RESEARCH ARTICLE Genomic epidemiology of SARS-CoV-2 during the first four waves in Mozambique Nalia IsmaelID1,2☯*, Stephanie van Wyk3,4☯*, Houriiyah Tegally3,4, Jennifer Giandhari3,4, James Emmanuel San3,4, Monika MoirID3,4, Sureshnee Pillay3,4, Christian Utpatel5, Lavanya SinghID3,4, Yeshnee Naidoo3,4, Upasana RamphalID3,4, Ne´dio Mabunda1, Nuro Abı´lioID1, Paulo Arnaldo1, Joicymara Xavier3,4,6, Daniel Gyamfi Amoako7,8, Josie EverattID7, Yajna Ramphal3,4, Arisha MaharajID3,4, Leonardo de Araujo5, Ugochukwu J. Anyaneji3,4, Derek Tshiabuila3,4, Sofia ViegasID1, Richard Lessells3,4, Susan Engelbrecht2, Eduardo Gudo1, Ilesh JaniID1, Stefan Niemann5,9, Eduan WilkinsonID3,4, Tu´lio de Oliveira3,4* 1 Instituto Nacional de Sau´de (INS), Marracuene, Mozambique, 2 Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, 3 Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa, 4 Kwazulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa, 5 Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany, 6 Institute of Agricultural Sciences, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Unaı´, Brasil, 7 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, Johannesburg, South Africa, 8 School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, KwaZulu-Natal, South Africa, 9 German Center for Infection Research, Partner Site Hamburg-Lu¨beck-Borstel-Riems, Borstel, Germany ☯These authors contributed equally to this work. * nalia.ismael@ins.gov.mz (NI); stephanievanwyk@sun.ac.za (SW); tulio@sun.ac.za (TO) Abstract Mozambique reported the first case of coronavirus disease 2019 (COVID-19) in March 2020 and it has since spread to all provinces in the country. To investigate the introduc- tions and spread of SARS-CoV-2 in Mozambique, 1 142 whole genome sequences sam- pled within Mozambique were phylogenetically analyzed against a globally representative set, reflecting the first 25 months of the epidemic. The epidemic in the country was marked by four waves of infection, the first associated with B.1 ancestral lineages, while the Beta, Delta, and Omicron Variants of Concern (VOCs) were responsible for most infections and deaths during the second, third, and fourth waves. Large-scale viral exchanges occurred during the latter three waves and were largely attributed to southern African origins. Not only did the country remain vulnerable to the introductions of new vari- ants but these variants continued to evolve within the borders of the country. Due to the Mozambican health system already under constraint, and paucity of data in Mozambique, there is a need to continue to strengthen and support genomic surveillance in the country as VOCs and Variants of interests (VOIs) are often reported from the southern African region. PLOS GLOBAL PUBLIC HEALTH PLOS Global Public Health | https://doi.org/10.1371/journal.pgph.0001593 March 6, 2023 1 / 16 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Ismael N, van Wyk S, Tegally H, Giandhari J, San JE, Moir M, et al. (2023) Genomic epidemiology of SARS-CoV-2 during the first four waves in Mozambique. PLOS Glob Public Health 3(3): e0001593. https://doi.org/10.1371/journal. pgph.0001593 Editor: Julio Croda, Fundacao Oswaldo Cruz, BRAZIL Received: September 28, 2022 Accepted: January 20, 2023 Published: March 6, 2023 Copyright: © 2023 Ismael et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite