Malaria as a Protection Factor Against Severe COVID-19 (Known as SARS-COV-2) in the Democratic Republic of Congo (Palu-COVID) (Palu-COVID)

Malaria as a Protection Factor Against Severe COVID-19 in the Democratic Republic of Congo (Palu-COVID)

In this study, the investigators will explore the reasons for the apparently lower proportion of severe COVID-19 cases in many sub-Sahara African countries. Indeed, despite fragile health care systems, the burden of COVID-19 on the African continent seems substantially lower than initially feared. Many potential reasons for this discrepancy have been formulated: the different population age structure, experience of African nations with previous pandemics, warmer climate, and genetic preposition. However, another compelling hypothesis is that of trained immunity by endemic pathogens, such as plasmodia. According to this hypothesis, innate immune activation by endemic pathogens would prime a more robust initial innate immune response to SARS-CoV-2 and could therefore protect against severe COVID-19.

To explore this, the investigators propose conducting a case-control study in Kinshasa, in the Democratic Republic of the Congo (DRC). Kinshasa is an area with mixed prevalence of malaria and the area in DRC most affected by COVID-19. In this setting, the investigators will compare cases of severe COVID-19 with controls that have non-severe COVID-19 and that are matched for age, sex, and health zone. The aim is to compare pre-existing immunity against malaria, both cellular and humoral between the two groups.

Study Overview

• Status: Terminated
• Conditions: Covid19; Paludism

• Study Type: Observational
• Enrollment (Actual): 238

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Kinshasa, Congo, The Democratic Republic of the
    • Institut National De Recherche Biomédical (INRB)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This case-control study will be conducted in the Republic of Congo in the city of Kinshasa, the epicenter of COVID-19. Kinshasa is a malaria endemic area, the distribution of malaria prevalence is lower in urban areas compared to peri-urban areas. Indeed, the city of Kinshasa is structured in four health districts and sixteen hospitals, distributed in the thirty-five Health Zones for the management of COVID-19.

The study will consist of cases and controls:

• Cases will be severe COVID-19 cases that will consist of patients hospitalized and recruited in COVID-19 Treatment Centers.
• Controls will consist of asymptomatic or symptomatic cases without signs of severity. For each case, two controls will be recruited after having been matched in terms of age, gender and health zone of origin.

Description

INCLUSION CRITERIA

To be eligible, study patients must meet the following criteria:

For cases:

• Be at least 18 years of age
• Have an RT-PCR or Antigenic Rapid Test confirmed SARS-CoV-2 infection within 72 hours prior to inclusion.
• Have given informed consent or that of their guardian/ representative to participate in the study.

• Diagnosed as a severe COVID-19 case according to the following criteria:

  • Presenting clinical signs of pneumonia: fever, cough, dyspnea or crepitations AND
  • Presenting at least one of the following signs:

Respiratory rate > 30 cycles/min OR Severe respiratory distress or SpO2 < 90% on room air

• Be admitted to a care unit for COVID-19
• Residing in the health zone for at least 6 months

For controls:

• Be at least 18 years of age
• Have a PCR or Antigenic Rapid Test-confirmed SARS-CoV-2 infection within 72 hours prior to inclusion
• Have given informed consent to participate in the study

• Diagnosed as a non-severe COVID-19 case according to the following criteria:

  • Be asymptomatic OR
  • Symptomatic, but no evidence of severe pneumonia Respiratory rate > 30 cycles/min OR Severe respiratory distress or SpO2 < 90% on room air
• Reside in the study health area for at least 6 months
• Recruited within 10 weeks following the matched cases

EXCLUSION CRITERIA

To be eligible, study patients cannot meet the following criteria for cases and controls:

• Subject has a contraindication to venipuncture, as determined by clinical judgment
• Subject is vaccinated against SARS-CoV-2
• Subject has been infected with SARS-CoV-2 in the past and now presents with reinfection

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malaria Antibody Level	Malaria antibody level in severe and non-severe COVID-19 cases. This level will be assessed by measuring the concentration of IgG against Circum Sporozoite Protein (CSP) using the Luminex- MAGPIX, which is expressed in fluorescence intensity. Analysis of Conditional Maximum Likelihood Estimates.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-malaria IgG antibody levels	Anti-malaria IgG antibody levels to other antigens: AMAI, CSPM, GLURP, Pf/RESA55, and IgM antibodies	Day 1
The cellular response against malaria	The cellular response against malaria between severe and non-severe COVID-19 cases as measured by IFN-y ELISPOT	Day 1
Proportions of acute malaria infection	Proportions of acute malaria infection between severe and non-severe cases of COVID-19 using the Thick Drop and Rapid Diagnostic Test	Day 1
Clinical characteristics	Clinical characteristics (symptoms duration) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (type of symptoms) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (height) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (weight) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (blood pressure) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (heart rate) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (respiratory rate) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (temperature) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (spleen size) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical characteristics	Clinical characteristics (free oxygen saturation) of severe and non-severe COVID-19 cases with and without malaria	Day 1
Clinical status	Clinical status according to WHO scale of severe and non-severe COVID-19 cases with and without malaria	Day 1
SARS-COV-2 specific cellular response	SARS-COV-2 specific cellular (INF-y measure by ELISPOT) immune response of severe and non-severe cases	Day 1
SARS-COV-2 specific humoral immune response	SARS-COV-2 specific humoral (Malaria antibodies & antigens measured by Luminex) immune response of severe and non-severe cases	Day 1
SARS-COV-2 specific humoral immune response	SARS-COV-2 specific humoral (Covid-19 antibodies & antigens measured by Luminex) immune response of severe and non-severe cases	Day 1
Antiviral cytokine release levels	Antiviral cytokine (CXCL10 measure by ELISA) release levels, measured by ELISA and flow cytometry, of peripheral blood monocytes from controls and patients with acute malaria infection	Day 1
Antiviral cytokine release levels	Antiviral cytokine (IFN type I measure by ELISA) release levels, measured by ELISA and flow cytometry, of peripheral blood monocytes from controls and patients with acute malaria infection	Day 1

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2021
• Primary Completion (Actual): August 17, 2022
• Study Completion (Actual): August 17, 2022

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

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; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; COVID-19; Malaria
• Other Study ID Numbers: Palu-COVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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