PNS manifestations and complications, n (%) | 126 (12.7) | 80 (14.3) | 46 (10.6) | 0.082 | |||
Myalgias, n (%) | 185 (18.7) | 109 (19.5) | 76 (17.6) | 0.427 | |||
Dysgeusia, n (%) | 94 (9.5) | 60 (10.8) | 34 (7.9) | 0.122 | |||
Anosmia, n (%) | 82 (8.3) | 58 (10.4) | 24 (5.5) | - | |||
Myopathy, n (%) | 4 (0.7) | 4 (0.7) | 3 (0.7) | 1.000 | |||
Guillain Barré syndrome de novo, n (%) | 1 (0.1) | 1 (0.2) | 0 (0.0) | - | |||
Extraneurological complications associated with complications in patients hospitalized with COVID-19 | |||||||
Cardiovascular manifestations de novo, n (%) | 43 (4.3) | 10 (1.8) | 33 (7.6) | 4.52 (2.20–9.28) | 0.000 | ||
Laboratory findings | |||||||
Lymphopenia ≤ 0.900 (103/µL), n (%) | 386/978 (39.5) | 189/553 (34.2) | 197/425 (46.4) | 1.66 (1.28–2.16) | 0.000 | ||
Platelets ≤ 150 (103/µL), n (%) | 137/982 (14.0) | 53/553 (9.6) | 84/429 (19.6) | 2.30 (1.59–3.33) | 0.000 | ||
D-dimer ≥ 1000 ng/mL, n (%) | 361/912 (39.6) | 141/522 (27.0) | 220/390 (56.4) | 3.49 (2.65–4.62) | 0.000 | 2.25 (1.57–3.23) | 0.000 |
CORADS 6, n (%) | 141/803 (17.6) | 60/461 (13.0) | 81/342 (23.7) | 2.07 (1.44–2.99) | 0.000 | ||
Severe ARDS, n (%) on admission | 301/902 (33.4) | 59/473 (12.5) | 242/429 (56.4) | 9.08 (6.51–12.67) | 0.000 | ||
SOFA ≥ 5, n (%) | 191/702 (27.2) | 39/349 (11.2) | 152/353 (43.1) | 6.01 (4.05–8.91) | 0.000 | 4.52 (2.93–6.99) | 0.000 |
NEWS2 score ≥ 8, n (%) | 313/874 (35.8) | 120/469 (25.6) | 193/405 (47.7) | 2.65 (1.99–3.52) | 0.000 | ||
Outcomes | |||||||
IMV, n (%) | 310/989 (31.3) | 32 (5.7) | 278/431 (64.5) | 29.87 (19.87–44.90) | 0.000 | ||
Intensive care unit (ICU), n (%) | 146/889 (16.4) | 51/469 (10.9) | 95/420 (22.6) | 2.39 (1.66–3.47) | 0.000 |
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Corona-Nakamura, A.L.; Arias-Merino, M.J.; Morfín-Otero, R.; Rodriguez-Zavala, G.; León-Gil, A.; Camarillo-Escalera, J.R.; Reyes-Cortés, I.B.; Valdovinos-Ortega, M.G.; Nava-Escobar, E.R.; Villaseñor-Corona, A.M.d.l.P.; et al. Neurological Manifestations and Complications of the Central Nervous System as Risk Factors and Predictors of Mortality in Patients Hospitalized with COVID-19: A Cohort Study. J. Clin. Med. 2023, 12, 4065. https://doi.org/10.3390/jcm12124065
Corona-Nakamura AL, Arias-Merino MJ, Morfín-Otero R, Rodriguez-Zavala G, León-Gil A, Camarillo-Escalera JR, Reyes-Cortés IB, Valdovinos-Ortega MG, Nava-Escobar ER, Villaseñor-Corona AMdlP, et al. Neurological Manifestations and Complications of the Central Nervous System as Risk Factors and Predictors of Mortality in Patients Hospitalized with COVID-19: A Cohort Study. Journal of Clinical Medicine. 2023; 12(12):4065. https://doi.org/10.3390/jcm12124065
Chicago/Turabian StyleCorona-Nakamura, Ana Luisa, Martha Judith Arias-Merino, Rayo Morfín-Otero, Guillermo Rodriguez-Zavala, Alfredo León-Gil, Juan Ramsés Camarillo-Escalera, Idarmis Brisseida Reyes-Cortés, María Gisela Valdovinos-Ortega, Erick René Nava-Escobar, Ana María de la Paz Villaseñor-Corona, and et al. 2023. "Neurological Manifestations and Complications of the Central Nervous System as Risk Factors and Predictors of Mortality in Patients Hospitalized with COVID-19: A Cohort Study" Journal of Clinical Medicine 12, no. 12: 4065. https://doi.org/10.3390/jcm12124065