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At the end of 2020, the Network for Genomic Surveillance in South Africa (NGS-SA) detected a SARS-CoV-2 variant of concern (VOC) in South Africa (501Y.V2 or PANGO lineage B.1.351)1. 501Y.V2 is associated with increased transmissibility and resistance to neutralizing antibodies elicited by natural infection and vaccination2,3. 501Y.V2 has since spread to over 50 countries around the world and has contributed to a significant resurgence of the epidemic in southern Africa. In order to rapidly characterize the spread of this and other emerging VOCs and variants of interest (VOIs), NGS-SA partnered with the Africa Centres for Disease Control and Prevention and the African Society of Laboratory Medicine through the Africa Pathogen Genomics Initiative to strengthen SARS-CoV-2 genomic surveillance across the region.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute, highly transmissible respiratory infection in both humans and wide range of animal species. Its rapid spread globally and devasting effects have resulted into a major public health emergency prompting the need for methodological interventions to understand and control its spread. In particular, The ability to effectively retrace its transmission pathways in outbreaks remains a major challenge. This is further exacerbated by our limited understanding of its underlying evolutionary mechanism. Using NGS whole-genome data, we determined whether inter- and intra-host diversity coupled with bottleneck analysis can retrace the pathway of viral transmission in two epidemiologically well characterised nosocomial outbreaks in healthcare settings supported by phylogenetic analysis. Additionally, we assessed the mutational landscape, selection pressure and diversity of the identified variants. Our findings showed evidence of intrahost variant transmission and evolution of SARS-CoV-2 after infection These observations were consistent with the results from the bottleneck analysis suggesting that certain intrahost variants in this study could have been transmitted to recipients. In both outbreaks, we observed iSNVs and SNVs shared by putative source-recipients pairs. Majority of the observed iSNVs were positioned in the S and ORF1ab region. AG, CT and TC nucleotide changes were enriched across SARS-COV-2 genome. Moreover, SARS-COV-2 genome had limited diversity in some loci while being highly conserved in others. Overall, Our findings show that the synergistic effect of combining withinhost diversity and bottleneck estimations greatly enhances resolution of transmission events in Sars-Cov-2 outbreaks. They also provide insight into the genome diversity suggesting purifying selection may be involved in the transmission. Together these results will help in developing strategies to elucidate transmission events and curtail the spread of Sars-Cov-2
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In March 2020, the first cases of COVID-19 were reported in South Africa. The epidemic spread very fast despite an early and extreme lockdown and infected over 600,000 people, by far the highest number of infections in an African country. To rapidly understand the spread of SARS-CoV-2 in South Africa, we formed the Network for Genomics Surveillance in South Africa (NGS-SA). Here, we analyze 1,365 high quality whole genomes and identify 16 new lineages of SARS-CoV-2. Most of these unique lineages have mutations that are found hardly anywhere else in the world. We also show that three lineages spread widely in South Africa and contributed to [~]42% of all of the infections in the country. This included the first identified C lineage of SARS-CoV-2, C.1, which has 16 mutations as compared with the original Wuhan sequence. C.1 was the most geographically widespread lineage in South Africa, causing infections in multiple provinces and in all of the eleven districts in KwaZulu-Natal (KZN), the most sampled province. Interestingly, the first South-African specific lineage, B.1.106, which was identified in April 2020, became extinct after nosocomial outbreaks were controlled. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify and control the spread of SARS-CoV-2.
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Lockdown measures have been introduced worldwide to contain the transmission of COVID-19. This paper defines the term lockdown and describes the design, timing and implementation of lockdown in nine countries in Sub Saharan Africa: Ghana, Nigeria, South Africa, Sierra Leone, Sudan, Tanzania, Uganda, Zambia and Zimbabwe. It also discusses the manner in which lockdown is enforced, the need to mitigate the harms of lockdown, and the association between lockdown and the reported number of COVID-19 cases and deaths. While there are some commonalities in the implementation of lockdown, a more notable finding is the variation in the design, timing and implementation of lockdown measures across the nine countries. We found that the number of reported cases is heavily dependent on the number of tests done, and that testing rates ranged from 9 to 21,261 per million population. The reported number of COVID-19 deaths per million population also varies, but is generally low when compared to countries in Europe and North America. While lockdown measures may have helped inhibit some community transmission, the pattern and nature of the epidemic remains unclear. Of concern are signs of lockdown harming health by affecting the functioning of the health system and causing social and economic harms. This paper highlights the need for inter-sectoral and trans-disciplinary research capable of providing a rigorous and holistic assessment of the harms and benefits of lockdown.
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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.
