## Protocol Section
### Identification Module
**NCT ID:** NCT06435403

**Acronym:** CoVICIS

**Brief Title:** SARS-CoV-2 Specific Antibody Responses and Impact for COVID-19 Disease in Ethiopia

**Official Title:** SARS-CoV-2 Specific Antibody Responses and Impact for COVID-19 Disease in Health Care Worker and Community Members From Ethiopian Related to Natural SARS CoV-2 Infection and COVID-19 Vaccination

#### Organization Study ID Info
**ID:** ETH-02
#### Organization
**Class:** OTHER
**Full Name:** Ludwig-Maximilians - University of Munich
### Status Module
#### Completion Date
**Date:** 2025-02-28

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-02-28

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-11-10

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-24
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** St. Paul's Hospital Millennium Medical College, Ethiopia

**Class:** OTHER

**Name:** Jimma University

#### Lead Sponsor

**Class:** OTHER

**Name:** Michael Hoelscher

#### Responsible Party

**Investigator Affiliation:** Ludwig-Maximilians - University of Munich

**Investigator Full Name:** Michael Hoelscher

**Investigator Title:** Director, Division of Infectious Diseases and Tropical Medicine, LMU Munich

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** In this study we aim to characterize SARS CoV-2 strain specific immune response (SARS-CoV-2 Spike IgG) in health care workers and general populations at the Jimma Medical Center and the St. Paul Hospital in Addis Ababa in association to clinical immune protection and Covid-19 disease. Participants, stratified by SARS-CoV-2 infection and vaccination status, will be followed at 3-month intervals for a maximum of 2 years. Prevalence, incidence, and dynamics of SARS-CoV-2 specific antibodies as well as clinical assessments especially related to COVID-19 breakthrough disease in previously exposed/vaccinated participants will be performed. From a subset of selected participant blood sample, more in depth immunological analysis will be performed that include virus culture-based neutralization assays, antibody avidity assays, SARS-CoV-2 specific antibody epitope recognition using peptide arrays, and T-cell immunity assays (IGRA).

We also plan to analyze and model cost-effectiveness considerations related to adapted COVID-19 vaccine strategies, specifically if SARS-CoV-2 the costs for routine sero-diagnosis in high SARS-CoV-2 prevalent population prior to vaccination will impact the decision to vaccinate (no vaccination for low-risk populations or reduced vaccine dosing) and is cost-efficient. The study is largely exploratory, providing deeper insights in SARS-CoV-2 specific immune responses and interaction with SARS-CoV-2 viral variants.

**Detailed Description:** The COVID-19 pandemic has severely impacted health systems, interventions for infection control and resulting preventive public life restrictions. In a recent study, we determined high rates of previous SARS-CoV-2 infection in health care worker (over 70%) and communities in Ethiopia (up to 60%), with resulting potential natural acquired SARS-CoV-2 specific immunity. In contrast to the situation in Europe, the scale out of COVID-19 vaccination is however very low, and currently there is a scarcity of COVID-19 vaccines available all over Africa. Naturally acquired or vaccine induced SARS-CoV-2 immune responses have shown to protect against (severe) COVID-19 disease. However, immune responses are waning over time and new SARS-CoV-2 viral variants increasingly demonstrate immune escape properties. Correlates of clinical immune protections are currently investigated including binding SARS-CoV-2 spike IgG or neutralizing antibody levels, as well as cellular immune responses. However, threshold of immune protection are not yet defined that would guide the need of booster vaccinations, including for individuals with natural acquired immunity. There is evidence, that vaccination regimens in those individuals could be abbreviated to single shot booster, that would greatly economize challenged COVID-19 strategies in Africa.

The CoVICIS is a network of European and African researcher who collaborate on the overall objective to investigate SARS-CoV-2 specific immune response and correlates of immune protection in the context of circulating SARS-CoV-2 viral variants. In this affiliated study, we aim to investigate these outcomes in Ethiopian health care worker and community members throughout a longitudinal, prospective cohort study. Participants, stratified according to their SARS-CoV-2 infection and vaccination status, will be followed-up in 3-monthly intervals To characterize SARS CoV-2 strain specific immune response (SARS-CoV-2 Spike IgG) in health care workers and general populations stratified by previous (1) SARS CoV-2 exposure (SARS-CoV-2 anti-nucleocapsid antibody positive versus negative) and (2) vaccination status at the Jimma Medical Center (JMC) and the St. Paul Hospital in Addis Ababa in association to clinical immune protection and Covid-19 disease. Prevalence, incidence, and dynamics of SARS-CoV-2 specific antibodies as well as clinical assessments will be performed in 3-monthly intervals over a maximum period of 24 months.

At each study visits, immune responses including SARS-CoV-2 spike IgG and neutralizing antibody will be measured. In addition, SARS CoV-2-specific T cell responses will be studied in each of the study groups. COVID-19 disease or SARS-CoV-2 infections will be assessed throughout the study by clinical history, SARS-CoV-2 PCR diagnostics, and seroconversion of SARS-CoV-2 anti-nucleocapsid antibody testing as appropriate. In addition, more in-depth analysis will be performed in a subset of stored blood samples at collaborating specialized laboratories in Germany and Switzerland, including peptide array mapping, T-cell assays and affinity/avidity analysis against the ACE-II receptor. We further aim to characterize circulating SARS CoV-2 strains from PCR isolates in the context of investigated immune responses. Outcome results will be provided for computational analysis, integrating models for immune protection. Finally, we will explore the feasibility and cost-effectiveness of abbreviated single shot COVID-19 vaccination for individuals with pre-existing natural immunity to assess COVID-19 vaccine strategies that are especially applicable in African settings.

Findings from this study aim to help in guiding the current Covid-19 control strategy in Ethiopia. It might also give the first insight about the dynamics and level of antibodies produced against SARS-CoV-2 in the Ethiopian population.

### Conditions Module

**Conditions:**

- SARS CoV 2 Infection

- COVID-19 Breakthrough

- COVID-19 Recurrent

**Keywords:**

- COVID-19

- Seroepidemiologic Studies

- Longitudinal Studies

- Ethiopia / epidemiology

- SARS-CoV-2

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 1000

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** SARS-CoV-2 anti-nucleocapsid positive, vaccinated

**Label:** Group 1 (N=300)

#### Arm Group 2

**Description:** SARS-CoV-2 anti-nucleocapsid positive, not vaccinated

**Label:** Group 2 (N=300)

#### Arm Group 3

**Description:** SARS-CoV-2 anti-nucleocapsid negative, vaccinated

**Label:** Group 3 (N=300)

#### Arm Group 4

**Description:** SARS-CoV-2 anti-nucleocapsid negative, not vaccinated

**Label:** Group 4 (N=100)

### Outcomes Module

#### Other Outcomes

**Measure:** Difference of extended humoral (e.g. neutralizing antibodies) and cellular immune responses in a subset of participants by study groups at different time points

**Time Frame:** 24 months

**Measure:** Recognition of SARS-CoV-2 specific peptide in a subset of participants by study groups at different time points

**Time Frame:** 24 months

**Measure:** Detection and description of COVID19 and determination of upper respiratory viral load in subjects with (re)infection

**Time Frame:** 24 months

#### Primary Outcomes

**Measure:** Difference of antibody levels between study groups by month 12

**Time Frame:** 12 months

**Measure:** Proportion of participants with suspected clinically reported severe COVID-19 disease or evidence of SARS-CoV-2 exposure between study groups by month 12

**Time Frame:** 12 months

**Measure:** Proportion of SARS-CoV-2 breakthrough infections in previously exposed/vaccinated participants

**Time Frame:** 24 months

#### Secondary Outcomes

**Measure:** Difference of antibody levels between groups by month 6, 18 and 24

**Time Frame:** 24 months

**Measure:** Antibody levels after single 1st vaccination in previously infected persons

**Time Frame:** 24 months

**Measure:** Proportion of participants with suspected clinically reported severe COVID-19 disease or evidence of SARS-CoV-2 exposure between study groups by month 6, 18 and 24

**Time Frame:** 24 months

**Measure:** Prevalence and distribution of circulating SARS-CoV-2 variants around baseline and during the study period

**Time Frame:** 24 months

**Measure:** Costs related to SARS-CoV-2 anti-nucleocapsid diagnostics in relation to spared costs by abbreviated/not performed COVID-19 vaccine regimen

**Time Frame:** 24 months

### Eligibility Module

**Eligibility Criteria:** Inclusion criteria:

1. Adults, 18 years of above
2. Provision of oral as well as written informed consent
3. Available estimation of the period or the time-point when SARS-CoV-2 infection occurred (e.g. confirmed or highly suspected COVID-19 disease, SARS-CoV-2 anti-nucleocapsid seroconversion) (only applicable for participants included in group 1 and 2).
4. Employed/working in hospital (medical doctors, nurses/midwives, students, auxiliary personnel such as cleaner, runner, social worker) for HCW
5. Willingness to provide blood samples by venipuncture for serology and immunological characterization
6. Willingness to provide health information, report medical events and to performed SARS-CoV-2 diagnostics (swabs for PCR) in the case of suspected COVID-19 disease

Exclusion criteria:

1. Prisoners
2. Mentally disturbed persons
3. Persons for whom study participation will induce an unacceptable risk or burden as judged by the investigator (e.g. seriously sick persons)

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Healthcare workers (clinical staff, practicing medical interns, cleaners, guards, food handlers, and receptionists) at the two hospitals and potentially participants from the general urban population in Jimma and Addis Ababa will be included. N=500 participants at each site (N=1000 in total) will be stratified according to their SARS CoV-2 sero-s and Covid-19 vaccination status at inclusion into 4 groups. We aim to target at least 30% representation of HCW's, respectively community participants for each study group.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Arne.Kroidl@med.uni-muenchen.de

**Name:** Arne Kroidl, MD

**Phone:** +49-89-4400

**Phone Ext:** 59816

**Role:** CONTACT

**Contact 2:**

**Name:** Rebecca Kisch

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Addis Ababa

**Contacts:**

***Contact 1:***

- **Email:** solomon.ali@sphmmc.edu.et

- **Name:** Solomon Ali, PhD

- **Phone:** +251911488680

- **Role:** CONTACT

**Country:** Ethiopia

**Facility:** Department of Microbiology Immunology and Parasitology

**Status:** RECRUITING

**Location 2:**

**City:** Jimma

**Contacts:**

***Contact 1:***

- **Email:** Esayas.kebede@ju.edu.et

- **Name:** Esayas K Gudina, MD, PhD

- **Phone:** +251917550576

- **Role:** CONTACT

**Country:** Ethiopia

**Facility:** Jimma University

**Status:** RECRUITING

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000011024

- Term: Pneumonia, Viral

- ID: D000011014

- Term: Pneumonia

- ID: D000012141

- Term: Respiratory Tract Infections

- ID: D000014777

- Term: Virus Diseases

- ID: D000018352

- Term: Coronavirus Infections

- ID: D000003333

- Term: Coronaviridae Infections

- ID: D000030341

- Term: Nidovirales Infections

- ID: D000012327

- Term: RNA Virus Infections

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M2561

- Name: COVID-19

- Relevance: HIGH

- As Found: COVID-19

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13904

- Name: Pneumonia

- Relevance: LOW

- As Found: Unknown

- ID: M13914

- Name: Pneumonia, Viral

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M20490

- Name: Coronavirus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6555

- Name: Coronaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M23685

- Name: Nidovirales Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15149

- Name: RNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000086382

- Term: COVID-19

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
