Covid19, Paludism
Conditions
Brief summary
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.
Interventions
None listed
Sponsors
Institute of Tropical Medicine, Belgium
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Malaria Antibody Level | Day 1 | 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. |
Countries
Democratic Republic of the Congo
Participant flow
Recruitment details
137 cases and 101 controls were included in the trial. Total paired matched case-controls at the end of study: 95 (95 controls and 95 cases). Baseline characteristics were entered for the matched case-control participants.
Participants by arm
| Arm | Count |
|---|---|
| Cases Cases are severe COVID-19 cases and comprise inpatients recruited from CTCOs.
* Presenting clinical signs of pneumonia: fever, cough, or respiratory difficulties AND
* Presenting at least one of the following:
* Respiratory rate \> 30 breaths/min OR
* Severe respiratory distress (clarification: with oxygen) OR
* SpO2 \< 90% in room air (clarification: without oxygen)
* Be admitted to a care unit for COVID-19 (clarification: hospital) | 95 |
| Controls Controls are asymptomatic or symptomatic cases without signs of severity:
* Asymptomatic OR
* Symptomatic, but without any signs of severe pneumonia:
* Respiratory rate ≤ 30 breaths/min AND
* No severe respiratory distress AND
* SpO2 ≥ 90% in room air
* Recruited within 10 weeks of a matched case | 95 |
| Total | 190 |
Baseline characteristics
| Characteristic | Cases | Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 22 Participants | 52 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 73 Participants | 138 Participants |
| Age, Continuous | 56 years | 54 years | 55 years |
| Civil status Married | 63 Participants | 51 Participants | 114 Participants |
| Civil status No information | 0 Participants | 3 Participants | 3 Participants |
| Civil status Single | 18 Participants | 22 Participants | 40 Participants |
| Civil status Widow(er) | 14 Participants | 19 Participants | 33 Participants |
| Health Zone of Kinshasa Bandalungwa | 2 Participants | 2 Participants | 4 Participants |
| Health Zone of Kinshasa Barumbu | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Binza-Meteo | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Binza-Ozone | 4 Participants | 4 Participants | 8 Participants |
| Health Zone of Kinshasa Gombe | 5 Participants | 5 Participants | 10 Participants |
| Health Zone of Kinshasa Kalamu I | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Kalamu II | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Kasa-Vubu | 2 Participants | 2 Participants | 4 Participants |
| Health Zone of Kinshasa Kimbanseke | 7 Participants | 7 Participants | 14 Participants |
| Health Zone of Kinshasa Kintambo | 2 Participants | 2 Participants | 4 Participants |
| Health Zone of Kinshasa Kisenso | 2 Participants | 2 Participants | 4 Participants |
| Health Zone of Kinshasa Lemba | 14 Participants | 14 Participants | 28 Participants |
| Health Zone of Kinshasa Limete | 12 Participants | 12 Participants | 24 Participants |
| Health Zone of Kinshasa Lingwala | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Makala | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Masina I | 5 Participants | 5 Participants | 10 Participants |
| Health Zone of Kinshasa Masina II | 2 Participants | 2 Participants | 4 Participants |
| Health Zone of Kinshasa Matete | 4 Participants | 4 Participants | 8 Participants |
| Health Zone of Kinshasa Mont-Ngafula I | 8 Participants | 8 Participants | 16 Participants |
| Health Zone of Kinshasa Ndjili | 1 Participants | 1 Participants | 2 Participants |
| Health Zone of Kinshasa Ngaba | 2 Participants | 2 Participants | 4 Participants |
| Health Zone of Kinshasa Ngiri-Ngiri | 3 Participants | 3 Participants | 6 Participants |
| Health Zone of Kinshasa Nsele | 13 Participants | 13 Participants | 26 Participants |
| Health Zone of Kinshasa Selembao | 1 Participants | 1 Participants | 2 Participants |
| Level of education Higher education/university | 38 Participants | 37 Participants | 75 Participants |
| Level of education Illiterate | 4 Participants | 1 Participants | 5 Participants |
| Level of education No information | 2 Participants | 0 Participants | 2 Participants |
| Level of education Primary school degree | 14 Participants | 13 Participants | 27 Participants |
| Level of education Secondary school degree | 37 Participants | 44 Participants | 81 Participants |
| Occupation driver | 1 Participants | 7 Participants | 8 Participants |
| Occupation farmer | 1 Participants | 3 Participants | 4 Participants |
| Occupation gardener | 0 Participants | 1 Participants | 1 Participants |
| Occupation Maintenance worker | 1 Participants | 1 Participants | 2 Participants |
| Occupation no information | 3 Participants | 0 Participants | 3 Participants |
| Occupation No job occupation | 45 Participants | 30 Participants | 75 Participants |
| Occupation Office worker/Public servant | 11 Participants | 11 Participants | 22 Participants |
| Occupation other | 14 Participants | 21 Participants | 35 Participants |
| Occupation Shopkeeper/Store clerk | 10 Participants | 10 Participants | 20 Participants |
| Occupation teacher | 5 Participants | 7 Participants | 12 Participants |
| Occupation technician | 4 Participants | 2 Participants | 6 Participants |
| Occupation worker | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 95 Participants | 95 Participants | 190 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 56 Participants | 56 Participants | 112 Participants |
| Sex: Female, Male Male | 39 Participants | 39 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cases | Malaria Antibody Level | 3.8 fluorescence intensity (log scale) |
| Controls | Malaria Antibody Level | 3.3 fluorescence intensity (log scale) |
p-value: 0.11595% CI: [0.953, 1.564]Regression, Logistic
p-value: 0.1295% CI: [0.953, 1.564]Regression, Logistic