A Cross-sectional, Observational Study to Characterise Long COVID-19 in an Urban Sample of South African Adults

NCT05445713 | Completed

• 1 other identifier: EZ-FV-028
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 2

Brief Summary

"Long-COVID'' (also known as post-COVID-19 syndrome, post-acute sequelae of COVID-19, or chronic COVID syndrome, used here as 'Long-COVID' for brevity), is a complex array of postconvalescence symptoms following SARS-CoV-2 infection. The syndrome, common in COVID-19 survivors, can affect every organ system through as-yet uncharacterised but presumed immunological mechanisms. Prevalence depends on the definition used and time-period of follow-up, as well as the population being studied. The syndrome has been associated with significant and persistent disability in some survivors but has been hampered, until recently, by lack of a clinical definition, diagnostic criteria, and objective measures of disease or disability \[1\]. A Delphi-informed initial World Health Organisation (WHO) clinical definition was released in early October 2021 but has attracted much criticism from both clinicians and survivors for a host of reasons, ranging from a lack of precision to a lack of inclusion \[2\]. Further complicating the syndrome is the context in which the SARS-CoV-2 epidemic occurred, which was associated with severe lockdowns in many countries (including South Africa) with social isolation, widespread fear and disinformation, widespread economic hardship, and loss of family and acquaintances, all of which contribute to symptoms (psychiatric and sleep disturbances, pain, and other syndromes) reported to be associated with Long-COVID. Finally, many Long-COVID symptoms overlap with those seen in patients hospitalised for any severe illness, especially those admitted to intensive care and ventilated. However, the proliferation of literature reporting associations of Long-COVID symptoms with more severe COVID-19 disease, and objective immunological, radiological, and organ-specific dysfunction in those reporting symptoms, suggests that the entity is real. The pathogenesis of Long-COVID is poorly understood, but this association with more severe disease - where immune dysregulation plays a major role in those with hospitalization, respiratory failure, and death - suggests an immune-mediated inflammatory dysfunction that may impact all organs \[3-14\]. The sheer rapidity of four major infection waves in South Africa, the initial focus on containing the hospital burden of those with severe illness, and subsequent emphasis on the roll-out of a mass vaccination program, has left little space for studying SARS-COV-2 sequalae in survivors. This group, loosely and inaccurately termed "recovered'' in South African reporting, were largely unvaccinated or partly vaccinated at the time of infection, leaving them at risk of developing Long-COVID.

Conditions

Long COVID

Outcome Measures

Primary Outcomes (1)

• To characterise Long-COVID in four cohorts of patients

  Incidence, severity, and duration of Long-COVID symptoms.

  6 Months

Secondary Outcomes (38)

• Inflammatory markers

  6 Months

• Inflammatory markers

  6 Months

• Inflammatory markers

  6 Months

• Inflammatory markers

  6 Months

• Inflammatory markers

  6 Months

Study Arms (4)

Cohort 1

Asymptomatic subjects found to be PCR/antigen/antibody-positive during routine screening for SARS-CoV-2 infection

Cohort 2

Symptomatic outpatients who were confirmed to have COVID-19 through a positive PCR/antigen test

Cohort 3

Inpatients surviving hospitalisation for severe COVID-19 and who were PCR/antigen-positive

Cohort 4

Participants vaccinated in clinical trials in 2020 prior to widespread community exposure, and hence protected from severe COVID-19 (and possibly Long-COVID) if subsequently infected.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adults at least 18 years of age with previous confirmed SARS-CoV-2 infection (symptomatic or asymptomatic) will be invited to participate. Approximately 400 participants will be enrolled.

You may qualify if:

• Able and willing to provide written or electronic informed consent for the baseline visit prior to any study-specific assessment or procedure.
• Age at least 18 years at the time of signing the informed consent form.
• Previous asymptomatic SARS-CoV-2 infection, confirmed through a documented positive PCR, antigen, or antibody test, at least six months prior to the baseline visit \[Cohort 1 only\] or, previous symptomatic SARS-CoV-2 infection for which hospitalisation was not required, confirmed through a documented positive PCR or antigen test at the time, at least six months prior to the baseline visit \[Cohort 2 only\] or, previous hospitalisation for management and treatment of COVID-19 confirmed through a documented positive PCR or antigen test at the time, at least six months prior to the baseline visit \[Cohort 3 only\] or, previous asymptomatic or symptomatic SARS-CoV-2 infection, confirmed through a documented positive PCR, antigen, or antibody test, at least six months prior to the baseline visit and received a COVID-19 vaccine in a non-placebo arm of a COVID-19 vaccine study during 2020 \[Cohort 4 only\].
• Willing to consent to verification of vaccination status on the national Electronic Vaccination Data System (EVDS).
• Access to a reliable telephone or other device permitting information transfer.

You may not qualify if:

• Symptomatic SARS-CoV-2 infection at any stage prior to the baseline visit \[Cohort 1 only\].
• SARS-CoV-2 infection, confirmed through a documented positive PCR, antigen, or antibody test, prior to vaccination in a non-placebo arm of a COVID-19 vaccine study during 2020 \[Cohort 4 only\].
• COVID-19 within three months of the baseline visit.
• Personnel (e.g., investigator, sub-investigator, research assistant, pharmacist, study coordinator or anyone mentioned in the delegation log) directly involved in the conduct of the study.
• Any physical, mental, or social condition, that, in the Investigator's judgment, might interfere with the completion of the baseline assessments and evaluations. The Investigator should make this determination in consideration of the volunteer's medical history.
• Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results.

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead

Study Sites (2)

Sunnyside Office Park

Johannesburg, Gauteng, 2193, South Africa

Location

Charlotte Maxeke Johannesburg Academic Hospital (CMJAH)

Johannesburg, Gauteng, 2198, South Africa

Location

Biospecimen

Retention: SAMPLES WITH DNA

Full blood count: red cell count, haemoglobin, haematocrit, mean cellular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red cell distribution width (RDW), white cell count and differential (neutrophil count, lymphocyte count, monocyte count, eosinophil count, and basophil count), and platelet count Liver function: total protein, albumin, total bilirubin, direct bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) Renal function: urea, creatinine, estimated creatinine clearance (Cockcroft-Gault method), cystatin C DNA extraction for genotyping and sequencing at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) Additional blood (50 mL) and urine (100 mL) samples will be stored for possible future analysis.

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Francois WD Venter, MBBCh

  Ezintsha, a division of Wits Health Consortium

  PRINCIPAL INVESTIGATOR

• Simiso M Sokhela, MBBCh

  Ezintsha, a division of Wits Health Consortium

  STUDY DIRECTOR

• Nonkululeko Mashabane, BPharm

  Ezintsha, a division of Wits Health Consortium

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 4, 2022
• First Posted: July 6, 2022
• Study Start: August 10, 2022
• Primary Completion: October 30, 2024
• Study Completion: November 25, 2024
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Immediately following publication
• Access Criteria: Anyone who wishes to access the data

Locations

ZA (2)