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

• ClinicalTrials.gov Identifier: NCT05019300
• Recruitment Status: Recruiting
• First Posted: August 24, 2021
• Last Update Posted: August 31, 2021
• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Constanza Caneo, Pontificia Universidad Catolica de Chile

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Covid19; Neurocognitive Dysfunction	Biological: Exposure: COVID-19 severity

Study Design

• Study Type: Observational
• Estimated Enrollment: 80 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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.
• Actual Study Start Date: May 24, 2021
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: October 2021

Groups and Cohorts

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).

Outcome Measures

Primary Outcome Measures :

1. Cognitive impairment screening [ Time Frame: 12 months ]

   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

Secondary Outcome Measures :

1. Cognitive performance [ Time Frame: 12 months ]

   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

2. Neurological Soft Signs [ Time Frame: 12 months ]

   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

3. Anxiety [ Time Frame: 12 months ]

   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

4. Depressive syndrome [ Time Frame: 12 months ]

   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

5. Post Traumatic Stress Disorder [ Time Frame: 12 months ]

   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

6. Physical disability [ Time Frame: 12 months ]

   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

7. Exercise endurance [ Time Frame: 12 months ]

   Performance on 6 minutes- walk test

   Evaluation of aerobic capacity and exercise endurance.

   Setting: Home

8. Fatigue [ Time Frame: 12 months ]

   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

9. Global functionality [ Time Frame: 12 months ]

   Post-Covid-19 functional scale 5 levels of severity, where o is non impairment and 5 is the highest level of impairment.

   Setting: online

10. Quality of life related to health [ Time Frame: 12 months ]

    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

11. Muscle strength [ Time Frame: 12 months ]
    Dynamometry Setting: Home
12. Pain severity [ Time Frame: 12 months ]

    Scale: Stanford pain scale

    Min: 0 represents no pain Max: 10 represents unimaginable or unspeakable pain Setting: online

13. Spontaneous Speech [ Time Frame: 12 months ]

    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

14. Verbal fluency [ Time Frame: 12 months ]

    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

15. complex post-traumatic stress disorder [ Time Frame: 12 months ]

    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

16. irritable bowel syndrome [ Time Frame: 12 months ]
    Rome IV criteria Setting: online
17. Insomnia [ Time Frame: 12 months ]

    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

18. Dysautonomia [ Time Frame: 12 months ]

    Scales: Scales for outcomes in Parkinson's dysfunction-autonomic (SCOPA-AUT), Orthostatic hypotension symptom assessment (OHSA) and Orthostatic hypotension activity scale (OHACT).

    Setting: online

19. Dyspnea [ Time Frame: 12 months ]

    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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

Contacts

Contact: Constanza Caneo, MD; +56942909250; cmcaneo@uc.cl

Contact: Carolina Mendez, PhD; +56 942595693; carolinamendez@uc.cl

Locations

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; Recruiting

Santiago, Chile, 8320000

Contact: Constanza Caneo, MD +56942909250 cmcaneo@uc.cl

Contact: Carolina Mendez-Orellana, PhD +56 942595693 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

Sponsors and Collaborators

Pontificia Universidad Catolica de Chile

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

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

• Responsible Party: Constanza Caneo, Clinical Assistant Professor, C-L Psychiatrist, PI NPQCOVID, Advance Interdisciplinary Rehabilitation Register, (AIRR) Covid-19 Working group, Pontificia Universidad Catolica de Chile
• ClinicalTrials.gov Identifier: NCT05019300
• Other Study ID Numbers: 0000001; 1U19AI135972 ( U.S. NIH Grant/Contract )
• First Posted: August 24, 2021
• Last Update Posted: August 31, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: January 2024
• Access Criteria: contact to responsable researcher C Caneo

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Constanza Caneo, Pontificia Universidad Catolica de Chile:

COVID-19; Intensive Care Units; Functionality; Fatigue; Anxiety; Insomnia; Long-term cognitive impairment; language disorders; Verbal fluency; Depression; Post traumatic stress; exercise endurance

Additional relevant MeSH terms:

COVID-19; Cognitive Dysfunction; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders