Résilience - COVID-19 - Résilience - Coronavirus disease 2019

Pre-pandemic SARS-CoV-2 natural immunity in Africa and South-East Asia – PRECOV_

PRECOV: testing for natural pre-pandemic immunity to SARS-CoV-2

Almost two years after the emergence of COVID-19, significant regional differences in terms of morbidity persist, showing in particular lower incidence rates in some regions of Africa or Asia. The work reported here aims to test for a pre-pandemic natural immunity among populations in Africa and South-East Asia, and a suspected SARS-CoV-2 original antigenic sin.

Almost two years after the emergence of COVID-19, significant regional differences persist, showing the lowest incidence rates in sub-Saharan Africa, Southeast Asia, and Oceania. This trend was observed at the onset of the epidemic and has been confirmed during subsequent epidemic waves.<br /><br />Several hypotheses have been proposed to explain this situation, including among others: the morbidity and mortality counts likely to be underestimated in some low- and middle-income countries due to limited epidemiological surveillance and/or public health screening activity; the population of sub-Saharan Africa is younger with only 2.3% of the population over 65 years old, whereas people over 65 years old account for more than three-quarters of the deaths related to COVID-19 in Europe (where this population represents more than 20% of the population); more rural living conditions may increase social distancing and reduce the spread of the disease; climatic and environmental conditions unfavorable to the virus and its spread; a natural immunity innate (nonspecific) or secondary due to previous contact with a coronavirus closely related to SARS-CoV-2 and sharing common antigenic profiles, and a suspected SARS-CoV-2 original antigenic sin (OAS).<br />The objective of this present study was to identify the later hypothesis of a pre-existing natural humoral anti-SARS-CoV-2 immunity among African populations by testing sera samples from repository collected several months before the COVID-19 epidemic started. We tested the presence of a reacting antibodies against five SARS-CoV-2 proteins playing an essential role in virus attachment, fusion, entry and transmission.

Antibody detection
The INNOBIOCHIPS ELISA serological test used detects the IgG antibodies targeting the N protein, the S1 protein, the RBD domain of the S1 protein, the NTD domain of the S1 protein, and the S2 protein from SARS-CoV-2 virus (Wuhan strain). The test values are obtained by optical density reading using a laser reader.

Data analysis
After calculating the statistical moments and the distribution of the samples’ values for each antigen, several statistical tests and calculations were performed including: for each antigen, comparison of the means (Student's T-test) and the variances (F-test) between the samples group and the control group; difference between the two groups (samples and controls) considering all the five antigens together was tested using Hotelling test. Calculation of the number and percentage of samples considered positive for each antigen (with confidence interval), according to the cutoff value; calculation of the number of positive samples for two or more antigens.

Control sera collection
The controls sera were obtained by INNOBIOCHIPS company from 189 samples from blood donors collected in Northern France before the pandemic, randomly selected (EFS, Etablissement Français du Sang) and tested negative for SARS-CoV-2 by PCR. These sera collection was used by the manufacturer to define the thresholds of positivity as compared to the sera collected from patients infected by SARS-CoV-2 (PCR test positive). We used this control group to establish thresholds for the absence of SARS-CoV-2-like antibodies with respect to their geographic origin while such blood donors from France are supposed to have not been in direct or indirect contact with bats. To eliminate the risk of false negatives (samples may came from donors of African or South and South-East Asian origin), for each antigen the distribution of control values was modeled. For each antigen, the PRECOV threshold value correspond to a probability equal to 0.0002. All control samples with a value for an antigen above the threshold will be considered as false negatives for this antigen.

We already tested a total of 1655 samples from DRC (Democratic Republic of the Congo), Congo, Cameroon and Senegal. DRC samples originated from the Monkole Hospital Center biobank (190 samples, collected in 2019 from healthy subjects from the hospital staff, from volunteers, and from young sickle-cell disease patients who are part of a study cohort), and from the ALTADEVA/Monkole biobank (384 samples, collected in 2014 and 2015 as part of a study of Plasmodium falciparum chemoresistance in the city-province of Kinshasa, in the central province of Kongo, and southwestern DRC).
The 383 tested samples from Cameroon were selected among samples received from various laboratories between June 2018 and June 2019 at the Chantal BIYA International Research Center for HIV Prevention and Management (CIRCB), as part of continual health monitoring among PLHIV. 51% of the 383 samples selected were among samples received from some Central and General Hospitals within the country. The remaining 49% were selected among samples received from peripheral healthcare facilities.
The samples from the Republic of Congo (536 tested samples) were collected by The Fondation Congolaise pour la Recherche Médicale in Southern district of Brazzaville, Madibou and in the Northern part of the country (Sangha) in the district of Bomassa, in 2016 and 2019, respectively.
The samples from Senegal (162 samples) were randomly selected from serums collected in 2018 and 2019 and conserved in the biobank of the Institut de Recherche en Sciences de la Santé, Epidémiologie et formation (IRESSEF, Health Sciences Research Institute of Epidemiology and Training).
All samples were aliquoted and kept frozen as appropriate and each sample had companion data including date of collection, age, sex, and province of origin.

Antibodies against the five tested SARS-CoV-2 antigens were detected in the pre-COVID samples, with differential optical density mean value for African samples significantly higher than for the control samples. The S1 antigen shows the highest percentage of positives: 19.64% for African samples versus 2.11% for the control samples. The S2 and RBD antigens also show significantly higher rates. We find also a high significant difference with control samples (p-value< 10-6) when all antigens were considered together.
Among the 1655 tested samples, 630 samples reacted at least against 1 antigen above the threshold (38.1%, vs. 9.5% for the controls), while 205 samples reacted at least against 2 antigens above the threshold (12.4%, vs 0% for the controls).

We are extending the survey in new countries in Africa (Uganda, Chad, Burkina, maybe Kenya) and South-East Asia (Thailand).

Pre-pandemic SARS-CoV-2 potential natural immunity among population of the Democratic Republic of Congo, doi.org/10.1101/2021.04.28.21256243
Pre-Pandemic SARS-CoV-2 Potential Natural Immunity Among Population of Central Africa, doi.org/10.21203/rs.3.rs-588697/v1
Suspected SARS-CoV-2 original antigenic sin among Central and West African populations, submitted to PLoS One, dec 2021

More than a year after the start of the COVID-19 epidemic, there are still significant regional differences in the incidence of the disease, particularly in sub-Saharan Africa and South-East Asia. This trend, which has been observed since the beginning of the epidemic, has been confirmed in successive waves.
Among the hypotheses proposed to explain these differences, we have looked for the presence of pre-existing natural immunity to the SARS-CoV-2 virus due to pre-pandemic exposure to coronavirus antigens close to SARS-CoV-2.
Preliminary results from DR Congo and Congo show, in sera collected before 2020, a prevalence close to 20% for the S1 antigen, and between 6 and 10% for the other antigens tested (N, S2, RBD, NTD).
In this new project, we propose to develop our research in several directions:
- expand research in other countries (Chad, Burkina Faso, Cameroon, Thailand, Laos)
- study the neutralizing power of detected antibodies
- study the evolution of seroprevalence and neutralizing antibodies between the pre-pandemic period and the current period.

Project coordination

Marc SOURIS (Unité des Virus Emergents)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


UVE Unité des Virus Emergents

Help of the ANR 79,000 euros
Beginning and duration of the scientific project: May 2021 - 12 Months

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