Clinical trial NCT04473365: Rapid Diagnostic Profiling of SARS-CoV-2 (COVID-19)
Official title: Rapid Diagnostic Profiling of SARS-CoV-2 in the Context of Persistent Immune Activation in Sub-Saharan Africa (Profile-Cov)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SARS-CoV-2
COVID-19
Keywords: Immune profile
Serology
Antibody test
Antigen test
SARS-CoV-2
COVID-19
Immune response
Severity
Lead sponsor: Mekelle University
Sponsor class: OTHER
Collaborators: name: Ethiopian Public Health Institute
name: Liverpool School of Tropical Medicine
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Tigray Health Research Institute
First posted: 2020-07-16
Enrollment: 838
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients suspected of having SARS-CoV-2 infection and admitted to Covid-19 isolation and treatment centers.

Brief summary: The investigators will evaluate the profile of the immune response of Ethiopian population and examine its relationship with the noted low CD4+ T-cell count and underlying immune activation status among participants with COVID-19 and will compare results with those residing in Europe. In addition, this project will evaluate the performance of various rapid diagnostic tests (RDTs) for SARS-CoV-2, taking into account the above-determined immune system characteristics. We will also evaluate the effect of co-infection with parasites on COVID-19 severity

Detailed description: In December 2019, a cluster of patients with pneumonia of unknown aetiology was linked to an infection with a novel coronavirus - the SARS-CoV-2. Since then, the infection has become pandemic and spread affecting almost every country in the world. Knowledge of virus dynamics and the host's immune response to it is essential to understanding the pathogenesis as well as in formulating diagnostic, therapeutic and preventive strategies. There are no studies, however, related to these issues, particularly in Sub-Saharan Africa (SSA) context. Previous studies by the investigators have shown that the immune profile of healthy Ethiopians shows evidence of chronic immune activation with significant low naïve cells but high activated memory cells, of both CD4+ and CD8+ T-cell sub populations. The above immune system characteristics of Ethiopians as compared to Europeans led the investigators to the assumption that these could contribute to the pathogenesis of and severity of clinical presentation of COVID-19. Persistent immune activation due to continuous infections with helminths is common in the entire SSA region. Such activation usually skewes the immune system towards T helper (Th)-2-type responses. The immune response against SARS-CoV-2 is typically of so called "cytokine storm". Here, the investigators hypothesize that SARS-CoV-2 infection induced immune activation as observed in patients in the industrialized world (with concomitant cytokine storms and extensive non-specific CD8 T-cell cytotoxicity) might be more prominent than in people from SSA, due to the Th2 profile of their immune system.

The investigators propose to study the profile of the immune response of Ethiopian population and will examine its relationship with the noted low CD4+ T-cell count and underlying immune activation status among patients with COVID-19 and will compare results with those residing in Europe. In addition, this project will evaluate the performance of various rapid diagnostic tests (RDTs) for SARS-CoV-2, taking into account the above-determined immune system characteristics. In addition, the investigators will evaluate the RDTs for use in the screening of infected patients who are asymptomatic, in particular in health-care settings, as well as for monitoring recovery or clearance of virus shedding for use in resource-constrained setting. Such comparative studies will help identify immune factors that could play a role in attenuating the disrupted immune responses caused by SARS-CoV-2 infection and thus contribute to the design and development of effective diagnostic, therapeutic or vaccine.

The pathogenesis of severe COVID-19 is related to hyper-inflammation. However, COVID-19 symptomatology in SSA appears significantly less serious than in industrialized world. We postulate that individuals residing in SSA and co-infected with intestinal parasites down regulate immune to SARS-CoV-2 and mute COVID-19 severity.

Eligibility criteria: Inclusion Criteria:

* Clinical case-definition confirmed by RT-PCR.

Exclusion Criteria:

* Recent history of COVID-19
* Not capable of understanding or complying with the study protocol
* Anticipated transfer to another hospital which is not a study site within 72 hours
* Refusal to consent and participate in the study

Primary outcomes:
measure: Proportion of patients identified as Covid-19 by and monitoring virus clearance with COVID-19 using algorithm of RDTs.
timeFrame: Up to 30 days after onset of infection
measure: Proportion of non-Covid-19 cases identified as negative by antibody assay
timeFrame: Up to 30 days after onset of infection other than SARS-CoV-2
Secondary outcomes:
Other outcomes:
measure: Proportion of Ethiopian vs. European COVID-19 patients with predominant Th1 type immune responses.
timeFrame: Up to 30 days after onset of infection
measure: Proportion of severe COVID-19 patients with or without parasite co-infection
timeFrame: Up to 45 days after onset of infection/during hospitalization)
measure: Proportion of patients with SARS-CoV-2 neutralizing antibody titer
timeFrame: Up to 45 days of follow-up after symptom onset
Locations:
city: Mekelle
country: Ethiopia
facility: Mekelle University College of Health Sciences
Study officials:
affiliation: Mekelle University
name: Dawit Wolday, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gebrecherkos T, Challa F, Tasew G, Gessesse Z, Kiros Y, Gebreegziabxier A, Abdulkader M, Desta AA, Atsbaha AH, Tollera G, Abrahim S, Urban BC, Schallig H, Rinke de Wit T, Wolday D. Prognostic Value of C-Reactive Protein in SARS-CoV-2 Infection: A Simplified Biomarker of COVID-19 Severity in Northern Ethiopia. Infect Drug Resist. 2023 May 16;16:3019-3028. doi: 10.2147/IDR.S410053. eCollection 2023.
citation: Gebrecherkos T, Kiros YK, Challa F, Abdella S, Gebreegzabher A, Leta D, Desta A, Hailu A, Tasew G, Abdulkader M, Tessema M, Tollera G, Kifle T, Arefaine ZG, Schallig HH, Adams ER, Urban BC, de Wit TFR, Wolday D. Longitudinal profile of antibody response to SARS-CoV-2 in patients with COVID-19 in a setting from Sub-Saharan Africa: A prospective longitudinal study. PLoS One. 2022 Mar 23;17(3):e0263627. doi: 10.1371/journal.pone.0263627. eCollection 2022.
citation: Wolday D, Gebrecherkos T, Arefaine ZG, Kiros YK, Gebreegzabher A, Tasew G, Abdulkader M, Abraha HE, Desta AA, Hailu A, Tollera G, Abdella S, Tesema M, Abate E, Endarge KL, Hundie TG, Miteku FK, Urban BC, Schallig HHDF, Harris VC, de Wit TFR. Effect of co-infection with intestinal parasites on COVID-19 severity: A prospective observational cohort study. EClinicalMedicine. 2021 Sep;39:101054. doi: 10.1016/j.eclinm.2021.101054. Epub 2021 Jul 31.
citation: Wolday D, Tasew G, Amogne W, Urban B, Schallig HD, Harris V, Rinke de Wit TF. Interrogating the Impact of Intestinal Parasite-Microbiome on Pathogenesis of COVID-19 in Sub-Saharan Africa. Front Microbiol. 2021 Apr 16;12:614522. doi: 10.3389/fmicb.2021.614522. eCollection 2021. No abstract available.
citation: Abraha HE, Gessesse Z, Gebrecherkos T, Kebede Y, Weldegiargis AW, Tequare MH, Welderufael AL, Zenebe D, Gebremariam AG, Dawit TC, Gebremedhin DW, de Wit TR, Wolday D. Clinical features and risk factors associated with morbidity and mortality among patients with COVID-19 in northern Ethiopia. Int J Infect Dis. 2021 Apr;105:776-783. doi: 10.1016/j.ijid.2021.03.037. Epub 2021 Mar 16.