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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Covid19; Neurocognitive Dysfunction
• Intervention / Treatment: Biological: Exposure: COVID-19 severity

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Constanza Caneo, MD; Phone Number: +56942909250; Email: cmcaneo@uc.cl
• Study Contact Backup: Name: Carolina Mendez, PhD; Phone Number: +56 942595693; Email: carolinamendez@uc.cl

Study Locations

• Chile
  • Santiago, Chile, 8320000
    • Recruiting
    • 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
    • Contact: Constanza Caneo, MD; Phone Number: +56942909250; Email: cmcaneo@uc.cl
    • Contact: Carolina Mendez-Orellana, PhD; Phone Number: +56 942595693; Email: carolinamendez@uc.cl
    • Sub-Investigator: Felipe Leon, MD
    • Sub-Investigator: Francisco Palacios, MD
    • Principal Investigator: Carolina Astudillo, PhD
    • Principal Investigator: Felix Bacigalupo, PhD
    • Principal Investigator: Claudia Gonzalez, PhD
    • Principal Investigator: Bernardita Soler, PhD
    • Principal Investigator: Jaime Godoy, MD
    • Principal Investigator: Sebastian Bravo, MD
    • Principal Investigator: Claudia Saez, MD
    • Principal Investigator: Luis Rojas, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

COVID-19 patients over 18 years of age discharged from critical care units at Red de Salud UC Christus who presented MoCA® cognitive test result less than 26 points at the time of discharge.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

COVID-19 patients discharged from critical care units; Adults over 18 years of age who have been hospitalized after COVID-19 diagnosis in the critical care units of Red Salud UC Christus who have been cognitively evaluated with Montreal Cognitive Assessment (MoCA) days prior to their discharge. All patients with a previous history of confirmed neurocognitive or psychotic disorders, prior to hospital admission, were excluded.

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Exercise endurance	Performance on 6 minutes- walk test Evaluation of aerobic capacity and exercise endurance. Setting: Home	12 months
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
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
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
Muscle strength	Dynamometry Setting: Home	12 months
Pain severity	Scale: Stanford pain scale Min: 0 represents no pain Max: 10 represents unimaginable or unspeakable pain Setting: online	12 months
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
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
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
irritable bowel syndrome	Rome IV criteria Setting: online	12 months
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
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
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

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Director: Rafael Medina, PhD, Pontificia Universidad Catolica de Chile; Study Director: Arnoldo Riquelme, PhD, Pontificia Universidad Catolica de Chile; Principal Investigator: Constanza Caneo, MD, Pontificia Universidad Catolica de Chile; Principal Investigator: Carolina Mendez, PhD, Pontificia Universidad Catolica de Chile

Publications and helpful links

General Publications

• 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. No abstract available.
• 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.
• 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.
• 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.
• 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. No abstract available.
• 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.
• 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.
• 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.
• Alberti P, Beretta S, Piatti M, Karantzoulis A, Piatti ML, Santoro P, Vigano M, Giovannelli G, Pirro F, Montisano DA, Appollonio I, Ferrarese C. Guillain-Barre syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm. 2020 Apr 29;7(4):e741. doi: 10.1212/NXI.0000000000000741. Print 2020 Jul. No abstract available.
• 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-Barre 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. No abstract available.
• 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.
• 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. No abstract available.
• Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, Humphries F, Jager 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. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Fatigue; COVID-19; Insomnia; Functionality; Intensive Care Units; Long-term cognitive impairment; Post traumatic stress; exercise endurance; Verbal fluency; language disorders
• Additional Relevant MeSH Terms: Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurocognitive Disorders; Cognition Disorders; COVID-19; Cognitive Dysfunction
• Other Study ID Numbers: 0000001; 1U19AI135972 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are available to be contacted by researchers aiming to conduct secondary analyses based on our study, after providing a study protocol based on international guidelines, in order to ensure adequate use of our data.
• IPD Sharing Time Frame: January 2024
• IPD Sharing Access Criteria: contact to responsable researcher C Caneo
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No