Depression and Anxiety in Long Term Coronavirus Disease COVID-19 (DALT-COV)

Depression and Anxiety in Long Term COVID 19. A Study in Neurotransmitter Impact of Severe Acute Respiratory Syndrome-Coronavirus 2 Infection.

Background :

Depression and Anxiety are linked to COVID (Coronavirus Disease)-19 long-term impact through several mechanisms. The possible way is the alteration of neurotransmitter regulation from the interaction of severe acute respiratory syndrome -Coronavirus-2 (SARS-COV2) with Angiotensin-Converting Enzyme 2 (ACE2) receptor, and Dopa Decarboxylase (DDC), an enzyme that associated with the production of dopamine, serotonin, and other neurotransmitters. However, some arguments exist that depression and anxiety occur naturally due to external stressors, as the impact of public health measures, and not associated with physiological changes due to viral infection.

Objective:

1. This study aims to identify whether the patient discharged after COVID 19 treatment has significant changes in serotonin and dopamine level which might induce depression and anxiety internally and,
2. To distinguish external etiologies that might induce depression and anxiety such as social isolation and stress due to public health restriction.

Method:

A prospective longitudinal study of people with the interest exposure is COVID 19 and the primary outcome is Depression, Anxiety, and Neurotransmitter level

Hypothesis:

People with a previous infection of COVID 19 have a significant difference in neurotransmitter level over time and compared to non exposed group and a higher prevalence of anxiety and depression.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Covid19; Anxiety
• Intervention / Treatment: Other: Depression; Other: Anxiety

Detailed Description

Method :

Prospective Longitudinal study for 6 months. with both exposed and unexposed group

Target population :

A cohort of the population in multiple centers (3 centers)

Sample Size Calculation with Longitudinal study formula:

1. Effect Size: 0.15
2. Type I error: 0.05
3. Power of Study: 80%
4. Number of Group: 2
5. Repeated measurement: 3 times
6. Correlation among Repeated Measures: 0.5
7. Nonsphericity Correction: 1
8. Initial Sample size: 75

Adjusted by clustering effect:

1. Intraclass Correlation Coefficient = 0.05
2. Number of people per cluster = 25
3. Design Effect= 1 + 0.05(25-1) = 2.2
4. Total sample size = 75 x 2.2 = 165 participants

Procedure:

1. Participants will be assessed for eligibility
2. Screening for Depression, Anxiety, and Stress using Depression Anxiety Stress Scale (DASS) Questionnaire. Health-Related Quality of Life (QoL) and Pittsburgh Sleep Quality Index (PSQI)
3. Sample Collection and assessment of QoL, DASS, PSQI on the first day
4. Sample Collection and assessment of QoL, DASS, PSQI on day 60
5. Sample Collection and assessment of QoL, DASS, PSQI on day 120

Variables

1. Case Definition: Realtime Polymerase Chain Reaction (RT-PCR) and Cycle Threshold Value (CT)
2. Degree of COVID 19 Symptom-based on World Health Organization Criteria (Asymptomatic, Mild, Moderate, Severe, Critical)
3. Sociodemographic Variables (Age, Gender, Education, Income, Marital Status)
4. Sleep Quality using Pittsburgh Sleep Quality Index (PSQI)
5. Treatment of COVID: Antiviral, Antibiotic, Interleukin-6 Antagonist, Steroid, Plasma Convalescent, Ventilator, Human Intravenous Immunoglobulin, anticoagulant
6. Chronic Disease including Diabetes Mellitus, Hypertension, Chronic Kidney Disease
7. Medication that affects neurotransmitter level taken prior to recruitment.
8. History of Smoking classified by Brinkmann Index.
9. Body Mass Index
10. Complete Blood Count
11. Vaccination history

Outcome

1. Dopamine Serum
2. Serotonin Serum
3. Prevalence of Anxiety, and Depression according to Diagnostic and Statistical Manual of Mental disorders (DSM) 5

Statistical analysis Basic Analysis: Intention to Treat analysis

1. Linear Mixed Model for Neurotransmitter
2. Generalized Estimating Equation for Prevalence of Anxiety and Depression
3. Sensitivity analysis will be conducted, concerning the lost-to-follow up
4. A subgroup analysis will be conducted, particularly the participants with specific comorbidities

• Study Type: Observational
• Enrollment (Anticipated): 165

Contacts and Locations

• Study Contact: Name: Bumi Herman, M.D.Ph.D; Phone Number: +66638275008; Email: bumiherman@med.unhas.ac.id

Study Locations

• Indonesia
  • South Sulawesi
    • Makasar, South Sulawesi, Indonesia, 90245
      • Hasanuddin University Medical Research Center / HUMRC
      • Principal Investigator: Bumi Herman, M.D Ph.D
      • Principal Investigator: Firman Hasan, M.D
      • Principal Investigator: Karina Patricia, M.D
      • Contact: Bumi Herman, M.D, Ph.D; Phone Number: +62411586010; Email: bumiherman@med.unhas.ac.id

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: Probability Sample

Study Population

Three clusters will be appointed as the study center. The level of the cluster is at the municipality level where participants will be recruited consecutively

Description

Inclusion Criteria:

1. Age minimum 18 years old
2. For exposed group should be confirmed with RT-PCR
3. Not being diagnosed by depression or anxiety prior to recruitment

Exclusion Criteria:

1. The unexposed participants will be excluded from the unexposed group if contracted with the virus within the 6-month observation.
2. Patient falls into critical condition and it is unlikely to attend at least one follow-up measurement
3. Patient refuses to continue observation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exposed with COVID 19; The participant with confirmed RT-PCR Covid 19 at the beginning of the study	Other: Depression; Any participants who develop depression symptoms according to DSM 5 criteria; Other: Anxiety; Any participants who develop anxiety symptoms according to DSM 5 criteria
Unexposed with COVID 19; The participant without confirmed RT-PCR Covid 19 at the beginning of the study until 6 month follow up period	Other: Depression; Any participants who develop depression symptoms according to DSM 5 criteria; Other: Anxiety; Any participants who develop anxiety symptoms according to DSM 5 criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of Serotonin	The level of serotonin (5-hydroxytryptamine) measured from the blood serum with the normal range between 50 to 200 ng/mL	Changes of Serotonin level from the baseline to 60 days and 120 days
Level of Dopamine	The level of serotonin (4- (2-aminoethyl) benzene-1, 2-diol) measured from the blood serum with the normal range between 0 to 30 pg/mL	Changes of Dopamine level from the baseline to 60 days and 120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Depression	Prevalence of depression defined in Diagnostic and Statistical Manual of Mental disorders fifth edition / DSM 5	changes of prevalence of depression from the baseline to 60 days and 120 days
Prevalence of Anxiety	Prevalence of Anxiety defined in Diagnostic and Statistical Manual of Mental disorders fifth edition / DSM 5	changes of prevalence of Anxiety from the baseline to 60 days and 120 days

Collaborators and Investigators

• Sponsor: Hasanuddin University
• Investigators: Principal Investigator: Bumi Herman, M.D Ph.D, Chulalongkorn University

Publications and helpful links

General Publications

• 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.
• Nataf S. An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19. J Med Virol. 2020 Oct;92(10):1743-1744. doi: 10.1002/jmv.25826. Epub 2020 Apr 8. No abstract available.
• Antonini A, Leta V, Teo J, Chaudhuri KR. Outcome of Parkinson's Disease Patients Affected by COVID-19. Mov Disord. 2020 Jun;35(6):905-908. doi: 10.1002/mds.28104. Epub 2020 May 28. No abstract available.
• Adhanom Ghebreyesus T. Addressing mental health needs: an integral part of COVID-19 response. World Psychiatry. 2020 Jun;19(2):129-130. doi: 10.1002/wps.20768. No abstract available.
• Basagana X, Xiaomei Liao, Spiegelman D. Power and sample size calculations for longitudinal studies estimating a main effect of a time-varying exposure. Stat Methods Med Res. 2011 Oct;20(5):471-87. doi: 10.1177/0962280210371563. Epub 2010 Jun 14.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Depression; Covid19; Anxiety; Dopamine; Serotonin
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Mood Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Depression; Depressive Disorder; COVID-19; Anxiety Disorders
• Other Study ID Numbers: 1105211301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Protocol, Statistical Analysis Plan and De-identified data will be shared accordingly

Drug and device information, study documents

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