SARS-CoV-2 exposure in Malawian blood donors: an analysis of seroprevalence and variant dynamics between January 2020 and July 2021

  1. Jonathan Mandolo
  2. Jacquline Msefula
  3. Marc Y. R. Henrion
  4. Comfort Brown
  5. Brewster Moyo
  6. Aubrey Samon
  7. Thandeka Moyo-Gwete
  8. Zanele Makhado
  9. Frances Ayres
  10. Thopisang Motlou
  11. Nonkululeko Mzindle
  12. Newton Kalata
  13. Adamson S. Muula
  14. Gaurav Kwatra
  15. Natasha Nsamala
  16. Andrew Likaka
  17. Thom Mfune
  18. Penny L. Moore
  19. Bridon Mbaya
  20. Neil French
  21. Robert S. Heyderman
  22. Todd Swarthout
  23. Kondwani C. Jambo

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Abstract

Background

By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi.

Methods

We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant.

Results

A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20–49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% [7/9]) than the beta variant (22% [2/9]), while more second wave sera showed neutralisation activity against the beta variant (75% [12/16]) than the original variant (63% [10/16]).

Conclusion

The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity across a panel of SARS-CoV-2 variants of concern/interest to estimate community immunity.

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  1. Version published to 10.1186/s12916-021-02187-y
  2. ScreenIT

    SciScore for 10.1101/2021.08.18.21262207: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical approval for this study was obtained from the Kamuzu University of Health Sciences Research Ethics Committee (P.09/20/3123).
    Consent: At time of donation, blood donors provide consent to draw blood for transfusion and for use in studies of public health importance.
    Sex as a biological variablenot detected.
    RandomizationSample selection and processing: Using the MBTS sample archive database, we randomly selected (using STATA’s gsample command) sera collected from HIV-seronegative individuals aged 16-65 years old.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurement of SARS-CoV-2 antibodies by Enzyme Linked-Immunosorbent Assay: SARS-CoV-2 Receptor Binding Domain (RBD) Total Antibody ELISA: We used the WHO-approved WANTAI SARS-CoV-2 Ab commercial Enzyme Linked-Immunosorbent Assay (ELISA) kit to detect total SARS-CoV-2 antibodies, following manufacturer’s instructions (Beijing Wantai Biological Pharmacy Enterprise co.
    SARS-CoV-2
    suggested: None
    The manufacturer’s sensitivity and specificity estimates for the assay are 94% [90.9 to 96.8] and 100% [98.8 to 100], respectively33. Confirmatory SARS-CoV-2 Spike 2 and Nucleoprotein IgG antibody ELISA: The COVID-19 IgG RUO commercial ELISA kit (Omega diagnostics, UK) kit uses 96-well microtiter plates pre-coated with purified SARS-COV-2 Spike (S2) and Nucleoprotein (N) antigens to detect SARS-COV-2 IgG.
    Nucleoprotein IgG
    suggested: (Virostat Cat# 3862, RRID:AB_2889989)
    Nucleoprotein ( N )
    suggested: None
    SARS-COV-2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Subsequently, 1×104 HEK 293T cells engineered to over-express ACE-2, kindly provided by Dr Michael Farzan (Scripps Research), were added and incubated at 37°C, 5% CO2 for 72 hours upon which the luminescence of the luciferase gene was measured.
    HEK 293T
    suggested: None
    Recombinant DNA
    SentencesResources
    ) plasmids in conjunction with a firefly luciferase encoding pNL4 lentivirus backbone plasmid.
    pNL4
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: We performed statistical analyses and graphical presentation using R statistical package, version 4.1.0 and GraphPad Prism v9.1.0 (
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad Software, LLC).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    There are however some important limitations. First, inherent in using a blood donor sampling frame is that the convenience sampling was not representative of the general population, skewed towards males and individuals aged 18 to 45 years old. In addition, we were unable to evaluate the association between the behaviour of blood donors and risk of acquisition to SARS-CoV-2 infection, as this may bias the measured results away from the true population seropositivity. Though random sampling from the larger population would have been ideal, restrictions on movement and gathering make these study designs extremely challenging to implement. Second, in some individuals, SARS-CoV-2 antibodies wane over time to undetectable levels leading to false negatives, especially in those who had asymptomatic COVID-19 12-14. Therefore, the seroprevalence estimates are likely an underestimate of the cumulative exposure within this sampled population. However, the selection bias and waning of antibody levels is unlikely to substantially alter the temporal trends reported in this study. In conclusion, we report a dramatic rise in SARS-CoV-2 seroprevalence from 6.2% in July 2020 to 49.7% in February 2021 in healthy blood donors as Malawi experienced the first and second COVID-19 epidemic waves, likely driven initially by the original variant (D614G WT) and then the Beta variant. Based on data showing prior exposure to SARS-CoV-2 augments COVID-19 vaccine responses 41-44, prioritisation of the firs...

    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.

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  3. Version published to 10.1101/2021.08.18.21262207 on medRxiv