Depression and Anxiety in Long Term Coronavirus Disease COVID-19

• Conditions: Covid19; Anxiety; Depression
• Interventions: Other: Depression; Other: Anxiety

• Registration Number: NCT04893668
• Lead Sponsor: Hasanuddin University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-05-11
• Study First Submitted QC: 2021-05-11
• Study First Posted: 2021-05-19
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-03
• Last Update Posted: 2021-06-07
• Study Start: 2021-10-01
• Primary Completion: 2022-04-01
• Study Completion: 2022-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 165

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Unexposed with COVID 19	Depression	The participant without confirmed RT-PCR Covid 19 at the beginning of the study until 6 month follow up period
Exposed with COVID 19	Depression	The participant with confirmed RT-PCR Covid 19 at the beginning of the study
Exposed with COVID 19	Anxiety	The participant with confirmed RT-PCR Covid 19 at the beginning of the study
Unexposed with COVID 19	Anxiety	The participant without confirmed RT-PCR Covid 19 at the beginning of the study until 6 month follow up period

Primary Outcome Measures

Name	Time	Method
Level of Serotonin	Changes of Serotonin level from the baseline to 60 days and 120 days	The level of serotonin (5-hydroxytryptamine) measured from the blood serum with the normal range between 50 to 200 ng/mL
Level of Dopamine	Changes of Dopamine level from the baseline to 60 days and 120 days	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hasanuddin University Medical Research Center / HUMRC; 🇮🇩 Makasar, South Sulawesi, Indonesia