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New COVID variant — More mutated, more transmissible, and all over SA

A coronavirus variant first detected in South Africa and since found in EnglandChina, the Democratic Republic of the CongoMauritiusNew ZealandPortugal and Switzerland, could be more infectious than other mutations and have the potential to evade vaccines. But the South African health experts who identified and are monitoring the new lineage say that they believe vaccines will still offer high levels of protection.

The experts from the universities of Stellenbosch, the Witwatersrand, Pretoria and KwaZulu-Natal and the National Institute for Communicable Diseases wrote in The Conversation that the new variant had been found in all provinces.

However, it had not yet fulfilled World Health Organization (WHO) criteria to be classified as a variant of interest or variant of concern, and research was still underway to understand the lineage’s transmissibility and on vaccines.

“Based on our current understanding of the mutations in this particular lineage, we suspect that it might be able to partially evade the immune response. Despite this, however, our view based on what we know now is that vaccines will still offer high levels of protection against hospitalisation and death.”

 

New COVID C.1.2 variant the 'most mutated variant so far'

According to a Daily Mail report, the C.1.2 strain, which is linked to increased transmissibility, is more mutations away from the original virus seen in Wuhan, experts at South Africa's National Institute for Communicable Diseases and the KwaZulu-Natal Research Innovation and Sequencing Platform said.

On Monday, the NiCD issued an alert about the “C.1.2 lineage”, saying it had been detected in all provinces in the country, but at a relatively low rate. C.1.2 was first detected in May, the alert said, but Delta is still the dominant variant spreading in South Africa and the world.

The new strain has a mutation rate of about 41.8 mutations per year. This rate is nearly double the current global mutation rate seen in any other Variant of Concern (VOC) so far.

The researchers found a monthly increase in the number of C.1.2 genomes in South Africa, rising from 0.2 percent in May to 1.6 percent in June and 2.0 percent in July. This short period of consistent increase has also been spotted in the Alpha, Beta and Gamma variants. They also found 14 mutations in nearly 50% of the variants, which had a C.1.2 sequence.While more research is required 'to determine the functional impact of t hese mutations', scientists warned the latest variant, which has “mutated substantially”, could help the virus evade antibodies and immune responses.

In their research, they said, “We describe and characterise a newly identified SARS-CoV-2 lineage with several spike mutations that is likely to have emerged in a major metropolitan area in South Africa after the first wave of the epidemic, and then to have spread to multiple locations within two neighbouring provinces.

“We show that this lineage has rapidly expanded and become dominant in three provinces, at the same time as there has been a rapid resurgence in infections.

“Although the full import of the mutations is not yet clear, the genomic and epidemiological data suggest that this variant has a selective advantage, from increased transmissibility, immune escape or both.

“These data highlight the urgent need to refocus the public health response in South Africa on driving transmission down to low levels, not only to reduce hospitalisations and deaths but also to limit the spread of this lineage and the further evolution of the virus.”

Earlier this month, adds the Daily Mail, a report published by Public Health England said that the C.1.2 strain was among 10 variants being monitored by scientists in the UK.

In April, scientists found another South African strain — called B.1.351 — had the potential to “break through” the Pfizer jab. Scientists examined 400 people who had tested positive for coronavirus at least 14 days after receiving one or two doses of the jab, and 400 who tested positive with no vaccine.

The variant was eight times more prevalent in those who had two jabs than none. It was seen in 5.4 percent of people with two doses, but 0.7 percent of people without any.

Scientists working on the Tel Aviv University study said their results suggested the vaccine is less effective against the South African variant, compared with the original coronavirus and the Kent variant. The B.1.351 has key mutations on its spike protein, which scientists fear might make it difficult for the immune system to recognise.

These alterations open the door to it being resistant to vaccines, which train the body to spot the spike protein, or natural immunity from previous infection.

Last month health chiefs spotted another COVID variant spreading in Britain, with 31 mutant strains now on the UK's watchlist. Sixteen cases of the version of the virus – which is thought to have originated in Colombia – were detected by experts. Public Health England insisted there was no proof it is deadlier than Delta, which makes up 99% of all cases in the UK. And they also said there was no evidence that the strain renders any of the vaccines currently deployed any less effective.

The latest study comes as Britain recorded a further 61 COVID deaths and 33,196 more new cases on Sunday, official data showed.

The number of new cases represents a 3 percent rise on the new daily cases from last Sunday, which stood at 32,253, while only 49 daily deaths were recorded. Infections in the past seven days rose by 5.8 percent on the week before, and weekly deaths jumped by 16%.

This means the new positive test rate over the past seven days is 240,528 while the number of deaths within 28 days of a positive test has been recorded as 797 – an increase of 110. The Sunday figure for fatalities tends to be lower than weekdays due to a delay by some hospitals in reporting deaths.

Britain is currently recording about 30,000 COVID cases a day, which SAGE scientists fear will surge when pupils go back to classrooms next week. This time last year there were nearly 2,000 cases a day.

 

South African health experts have identified a new lineage of SARS-CoV-2: What’s known so far

This article is republished from The Conversation, where it appeared on 31 August 2021. It was authored by professors: Wolfgang Preiser of Stellenbosch University; Cathrine Scheepers and Penny Moore of the University of the Witwatersrand; Jinal Bhiman of the National Institute for Communicable Diseases; Marietjie Venter of the University of Pretoria; and Tulio de Oliveira of the University of KwaZulu-Natal.

As a team of South African researchers we have identified a new lineage of SARS-CoV-2, the virus causing COVID-19. A lineage represents a genetically distinct virus population with a common ancestor. This virus may be designated as a variant in future, based on significantly altered properties, but first we need to understand it better. Our findings so far are set out in a non pre-peer reviewed paper.

The new lineage, assigned the name C.1.2, has been found in all provinces in the country. While it shares some mutations with other variants, it is different in some respects.

Viruses mutate all the time. Sometimes the mutations result in an added benefit for the virus, such as increased transmissibility. But often mutations don’t do anything beneficial for the virus. So more mutations do not always mean trouble for us, its host.

For C.1.2, a lot is still unknown. For example, it’s too early to tell whether these mutations will affect transmissibility or vaccine efficacy.

The  Network for Genomics Surveillance in South Africa has been monitoring changes in SARS-CoV-2 since March 2020. South Africa was one of the first countries globally to introduce systematic and coordinated genomic surveillance, sequencing genomes of SARS-CoV-2 from patient samples representative of different geographic regions and over time.

Its findings have provided insights into how and when SARS-CoV-2 was introduced into the country, and into its early spread. The Network has also been sequencing virus genomes to identify newly developing viral lineages of particular concern.

Later in 2020 the network detected what is now called the Beta variant of concern and more recently observed, almost in real-time, the arrival and rapid “take-over” of the Delta variant in South Africa.

What’s known, and what’s not known

We select patient samples from diagnostic laboratories throughout the country and perform sequencing to analyse the virus genomes. We then compare these sequences to those seen before and elsewhere. It’s very much like the game where you spot the difference between nearly identical pictures.

We’re playing spot the difference with SARS-CoV-2.

When we find many differences – or differences in certain particularly important places like the spike of the virus – we pay special attention. We then look to see how often we see this particular virus and where – in one region of the country or in multiple regions, only in South Africa or also in other parts of the world. We also monitor whether it increases over time, which would suggest that it is replacing previous versions of the virus.

When we sequence the virus and compare it to other SARS-CoV-2 viruses it gets assigned a name based on the closest matching virus. We then look at the virus and the one that it matches to see how similar they are to each other. If we see a lot of differences that could be an indication of a new lineage.

In May 2021 we first detected a mutated group of related SARS-CoV-2 viruses in South Africa which has been assigned the lineage, C.1.2. So far, from May to August 2021, C.1.2 has been detected in all provinces. Yet it occurs at relatively low frequency and though we see small increases in this lineage overtime they remain very low.

This lineage possesses mutations within the genome that have been seen in other SARS-CoV-2 variants.

The network alerted the World Health Organisation (WHO) and the South African National Department of Health to this lineage in July. The two months between our first discovery and the notification comes from the lengthy process of sequencing and analysis. In addition, mutated viruses appear from time to time – but many disappear again.

Therefore we needed to monitor this particular one to see if it would be detected in additional regions. Only when we started detecting it in other provinces and when it was reported also from other countries did we feel we had sufficient evidence to suggest a new lineage.

The surveillance network is continuing to monitor the frequency of the lineage across the country, and helping other African countries do the same. Also, tests to assess the functional impact of the mutations it harbours are under way – for example, how well do antibodies in people who have been vaccinated or infected previously neutralise the new virus, how well does it multiply in cell cultures compared to other virus variants, and so on.

The virus has not yet fulfilled the WHO criteria to be classified as a variant of interest or variant of concern.

A variant of interest has genetic changes affecting important virus characteristics (transmissibility, disease severity, immune, diagnostic or therapeutic escape) and epidemiological impacts suggesting a risk to global public health.

A variant of concern is the worst category – it’s a variant with proven increased transmissibility and/or virulence and/or decreased effectiveness of public health or medical tools such as vaccines, therapeutics and tests.

Delta is a good example of a variant of concern that rapidly came to dominate the epidemic globally, causing major waves in many countries including those with advanced vaccination roll-out programmes.

The C.1.2 lineage shares a few common mutations with all other variants of concern, including the Beta, Lambda and Delta variants. But the new lineage has a number of additional mutations.

The implications

We are still gathering more data to understand the impact of this lineage on transmissibility and on vaccines.

SARS-CoV-2, like all viruses, mutates with time, usually in a way that affords the virus some kind of advantage. Some of the mutations in the C.1.2 lineage have arisen in other SARS-CoV-2 variants of interest or concern.

But we still don’t have a full picture. It will take a combination of ongoing thorough surveillance (especially to see whether it perhaps displaces the currently prevalent delta variant) and laboratory-based studies to characterise its properties.

Based on our current understanding of the mutations in this particular lineage, we suspect that it might be able to partially evade the immune response. Despite this, however, our view based on what we know now is that vaccines will still offer high levels of protection against hospitalisation and death.

We expect new variants to continue to emerge wherever the virus is spreading. Vaccination remains critical to protect those in our communities at high risk of hospitalisation and death, to reduce the strain on the health system, and to help slow transmission. This has to be combined with all the other public health and social measures.

We therefore advise the public to remain vigilant and continue to follow COVID-19 protocol by including good ventilation in all shared spaces and wearing masks that cover your nose, mouth and chin. These non-pharmaceutical interventions are still shown to be preventing the spread of SARS-CoV-2 irrespective of the variant.

We are also of the view that the mutated lineage is unlikely to affect the sensitivity of PCR tests. These tests typically detect at least two different parts of the SARS-CoV-2 genome, which serves as a backup in the case of a mutation arising in one of them. Studies are ongoing to assess any implications for diagnostic testing.

Why vigilance is needed

The Network for Genomic Surveillance in South Africa links National Health Laboratory Service and private COVID-19 testing laboratories to academic sequencing centres. This collaboration has allowed South African experts to rapidly generate and analyse sequence data to inform regional and national responses.

As of late August 2021 the delta variant accounted for over 90% of sequences in Southern Africa. But virus evolution is ongoing, as long as the virus can spread from person to person, multiply, and be passed on. It is thus necessary to continue monitoring its evolution, to detect new problematic properties early and institute countermeasures, where possible.

Wolfgang Preiser is Professor and Head: Division of Medical Virology at Stellenbosch University.

Cathrine Scheepers is a Senior Medical Scientist at the University of the Witwatersrand.

Jinal Bhiman is Principal Medical Scientist at the National Institute for Communicable Diseases (NICD).

Marietjie Venter is Head: Zoonotic, Arbo and Respiratory Virus Programme, and Professor in the Department Medical Virology at the University of Pretoria.

Penny Moore is Reader and DST/NRF SARChI Chair of Virus-Host Dynamics at the National Institute for Communicable Diseases, and CAPRISA Research Associate at the University of the Witwatersrand.

Tulio de Oliveira is Director: KRISP – KwaZulu-Natal Research and Innovation Sequencing Platform at the University of KwaZulu-Natal.

 * This article is republished from The Conversation under a Creative Commons licence. Find the link to the original article below.

 

Study details

The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection

Cathrine Scheepers, Josie Everatt, Daniel G. Amoako, Anele Mnguni, Arshad Ismail, Boitshoko Mahlangu, Constantinos Kurt Wibmer, Eduan Wilkinson, Houriiyah Tegally, James Emmanuel San, Jennifer Giandhari, Noxolo Ntuli, Sureshnee Pillay, Thabo Mohale, Yeshnee Naidoo, Zamantungwa T. Khumalo, Zinhle Makatini, Alex Sigal, Carolyn Williamson, Florette Treurnicht, Koleka Mlisana, Marietjie Venter, Nei-yuan Hsiao, Nicole Wolter, Nokukhanya Msomi, Richard Lessells, Tongai Maponga, Wolfgang Preiser, Penny L. Moore, Anne von Gottberg, Tulio de Oliveira, Jinal N. Bhiman

Published in MedRxiv on 24 August 2021

Abstract
SARS-CoV-2 variants of interest have been associated with increased transmissibility, neutralisation resistance and disease severity. Ongoing SARS-CoV-2 genomic surveillance worldwide has improved our ability to rapidly identify such variants.

Here we report the identification of a potential variant of interest assigned to the PANGO lineage C.1.2. This lineage was first identified in May 2021 and evolved from C.1, one of the lineages that dominated the first wave of SARS-CoV-2 infections in South Africa and was last detected in January 2021. C.1.2 has since been detected across the majority of the provinces in South Africa and in seven other countries spanning Africa, Europe, Asia and Oceania.

The emergence of C.1.2 was associated with an increased substitution rate, as was previously observed with the emergence of the Alpha, Beta and Gamma variants of concern (VOCs).

C.1.2 contains multiple substitutions (R190S, D215G, N484K, N501Y, H655Y and T859N) and deletions (Y144del, L242-A243del) within the spike protein, which have been observed in other VOCs and are associated with increased transmissibility and reduced neutralisation sensitivity.

Of greater concern is the accumulation of additional mutations (C136F, Y449H and N679K) which are also likely to impact neutralisation sensitivity or furin cleavage and therefore replicative fitness. While the phenotypic characteristics and epidemiology of C.1.2 are being defined, it is important to highlight this lineage given its concerning constellations of mutations.

Conclusion
We have identified a new SARS-CoV-2 variant assigned to the PANGO lineage C.1.2. This variant has been detected throughout the third wave of infections in South Africa from May 2021 onwards and has been detected in seven other countries within Europe, Asia, Africa and Oceania. The identification of novel SARS-CoV-2 variants is commonly associated with new waves of infection. Like several other VOCs, C.1.2 has accumulated a number of substitutions beyond what would be expected from the background SARS-CoV-2 evolutionary rate. This suggests the likelihood that these mutations arose during a period of accelerated evolution in a single individual with prolonged viral infection through virus-host co-evolution19–21.

Deletions within the NTD (like Y144del, seen in C.1.2 and other VOCs) have been evident in cases of prolonged infection, further supporting this hypothesis.

C.1.2 contains many mutations that have been identified in all four VOCs (Alpha, Beta, Delta and Gamma) and three VOIs (Kappa, Eta and Lambda) as well as additional mutations within the NTD (C136F), RBD (Y449H), and adjacent to the furin cleavage site (N679K). Many of the shared mutations have been associated with improved ACE2 binding (N501Y)25–29 or furin cleavage (H655Y and P681H/R), and reduced neutralisation activity (particularly Y144del, 242-244del, and E484K)17,33–39, providing sufficient cause for concern of continued transmission of this variant.

Future work aims to determine the functional impact of these mutations, which likely include neutralising antibody escape, and to investigate whether their combination confers a replicative fitness advantage over the Delta variant.

The C.1.2 lineage is continuing to grow. At the time of submission (20 August 2021) there were 80 C.1.2 sequences in GISAID with it now having been detected in Botswana and in the Northern Cape of South Africa.

 

 

 

MedRxiv article – The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection (Open access)

 

Daily Mail article – New Covid variant detected in South Africa has already been found in England as scientists warn it is the 'most mutated variant so far' (Open access)

 

The Conversation: South African health experts have identified a new lineage of SARS-CoV-2: what’s known so far

 

 

See more from MedicalBrief archives:

 

Previous COVID infection may not offer long-term protection – UK study

 

Sanofi/GSK trials boosts vaccine hopes; turns to SA variant

 

Developing neutralising nanobodies against SARS-CoV-2 variants including SA variant — Alpaca preprint

 

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