RESEARCH ARTICLE ◥ CORONAVIRUS A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa Eduan Wilkinson1,2†, Marta Giovanetti3,4†, Houriiyah Tegally1†, James E. San1†, Richard Lessells1, Diego Cuadros5, Darren P. Martin6,7, David A. Rasmussen8,9, Abdel-Rahman N. Zekri10, Abdoul K. Sangare11, Abdoul-Salam Ouedraogo12, Abdul K. Sesay13, Abechi Priscilla14, Adedotun-Sulaiman Kemi14, Adewunmi M. Olubusuyi15, Adeyemi O. O. Oluwapelumi16, Adnène Hammami17, Adrienne A. Amuri18,19, Ahmad Sayed20, Ahmed E. O. Ouma21, Aida Elargoubi22,23, Nnennaya A. Ajayi24, Ajogbasile F. Victoria14, Akano Kazeem14, Akpede George25, Alexander J. Trotter26, Ali A. Yahaya27, Alpha K. Keita28,29, Amadou Diallo30, Amadou Kone31, Amal Souissi32, Amel Chtourou17, Ana V. Gutierrez26, Andrew J. Page26, Anika Vinze33, Arash Iranzadeh6,7, Arnold Lambisia34, Arshad Ismail35, Audu Rosemary36, Augustina Sylverken37, Ayoade Femi14, Azeddine Ibrahimi38, Baba Marycelin39, Bamidele S. Oderinde39, Bankole Bolajoko14, Beatrice Dhaala40, Belinda L. Herring27, Berthe-Marie Njanpop-Lafourcade27, Bronwyn Kleinhans41, Bronwyn McInnis10, Bryan Tegomoh42, Cara Brook43,44, Catherine B. Pratt45, Cathrine Scheepers35,46, Chantal G. Akoua-Koffi47, Charles N. Agoti34,48, Christophe Peyrefitte30, Claudia Daubenberger49, Collins M. Morang’a50, D. James Nokes34,51, Daniel G. Amoako35, Daniel L. Bugembe40, Danny Park33, David Baker26, Deelan Doolabh7, Deogratius Ssemwanga40,52, Derek Tshiabuila1, Diarra Bassirou30, Dominic S. Y. Amuzu50, Dominique Goedhals53, Donwilliams O. Omuoyo34, Dorcas Maruapula54, Ebenezer Foster-Nyarko26, Eddy K. Lusamaki18,19, Edgar Simulundu55, Edidah M. Ong’era34, Edith N. Ngabana18,19, Edwin Shumba56, Elmostafa El Fahime57, Emmanuel Lokilo18, Enatha Mukantwari58, Eromon Philomena14, Essia Belarbi59, Etienne Simon-Loriere60, Etilé A. Anoh47, Fabian Leendertz59, Faida Ajili61, Fakayode O. Enoch62, Fares Wasfi63, Fatma Abdelmoula32,64, Fausta S. Mosha27, Faustinos T. Takawira65, Fawzi Derrar66, Feriel Bouzid32, Folarin Onikepe14, Fowotade Adeola67, Francisca M. Muyembe18,19, Frank Tanser68,69,70, Fred A. Dratibi27, Gabriel K. Mbunsu19, Gaetan Thilliez26, Gemma L. Kay26, George Githinji34,71, Gert van Zyl41,72, Gordon A. Awandare50, Grit Schubert59, Gugu P. Maphalala73, Hafaliana C. Ranaivoson44, Hajar Lemriss74, Happi Anise14, Haruka Abe75, Hela H. Karray17, Hellen Nansumba76, Hesham A. Elgahzaly77, Hlanai Gumbo65, Ibtihel Smeti32, Ikhlas B. Ayed32, Ikponmwosa Odia25, Ilhem Boutiba Ben Boubaker78,79, Imed Gaaloul22, Inbal Gazy80, Innocent Mudau7, Isaac Ssewanyana76, Iyaloo Konstantinus81, Jean B. Lekana-Douk82, Jean-Claude C. Makangara18,19, Jean-Jacques M. Tamfum18,19, Jean-Michel Heraud30,44, Jeffrey G. Shaffer83, Jennifer Giandhari1, Jingjing Li84, Jiro Yasuda75, Joana Q. Mends85, Jocelyn Kiconco52, John M. Morobe34, John O. Gyapong85, Johnson C. Okolie14, John T. Kayiwa40, Johnathan A. Edwards68,86, Jones Gyamfi85, Jouali Farah87, Joweria Nakaseegu52, Joyce M. Ngoi50, Joyce Namulondo52, Julia C. Andeko82, Julius J. Lutwama40, Justin O’Grady26, Katherine Siddle33, Kayode T. Adeyemi14, Kefentse A. Tumedi88, Khadija M. Said34, Kim Hae-Young89, Kwabena O. Duedu85, Lahcen Belyamani38, Lamia Fki-Berrajah17, Lavanya Singh1, Leonardo de O. Martins26, Lynn Tyers7, Magalutcheemee Ramuth91, Maha Mastouri22,23, Mahjoub Aouni22, Mahmoud el Hefnawi92, Maitshwarelo I. Matsheka88, Malebogo Kebabonye93, Mamadou Diop30, Manel Turki32, Marietou Paye33, Martin M. Nyaga94, Mathabo Mareka95, Matoke-Muhia Damaris96, Maureen W. Mburu34, Maximillian Mpina49,97,98, Mba Nwando99, Michael Owusu100, Michael R. Wiley45, Mirabeau T. Youtchou101, Mitoha O. Ayekaba97, Mohamed Abouelhoda102,103, Mohamed G. Seadawy104, Mohamed K. Khalifa20, Mooko Sekhele95, Mouna Ouadghiri38, Moussa M. Diagne30, Mulenga Mwenda105, Mushal Allam35, My V. T. Phan40, Nabil Abid79,106, Nadia Touil107, Nadine Rujeni108,109, Najla Kharrat32, Nalia Ismael110, Ndongo Dia30, Nedio Mabunda110, Nei-yuan Hsiao7,111, Nelson B. Silochi97, Ngoy Nsenga27, Nicksy Gumede27, Nicola Mulder112, Nnaemeka Ndodo99, Norosoa H Razanajatovo44, Nosamiefan Iguosadolo14, Oguzie Judith14, Ojide C. Kingsley113, Okogbenin Sylvanus25, Okokhere Peter25, Oladiji Femi114, Olawoye Idowu14, Olumade Testimony14, Omoruyi E. Chukwuma67, Onwe E. Ogah115, Chika K. Onwuamah36,138, Oshomah Cyril25, Ousmane Faye30, Oyewale Tomori14, Pascale Ondoa56, Patrice Combe116, Patrick Semanda76, Paul E. Oluniyi14, Paulo Arnaldo110, Peter K. Quashie50, Philippe Dussart44, Phillip A. Bester53, Placide K. Mbala18,19, Reuben Ayivor-Djanie85, Richard Njouom117, Richard O. Phillips118, Richmond Gorman118, Robert A. Kingsley26, Rosina A. A. Carr85, Saâd El Kabbaj119, Saba Gargouri17, Saber Masmoudi32, Safietou Sankhe30, Salako B. Lawal36, Samar Kassim77, Sameh Trabelsi120, Samar Metha33, Sami Kammoun121, Sanaâ Lemriss122, Sara H. A. Agwa77, Sébastien Calvignac-Spencer59, Stephen F. Schaffner33, Seydou Doumbia31, Sheila M. Mandanda18,19, Sherihane Aryeetey123, Shymaa S. Ahmed123, Siham Elhamoumi33, Soafy Andriamandimby44, Sobajo Tope14, Sonia Lekana-Douki82, Sophie Prosolek26, Soumeya Ouangraoua124,125, Steve A. Mundeke18,19, Steven Rudder26, Sumir Panji112, Sureshnee Pillay1, Susan Engelbrecht41,72, Susan Nabadda76, Sylvie Behillil126, Sylvie L. Budiaki95, Sylvie van der Werf126, Tapfumanei Mashe65, Tarik Aanniz38, Thabo Mohale35, Thanh Le-Viet26, Tobias Schindler49,97, Ugochukwu J. Anyaneji1, Ugwu Chinedu14, Upasana Ramphal1,69,127, Uwanibe Jessica14, Uwem George14, Vagner Fonseca1,4,128, Vincent Enouf126, Vivianne Gorova129,130, Wael H. Roshdy123, William K. Ampofo50, Wolfgang Preiser41,72, Wonderful T. Choga54,131, Yaw Bediako50, Yeshnee Naidoo1, Yvan Butera108,132,133, Zaydah R. de Laurent34, Amadou A. Sall30, Ahmed Rebai32, Anne von Gottberg35,139, Bourema Kouriba12, Carolyn Williamson7,69,111, Daniel J. Bridges105, Ihekweazu Chikwe99, Jinal N. Bhiman35,139, Madisa Mine134, Matthew Cotten40,135, Sikhulile Moyo54,136, Simani Gaseitsiwe54,136, Ngonda Saasa55, Pardis C. Sabeti33, Pontiano Kaleebu40, Yenew K. Tebeje21, Sofonias K. Tessema21, Christian Happi14, John Nkengasong21, Tulio de Oliveira1,2,69,137* The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants. S evere acute respiratory syndrome coro- navirus 2 (SARS-CoV-2) emerged in late 2019 in Wuhan, China (1, 2). Since then, the virus has spread to all corners of the world, causing almost 150 million cases of COVID-19 and more than 3 million deaths by the end of April 2021. Throughout the pan- demic, it has been noted that Africa accounts for a relatively low proportion of reported cases and deaths—by the end of April 2021, there had been ~4.5 million cases and ~120,000 deaths on the continent, corresponding to less than 4% of the global burden. However, emerging data from seroprevalence surveys and autopsy studies in some African countries suggest that the true number of infections and deaths may be severalfold higher than reported (3, 4). In addition, a recent analysis has shown that in RESEARCH Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 1 of 9 UNIV ERSIT Y O F IB ADAN L IB RARY many African countries, the secondwave of the pandemicwasmore severe than the firstwave (5). The first cases of COVID-19 on the African continentwere reported inNigeria, Egypt, and South Africa between mid-February and early March 2020, and most countries had reported cases by the end of March 2020 (6–8). These early cases were concentrated among airline travelers returning from regions of the world with high levels of community transmission. Many African countries introduced early public health and social measures, including inter- national travel controls, quarantine for return- ing travelers, and internal lockdown measures, to limit the spread of the virus and give health services time to prepare (5, 9). The initial phase of the epidemic was then heterogeneous, with relatively high case numbers reported in North Africa and southern Africa, and fewer cases reported in other regions. From the onset of the pandemic, genomic surveillance has been at the forefront of the COVID-19 response in Africa (10). Rapid im- plementation of SARS-CoV-2 sequencing by various laboratories in Africa enabled genomic data to be generated and shared from the early imported cases. In Nigeria, the first genome sequence was released just 3 days after the announcement of the first case (6). Similarly, in Uganda, a sequencing program was set up rapidly to facilitate virus tracing, and the col- lection of samples for sequencing began im- mediately upon confirmation of the first case (11). In South Africa, the Network for Genomic Surveillance in South Africa (NGS-SA) was es- tablished in March 2020, and within weeks, genomic analysis was helping to characterize outbreaks and community transmission (12). Genomic surveillance has also been criti- cal formonitoring ongoing SARS-CoV-2 evolu- tion and detection of new SARS-CoV-2 variants in Africa. Intensified sampling by NGS-SA in the Eastern Cape Province of South Africa in November 2020, in response to a rapid resur- gence of cases, led to the detection of B.1.351 (501Y.V2) (13). This variant was subsequently designated a variant of concern (VOC) by the World Health Organization (WHO), owing to evidence of increased transmissibility (14) and resistance to neutralizing antibodies elicited by natural infection and vaccines (15–17). In this study, we performed phylogenetic and phylogeographic analyses of SARS-CoV-2 genomic data from 33 African countries and two overseas territories to help characterize the dynamics of the pandemic in Africa. We show that the early introductions were pre- dominantly from Europe, but that as the pan- demic progressed, there was increasing spread between African countries. We also describe the emergence and spread of a number of key SARS-CoV-2 variants in Africa and highlight how the spread of B.1.351 (501Y.V2) and other variants contributed to the more severe sec- ond wave of the pandemic in many countries. SARS-CoV-2 genomic data By 5 May 2021, 14,504 SARS-CoV-2 genomes had been submitted to the GISAID database (18) from 38 African countries and two over- seas territories (Mayotte andRéunion) (Fig. 1A). Overall, this corresponds to approximately one sequence per ~300 reported cases. Almost half of the sequences were from South Africa (n= 5362), consistentwith it being responsible for almost half of the reported cases in Africa. Overall, the number of sequences correlates closely with the number of reported cases per country (Fig. 1B). The countries and territories with the highest coverage of sequencing (de- fined as genomes per reported case) are Kenya (n = 856, one sequence per ~203 cases), Mayotte (n = 721, one sequence per ~21 cases), and Nigeria (n = 660, one sequence per ~250 cases). Although genomic surveillance started early in many countries, few have evidence of con- sistent sampling across the whole year. Half of all African genomes were deposited in the first 10 weeks of 2021, suggesting intensified surveillance in the second wave after the de- tection of B.1.351 (501Y.V2) and other var- iants (Fig. 1, C and D). Genetic diversity and lineage dynamics in Africa Of the 10,326 genomes retrieved from GISAID by the end ofMarch 2021, 8746 genomes passed quality control andmet theminimummetadata requirements. These genomes fromAfrica were compared in a phylogenetic framework with 11,891 representative genomes from around the world. Ancestral location state reconstruc- tion of the dated phylogeny (hereafter referred to as discrete phylogeographic reconstruction) allowed us to infer the number of viral imports and exports between Africa and the rest of the world, and between individual African coun- tries. African genomes in this study spanned the whole global genetic diversity of SARS- CoV-2, a pattern that largely reflects multiple introductions over time from the rest of the world (Fig. 2A). In total, we detected at least 757 [95% con- fidence interval (CI): 728 to 786] viral intro- ductions into African countries between the start of 2020 and February 2021, more than half of which occurred before the end of May 2020. Although the early phase of the pan- demic was dominated by importations from outside Africa, predominantly from Europe, there was then a shift in the dynamics, with an increasing number of importations from other African countries as the pandemic progressed (Fig. 2, B and C). A rarefaction analysis in which we systematically subsampled genomes shows that vastly more introductions would have likely been identified with increased sam- pling in Africa or globally, suggesting that the introductions we identified are really just the “ears of the hippo,” or a small part of a larger problem (fig. S1). South Africa, Kenya, and Nigeria appear as major sources of importations into other African countries (Fig. 2D), although this is likely to be influenced by these three countries having the greatest number of deposited se- quences. Particularly notable is the southern African region,where SouthAfrica is the source for a large proportion (~80%) of the impor- tations to other countries in the region. The North African region demonstrates a differ- ent pattern to the rest of the continent, with more viral introductions from Europe and Asia (particularly the Middle East) than from other African countries (fig. S2). Africa has also contributed to the interna- tional spread of the virus, with at least 324 (95% CI: 295 to 353) exportation events from Africa to the rest of the world detected in this dataset. Consistent with the source of impor- tations, most exports were to Europe (41%), Asia (26%), and North America (14%). As with the number of importations, exports were relatively evenly distributed over the 1-year period (fig. S3). However, an increase in the number of exportation events occurred be- tween December 2020 andMarch 2021, which coincided with the second wave of infections in Africa and with some relaxations of travel restrictions around the world. The early phase of the pandemic was char- acterized by the predominance of lineage B.1. This was introduced multiple times to African countries and has been detected in all but one of the countries included in this analysis. After its emergence in SouthAfrica, B.1.351 became the most frequently detected SARS-CoV-2 lineage found in Africa (n = 1769, ~20%) (Fig. 1C). It was first sampled on 8 October 2020 in South Africa (13) and has since spread to 20 other African countries. As air travel came to an almost complete halt in March and April 2020, the number(s) of de- tectable viral imports into Africa decreased and the pandemic entered a phase that was characterized in sub-Saharan Africa by sus- tained low levels of within-country movements and occasional international viral movements between neighboring countries, presumably via road and rail links between these. Though some border posts between countries were closed during the initial lockdownperiod (table S1), others remained open to allow trade to continue. Regional trade in southern Africa was only slightly affected by lockdown restric- tions and quickly rebounded to prepandemic levels (fig. S4) after the relaxation of restric- tions between June 2020 and December 2020. Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 2 of 9 All author affiliations are listed at the end of this paper. *Corresponding author. Email: tulio@sun.ac.za †These authors contributed equally to this work. RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY Although lineage A viruses were imported into several African countries, they only ac- count for 1.3% of genomes sampled in Africa. Despite lineageAviruses initially causingmany localized clustered outbreaks, each the result of independent introductions to several coun- tries (e.g., Burkina Faso, Côte d’Ivoire, and Nigeria), they were later largely replaced by lineage B viruses as the pandemic evolved. This is possibly due to the increased transmis- sibility of lineage B viruses by virtue of the D614G (Asp614→Gly) mutation in the spike protein (19, 20). However, there is evidence of an increasing prevalence of lineage A viruses in someAfrican countries (11). In particular, A.23.1 emerged inEast Africa and appears to be rapidly increasing inprevalence inUganda andRwanda (11). Furthermore, a highly divergent variant from lineage Awas recently identified in Angola from individuals arriving from Tanzania (21). Emergence and spread of new SARS-CoV-2 variants To determine how some of the key SARS-CoV-2 variants are spreading within Africa, we per- formed phylogeographic analyses on the VOC B.1.351, the variant of interest (VOI) B.1.525, and two additional variants that emerged and that we designated as VOIs for this analysis (A.23.1 and C.1.1). These African VOCs and VOIs have multiple mutations on the spike glyco- protein, and amolecular clock analysis of these four datasets provided strong evidence that these four lineages are evolving in a clock-like manner (Fig. 3, A and B). B.1.351 was first sampled in South Africa in October 2020, but phylogeographic analysis suggests that it emerged earlier, around August 2020. It is defined by 10 mutations in the spike protein, including K417N (Lys417→Asn), E484K (Glu484→Lys), and N501Y (Asn501→Tyr) in the receptor binding domain (Fig. 3B). After its emergence in the Eastern Cape, it spread ex- tensively within South Africa (Fig. 4A). By November 2020, the variant had spread into neighboring Botswana and Mozambique, and byDecember 2020, it had reached Zambia and Mayotte. Within the first 3 months of 2021, Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 3 of 9 Ethiopia Union of the Comoros Gabon Sierra Leone Benin Mauritius Algeria Lesotho Eswatini Mali Guinea Central African Republic Namibia Réunion Cameroon Republic of the Congo Tunisia Togo Burkina Faso Madagascar Côte d'Ivoire Mozambique Malawi Equatorial Guinea Morocco Angola Botswana Zambia Rwanda Senegal Uganda Zimbabwe Democratic Republic of the Congo Ghana Egypt Gambia Nigeria Mayotte Kenya South Africa Feb 2020 Mar 2020 Apr 2020 May 2020 Jun 2020 Jul 2020 Aug 2020 Sep 2020 Oct 2020 Nov 2020 Dec 2020 Jan 2021 Feb 2021 Mar 2021 Apr 2021 May 2021 Sampling Dates VOCs A.23.1 B.1.1.7 B.1.351 B.1.525 Other Lineages African countries with sequencing data 0% 25% 50% 75% 100% Mar 2020 May 2020 Jul 2020 Sep 2020 Nov 2020 Jan 2021 Mar 2021 Date P ro p o rt io n o f G en o m es Lineage A A.23.1 B.1 B.1.1 B.1.1.273 B.1.1.412 B.1.1.448 B.1.1.54 B.1.1.7 B.1.160 B.1.160.18 B.1.192 B.1.237 B.1.351 B.1.380 B.1.416 B.1.525 C.1 C.16 C.36 404 855 53595999 18 399 19352 308 24 12 658 58 1221111194999999408145 40444 11 96 42 718 167 221 159 153 23 189 122 3080308480 90 18171 445 4 353 286 5000 500 50 5 Sequence Count Angola Botswana Cote d'Ivoire Egypt Equatorial Guinea Gambia Ghana Kenya Madagascar Malawi Mayotte MoroccoMozambique Nigeria Rwanda Senegal South Africa Uganda Zambia Zimbabwe Spearman correlation = 0.45 2 4 6 8 8 10 12 14 Total Cases (Log) S eq u en ce C o u n t (L o g ) A B C D Fig. 1. SARS-CoV-2 sequences in Africa. (A) Map of the African continent with the number of SARS-CoV-2 sequences reflected in GISAID as of 5 May 2021. (B) Regression plot of the number of viral sequences versus the number of reported COVID-19 cases in various African countries as of 5 May 2021. Countries with >500 sequences are labeled. The shaded region indicates the 95% confidence interval. (C) Progressive distribution of the top 20 PANGO lineages on the African continent. (D) Temporal sampling of SARS-CoV-2 sequences in African countries (ordered by total number of sequences) through time, with VOCs of note highlighted and annotated according to their PANGO lineage assignment. RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY further exports fromSouthAfrica intoBotswana, Zimbabwe,Mozambique, andZambia occurred. By March 2021, B.1.351 had become the dom- inant lineage within most southern African countries as well as the overseas territories of Mayotte and Réunion (fig. S5). Our phylogeo- graphic reconstruction also demonstrates movement of B.1.351 into East and Central Africa directly from southern Africa. Our dis- crete phylogeographic analysis of a wider sam- ple of B.1.351 isolates demonstrates the spread of the lineage into West Africa. This patient from West Africa had a known travel history to Europe, so it is possible that the patient ac- quired the infection while in Europe or in tran- sit and not from other African sources (fig. S6). B.1.525 is a VOI defined by six substitu- tions in the spike protein [Q52R (Gln52→Arg), A67V (Ala67→Val), E484K, D614G, Q677H (Gln677→His), and F888L (Phe888→Leu)] and two deletions in the N-terminal domain [HV69- 70D (deletion of His and Val at positions 69 and 70) and Y144D (deletion of Tyr at posi- tion 144)]. This was first sampled in the United Kingdom in mid-December 2020, but our phylogeographic reconstruction suggests that the variant originated in Nigeria in November 2020 [95% highest posterior den- sity (HPD) 2020-11-01 to 2020-12-03] (Fig. 4B). Since then, it has spread throughout much of Nigeria and neighboring Ghana. Given sparse sampling from other neighboring countries withinWest andCentral Africa (Fig. 1, A andC), the extent of the spread of this VOI in the re- gion is not clear. Beyond Africa, this VOI has spread to Europe and the United States (fig. S6). We designatedA.23.1 andC.1.1 as VOIs for the purposes of this analysis because they present good examples of the continued evolution of the virus within Africa (11, 13). Lineage A.23, characterized by three spike mutations [F157L (Phe157→Leu), V367F (Val367→Phe), and Q613H (Gln613→His)], was first detected in a Ugandan prison in Amuru in July 2020 (95% HPD: 2020- 07-15 to 2020-08-02). From there, the lineage was transmitted to Kitgum prison, possibly facilitated by the transfer of prisoners. Sub- sequently, the A.23 lineage spilled into the Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 4 of 9 Fig. 2. Phylogenetic reconstruction of the SARS-CoV-2 pandemic on the con- tinent of Africa. (A) Time-resolved maximum likelihood tree containing 8746 high- quality African SARS-CoV-2 near-full-genome sequences analyzed against a backdrop of global reference sequences. VOIs and VOCs are highlighted on the phylogeny. (B) Sources of viral introductions into African countries characterized as external introductions from the rest of the world versus internal introductions from other African countries. (C) Total external viral introductions over time into Africa. (D) The number of viral imports and exports into and out of various African countries depicted as internal (between African countries, in pink) or external (between African and non-African countries, in blue and gray). RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY general population and spread to Kampala, adding other spike mutations [R102I (Arg102→- Ile), L141F (Leu141→Phe), E484K, and P681R (Pro681→Arg)] along with additionalmutations in nsp3, nsp6, ORF8, and ORF9, prompting a new lineage classification, A.23.1 (Fig. 3, A and B). Since the emergence of A.23.1 in September 2020 (95% HPD: 2020-09-02 to 2020-09-28), it has spread regionally into neighboring Rwanda and Kenya and has now also reached South Africa and Botswana in the south and Ghana in the west (Fig. 4C). However, our phylogeo- graphic reconstruction of A.23.1 suggests that the introduction into Ghanamay have occurred via Europe (fig. S6), whereas the introductions Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 5 of 9 r = 0.82 r2 = 0.67 0.0e+00 3.0e−04 6.0e−04 9.0e−04 1.2e−03 Jun 2020 Sep 2020 Dec 2020 R oo t− to − tip D is ta nc e r = 0.54 r2 = 0.3 1.25e−03 1.50e−03 1.75e−03 2.00e−03 Nov 2020 Jan 2021 Mar 2021 Date R oo t− to − tip D is ta nc e r = 0.73 r2 = 0.53 0e+00 2e−04 4e−04 6e−04 8e−04 Oct 2020 Dec 2020 Feb 2021 R oo t− to − tip D is ta nc e Location Americas Asia Central Africa East Africa Europe Oceania Southern Africa West Africa 1 50 100 150 200 245 295 345 395 445 495 545 590 640 690 795 900 1005 1110 1210 1274 /501Y.V2 ORF1ab Spike NTD RBD RBM SD1 SD2 S1/S2 N A.23.1 ORF1ab Spike NTD RBD RBM SD1 SD2 S1/S2 N B.1.525 ORF1ab Spike NTD RBD RBM SD1 SD2 S1/S2 N C.1.1 ORF1ab Spike NTD RBD RBM SD1 SD2 S1/S2 N r = 0.42 r2 = 0.18 1e−04 2e−04 3e−04 Dec 2020 Jan 2021 Jan 2021 Date Date Date R oo t− to − tip D is ta nc e A B Fig. 3. Genetic profile of VOCs and VOIs under investigation. (A) Root-to-tip regression plots for four lineages of interest. C.1 and A.23 show continued evolution into VOIs C.1.1 and A.23.1, respectively. r, coefficient of correlation; r2, coefficient of determination. (B) Genome maps of four VOCs and VOIs, where the spike region is shown in detail and in color and the rest of the genome is shown in gray. ORF, open reading frame; NTD, N-terminal domain; RBD, receptor binding domain; RBM, receptor binding motif; SD1, subdomain 1; SD2, subdomain 2. RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY into southern Africa likely occurred directly from East Africa. This is consistent with epide- miological data suggesting that the case detected in South Africa was a contact of an individual who had recently traveled to Kenya. Lineage C.1 emerged in SouthAfrica inMarch 2020 (95% HPD: 2020-03-13 to 2020-04-17) during a cluster outbreak before the first wave of the epidemic (13). C.1.1 is defined by the spikemutations S477N (Ser477→Asn), A688S (Ala688→Ser), and M1237I (Met1237→Ile) and also contains the Q52R and A67V mutations similar to B.1.525 (Fig. 3B). A continuous trait phylogeographic reconstruction of the move- ment dynamics of these lineages suggests that C.1 emerged in the city of Johannesburg and spreadwithin SouthAfrica during the first wave (Fig. 4D). Independent exports of C.1 from South Africa led to regional spread to Zambia (June to July 2020) and Mozambique (July to August 2020), and the evolution to C.1.1 seems to have occurred in Mozambique around mid- September 2020 (95% HPD: 2020-09-07 to 2020-10-05). An in-depth analysis of SARS- CoV-2 genotypes fromMozambique suggests that the C.1.1 lineagewas themost prevalent in the country until the introduction of B.1.351, whichhas dominated the epidemic since (fig. S5). The VOC B.1.1.7, which was first sampled in Kent, England, in September 2020 (22), has also increased in prevalence in several African countries (fig. S5). To date, this VOC has been detected in 11 African countries, as well as the Indian Ocean islands of Mauritius and Mayotte (fig. S7). The time-resolved phylogeny suggests that this lineage was introduced into Africa on at least 16 occasions between November 2020 and February 2021, with evidence of local trans- mission in Nigeria and Ghana. Conclusions Our phylogeographic reconstruction of past viral dissemination patterns suggests a strong epidemiological linkage between Europe and Africa, with 64% of detectable viral imports into Africa originating in Europe and 41% of detect- able viral exports from Africa landing in Europe (Fig. 1C). This phylogeographic analysis also Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 6 of 9 19 48 40 Aug 2020 Sep 2020 Oct 2020 Nov 2020 Jan 2021 15 41 35 May 2020 Aug 2020 Oct 2020 Jan 2021 Aug 2020 Sep 2020 Oct 2020 Nov 2020 Jan 2021 Feb 2021 8 Nov 2020 Dec 2020 Jan 2021 B.1.525 C.1/C.1.1 A.23/A.23.1B.1.351A Mayotte Ghana South Africa M oz am bi qu e Botswana Zambia Botswana Zimbabwe South Africa Zimbabwe 10 44 35 Mozambique Zambia Uganda Kenya Rwanda NigeriaGhana C B D DRC Abuja Ibadan Lagos Benin Togo Tanzania Botswana South Africa Fig. 4. Phylogeographic reconstruction of the spread of four VOCs and VOIs across the African continent. (A to D) Phylogeographic reconstruction of the spread of four VOCs and VOIs across the African continent using sequences showing strict continuous transmission across geographical regions: B.1.351 (A), B.1.525 (B), A.23/A.23.1 (C), and C.1/C.1.1 (D). Curved lines denote the direction of transmission in the counterclockwise direction. Solid lines show transmission paths as inferred by phylogeographic reconstruction and colored by date, whereas dashed lines show the known travel history of the particular case considered. RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY suggests a changing pattern of viral diffusion into and within Africa over the course of 2020. In almost all instances, the earliest introduc- tions of SARS-CoV-2 into individual African countries were from countries outside Africa. High rates of COVID-19 testing and con- sistent genomic surveillance in the south of the continent have led to the early identifi- cation of VOCs such as B.1.351 and VOIs such as C.1.1 (13). Since the discovery of these south- ern African variants, several other SARS-CoV-2 VOIs have emerged in different parts of the world, including elsewhere on the African continent, such as B.1.525 in West Africa and A.23.1 in East Africa. There is strong evidence that both of these VOIs are rising in frequency in the regions where they have been detected, which suggests that they may possess higher fitness than other variants in these regions. Although more-focused research on the bio- logical properties of these VOIs is needed to confirm whether they should be considered VOCs, it would be prudent to assume the worst and focus on limiting their spread. It will be important to investigate how these different variants compete against one another if they occupy the same region. Our focused phylogenetic analysis of the B.1.351 lineage revealed that in the finalmonths of 2020, this variant spread from South Africa into neighboring countries, reaching as far north as the Democratic Republic of the Congo (DRC) by February 2021. This spread may have been facilitated through rail and road net- works that formmajor transport arteries link- ing South Africa’s ocean ports to commercial and industrial centres in Botswana, Zimbabwe, Zambia, and the southern parts of the DRC. The rapid, apparently unimpeded spread of B.1.351 into these countries suggests that current land- border controls that are intended to curb the international spread of the virus are ineffec- tive. Perhaps targeted testing of cross-border travelers, genotyping of positive cases, and the focused tracking of frequent cross-border trav- elers, such as long distance truckers, would more effectively contain the spread of future VOCs and VOIs that emerge within this region. The dominance of VOIs and VOCs in Africa has important implications for vaccine roll- outs on the continent. For one, slow rollout of vaccines in most African countries creates an environment in which the virus can replicate and evolve: This will almost certainly produce additional VOCs, any of which could derail the global fight against COVID-19. Conversely, with the already widespread presence of known variants, difficult decisions about balancing reduced efficacy and availability of vaccines have to be made. This also highlights how crucial it is that trials are done. From a public health perspective, genomic surveillance is only one item in the toolkit of pandemic prepared- ness. It is important that such work is closely followed by genotype-to-phenotype research to determine the actual relevance of continued evolution of SARS-CoV-2 and other emerging pathogens. The rollout of vaccines across Africa has been painfully slow (figs. S8 and S9). There have, however, been notable successes that suggest that the situation is not hopeless. The small island nation of the Seychelles had vac- cinated 70% of its population by May 2021. Morocco has kept pace withmany developed nations and, by mid-March, had vaccinated ~16% of its population. Rwanda, one of Africa’s most resource-constrained countries, had, within 3 weeks of obtaining its first vaccine doses in early March, managed to provide first doses to ~2.5% of its population. For all other African countries, at the time ofwriting, vaccine coverage (first dose) was <1.0% of the general population. The effectiveness of molecular surveillance as a tool for monitoring pandemics is largely dependent on continuous and consistent sam- pling through time, rapid virus genome se- quencing, and rapid reporting. When this is achieved, molecular surveillance can ensure the early detection of changing pandemic char- acteristics. Further, when such changes are dis- covered, molecular surveillance data can also guide public health responses. In this regard, themolecular surveillance data that are being gathered by most African countries are less useful than they could be. For example, the time lag betweenwhen virus samples are taken and when sequences for these samples are deposited in sequence repositories is so great in some cases that the primary utility of ge- nomic surveillance data is lost (fig. S10). This lag is driven by several factors, depending on the laboratory or country in question: (i) lack of reagents owing to disruptions in global sup- ply chains, (ii) lack of equipment and infrastruc- ture within the originating country, (iii) scarcity of technical skills in laboratory methods or bio- informatic support, and (iv) hesitancy by some health officials to release data. More-recent sampling and prompt reporting is crucial to reveal the genetic characteristics of currently circulating viruses in these countries. The patchiness of African genomic surveil- lance data is therefore the main weakness of our study. However, there is evidence that the situation is improving, with ~50% of African SARS-CoV-2 genome sequences having been submitted to the GISAID database within the first 10 weeks of 2021. Although the precise factors underlying this surge in sequencing efforts are unclear, an important driver is al- most certainly increased global interest in genomic surveillance after the discovery of multiple VOCs and VOIs since December 2020. We cannot reject that the observed increase in exports from Africa may be due to inten- sified sequencing activity after the detection of variants around the world. It is important to note here that phylogeographic reconstruc- tion of viral spread is highly dependent on sampling where there is the caveat that the exact routes of viral movements between coun- tries cannot be inferred if there is no sam- pling in connecting countries. Furthermore, our efforts to reconstruct the movement dy- namics of SARS-CoV-2 across the continent are almost certainly biased by uneven sampling between different African countries. It is not a coincidence that we identified South Africa, Kenya, and Nigeria, which have sampled and sequenced the most SARS-CoV-2 genomes, as major sources of viral transmissions between sub-Saharan African countries. However, these countries also had the highest number of infec- tions, which may decrease the sampling biases (Fig. 1A). The reliability of genomic surveillance as a tool to prevent the emergence and spread of dangerous variants is dependent on the in- tensity with which it is embraced by national public health programs. As with most other parts of the world, the success of genomic sur- veillance in Africa requires that more samples are tested for COVID-19, higher proportions of positive samples are sequenced within days of sampling, and persistent analyses of these sequences are performed for concerning sig- nals such as (i) the presence of novel nonsynon- ymous mutations at genomic sites associated with pathogenicity and immunogenicity, (ii) evidence of positive selection at codon sites where nonsynonymous mutations are observed, and (iii) evidence of lineage expansions. Des- pite limited sampling, Africa has identified many of the VOCs and VOIs that are being transmitted across the world. Detailed char- acterization of the variants and their impact on vaccine-induced immunity is of extreme importance. If the pandemic is not controlled in Africa, we may see the production of vaccine escape variants that may profoundly affect the population in Africa and across the world. REFERENCES AND NOTES 1. C. Wang, P. W. Horby, F. G. Hayden, G. F. Gao, Lancet 395, 470–473 (2020). 2. Q. Li et al., N. Engl. J. Med. 382, 1199–1207 (2020). 3. S. Uyoga et al., Science 371, 79–82 (2021). 4. L. Mwananyanda et al., BMJ 372, n334 (2021). 5. S. J. Salyer et al., Lancet 397, 1265–1275 (2021). 6. P. Oluniyi, First African SARS-CoV-2 genome sequence from Nigerian COVID-19 case. Virological (2020); https://virological.org/t/first- african-sars-cov-2-genome-sequence-from-nigerian-covid-19-case/421. 7. M. A. Medhat, M. El Kassas, J. Glob. Health 10, 010368 (2020). 8. M. Allam et al., Microbiol. Resour. Announc. 9, e00572-e20 (2020). 9. N. Haider et al., BMJ Glob. Health 5, e003319 (2020). 10. S. C. Inzaule, S. K. Tessema, Y. Kebede, A. E. Ogwell Ouma, J. N. Nkengasong, Lancet Infect. Dis. 21, e281–e289 (2021). 11. D. L. Bugembe et al., medRxiv 2021.02.08.21251393 (2021); https://doi.org/10.1101/2021.02.08.21251393. 12. J. Giandhari et al., Int. J. Infect. Dis. 103, 234–241 (2021). 13. H. Tegally et al., Nat. Med. 27, 440–446 (2021). 14. C. A. Pearson, T. W. Russell, N. Davies, A. J. Kucharski, Estimates of severity and transmissibility of novel SARS-CoV-2 variant 501Y.V2 in South Africa. CMMID Repository (2021); https://cmmid.github.io/topics/covid19/ sa-novel-variant.html. Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 7 of 9 RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY https://virological.org/t/first-african-sars-cov-2-genome-sequence-from-nigerian-covid-19-case/421 https://virological.org/t/first-african-sars-cov-2-genome-sequence-from-nigerian-covid-19-case/421 https://doi.org/10.1101/2021.02.08.21251393 https://cmmid.github.io/topics/covid19/sa-novel-variant.html https://cmmid.github.io/topics/covid19/sa-novel-variant.html 15. S. Cele et al., medRxiv 2021.01.26.21250224 (2021); https://doi.org/10.1101/2021.01.26.21250224. 16. S. A. Madhi et al., N. Engl. J. Med. 384, 1885–1898 (2021). 17. C. K. Wibmer et al., Nat. Med. 27, 622–625 (2021). 18. Y. Shu, J. McCauley, Euro Surveill. 22, 30494 (2017). 19. E. Volz et al., Cell 184, 64–75.e11 (2021). 20. B. Korber et al., Cell 182, 812–827.e19 (2020). 21. T. de Oliveira et al., medRxiv 2021.03.30.21254323 (2021); https://doi.org/10.1101/2021.03.30.21254323. 22. B. Meng et al., Cell Rep. 35, 109292 (2021). 23. S. E. James, T. Houriiyah, krisp-kwazulu-natal/africa-covid19- genomics: A year of genomic surveillance reveals how the SARS- CoV-2 pandemic unfolded in Africa - Code and scripts. Zenodo (2021); https://doi.org/10.5281/zenodo.5386379. ACKNOWLEDGMENTS We acknowledge the authors from the originating laboratories and the submitting laboratories, who generated and shared, via GISAID, the genetic sequence data on which this research is based (table S4). We also acknowledge the contribution of K. Maria from the NGS-SA platform for their contribution toward the sequencing effort in Cape Town, South Africa. Similarly, we thank A. M. Elsaame, S. M. Elsayed, and R. M. Darwish from the Faculty of Medicine Ain Shams Research Institute (MASRI) for their efforts toward sequencing in Egypt. We thank S. Bane, M. Sanogo, D. Diallo, A. Combo Georges Togo, and A. Coulibaly from the University Clinical Research Centre (UCRC) at the University of Sciences, Techniques, and Technologies of Bamako for the contribution they have made toward sequencing efforts in Mali. We acknowledge the contribution of M. Moeti and A. Salam Gueye from the WHO for their contribution toward combating SARS-CoV-2 on the African continent. We further wish to extend acknowledgment to S. Lutucuta and J. Morais from the Angolan Ministry of Health for their continued hard work with regards to SARS-CoV-2 sampling, sequencing, and pandemic response in Angola. From Malawi we wish to acknowledge the work of B. Chilima, B. Mvula, and M. Chitenje from the Malawian Ministry of Health for their work on the COVID-19 response within the country. Funding:The University of Ghana (WACCBIP) team was funded by a Wellcome/African Academy of Sciences Developing Excellence in Leadership Training and Science (DELTAS) grant (DEL- 15-007 and 107755/Z/15/Z: Awandare); National Institute of Health Research (NIHR) (17.63.91) grants using UK aid from the UK government for a global health research group for genomic surveillance of malaria in West Africa (Wellcome Sanger Institute, UK) and the global research unit for Tackling Infections to Benefit Africa (TIBA partnership, University of Edinburgh); and a World Bank African Centres of Excellent grant (WACCBIP-NCDs: Awandare). Project ADAGE PRFCOV19-GP2 (2020-2022) includes 40 researchers from the Center of Biotechnology of Sfax, the University of Sfax, the University of Monastir, the University Hospital Hédi Chaker of Sfax, the Military Hospital of Tunis, and Dacima Consulting. Ministry of Higher Education and Scientific Research and Ministry of Health of the Republic of Tunisia. The Uganda contributions were funded by the UK Medical Research Council (MRC/UKRI) and the UK Department for International Development (DFID) under the MRC/ DFID concordat agreement (grant agreement number NC_PC_19060) and by the Wellcome, DFID–Wellcome Epidemic Preparedness–Coronavirus (grant agreement number 220977/Z/ 20/Z) awarded to M.C. Work from Quadram Institute Bioscience was funded by The Biotechnology and Biological Sciences Research Council Institute Strategic Programme Microbes in the Food Chain BB/ R012504/1 and its constituent projects BBS/E/F/000PR10348, BBS/E/F/000PR10349, BBS/E/F/000PR10351, and BBS/E/F/ 000PR10352 and by the Quadram Institute Bioscience BBSRC– funded Core Capability Grant (project number BB/CCG1860/1). The Africa Pathogen Genomics Initiative (Africa PGI) at the Africa CDC is supported by the Bill & Melinda Gates Foundation (INV018978 and INV018278), Illumina Inc, the US Centers for Disease Control and Prevention (CDC), and Oxford Nanopore Technologies. Sequences generated in Zambia through PATH were funded by the Bill & Melinda Gates Foundation. 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. Funding for sequencing in Côte d’Ivoire, Burkina Faso, and part of the sequencing in the DRC was granted by the German Federal Ministry of Education and Research (BMBF). Sequencing efforts from Morocco have been supported by Academie Hassan II of Science and Technology, Morocco. Funding for surveillance, sampling, and testing in Madagasar was provided by the WHO, the CDC (grant U5/ IP000812-05), the US Agency for International Development (USAID; cooperation agreement 72068719CA00001), and the Office of the Assistant Secretary for Preparedness and Response in the US Department of Health and Human Services (DHHS; grant number IDSEP190051-01-0200). Funding for sequencing was provided by the Bill & Melinda Gates Foundation (GCE/ID OPP1211841), Chan Zuckerberg Biohub, and the Innovative Genomics Institute at UC Berkeley. The Botswana Harvard AIDS Institute was supported by the following funding: H3ABioNet through funding from the National Institutes of Health Common Fund (U41HG006941)—H3ABioNet is an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) program of the African Academy of Science (AAS); DHHS–NIH–National Institute of Allergy and Infectious Diseases (NIAID) (5K24AI131928-04 and 5K24AI131924-04); Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE); a DELTAS Africa Initiative (grant DEL-15-0060—the DELTAS Africa Initiative is an independent funding scheme of the AAS’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant 107752/Z/15/Z] and the UK government; and the South African Medical Research Council (SAMRC) and the Department of Technology and Innovation as part of the Network for Genomic Surveillance in South Africa (NGS-SA) and the Stellenbosch University Faculty of Medicine & Health Sciences, Strategic Equipment Fund. D.P.M. is funded by the Wellcome Trust (Wellcome Trust grant 222574/Z/21/Z). Sequencing activities at the NICD were supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the U.S. Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); the South African Medical Research Council (Reference number SHIPNCD 76756); the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. Furthermore, pandemic surveillance in South Africa and Senegal was supported in part through NIH grant U01 AI151698 for the United World Antiviral Research Network (UWARN). Support for pandemic surveillance from the Tulio de Oliveira group to other African countries is funded by the Rockefeller Foundation. Sequencing efforts in the DRC were funded by the Bill & Melinda Gates Foundation under grant INV-018030 awarded to C.B.P. and further supported by funding from the Africa CDC through the ASLM (African Society of Laboratory Medicine) for Accelerating SARS- CoV-2 Genomic Surveillance in Africa. Sequencing efforts in Rwanda were commissioned by the NIHR Global Health Research program (16/ 136/33) using UK aid from the UK government (funding to E.M. and N. R. through TIBApartnership) and additional funds from the government of Rwanda through RBC/National Reference Laboratory in collaboration with the Belgian Development Agency (ENABEL) for additional genomic sequencing at GIGA Research Institute–Liege/ Belgium. The sequencing effort in Equatorial Guinea was supported by a public-private partnership, the Bioko Island Malaria Elimination Project, composed of the government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon EG Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG. Sample collection and typing in Mali were supported by Fondation Merieux–France, and sequence efforts have been supported by the Enable and Enhance Initiative of the German Federal Government’s Security Cooperation against Biological Threats in the G5 Sahel Region. The Nigeria work was made possible by support from Flu Lab and a cohort of generous donors through TED’s Audacious Project, including the ELMA Foundation, MacKenzie Scott, the Skoll Foundation, and Open Philanthropy. Further Nigeria funding came from grants from the NIAID (www.niaid.nih. gov), NIH-H3Africa (https://h3africa.org) (U01HG007480 and U54HG007480), and the World Bank grant (worldbank.org) (ACE IMPACT project) to C.H. Analysis for the Gabon strains was supported by the Science and Technology Research Partnership for Sustainable Development (SATREPS), Japan International Cooperation Agency (JICA), and Japan Agency for Medical Research and Development (AMED) (grant number JP20jm0110013) and a grant from AMED (grant number JP20wm0225003). Sequencing at KEMRI-Wellcome Trust Research Programme site in Kenya was supported by the National Institute for Health Research (NIHR) (project references 17/ 63/82 and 16/136/33), using UK aid from the UK Government to support global health research, and the UK Foreign, Commonwealth and Development Office and Wellcome Trust (grant# 102975; 220985). Author contributions: Conceptualization: E.W., H.T., J.G.S., J.O., J.O.G., K.O.D., R.A.D., R.A.K., R.L., S.K.T., S.Ma., T.d.O. Methodology: A.-R.N.Z., A.Re., C.N.A., D.P.M., D.A.R., E.W., H.T., J.A.E., J.Gy., J.G.S., K.H.Y., K.O.D., L.d.O.M., M.A.B., M.C., M.G., M.M.N., M.V.T.P., P.A., T.d.O., V.F. Investigation: A.E., A.Ir., A.-R.N.Z., A.Re., A.So., A.v.G., C.A.K., C.W., D.C., D.J.N., D.P.M., D.A.R., D.S., E.M., E.N.N., E.W., F.L., G.G., H.T., J.A.E., J.E.S., J.Gy., J.G.S., J.-J.M.T., J.L., J.Nk., J.Q.M., K.H.Y., M.-M.D., M.A.B., M.C., M.G., M.Mar., M.Mas., M.S., M.V.T.P., N.A., N.H.R., N.K., P.K., R.A.A.C., R.A.D., R.G., S.A.M., S.F.A., S.Ma., S.O., T.L.V., V.F., W.P. Sampling: A.-S.K., A.N.A., A.A.A., A.A.S., A.D., A.E., A.E.O.O., A.F., A.G., A.H., A.Ib., A.Ka., A.K.Sa., A.K.Se., A.L., A.M.O., A.O.O.O., A.P., A.Ro., A.Sy., A.F.V., A.V.G., A.v.G., B.B., B.L.H., B.Ko., B.Kl., B.Ma., B.N., B.S.O., B.T., C.N.A., C.D., C.P., C.S., C.W., D.Bas., D.C., D.D., D.G., D.G.A., D.J.N., D.S., E.K.L., E.M., E.M.O., E.N.N., E.P., E.Sh., F.Ab., F.Ad., F.O.E., F.M.M., F.S.M., F.O., F.T., F.T.T., G.A.A., G.G., G.K.M., G.P.M., G.T., G.v.Z., H.C., H.A.E., H.N., I.C., I.Gaa., I.Gaz., I.K., I.M., I.O., I.Ss., J.C.A., J.-C.M., J.B.L.-D., J.E.S., J.Gi., J.Gy., J.J.L., J.K., J.L., J.M.H., J.M.M., J.Nam., J.Nak., J.T.K., K.T.A., K.M.S., L.B., M.-M.D., M.Al., M.C., M.D., M.e.H., M.G.S., M.K.K., M.Mp., M.Mar., M.Mas., M.M.D., M.N., M.Ou., M.O.A., M.R., M.S., M.W.M., M.T.Y., N.A., N.G., N.H., N.H.R., N.Ig., N.K., N.Ma., N.Nd., N.B.S., N.S., O.Ch., O.E.C., O.Fa., O.Fe., O.I., O.J., O.C.K., O.E.O., O.P., O.S., O.Te., P.E.O., P.A.B., P.C., P.C.S., P.D., P.K., P.K.Q., P.O., P.S., R.A.D., R.G., R.N., S.A., S.S.A., S.B., S.B.L., S.D., S.El., S.E.K., S.F.A., S.Gas., S.Kam., S.L., S.L.D., S.Me., S.Mo., S.M.M., S.N., S.Pi., S.S., S.To., T.L.V., T.Ma., T.S., U.C., U.G., U.J., U.R., V.G., W.K.A., W.T.C., W.P., W.H.R., Y.Bu., Y.K.T., Y.N., Z.R.D. Sequencing: A.-S.Kam., A.N.A., A.A.A., A.A.S., A.C., A.D., A.E.O.O., A.F., A.Ib., A.Is., A.Ko., A.Ka., A.K.K., A.K.Sa., A.K.Se., A.L., A.-R.N.Z., A.P., A.Sa., A.So., A.Sy., A.S.O., A.J.T., A.F.V., A.V.G., A.v.G., A.A.Y., B.B., B.D., B.L.H., B.Ko., B.Kl., B.Mc., B.N., B.T., C.N.A., C.B., C.B.P., C.D., C.M.M., C.P., C.S., D.Bas., D.D., D.G., D.G.A., D.J.B., D.L.B., D.M., D.O.O., D.P., D.S.Y.A., D.T., E.E.F., E.F.N., E.K.L., E.L., E.M.O., E.P., E.Sh., E.Si., E.S.L., F.Ab., F.Aj., F.A.D., F.D., F.M.M., F.S.M., F.O., F.T.T., F.W., G.A.A., G.G., G.P.M., G.T., G.v.Z., H.Ab., H.An., H.C., H.C.R., H.A.E., H.G., H.H.K., H.N., I.B.-B.B., I.C., I.Gaa., I.Gaz., I.K., I.M., I.Ss., J.C.A., J.B., J.-C.M., J.B.L.-D., J.F., J.Gi., J.Gy., J.J.L., J.K., J.M.H., J.M.M., J.M.N., J.Nam., J.Nak., J.Q.M., J.T.K., J.Y., K.T.A., K.M.S., K.O.D., K.S., K.A.T., L.B., L.F., L.S., L.T., M.-M.D., M.Al., M.A.B., M.C., M.D., M.e.H., M.G.S., M.I.M., M.K.K., M.Mi., M.Mp., M.Mw., M.M.D., M.M.N., M.Ow., M.Ou., M.O.A., M.V.T.P., M.W.M., M.T.Y., N.D., N.G., N.H., N.Ig., N.Is., N.Ma., N.Nd., N.Ns., N.B.S., N.S., N.T., O.Cy., O.Ch., O.E.C., O.Fa., O.I., O.J., O.Te., P.A., P.A.B., P.C.S., P.D., P.E.O., P.K., P.K.Q., P.K.M., P.O., P.S., R.A.A.C., R.G., R.N., R.O.P., S.A., S.S.A., S.B., S.B.L., S.C.S., S.D., S.El., S.En., S.E.K., S.Gar., S.Gas., S.H.Ab., S.Kas., S.L., S.L.D., S.Me., S.Mo., S.Ma., S.M.M., S.N., S.Pi., S.Pr., S.R., S.S., S.To., S.Tr., S.v.d.W., T.A., T.Ma., T.Mo., T.S., U.C., U.G., U.J., U.J.A., U.R., V.G., W.K.A., W.T.C., W.H.R., Y.Bu., Y.Be., Y.K.T., Y.N., Z.R.D. Visualization: A.C., A.Is., A.Ko., A.K.K., A.Sa., A.So., A.A.Y., B.T., C.B., C.M.M., D.Bak., D.O.O., D.P., D.A.R., D.S.Y.A., E.A.A., E.B., E.S.L., E.W., F.A.D., F.B., F.D., F.W., G.S., H.Ab., H.An., H.G., H.L., H.T., I.B.A., I.Ss., J.A.E., J.B., J.F., J.Gy., J.M.N., J.Y., K.H.Y., K.S., L.F., L.S., L.T., M.Ao., M.Al., M.G., M.T., M.V.T.P., M.R.W., N.D., N.Is., N.K., N.Ns., N.T., O.Cy., O.To., P.A., P.C.S., P.E.O., R.A.A.C., S.B., S.F.S., S.H.A., S.Kas., S.Ma., T.A., T.Mo., V.E., Y.Be. Funding acquisition: A.J.P., A.Re., A.v.G., B.Ko., C.N.A., C.A.K., C.B.P., C.W., D.C., D.J.B., D.J.N., F.L., G.A.A., G.G., G.P.M., H.C., J.E.S., J.-J.M.T., J.L., J.M.H., J.Nk., J.O., K.O.D., M-M.D., M.C., M.I.M., M.Mas., M.V.T.P., N.A., P.C.S., P.K., P.K.M., R.A.K., S.A.M., S.El., S.Mo., S.v.d.W., T.d.O., W.P. Project administration: A.J.P., A.Re., A.F.V., A.v.G., B.Ko., C.W., D.J.B., D.J.N., E.W., F.Aj., F.T., G.A.A., G.P.M., G.S., G.T., H.C., J.C.O., J.-J.M.T., J.M.H., J.O., J.O.G., J.Y., K.O.D., M.C., M.K., M.Mar., M.P., M.V.T.P., M.R.W., N.R., O.To., P.C.S., P.K., P.K.M., R.A.K., S.A.M., S.El., S.F.S., S.Gas., S.Mo., T.d.O. Supervision: A.J.P., A.Re., B.Ko., C.W., D.J.N., E.N.N., E.W., F.T., G.A.A., G.L.K., H.C., J.B., J.M.H., J.Nk., J.O., J.O.G., K.O.D., M.Al., M.C., M.I.M., M.Mar., M.M.N., M.S., N.Mu., N.R., P.C.S., P.K., P.K.M., R.A.K., S.El., S.E.K., S.Gas., S.Me., S.Mo., S.Pa., T.d.O. Writing – original draft: A.K.Sa., A.-R.N.Z., B.Ko., D.P.M., E.W., F.T., G.L.K., H.T., J.B., J.-C.M., M.Al., M.A.B., M.C., M.G., M.Mi., N.Mu., R.L. Writing – review and editing: A.-R.N.Z., B.Ko., C.M.M., D.J.N., D.P.M., D.A.R., D.S.Y.A., D.T., E.K.L., E.L., E.S.L., E.W., H.T., J.E.S., J.G.S., L.d.O.M., M.A.B., M.C., M.e.H., P.K.Q., P.K.M., R.L., S.K.T., T.d.O., U.J.A. Author contributions are listed alphabetically. A full list of author abbreviations is included on the GitHub repository (https://github.com/krisp-kwazulu-natal/africa- covid19-genomics) (23).Competing interests: P.C.S. is a founder and shareholder of Sherlock Biosciences and is on the board and serves as shareholder of the Danaher Corporation. The authors declare no other conflicts of interest. Data and materials availability: All sequences that were used in the present study are listed in table S4 (accessible on the GitHub repository) along with their GISAID sequence IDs, dates of sampling, the originating and submitting laboratories, and main authors. All input files (e.g., alignments or XML files), all resulting output files, and scripts used in the study are shared publicly on GitHub (https://github.com/krisp-kwazulu-natal/africa-covid19-genomics) (23). This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https:// creativecommons.org/licenses/by/4.0/. This license does not apply to Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 8 of 9 RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY https://doi.org/10.1101/2021.01.26.21250224 https://doi.org/10.1101/2021.03.30.21254323 https://doi.org/10.5281/zenodo.5386379 https://www.niaid.nih.gov/ https://www.niaid.nih.gov/ https://h3africa.org https://www.worldbank.org/en/home https://github.com/krisp-kwazulu-natal/africa-covid19-genomics https://github.com/krisp-kwazulu-natal/africa-covid19-genomics https://github.com/krisp-kwazulu-natal/africa-covid19-genomics https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ figures/photos/artwork or other content included in the article that is credited to a third party, obtain authorization from the rights holder before using such material. SUPPLEMENTARY MATERIALS science.org/doi/10.1126/science.abj4336 Materials and Methods Figs. S1 to S10 Tables S1 to S4 References (24–38) MDAR Reproducibility Checklist View/request a protocol for this paper from Bio-protocol. 12 May 2021; accepted 3 September 2021 Published online 9 September 2021 10.1126/science.abj4336 Wilkinson et al., Science 374, 423–431 (2021) 22 October 2021 9 of 9 1KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 2Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa. 3Laboratorio de Flavivirus, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. 4Laboratório de Genética Celular e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 5Department of Geography and GIS, University of Cincinnati, Cincinnati, OH, USA. 6Institute of Infectious Diseases and Molecular Medicine, Department of Integrative Biomedical Sciences, Computational Biology Division, University of Cape Town, Cape Town, South Africa. 7Division of Medical Virology, Wellcome Centre for Infectious Diseases in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 8Department of Entomology and Plant Pathology, North Carolina State University, Raleigh, NC, USA. 9Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA. 10Cancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, Egypt. 11Centre d’Infectiologie Charles Mérieux-Mali (CICM- Mali), Bamako, Mali. 12Bacteriology and Virology Department Souro Sanou University Hospital, Bobo-Dioulasso, Burkina Faso. 13MRCG at LSHTM Genomics Lab, Fajara, Gambia. 14African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Osun State, Nigeria. 15Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria. 16Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria. 17CHU Habib Bourguiba, Laboratory of Microbiology, Faculty of Medicine of sFax, University of sFax, sFax, Tunisia. 18Pathogen Sequencing Lab, Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of the Congo. 19Université de Kinshasa (UNIKIN), Kinshasa, Democratic Republic of the Congo. 20Genomics Research Program, Children’s Cancer Hospital, Cairo, Egypt. 21Institute of Pathogen Genomics, Africa Centres for Disease Control and Prevention (Africa CDC), Addis Ababa, Ethiopia. 22Laboratory of Transmissible Diseases and Biological Active Substances (LR99ES27), Faculty of Pharmacy of Monastir, Monastir, Tunisia. 23Laboratory of Microbiology, University Hospital of Monastir, Monastir, Tunisia. 24Internal Medicine Department, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria. 25Irrua Specialist Teaching Hospital, Irrua, Nigeria. 26Quadram Institute Bioscience, Norwich, UK. 27World Health Organization, Africa Region, Brazzaville Congo. 28Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG), Université de Conakry, Conakry, Guinea. 29TransVIHMI, Montpellier University/IRD/INSERM, Montpellier, France. 30Virology Department, Institut Pasteur de Dakar, Dakar, Senegal. 31Mali-University Clinical Research Center (UCRC), Bamako, Mali. 32Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia. 33Broad Insitute of Harvard and MIT, Cambridge, MA, USA. 34KEMRI-Wellcome Trust Research Programme/KEMRI-CGMR-C, Kilifi, Kenya. 35National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. 36The Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria 37Institute of Virology, Charité – Universitätsmedizin, Berlin, Germany. 38Medical Biotechnology Laboratory, Rabat Medical and Pharmacy School, Mohammed V University, Rabat, Morocco. 39Department of Immunology, University of Maiduguri Teaching Hospital, P.M.B. 1414, Maiduguri, Nigeria. 40MRC/ UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda. 41Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. 42The Biotechnology Center of the University of Yaoundé I, Cameroon and CDC Foundation, Yaounde, Cameroon. 43Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA. 44Virology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar. 45University of Nebraska Medical Center (UNMC), Omaha, NE, USA. 46Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa. 47CHU de Bouaké, Laboratoire/Unité de Diagnostic des Virus des Fièvres Hémorragiques et Virus Émergents, Bouaké, Côte d’Ivoire. 48School of Public Health, Pwani University, Kilifi, Kenya. 49Swiss Tropical and Public Health Institute, Basel, Switzerland. 50West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana. 51School of Life Sciences and Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry, UK. 52Uganda Virus Research Institute, Entebbe, Uganda. 53Division of Virology, National Health Laboratory Service and University of the Free State, Bloemfontein, South Africa. 54Botswana Harvard AIDS Institute Partnership and Botswana Harvard HIV Reference Laboratory, Gaborone, Botswana. 55University of Zambia, School of Veterinary Medicine, Department of Disease Control, Lusaka, Zambia. 56African Society for Laboratory Medicine, Addis Ababa, Ethiopia. 57Functional Genomic Platform/National Centre for Scientific and Technical Research (CNRST), Rabat, Morocco. 58Rwanda National Reference Laboratory, Kigali, Rwanda. 59Robert Koch-Institute, Berlin, Germany. 60G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France. 61Research Unit of Autoimmune Diseases UR17DN02, Military Hospital of Tunis, University of Tunis El Manar, Tunis, Tunisia. 62Department of Public Health, Ministry of Health, Ilorin, Kwara State, Nigeria. 63Laboratory of Clinical Virology, Institut Pasteur de Tunis, Tunis, Tunisia. 64Faculty of Pharmacy of Monastir, Monastir, Tunisia. 65National Microbiology Reference Laboratory, Harare, Zimbabwe. 66National Influenza Centre, Viral Respiratory Laboratory, Algiers, Algeria. 67Medical Microbiology and Parasitology Department, College of Medicine, University of Ibadan, Ibadan, Nigeria. 68Lincoln International Institute for Rural Health, University of Lincoln, Lincoln, UK. 69Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa. 70Africa Health Research Institute, KwaZulu-Natal, Durban, South Africa. 71Department of Biochemistry and Biotechnology, Pwani University, Kilifi, Kenya. 72National Health Laboratory Service (NHLS), Tygerberg, Cape Town, South Africa. 73Institution and Department, Ministry Of Health, COVID-19 Testing Laboratory, Mbabane, Kingdom of Eswatini. 74Laboratory of Health Sciences and Technologies, High Institute of Health Sciences, Hassan 1st University, Settat, Morocco. 75Department of Emerging Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. 76Central Public Health Laboratories (CPHL), Kampala, Uganda. 77Faculty of Medicine Ain Shams Research institute (MASRI), Ain Shams University, Cairo, Egypt. 78Charles Nicolle Hospital, Laboratory of Microbiology, National Influenza Center, 1006 Tunis, Tunisia. 79Laboratory of Transmissible Diseases and Biological Active Substances (LR99ES27), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia. 80Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel. 81Namibia Institute of Pathology, Windhoek, Namibia. 82Centre Interdisciplinaires de Recherches Medicales de Franceville (CIRMF), Franceville, Gabon. 83Department of Biostatistics and Data Science, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. 84Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA. 85UHAS COVID-19 Testing and Research Centre, University of Health and Allied Sciences, Ho, Ghana. 86Rollins School of Public Health, Emory University, Atlanta, GA, USA. 87Anoual Laboratory, Casablanca, Morocco. 88Botswana Institute for Technology Research and Innovation, Gaborone, Botswana. 89New York University Grossman School of Medicine, New York City, NY, USA. 90Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon. 91Virology/Molecular Biology Department, Central Health Laboratory, Ministry of Health and Wellness, Mauritius. 92Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Cairo Egypt. 93Ministry of Health and Wellness, Gaborone, Botswana. 94Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa. 95National Reference Laboratory Lesotho, Maseru, Lesotho. 96Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi, Kenya. 97Laboratorio de Investigaciones de Baney, Baney, Equatorial Guinea. 98Ifakara Health Institute, Dar-es-Salaam, Tanzania. 99Nigeria Centre for Disease Control, Abuja, Nigeria. 100Department of Medical Diagnostics, Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. 101Department of Medical Laboratory Science, Niger Delta University, Bayelsa State, Nigeria. 102Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Cairo 12613, Egypt. 103King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. 104Biological Prevention Department, Main Chemical Laboratories, Egypt Army, Cairo, Egypt. 105PATH, Lusaka, Zambia. 106Department of Biotechnology, High Institute of Biotechnology of Sidi Thabet, University of Manouba, BP-66, 2020 Ariana-Tunis, Tunisia. 107Genomic Center for Human Pathologies (GENOPATH), Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco. 108Rwanda National Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health, Kigali, Rwanda. 109School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda. 110Instituto Nacional de Saude (INS), Maputo, Mozambique. 111National Health Laboratory Service (NHLS), Cape Town, South Africa. 112Computational Biology Division, Department of Integrative Biomedical Sciences, IDM, CIDRI Africa Wellcome Trust Centre, University of Cape Town, Cape Town, South Africa. 113Virology Laboratory, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria. 114Department of Epidemiology and Community Health, Faculty of Clinical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria. 115Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria. 116Mayotte Hospital Center, Mayotte, France. 117Virology Service, Centre Pasteur of Cameroun, Yaounde, Cameroon. 118Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. 119Laboratoire de Recherche et d'Analyses Médicales de la Gendarmerie Royale, Rabat, Morocco. 120Clinical and Experimental Pharmacology Lab, LR16SP02, National Center of Pharmacovigilance, University of Tunis El Manar, Tunis, Tunisia. 121CHU Hedi Chaker Sfax, Service de Pneumologie, Tunis, Tunisia. 122Laboratoire de Recherche et d'Analyses Médicales de la Gendarmerie Royale, Rabat, Morocco. 123Central Public Health Laboratories (CPHL), Cairo, Egypt. 124Centre MURAZ, Ouagadougou, Burkina Faso. 125National Institute of Public Health of Burkina Faso (INSP/BF), Ouagadougou, Burkina Faso. 126National Reference Center for Respiratory Viruses, Molecular Genetics of RNA Viruses, UMR 3569 CNRS, University of Paris, Institut Pasteur, Paris, France. 127Sub-Saharan African Network For TB/HIV Research Excellence (SANTHE), Durban, South Africa. 128Coordenação Geral de Laboratórios de Saúde Pública/ Secretaria de Vigilância em Saúde, Ministério da Saúde, Brasília, Distrito Federal, Brazil. 129World Health Organization, WHO Lesotho, Maseru, Lesotho. 130Med24 Medical Centre, Ruwa, Zimbabwe. 131Division of Human Genetics, Department of Pathology, University of Cape Town, Cape Town, South Africa. 132Center for Human Genetics, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda. 133Laboratory of Human Genetics, GIGA Research Institute, Liège, Belgium. 134National Health Laboratory, Gaborone, Botswana. 135MRC- University of Glasgow Centre for Virus Research, Glasgow, UK.136Harvard T.H. Chan School of Public Health, Boston, MA, USA. 137Department of Global Health, University of Washington, Seattle, WA, USA. 138Centre for Human Virology and Genomics, Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria. 139School of Pathology, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa. RESEARCH | RESEARCH ARTICLE UNIV ERSIT Y O F IB ADAN L IB RARY https://science.org/doi/10.1126/science.abj4336 https://en.bio-protocol.org/cjrap.aspx?eid=10.1126/science.abj4336