Pre-pandemic SARS-CoV-2 potential natural immunity among population of the Democratic Republic of Congo

  1. Marc Souris
  2. Léon Tshilolo
  3. Daniel Parzy
  4. Rachel Kamgaing
  5. Destin Mbongi
  6. Baltazar Phoba
  7. Marie-Anasthasie Tshilolo
  8. René Mbungu
  9. Pierre Morand
  10. Jean-Paul Gonzalez

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Abstract

More than a year after the emergence of COVID-19, significant regional differences in terms of morbidity persist, showing lower incidence rates in sub-Saharan Africa, Southeast Asia, and Oceania. Like SARS-CoV-1 and MERS viruses, SARS-CoV-2 is monophyletically positioned with parental species of chiropteran coronavirus. Furthermore, we observe that the spatial distribution of several targeted bat species (i.e., Coronavirus species hosts) overlaps the distribution of countries with low COVID-19 incidence.

The work presented here aims to test the presence of natural immunity among population with a low COVD-19 prevalence, potentially due to a previous exposure to coronavirus antigens of a virus close related to SARS-CoV-2. To identify such pre-existing immunity, an ELISA serological test was used to detect IgG antibodies targeting main SARS-CoV-2 proteins including: the N-protein, the Spike 1 (S1) protein, the receptor binding domain (RBD) of the S1 protein, the N-terminal domain (NTD) of the S1 protein, and the S2 protein.

A total of 574 sera samples collected before 2019 in the population of the Democratic Republic of Congo (DRC) were tested). 189 control sera from blood donors in France were used as control samples.

The results showed a statistically significant difference between the DRC samples and control samples for all antigens (N, S1, S2, NTD) except for RBD. The percentage of positive samples presenting reactive antibodies for S1 antigen was respectively of 19.2% for RDC versus 2.11% for the control, and of 9.3% versus 1.6% for the S2 antigen.

In conclusion, our data showed that the study population has been potentially exposed to a SARS-CoV-2-like virus antigen before the pandemic in the Central African sub-region. Therefore, it is quite legitimate to think that this prior immunity may be protective and responsible for the observed low prevalence of COVID-19. Moreover, we can assume that this not yet identified SARS-CoV-2-like could be associated to a chiropteran species in close contact with the studied population. In order to confirm the presence of SARS-CoV-2-like virus antibodies and ultimately identify the neutralizing potential for the detected antibodies, our study is underway in other African and Asian countries, where the COVID-19 prevalence is limited.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.28.21256243: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Ethical approval was obtained from the Ethics Committee of the Centre de Formation et d’Appui Sanitaire/Centre Hospitalier Monkole (N/Ref: 01/CEFAMONKOLE/CEL/2013).
    Consent: Blood samples were collected after obtaining informed consent, written in French and in the vernacular language used in Kinshasa and Central Kongo, from each patient or from his or her parent/guardian in the case of minors.
    Sex as a biological variablenot detected.
    RandomizationControl sera collection: The controls sera were obtained by INNOBIOCHIPS company from 189 samples from blood donors collected in Northern France, randomly selected (EFS, Etablissement Français du Sang) and tested negative for SARS-CoV-2 by PCR.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    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.
    IgG
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We are aware of the limitations of this somewhat pioneering study. The next step is to conduct sensitive investigations of populations potentially exposed to wild animals and to perform back-to-back with the present ELISA test, an essential SARS-Cov-2 neutralization assays to confirm the surprisingly high S1 cross-reactivity and the potential of the antibody to protect against SARS-CoV-2. In addition, most of the samples tested came from rural areas of Central Congo (e.g.: Kimpese of Lower Congo, Kisantu of Western Congo). Furthermore, if it is true that background reactivity in SARS-CoV-2 serological tests is higher, especially in African populations, this may be due not only to widespread circulation/exposure of/to Sarbecoviruses (alias Betacoronavirus) of animals or chiropterans, but to a potential increased cross-reactivity induced by other microorganisms (e.g., malaria, tuberculosis, etc.) as previously observed [Ng 2020] [Stettler 2016] [Welsh 2010].

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.04.28.21256243 on medRxiv