Tuberculosis as a Risk Factor for a Worse Outcome Post-Sars-CoV-2 Infection (Co-TB)

Tuberculosis as a Risk Factor for a Severe Course and Adverse Long-term Outcome of a Symptomatic Sars-CoV-2 Infection in Johannesburg, South Africa

This study has two main objectives. First, the clinical characteristics and outcomes of hospitalized patients with symptomatic Covid-19 disease will be compared between persons with a history of past or current TB infection or disease and those, who have had no TB history. The possible impact of an HIV-coinfection will be also addressed in the planned investigations and analysis. Second, the long-term consequences and clinical outcomes of Covid-19 up to 12 months post-infection will be analysed in both groups (with and without TB history) with the main focus on cardio-pulmonary outcomes.

Study Overview

• Status: Completed
• Conditions: COVID-19; Tuberculosis; Post-acute COVID-19 Syndrome

Detailed Description

This study is retrospective/prospective clinical observational study.

Primary Objective, Study Phase A (hospitalization, retrospective data collection):

• To describe the development and characteristics of Covid-19 pneumonia, clinically and using radiological methods (i.e. CT-thorax)
• To describe disease severity of Covid-19 disease, including treatment in Intensive Care Unit (ICU) and ventilation support measures
• To describe different types of organ failures apart from respiratory failure (e.g. kidney, liver, heart)
• To describe treatment outcomes at discharge, including cause of death
• To assess the significance of additional risk factors such as HIV infection, smoking, malnutrition, etc., for the clinical course and characteristics of a Covid-19 disease Primary Objective, Study Phase B (after end of hospitalization, prospective data collection): The primary objective of the study phase B (after end of hospitalization) is the description of Covid-19 sequelae (focus on cardio-pulmonary morbidity) in patients with and without previous TB disease during a six month follow up period after discharge from hospital, including:
• the description (characteristics and severity) of abnormal function tests and clinical examination results (e.g. in lung function measurement, cardiac tests and ECG, kidney function, neurological & mental tests)
• the definition of time to healing (ad integrum) after a Covid-19 infection
• the studying of chronic restrictions of the long-term quality of life at 12 months after discharge from hospital that are based on chronic organ failures and mental disorders
• the assessment of exacerbations of chronic organ failures, hospitalizations and deaths in 12 months phase after discharge from hospital

Secondary Objective(s):

• To collect longitudinal data that could allow for further insights on whether previous Covid-19 disease results in an increased risk for re-activation of

  /infection with M. tuberculosis

• To perform longitudinal immunological investigations in a sub-set of patients to study Covid-19- immune-activation, depending on M.tb and/or HIVcoinfection status

• Study Type: Observational
• Enrollment (Actual): 157

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • The Aurum Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population comprises the general population (of 18 years and older), which is served by the study hospital. Those who cannot give informed consent, or are under imprisonment, or suffer from other medical or mental conditions and/or life under circumstances that may prevent the completion of 6 months follow up will also not be included.

Description

Inclusion Criteria:

• Willingness to provide a written informed consent or witnessed oral consent in the case of illiteracy for participation in the study prior to all study-related procedures
• Be ≥ 18 years and <70 years of age
• Having a diagnosis of SARS-CoV-2 infection, confirmed by PCR tests and/or chest CT-scan
• Willing to be tested for active and latent M.tb infection and to provide information on previous TB disease episodes (including agreement for confirmation of active TB disease by the investigators, e.g. via NTP/lab registration number)
• Willing to be tested for HIV, if status is not known or the last documented negative is more than 4 weeks old
• Willingness to comply with the protocol and visit schedule, at the discretion of the investigator
• Having a firm home address that is readily accessible for visiting and is willing to inform the study team of any change of address during study participation

Exclusion Criteria:

• Has a recent history of a medical condition that is the leading cause for the current clinical symptoms and/or survival, e.g. advanced stages of cancer
• Has severe medical or psychiatric condition which in the opinion of the site investigator or designee, might interfere with the ability to give true informed consent and to adhere to the study requirements.
• Is currently imprisoned
• Confirmed or suspected pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Co-TB Group; Follow up all participants from hospital discharge until 12 months post-Covid-19 infection. Conduct investigations assessing cardiopulmonary, socioeconomic, quality of life outcomes. No interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Covid-19 recovery and course and the impact of tuberculosis (TB) or no tuberculosis infection.	Describe the long-term clinical characteristics and course of recovery post-Covid-19 and compare patients groups with TB infection and those without TB infection. TB infection will be determined by a history of TB disease, or current TB disease on medical records, and latent TB infection will be determined by Interferon-Gamma release assay blood test. Those with any positive of the above tests will be considered to have TB infection, and those with all negative tests will be considered to have no TB infection.	March 2021 to December 2022

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac outcomes post-Covid-19.	Determine Covid-19 pneumonia cardiac characteristics in our post-hospitalisation cohort up to 12 months post-infection.	March 2021 to December 2022
Hospitalisation and Covid-19 severity	Describe Covid-19 pneumonia hospitalisation with Covid severity in our post-hospitalisation cohort up to 12 months post-infection.	March 2021 to December 2022
Lung function assessment post-Covid-19.	Describe respiratory assessment in our post-hospitalisation cohort up to 12 months post-infection.	March 2021 to December 2022

Collaborators and Investigators

• Sponsor: The Aurum Institute NPC
• Collaborators: Ludwig-Maximilians - University of Munich; Chris Hani Baragwanath Academic Hospital
• Investigators: Principal Investigator: Andrea Rachow, PhD, med, Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU)

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: November 29, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; COVID-19; Tuberculosis
• Other Study ID Numbers: AUR2-8-296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Currently conducting study analysis with the database and once study is complete will discuss the plan to share IPD

Drug and device information, study documents

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