BackgroundThe emergence of a novel coronavirus, SARS-CoV-2, in December 2019, progressed to become a world pandemic in a few months and reached South Africa at the beginning of March. To investigate introduction and understand the early transmission dynamics of the virus, we formed the South African Network for Genomics Surveillance of COVID (SANGS_COVID), a network of ten government and university laboratories. Here, we present the first results of this effort, which is a molecular epidemiological study of the first twenty-one SARS-CoV-2 whole genomes sampled in the first port of entry, KwaZulu-Natal (KZN), during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), we aim to shed light on the patterns of infections that define the epidemic in South Africa.MethodsR was calculated using positive cases and deaths from reports provided by the four major provinces. Molecular epidemiology investigation involved sequencing viral genomes from patients in KZN using ARCTIC protocols and assembling whole genomes using meticulous alignment methods. Phylogenetic analysis was performed using maximum likelihood (ML) and Bayesian trees, lineage classification and molecular clock calculations.FindingsThe epidemic in South Africa has been very heterogeneous. Two of the largest provinces, Gauteng, home of the two large metropolis Johannesburg and Pretoria, and KwaZulu-Natal, home of the third largest city in the country Durban, had a slow growth rate on the number of detected cases. Whereas, Western Cape, home of Cape Town, and the Eastern Cape provinces the epidemic is spreading fast. Our estimates of transmission potential for South Africa suggest a decreasing transmission potential towards R=1 since the first cases and deaths have been reported. However, between 06 May and 18 May 2020, we estimate that R was on average 1.39 (1.04–2.15, 95% CI). We also demonstrate that early transmission in KZN, and most probably in all main regions of SA, was associated with multiple international introductions and dominated by lineages B1 and B. The study also provides evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic, which inflated early mortality in KZN.InterpretationThis first report of SANGS_COVID consortium focuses on understanding the epidemic heterogeneity and introduction of SARS-CoV-2 strains in the first month of the epidemic in South Africa. The early introduction of SARS-CoV-2 in KZN included caused a localized outbreak in a hospital, provides potential explanations for the initially high death rates in the province. The current high rate of transmission of COVID-19 in the Western Cape and Eastern Cape highlights the crucial need to strength local genomic surveillance in South Africa.FundingUKZN Flagship Program entitled: Afrocentric Precision Approach to Control Health Epidemic, by a research Flagship grant from the South African Medical Research Council (MRC-RFA-UFSP-01- 2013/UKZN HIVEPI, by the the Technology Innovation Agency and the the Department of Science and Innovation and by National Human Genome Re- search Institute of the National Institutes of Health under Award Number U24HG006941. H3ABioNet is an initiative of the Human Health and Heredity in Africa Consortium (H3Africa).Research in context Evidence before this studyWe searched PubMed, BioRxiv and MedRxiv for reports on epidemiology and phylogenetic analysis using whole genome sequencing (WGS) of SARS-CoV-2. We used the following keywords: SARS-CoV-2, COVID-19, 2019-nCoV or novel coronavirus and transmission genomics, epidemiology, phylogenetic or reproduction number. Our search identified an important lack of molecular epidemiology studies in the southern hemisphere, with only a few reports from Latin America and one in Africa. In other early transmission reports on SARS-CoV-2 infections in Africa, authors focused on transmission dynamics, but molecular and phylogenetic methods were missing.Added value of this studyWith a growing sampling bias in the study of transmission genomics of the SARS-CoV-2 pandemic, it is important for us to report high-quality whole genome sequencing (WGS) of local SARS-CoV-2 samples and in-depth phylogenetic analyses of the first month of infection in South-Africa. In our molecular epidemiological investigation, we identify the early transmission routes of the infection in the KZN and report thirteen distinct introductions from many locations and a cluster of localized transmission linked to a healthcare setting that caused most of the initial deaths in South Africa. Furthermore, we formed a national consortium in South Africa, funded by the Department of Science and Innovation and the South African Medical Research Council, to capacitate ten local laboratories to produce and analyse SARS-CoV-2 data in near real time.Implications of all the available evidenceThe COVID-19 pandemic is progressing around the world and in Africa. Early transmission genomics and dynamics of SARS-CoV-2 throw light on the early stages of the epidemic in a given region. This facilitates the investigation of localized outbreaks and serves to inform public health responses in South Africa.
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