Ineffectiveness of International Travel Restrictions to Contain Spread of the SARS-CoV-2 Omicron BA.1 Variant: a Continent-Wide Laboratory-Based Observational Study from Africa

Background: In mid-November 2021, the SARS-CoV-2 Omicron BA.1 variant was detected in Southern Africa, prompting international travel restrictions of unclear effectiveness that exacted a substantial economic toll. Methods: Amidst the BA.1 wave, we tested 13,294 COVID-19 patients in 24 African countries between mid-2021 to early 2022 for BA.1 and Delta variants using real-time reverse transcription-PCR tests. The diagnostic precision of the assays was evaluated by high-throughput sequencing in four countries. The observed BA.1 spread was compared to mobility-based mathematical simulations. Findings: By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a median Rt of 2.4 up to 30 days before BA.1 became predominant. PCR-based South-North spread was in agreement with phylogeographic reconstructions relying on 939 SARS-CoV-2 genomes from GISAID. PCR-based reconstructions of country-level BA.1 predominance correlated significantly in time with the emergence of BA.1 genomic sequences on GISAID (p=0.0035, cor=0.70). First BA.1 detections in affluent settings beyond Africa were predicted adequately in time by mobility-based mathematical simulations (p<0.0001). BA.1-infected inbound travelers departing from five continents were identified in five Western countries and one Northern African country by late November/early December 2021, highlighting fast global BA.1 spread aided by international travel. Interpretation: Unilateral travel bans were poorly effective because by the time they came into effect, BA.1 was already widespread in Africa and beyond. PCR-based variant typing combined with mobility-based mathematical modelling can inform rapidly and cost-efficiently on Rt, spread to inform non-pharmaceutical interventions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement African Academy of Sciences grant SARSCov2-4-20-004 (IOD) AFROSCREEN project (grant agreement CZZ3209) through Agence Francaise de Developpement, coordinated by ANRS | Maladies infectieuses emergentes in partnership with Institut Pasteur and IRD (IPdG). We would additionally like to thank members from the AFROSCREEN Consortium (https://www.afroscreen.org/en/network/) for their work and support on genomic surveillance in Africa. Bill & Melinda Gates Foundation grant INV-005971 (JFD, CD); grant INV-024130 (IOD); The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation CIRMF is a member of CANTAM funding by EDCTP CSA2020NoE-3100 - CANTAM 3 and supported by the Gabonese Government and Total Gabon French Ministry of Europe and Foreign affairs (Bamako-Bordeaux decentralized cooperation in riposte to Covid-19) Horizon 2020, European and Developing Countries Clinical Trials Partnership (EDCTP2) programme, PANDORA-ID-NET Grant RIA2016E-1609 (AASy, ROP) Poliomyelitis Research Foundation grant 21/40 (KKP)Programa de Desenvolvimento de Ciencia e Tecnologia grant No11/MESCTI/PDCT/2020 (JFMdM) REPAIR Covid-19-Africa, coordinated by the Pasteur Network association and funded by French Ministry for Europe and Foreign Affairs (MEAE), funded COVID diagnosis and typing (IPdG). South African Department of Science and Innovation (sub-award via University of KwaZulu-Natal) grant S006872 (TGM) Stellenbosch University Postgraduate Scholarship Programme grant 25095676 (KKP) UKRI Global Challenges Research Fund, grant number NF118 (RB, RE, JMw) World Health Organization grant 2021/1113013-0 (IOD) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for re-testing and scientific usage was provided by the institutional research ethics board (IRB) of Charite-Universitaetsmedizin Berlin (EA2/028/22) and by IRBs from Burkina Faso, Laboratoire National de Reference-Grippes (2020-7-126), Cameroon, Centre Pasteur du Cameroun (2020/05/1224/CE/CNERSH/SP), Ghana, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), KNUST (CHRPE/AP/566/21), Kenya, Jomo Kenyatta University of Agriculture and Technology, Department of Biochemistry (JKU/2/4/896B), Uganda, Gulu University Multifunctional Laboratories (GUREC-093-20), Makerere University, College of Health Science, Kamala, Uganda (SBS-2022-130) and Zambia, Tropical Diseases Research Centre, Ndola Teaching Hospital (00003729). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Respiratory samples sent to laboratories for COVID-19 testing by attending physicians were re-tested in an anonymized fashion using the COVID-19 test developed in this study. Ethical approval for re-testing and scientific usage was provided by the institutional research ethics board (IRB) of Charite-Universitaetsmedizin Berlin (EA2/028/22) and by IRBs from Burkina Faso, Laboratoire National de Reference-Grippes (2020-7-126), Cameroon, Centre Pasteur du Cameroun (2020/05/1224/CE/CNERSH/SP), Ghana, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), KNUST (CHRPE/AP/566/21), Kenya, Jomo Kenyatta University of Agriculture and Technology, Department of Biochemistry (JKU/2/4/896B), Uganda, Gulu University Multifunctional Laboratories (GUREC-093-20), Makerere University, College of Health Science, Kamala, Uganda (SBS-2022-130) and Zambia, Tropical Diseases Research Centre, Ndola Teaching Hospital (00003729). In all other countries, IRB approval for re-testing anonymized specimens was not required. Scripts for data analyses and data are available at GitHub (https://github.com/CarloFischer88/Analyse-the-BA.1-spread-in-Africa.git). Phylogenetic analyses of African BA.1 sequences (Fig. S6) and phylogeographic analyses (Fig. 3, Fig. S7) are based on 942 sequences available on GISAID, via 10.55876/gis8.230818aq. The performance of the used real-time RT-PCR assays was validated in this study against SARS-CoV-2 genomes generated by HTS (https://github.com/CarloFischer88/Analyse-the-BA.1-spread-in-Africa.git). Those genomes that were submitted to GISAID (Botswana, Guinea, South Africa) are available via 10.55876/gis8.240201eb. Mapped genomic reads for SARS-CoV-2 genomes generated from Beninese samples are available via the European Nucleotide Archive (ENA) (Project accession number PRJEB64297).