Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05445713 |
| Other study ID # |
EZ-FV-028 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 10, 2022 |
| Est. completion date |
June 25, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
University of Witwatersrand, South Africa |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
Description:
This is a single-centre, follow-up, observational, cross-sectional study of four distinct,
longitudinal cohorts. Extensive clinical history will be obtained from each participant, and
symptom questionnaire characterisation of Long-COVID (with a strong focus on organ-specific
dysfunction, psychiatric, sleep, and pain parameters - all of which appear to be major
features of Long-COVID), as well as laboratory and genetic characterisation will be
performed. A subset of each cohort will be randomly selected for more specific syndrome
characterisation related to sleep and pain, respiratory, cardiology, renal and glucose
metabolism.
The consequences of Long-COVID will be described and compared in four large, well-described
clinical cohorts of African patients surviving SARS-CoV-2:
- 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.
After obtaining informed consent from potential participants, a single cross-sectional,
baseline visit will be conducted for each participant. Demographic data, clinical history
(including COVID-19 history, targeted symptoms, and risk factors), COVID-19 vaccination dates
(if administered), and details of previous and concomitant medications will be collected.
Multiple questionnaires related to psychiatric screening, psychosocial factors, work function
assessment, sleep quality, and pain assessment will be administered. Respiratory and cardiac
function will be evaluated through a dyspnoea scale, walking test and an ECG. Laboratory
evaluations will include a full blood count, serum chemistry, liver function tests, renal
function assessment, inflammatory markers, and DNA extraction for genotyping. Blood and urine
samples will be stored locally for possible future analysis. Human immunodeficiency virus
(HIV) testing will be performed for participants consenting to this optional assessment.
After the baseline visit, participants with Long-COVID will be identified using the WHO
clinical definition and general health assessments [2]. Randomly selected sub-groups of
participants with, and without, Long-COVID will be selected from each of the four cohorts for
additional investigations through participation in the following sub-studies:
- Respiratory evaluation: dyspnoea assessment, high-resolution computed tomography (CT)
scan, lung function studies including spirometry and diffusion capacity (DLCO) [Section
7.2.2.1]
- Cardiac evaluation: clinical history and examination, serial blood pressure, six minute
walk test (distance), ECG, echocardiogram including speckle tracking, cardiac magnetic
resonance imaging (MRI), creatine kinase MB fraction (CK-MB), cardiac troponin T (cTnT),
prohormone brain natriuretic peptide (pro-BNP), and possible coronary angiography in
patients with acute coronary syndromes and unstable angina [Section 7.2.2.2]
- Psychiatric and neuroendocrine evaluation: questionnaires/surveys, semi-structured
interview, home visit, saliva cortisol analysis, collection of diary data, actigraphy,
adrenocorticotropic hormone (ACTH) challenge (cosyntropin sensitivity test [CST]),
cellular immunity assessment [Section 7.2.2.3]
- Sleep evaluation: questionnaires, actigraphy with sleep diaries, polysomnography (PSN)
[Section 7.2.2.4]
- Pain evaluation: quantitative sensory testing (QST) and conditioned pain modulation
(CPM) assessments [Section 7.2.2.5]
- Glucose metabolism evaluation: oral glucose tolerance test (OGTT) including assessment
of glucose, insulin, and c-peptide to estimate insulin sensitivity and beta-cell
function [16]. [Section 7.2.2.6] Abnormalities detected in the assessments (including
undiagnosed mental health issues) will be managed by on-study medical personnel with
referral as appropriate.
