Long-term Neurocognitive and Psychiatric Consequences in Severe COVID-19 Survivors.

Covid19 Clinical Trial

— NPQCOVID  

Official title:

Long-term Neurocognitive and Psychiatric Consequences of COVID-19 in Patients Discharged From Critical Care Units. A Cohort Study of the Advance Interdisciplinary Rehabilitation Register (AIRR) Covid-19 Working Group.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05019300
• Other study ID #: 0000001
• Secondary ID: 1U19AI135972
• Status: Recruiting
• Start date: May 24, 2021
• Est. completion date: October 2021

Study information

• Verified date: August 2021
• Source: Pontificia Universidad Catolica de Chile
• Contact: Constanza Caneo, MD
• Phone: +56942909250
• Email: cmcaneo[@]uc.cl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Long-term neurocognitive and psychiatric consequences of COVID-19 remain mostly unknown to date. It has been reported that coronaviruses cause direct central nervous system infection (Needham et al. 2020). Besides that, new or worsening cognitive impairment commonly occurs and persists in survivors of intensive care unit (ICU) stay (Hosey & Needham. 2020). The purpose of our study is to search and describe the cognitive and psychiatric long-term consequences of COVID-19 on patients who have been discharged from critical care units. This is an ambidirectional cohort study, that attempts to follow adults discharged from critical Care Units Adults due to COVID-19 up to 12 months after discharge, to evaluate the presence of cognitive impairment, linguistic and phonation function, depression, fatigue, functional gastroenterological symptoms, anxiety, or post traumatic disorder, and performance in activities of daily living and physical response to exercise as well.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults over 18 years of age who have been hospitalized at critical care units, who were admitted for a diagnosis of COVID-19 and who present a score on the MOCA® cognitive test of less than 26 points at the time of hospital discharge .

Exclusion Criteria:

• History of underlying cognitive disorder. History of underlying primary psychotic disorder. MOCA® cognitive test score greater than or equal to 26 points at the time of hospital discharge.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Covid19
• Neurocognitive Dysfunction

Intervention

Biological:
• Exposure: COVID-19 severity
COVID-19 severity between 4 to 7 points according the seven-category scale of clinical status reported by Huang et al. (2021) and severe to critical symptomatic levels on spectrum of disease reported by Wu and McGoogan (2020).

Locations

Country	Name	City	State
Chile	Centro de Investigaciones Médicas, Centro de Investigación Clínica UC, Hospital Clínico UC, San Carlos de Apoquindo, Departamento de Ciencias de la Salud, Escuela de Medicina, Red UC-Christus, Campus Clínico San JoaPontificia Universidad Catolica de Chile	Santiago

Sponsors (2)

Lead Sponsor	Collaborator
Pontificia Universidad Catolica de Chile	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Chile, 

References & Publications (13)

Alberti P, Beretta S, Piatti M, Karantzoulis A, Piatti ML, Santoro P, Viganò M, Giovannelli G, Pirro F, Montisano DA, Appollonio I, Ferrarese C. Guillain-Barré syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm. 2020 Apr 29;7(4). pii: e741. doi: 10.1212/NXI.0000000000000741. Print 2020 Jul. — View Citation

Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, Humphries F, Jäger HR, Losseff NA, Perry RJ, Shah S, Simister RJ, Turner D, Chandratheva A, Werring DJ. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020 Aug;91(8):889-891. doi: 10.1136/jnnp-2020-323586. Epub 2020 Apr 30. — View Citation

Hosey MM, Needham DM. Survivorship after COVID-19 ICU stay. Nat Rev Dis Primers. 2020 Jul 15;6(1):60. doi: 10.1038/s41572-020-0201-1. — View Citation

Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, Kang L, Guo L, Liu M, Zhou X, Luo J, Huang Z, Tu S, Zhao Y, Chen L, Xu D, Li Y, Li C, Peng L, Li Y, Xie W, Cui D, Shang L, Fan G, Xu J, Wang G, Wang Y, Zhong J, Wang C, Wang J, Zhang D, Cao B. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 Jan 16;397(10270):220-232. doi: 10.1016/S0140-6736(20)32656-8. Epub 2021 Jan 8. — View Citation

Kotfis K, Williams Roberson S, Wilson JE, Dabrowski W, Pun BT, Ely EW. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020 Apr 28;24(1):176. doi: 10.1186/s13054-020-02882-x. Review. — View Citation

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127. — View Citation

Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, Zawistowski C, Bemis-Dougherty A, Berney SC, Bienvenu OJ, Brady SL, Brodsky MB, Denehy L, Elliott D, Flatley C, Harabin AL, Jones C, Louis D, Meltzer W, Muldoon SR, Palmer JB, Perme C, Robinson M, Schmidt DM, Scruth E, Spill GR, Storey CP, Render M, Votto J, Harvey MA. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med. 2012 Feb;40(2):502-9. doi: 10.1097/CCM.0b013e318232da75. Review. — View Citation

Needham EJ, Chou SH, Coles AJ, Menon DK. Neurological Implications of COVID-19 Infections. Neurocrit Care. 2020 Jun;32(3):667-671. doi: 10.1007/s12028-020-00978-4. — View Citation

Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, De Leacy RA, Shigematsu T, Ladner TR, Yaeger KA, Skliut M, Weinberger J, Dangayach NS, Bederson JB, Tuhrim S, Fifi JT. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020 May 14;382(20):e60. doi: 10.1056/NEJMc2009787. Epub 2020 Apr 28. — View Citation

Solomon T. Neurological infection with SARS-CoV-2 - the story so far. Nat Rev Neurol. 2021 Feb;17(2):65-66. doi: 10.1038/s41582-020-00453-w. Review. — View Citation

Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, Franciotta D, Baldanti F, Daturi R, Postorino P, Cavallini A, Micieli G. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020 Jun 25;382(26):2574-2576. doi: 10.1056/NEJMc2009191. Epub 2020 Apr 17. — View Citation

Valderrama EV, Humbert K, Lord A, Frontera J, Yaghi S. Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Ischemic Stroke. Stroke. 2020 Jul;51(7):e124-e127. doi: 10.1161/STROKEAHA.120.030153. Epub 2020 May 12. Review. — View Citation

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive impairment screening	Montreal Cognitive Assessment (MoCA®). Evaluation of cognitive domains (visuospatial, executive function; attention and memory; orientation; language).; Min score: 0 Max score: 30 Cut-off for chilean population: < 21 for mild cognitive impairment. < 20 for dementia; Setting: Home and online	12 months
Secondary	Cognitive performance	Cambridge Neuropsychological Test Automated Battery (CANTAB®); Included tests: Reaction time test, (RTI) Paired associate learning (PAL) Spatial Working Memory (SWM) Spatial Span (SSP) Rapid Visual Information Processing (RVP) Cambridge Gambling Task (CGT) Intra/Extra Dimensional Set Shift (IED) Stockings of Cambridge (SOC); Scores: z-scores normalized by sex and educational level; Setting: Home	12 months
Secondary	Neurological Soft Signs	Test: Heidelberg Neurological Soft Signs Scale; 16 items on five factors ("motor coordination": Ozeretzki's test, diadochokinesis, pronation/supination, finger-to-thumb opposition, speech and articulation; "sensory integration": gait, tandem walking, two-point discrimination; "complex motor tasks": finger-to-nose test, fist-edge-palm test; "right/left and spatial orientation": right/left orientation, graphesthesia, face-hand test, stereognosis; "hard signs": arm holding test, mirror movements). All items except for gait, tandem gait, Ozeretzki's test, speech and articulation and right/left orientation are assessed separately for both, right and left sites respectively. Ratings are given on a 0-3 point scale (no/slight/moderate/marked abnormality).; Higher scores mean worse outcomes. Min score: 0 Max score: 48 No cut-off point established in the literature.; Setting: Home	12 months
Secondary	Anxiety	Test: Generalized Anxiety Disorder-7 score; The seven items assess (1) feeling nervous, anxious, or on edge; (2) being able to stop or control worrying; (3) worrying too much about different things; (4) trouble relaxing; (5) being restless; (6) becoming easily annoyed or irritable; and (7) feeling afraid as if something awful might happen.; Increasing scores on the scale are strongly associated with multiple domains of functional impairment and increasing anxiety.; The cut-off point suggested is of =10 Min score: 0 Max score: 21; Setting: online	12 months
Secondary	Depressive syndrome	Test: Patient Health Questionary-2 (PHQ-2) score for screening of depressive syndrome; The cut-off point suggested is of =3 Min score: 0 Max score: 6; Setting: online	12 months
Secondary	Post Traumatic Stress Disorder	Test: Post Traumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) score; 20-item self-report measure that assesses the 20 DSM-5 symptoms of Post Traumatic Stress Disorder.; The cut-off point suggested is of =33 Min score: 0 Max score: 80; Setting: online	12 months
Secondary	Physical disability	Test: Barthel Index score; Measures physical disability behaviour relating to activities of daily living.; Scores of 0-20 indicate "total" dependency, 21-60 indicate "severe" dependency, 61-90 indicate "moderate" dependency, and 91-99 indicates "slight" dependency.; Setting: online	12 months
Secondary	Exercise endurance	Performance on 6 minutes- walk test; Evaluation of aerobic capacity and exercise endurance.; Setting: Home	12 months
Secondary	Fatigue	Measured by the Modified fatigue impact scale (MFIS). The MFIS is a modified version of the 40-item Fatigue Impact Scale (FIS), which was originally developed to assess the effects of fatigue on quality of life in patients with chronic diseases. The FIS has patients rate the extent to which fatigue has affected their life in the past 4 weeks on a questionnaire consisting of 10 "physical" items, 10 "cognitive" items, and 20 "social" items, with 0 indicating "no problem" and 4 indicating "extreme problem."; The cut-off point suggested is of =38 Min score: 0 Max score: 160; Setting: online	12 months
Secondary	Global functionality	Post-Covid-19 functional scale 5 levels of severity, where o is non impairment and 5 is the highest level of impairment.; Setting: online	12 months
Secondary	Quality of life related to health	Test: The 5-level EuroQol 5D health questionnaire. (EQ-5D-5L) Self rated.; Min score: 0 Max score: 100 highest score means worst quality of life.; Setting: online	12 months
Secondary	Muscle strength	Dynamometry Setting: Home	12 months
Secondary	Pain severity	Scale: Stanford pain scale; Min: 0 represents no pain Max: 10 represents unimaginable or unspeakable pain Setting: online	12 months
Secondary	Spontaneous Speech	Spontaneous Speech is a useful research tool to assess the scope of language disorders in people with neurological deficits. Short samples be analyzed during a brief interview and based of 10 linguistics parameters, it will characterized level and the type of language deficit. The 10 linguistic parameters are based on the ALEA method; Setting: Home and online	12 months
Secondary	Verbal fluency	Verbal fluency (phonological and sematic) will be assed by requesting the participants to elicit word under 1 minute for letter F, A and S and for the category animals.; Setting: Home and online	12 months
Secondary	complex post-traumatic stress disorder	Test: International Trauma Questionnaire self-report measure for post-traumatic stress disorder (PTSD) and complex post-traumatic stress disorder (CPTSD), corresponding to the diagnostic criteria in the International Classification of Diseases, 11th Revision (ICD-11).; Setting: online	12 months
Secondary	irritable bowel syndrome	Rome IV criteria Setting: online	12 months
Secondary	Insomnia	Scale: Pittsburgh insomnia rating scale; Seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.; Setting: online	12 months
Secondary	Dysautonomia	Scales: Scales for outcomes in Parkinson's dysfunction-autonomic (SCOPA-AUT), Orthostatic hypotension symptom assessment (OHSA) and Orthostatic hypotension activity scale (OHACT).; Setting: online	12 months
Secondary	Dyspnea	Test: Chronic obstructive pulmonary disease (COPD) assessment test (CAT).; Min: 0 Max: 40 CAT =10 corresponds to either GOLD Group B or D. Group B patients' preferred treatment is to start either on LABA, or LAMA and if persistent symptoms then combination LAMA/LABA therapy-these are the minimum for patients with CAT Score =10.; CAT <10 corresponds to GOLD Group A or C. Group A patients' preferred treatment is to start bronchodilator (LABA or LAMA) and evaluate the effect.; Setting: online	12 months