How worried should you be about coronavirus variants? A virologist explains his concerns


A COVID-19 patient in an ICU unit in a hospital in Capetown, South Africa, in December 2020. A variant emerged in South Africa that has since spread to other parts of the world. Other new variants could emerge elsewhere.
Rodger Bosch/AFP via Getty Images

Paulo Verardi, University of ConnecticutSpring has sprung, and there is a sense of relief in the air. After one year of lockdowns and social distancing, more than 171 million COVID-19 vaccine doses have been administered in the U.S. and about 19.4% of the population is fully vaccinated. But there is something else in the air: ominous SARS-CoV-2 variants.

I am a virologist and vaccinologist, which means that I spend my days studying viruses and designing and testing vaccine strategies against viral diseases. In the case of SARS-CoV-2, this work has taken on greater urgency. We humans are in a race to become immune against this cagey virus, whose ability to mutate and adapt seems to be a step ahead of our capacity to gain herd immunity. Because of the variants that are emerging, it could be a race to the wire.

A variant in Brazil is overwhelming the country’s health care system.

Five variants to watch

RNA viruses like SARS-CoV-2 constantly mutate as they make more copies of themselves. Most of these mutations end up being disadvantageous to the virus and therefore disappear through natural selection.

Occasionally, though, they offer a benefit to the mutated or so-called genetic-variant virus. An example would be a mutation that improves the ability of the virus to attach more tightly to human cells, thus enhancing viral replication. Another would be a mutation that allows the virus to spread more easily from person to person, thus increasing transmissibility.

None of this is surprising for a virus that is a fresh arrival in the human population and still adapting to humans as hosts. While viruses don’t think, they are governed by the same evolutionary drive that all organisms are – their first order of business is to perpetuate themselves.

These mutations have resulted in several new SARS-CoV-2 variants, leading to outbreak clusters, and in some cases, global spread. They are broadly classified as variants of interest, concern or high consequence.

Currently there are five variants of concern circulating in the U.S.: the B.1.1.7, which originated in the U.K.; the B.1.351., of South African origin; the P.1., first seen in Brazil; and the B.1.427 and B.1.429, both originating in California.

Each of these variants has a number of mutations, and some of these are key mutations in critical regions of the viral genome. Because the spike protein is required for the virus to attach to human cells, it carries a number of these key mutations. In addition, antibodies that neutralize the virus typically bind to the spike protein, thus making the spike sequence or protein a key component of COVID-19 vaccines.

India and California have recently detected “double mutant” variants that, although not yet classified, have gained international interest. They have one key mutation in the spike protein similar to one found in the Brazilian and South African variants, and another already found in the B.1.427 and B.1.429 California variants. As of today, no variant has been classified as of high consequence, although the concern is that this could change as new variants emerge and we learn more about the variants already circulating.

More transmission and worse disease

These variants are worrisome for several reasons. First, the SARS-CoV-2 variants of concern generally spread from person to person at least 20% to 50% more easily. This allows them to infect more people and to spread more quickly and widely, eventually becoming the predominant strain.

For example, the B.1.1.7 U.K. variant that was first detected in the U.S. in December 2020 is now the prevalent circulating strain in the U.S., accounting for an estimated 27.2% of all cases by mid-March. Likewise, the P.1 variant first detected in travelers from Brazil in January is now wreaking havoc in Brazil, where it is causing a collapse of the health care system and led to at least 60,000 deaths in the month of March.

Second, SARS-CoV-2 variants of concern can also lead to more severe disease and increased hospitalizations and deaths. In other words, they may have enhanced virulence. Indeed, a recent study in England suggests that the B.1.1.7 variant causes more severe illness and mortality.

Another concern is that these new variants can escape the immunity elicited by natural infection or our current vaccination efforts. For example, antibodies from people who recovered after infection or who have received a vaccine may not be able to bind as efficiently to a new variant virus, resulting in reduced neutralization of that variant virus. This could lead to reinfections and lower the effectiveness of current monoclonal antibody treatments and vaccines.

Researchers are intensely investigating whether there will be reduced vaccine efficacy against these variants. While most vaccines seem to remain effective against the U.K. variant, one recent study showed that the AstraZeneca vaccine lacks efficacy in preventing mild to moderate COVID-19 due to the B.1.351 South African variant.

On the other hand, Pfizer recently announced data from a subset of volunteers in South Africa that supports high efficacy of its mRNA vaccine against the B.1.351 variant. Other encouraging news is that T-cell immune responses elicited by natural SARS-CoV-2 infection or mRNA vaccination recognize all three U.K., South Africa, and Brazil variants. This suggests that even with reduced neutralizing antibody activity, T-cell responses stimulated by vaccination or natural infection will provide a degree of protection against such variants.

Stay vigilant, and get vaccinated

What does this all mean? While current vaccines may not prevent mild symptomatic COVID-19 caused by these variants, they will likely prevent moderate and severe disease, and in particular hospitalizations and deaths. That is the good news.

However, it is imperative to assume that current SARS-CoV-2 variants will likely continue to evolve and adapt. In a recent survey of 77 epidemiologists from 28 countries, the majority believed that within a year current vaccines could need to be updated to better handle new variants, and that low vaccine coverage will likely facilitate the emergence of such variants.

What do we need to do? We need to keep doing what we have been doing: using masks, avoiding poorly ventilated areas, and practicing social distancing techniques to slow transmission and avert further waves driven by these new variants. We also need to vaccinate as many people in as many places and as soon as possible to reduce the number of cases and the likelihood for the virus to generate new variants and escape mutants. And for that, it is vital that public health officials, governments and nongovernmental organizations address vaccine hesitancy and equity both locally and globally.

[Insight, in your inbox each day. You can get it with The Conversation’s email newsletter.]The Conversation

Paulo Verardi, Associate Professor of Virology and Vaccinology, University of Connecticut

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Why variants are most likely to blame for India’s COVID surge


Rajib Dasgupta, Jawaharlal Nehru University With more than 300,000 new COVID cases a day and hospitals and crematoria facing collapse, Director-General of the World Health Organization Tedros Adhanom Ghebreyesus has called the situation in India “beyond heartbreaking”.

India’s government has blamed the people for not following COVID-safe public health directives, but recent data shows mask use has only fallen by 10 percentage points, from a high of 71% in August 2020 to a low of 61% by the end of February.

And the mobility index increased by about 20 percentage points, although most sectors of the economy and activity had opened up. These are modest changes and do not adequately explain the huge increase in cases.




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A more likely explanation is the impact of variants that are more transmissible than the original SARS-CoV-2 virus.

Variants in India

Viruses keep changing and adapting through mutations, and new variants of a virus are expected and tracked in a pandemic situation such as this.

The Indian SARS-CoV-2 Genomics Consortium (INSACOG), a group of ten national laboratories, was set up in December 2020 to monitor genetic variations in the coronavirus. The labs are required to sequence 5% of COVID-positive samples from states and 100% of positive samples from international travellers.

The United Kingdom is currently testing about 8% of its positive samples and the United States about 4%. India has been testing about 1% altogether. INSACOG has so far tested 15,133 SARS-CoV-2 genomes. This means of every 1,000 cases, the UK has sequenced 79.5, the US 8.59, and India only 0.0552.

In the final week of December, India detected six cases of the UK variant (B.1.1.7) among international travellers.




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The current second wave started in the northwestern state of Punjab in the first half of February and has not yet plateaued. One of the advisers to the Punjab government confirmed that more than 80% of the cases were attributed to the UK variant.

Significantly, the most affected districts are from Punjab’s Doaba region, known as the NRI (non-resident Indian) belt. An estimated 60-70% of the families in these districts have relatives abroad, mostly in the UK or Canada, and a high volume of travel to and from these countries.




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B.1.617, or what has been called the “Indian double mutation”, has drawn attention because it contains two mutations (known as E484Q and L452R) that have been linked to increased transmissibility and an ability to evade our immune system.

Many experts in India now think this is driving the surge.

Even as India’s health ministry announced the detection of the mutants on March 24, it went on to add:

[…] these have not been detected in numbers sufficient to either establish or direct relationship or explain the rapid increase in cases in some states.

The head of the Indian Council of Medical Research said there was no reason for panic because mutations are sporadic, and not significant. That day, the states of Maharashtra and Punjab accounted for 62.5% and 4.5% of 40,715 new cases, respectively.




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Across the world, several key mutant strains have emerged thanks to ongoing virus replication in humans. Both ability to replicate and transmit, and a better ability to escape our immune systems, led to the variants establishing themselves as dominant strains across geographies and populations.

The UK variant (B.1.1.7) is at least 30% more transmissible. At a recent webinar, Indian experts observed the “Indian strain” (B.1.617) is similarly transmissible to the UK variant, but there is little evidence so far of it being more lethal than the original virus.

Why higher transmissibility is so concerning

According to epidemiologist Adam Kucharski at the London School of Hygiene and Tropical Medicine, the conundrum is this:

[…] suppose 10,000 people are infected in a city and each infects 1.1 other people on average, the low end for the estimated rate of infection in England. After a month, 16,000 people would have been infected. If the infection fatality rate is 0.8%, as it was in England at the end of the first wave of infections, it would mean 128 deaths. With a variant that is 50% more deadly, those 16,000 cases would result in 192 deaths. But with a variant that is 50% more transmissible, though no more deadly, there would be 122,000 cases after a month, leading to 976 deaths.

In all likelihood, this is the current Indian scenario: a higher overall death count despite the variants being no more fatal in relative terms.

Setting up a genomic surveillance system and consistently testing 5% of the positive samples is an expensive but important tool in the journey ahead. This can help us identify emerging hotspots, track transmission and enable nimble-footed decision-making and tailored interventions.The Conversation

Rajib Dasgupta, Chairperson, Centre of Social Medicine and Community Health, Jawaharlal Nehru University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

New COVID variants have changed the game, and vaccines will not be enough. We need global ‘maximum suppression’


Daniel Cole/AP

Susan Michie, UCL; Chris Bullen, University of Auckland; Jeffrey V Lazarus, Barcelona Institute for Global Health (ISGlobal); John N. Lavis, McMaster University; John Thwaites, Monash University; Liam Smith, Monash University; Salim Abdool Karim, Centre for the AIDS Program of Research in South Africa (CAPRISA), and Yanis Ben Amor, Columbia UniversityAt the end of 2020, there was a strong hope that high levels of vaccination would see humanity finally gain the upper hand over SARS-CoV-2, the virus that causes COVID-19. In an ideal scenario, the virus would then be contained at very low levels without further societal disruption or significant numbers of deaths.

But since then, new “variants of concern” have emerged and spread worldwide, putting current pandemic control efforts, including vaccination, at risk of being derailed.

Put simply, the game has changed, and a successful global rollout of current vaccines by itself is no longer a guarantee of victory.

No one is truly safe from COVID-19 until everyone is safe. We are in a race against time to get global transmission rates low enough to prevent the emergence and spread of new variants. The danger is that variants will arise that can overcome the immunity conferred by vaccinations or prior infection.

What’s more, many countries lack the capacity to track emerging variants via genomic surveillance. This means the situation may be even more serious than it appears.

As members of the Lancet COVID-19 Commission Taskforce on Public Health, we call for urgent action in response to the new variants. These new variants mean we cannot rely on the vaccines alone to provide protection but must maintain strong public health measures to reduce the risk from these variants. At the same time, we need to accelerate the vaccine program in all countries in an equitable way.

Together, these strategies will deliver “maximum suppression” of the virus.

What are ‘variants of concern’?

Genetic mutations of viruses like SARS-CoV-2 emerge frequently, but some variants are labelled “variants of concern”, because they can reinfect people who have had a previous infection or vaccination, or are more transmissible or can lead to more severe disease.




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There are currently at least three documented SARS-CoV-2 variants of concern:

  • B.1.351, first reported in South Africa in December 2020
  • B.1.1.7, first reported in the United Kingdom in December 2020
  • P.1, first identified in Japan among travellers from Brazil in January 2021.

Similar mutations are arising in different countries simultaneously, meaning not even border controls and high vaccination rates can necessarily protect countries from home-grown variants, including variants of concern, where there is substantial community transmission.

If there are high transmission levels, and hence extensive replication of SARS-CoV-2, anywhere in the world, more variants of concern will inevitably arise and the more infectious variants will dominate. With international mobility, these variants will spread.

South Africa’s experience suggests that past infection with SARS-CoV-2 offers only partial protection against the B.1.351 variant, and it is about 50% more transmissible than pre-existing variants. The B.1.351 variant has already been detected in at least 48 countries as of March 2021.

The impact of the new variants on the effectiveness of vaccines is still not clear. Recent real-world evidence from the UK suggests both the Pfizer and AstraZeneca vaccines provide significant protection against severe disease and hospitalisations from the B.1.1.7 variant.

On the other hand, the B.1.351 variant seems to reduce the efficacy of the AstraZeneca vaccine against mild to moderate illness. We do not yet have clear evidence on whether it also reduces effectiveness against severe disease.

For these reasons, reducing community transmission is vital. No single action is sufficient to prevent the virus’s spread; we must maintain strong public health measures in tandem with vaccination programs in every country.

Why we need maximum suppression

Each time the virus replicates, there is an opportunity for a mutation to occur. And as we are already seeing around the world, some of the resulting variants risk eroding the effectiveness of vaccines.

That’s why we have called for a global strategy of “maximum suppression”.

Public health leaders should focus on efforts that maximally suppress viral infection rates, thus helping to prevent the emergence of mutations that can become new variants of concern.

Prompt vaccine rollouts alone will not be enough to achieve this; continued public health measures, such as face masks and physical distancing, will be vital too. Ventilation of indoor spaces is important, some of which is under people’s control, some of which will require adjustments to buildings.

Fair access to vaccines

Global equity in vaccine access is vital too. High-income countries should support multilateral mechanisms such as the COVAX facility, donate excess vaccines to low- and middle- income countries, and support increased vaccine production.

However, to prevent the emergence of viral variants of concern, it may be necessary to prioritise countries or regions with the highest disease prevalence and transmission levels, where the risk of such variants emerging is greatest.




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Those with control over health-care resources, services and systems should ensure support is available for health professionals to manage increased hospitalisations over shorter periods during surges without reducing care for non-COVID-19 patients.

Health systems must be better prepared against future variants. Suppression efforts should be accompanied by:

  • genomic surveillance programs to identify and quickly characterise emerging variants in as many countries as possible around the world
  • rapid large-scale “second-generation” vaccine programs and increased production capacity that can support equity in vaccine distribution
  • studies of vaccine effectiveness on existing and new variants of concern
  • adapting public health measures (such as double masking) and re-committing to health system arrangements (such as ensuring personal protective equipment for health staff)
  • behavioural, environmental, social and systems interventions, such as enabling ventilation, distancing between people, and an effective find, test, trace, isolate and support system.



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COVID-19 variants of concern have changed the game. We need to recognise and act on this if we as a global society are to avoid future waves of infections, yet more lockdowns and restrictions, and avoidable illness and death.The Conversation

Susan Michie, Professor of Health Psychology and Director of the UCL Centre for Behaviour Change, UCL; Chris Bullen, Professor of Public Health, University of Auckland; Jeffrey V Lazarus, Associate Research Professor, Barcelona Institute for Global Health (ISGlobal); John N. Lavis, Professor and Canada Research Chair in Evidence-Informed Health Systems, McMaster University; John Thwaites, Chair, Monash Sustainable Development Institute & ClimateWorks Australia, Monash University; Liam Smith, Director, BehaviourWorks, Monash Sustainable Development Institute, Monash University; Salim Abdool Karim, Director, Centre for the AIDS Program of Research in South Africa (CAPRISA), and Yanis Ben Amor, Assistant Professor of Global Health and Microbiological Sciences, Executive Director – Center for Sustainable Development (Earth Institute), Columbia University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Flu vaccines are updated every year. We can learn from this process as we respond to COVID variants


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Sheena G. Sullivan, WHO Collaborating Centre for Reference and Research on Influenza and Kanta Subbarao, The Peter Doherty Institute for Infection and ImmunityWhile the future of the pandemic remains uncertain, we’ll probably have to live with COVID-19 for some time.

We face a range of possible scenarios. At the most optimistic end of the spectrum, new vaccines will protect against all current and future variants of concern. At the other extreme, we’ll see the frequent emergence and spread of new variants, against which existing vaccines will have limited effect.

It’s likely we’ll land somewhere in the middle.

Notably, although new variants do threaten the effectiveness of COVID-19 vaccines, decades of experience updating influenza vaccines can inform our global response.

Evolving variants

We’re still learning about how new viral variants affect vaccine effectiveness.

The B.1.1.7 variant, which emerged in the United Kingdom in late 2020, is more infectious and deadlier than the original strain of SARS-CoV-2 (the virus that causes COVID-19). Fortunately, though, preliminary data indicates COVID vaccines still work well against it (although this research hasn’t yet been peer-reviewed).

Meanwhile, a study published yesterday found the Oxford/AstraZeneca vaccine is ineffective against mild or moderate COVID-19 caused by the B.1.351 variant. This study was done in South Africa, where this variant emerged and is currently dominant.

Results of clinical trials of the Novavax and Johnson & Johnson vaccines indicated about 60% overall effectiveness in South Africa, according to the vaccine manufacturers. This is lower than the 70-90% reported in the United States and the UK.




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Notwithstanding differences in each country’s health systems and health status of their populations, which may explain some of the differences, this is a concerning trend.

Reassuringly, Johnson & Johnson reported 85% effectiveness against severe disease, regardless of country or variant. This suggests while some existing vaccines may not entirely prevent infection and mild illness caused by certain variants, they may still protect from severe illness and reduce the load on hospitals.

But if new variants continue to emerge, COVID vaccines may need to be reformulated regularly.

Several manufacturers have announced they’re already working on boosters designed to be more effective against the B.1.351 variant, which has now been detected in 48 countries.

An illustration of SARS-CoV-2, the virus that causes COVID-19.
New variants of SARS-CoV-2 pose a threat to vaccine effectiveness.
Shutterstock

Understanding the global spread of new variants

To develop updated vaccines that best respond to new variants, we need to understand the spread of the variants around the world. This is a big challenge.

To know which variant a person is infected with we need to sequence the viral genome (the genetic material of the virus), which can be expensive and time-consuming. While global access to diagnostic tests is improving, huge disparities in access to sequencing technology remain.

These disparities are reflected in information we have about currently circulating variants. Another variant of concern, P.1, shares some of the key mutations present in the B.1.351 variant. So it may present similar problems with vaccine effectiveness, although clinical trial data are lacking.

The P.1 variant was first identified in Tokyo in travellers from Brazil in January 2021. However, we now understand it’s been circulating in Brazil since early December 2020.

Around the world there have only been about 700 shared P.1 sequences, compared with more than 150,000 sequences of the B.1.1.7 variant. There are certainly far more than 700 cases of P.1, but resource constraints mean we’re not getting the full picture of how different variants are spreading.




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What’s the difference between mutations, variants and strains? A guide to COVID terminology


Further, while sequencing capacity has been massively scaled up during the pandemic, it cannot determine whether a mutation will change how the SARS-CoV-2 virus interacts with our immune system. This requires more lab work, called “antigenic characterisation”, with limited global capacity to undertake this specialised testing.

Patchy understanding of the nature and spread of new variants may lead manufacturers to focus on modifying their vaccines towards better-known variants, which at the moment are those found in more developed countries. These vaccines may be less effective in developing countries where less well-understood variants may predominate.

So we need ongoing, coordinated and global sharing of sequencing information and virus samples to track virus evolution and vaccine effectiveness.

Lessons from influenza surveillance

We’ve encountered similar challenges in the development of influenza vaccines, which are updated annually to ensure they remain effective against new strains.

Existing ‘flu surveillance has already been adapted to some degree for COVID. The Global Initiative on Sharing All Influenza Data, an online platform set up in 2008, has become the main tool used to share SARS-CoV-2 sequences.

In the case of influenza, we’ve seen a coordinated global response. The Global Influenza Surveillance and Response System, established in 1952, includes more than 140 laboratories across 114 countries. These labs share information on influenza viruses with five WHO Collaborating Centres, including genomic sequences, antigenic characterisation, and epidemiological data.

The WHO collaborating centres are then responsible for conducting further analysis to guide vaccine composition, inform regular global updates on circulating strains, and provide training and support to national laboratories.

Twice a year, WHO makes recommendations on vaccine composition for the following influenza season. These recommendations are not binding, but national regulatory agencies and manufacturers have consistently used them to develop ‘flu vaccines for more than 40 years.

A health-care worker dressed in PPE draws up a vaccine.
COVID vaccines are now rolling out around the world.
Shutterstock

A similar approach may prove useful for COVID-19. So far, manufacturers have made decisions about COVID-19 vaccine composition in consultation with national regulatory agencies. Developing a global framework to identify variants that warrant a vaccine update will allow manufacturers to focus on the technical aspects of vaccine development.

In turn, this will facilitate more rapid rollout of vaccines — and importantly, vaccines that are effective against variants circulating around the world, rather than only those affecting developed countries.

Some positives

Despite these challenges, current COVID-19 vaccines appear to provide strong protection against moderate to severe illness caused by most variants, and are likely to provide at least reasonable protection against others.

Also, SARS-CoV-2 mutates more slowly than influenza, meaning vaccines may need to be updated less frequently.

And finally, it will be easier and faster to modify new mRNA and vectored SARS-CoV-2 vaccines than traditional influenza vaccines.




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The Conversation


Sheena G. Sullivan, Epidemiologist, WHO Collaborating Centre for Reference and Research on Influenza and Kanta Subbarao, Professor, The Peter Doherty Institute for Infection and Immunity

This article is republished from The Conversation under a Creative Commons license. Read the original article.

What’s the difference between mutations, variants and strains? A guide to COVID terminology



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Lara Herrero, Griffith University and Eugene Madzokere, Griffith University

Living through a global pandemic over the past year has seen all of us expanding our vocabularies. We now understand terms like PPE, social distancing and contact tracing.

But just when perhaps we thought we had a handle on most of the terminology, we’re faced with another set of new words: mutation, variant and strain.

So, what do they mean?

The genetic material of SARS-CoV-2, the coronavirus that causes COVID-19, is called ribonucleic acid (RNA). To replicate, and therefore establish infection, SARS-CoV-2 RNA must hijack a host cell and use the cell’s machinery to duplicate itself.

Errors often occur during the process of duplicating the viral RNA. This results in viruses that are similar but not exact copies of the original virus. These errors in the viral RNA are called mutations, and viruses with these mutations are called variants. Variants could differ by a single or many mutations.

Not all mutations have the same effect. To understand this better, we need to understand the basics of our genetic code (DNA for humans; RNA for SARS-CoV-2). This code is like a blueprint on which all organisms are built. When a mutation occurs at a single point, it won’t necessarily change any of the building blocks (called amino acids). In this case, it won’t change how the organism (human or virus) is built.

On occasion though, these single mutations occur in a part of the virus RNA that causes a change in a particular building block. In some cases, there could be many mutations that together alter the building block.




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A variant is a referred to as a strain when it shows distinct physical properties. Put simply, a strain is a variant that is built differently, and so behaves differently, to its parent virus. These behavioural differences can be subtle or obvious.

For example, these differences could involve a variant binding to a different cell receptor, or binding more strongly to a receptor, or replicating more quickly, or transmitting more efficiently, and so on.

Essentially, all strains are variants, but not all variants are strains.

A diagram depicting the evolution from mutation to variant to strain.
Viruses with mutations become variants. If the variant displays different physical properties to the original virus, we call it a new strain.
Lara Herrero, created using BioRender, Author provided

Common variants (which are also strains)

Three of the most common SARS-CoV-2 variants are what we’ve come to know as the UK variant (B.1.1.7), the South African variant (B.1.351) and the Brazilian variant (P.1). Each contains several different mutations.

Let’s look at the UK variant as an example. This variant has a large number of mutations in the spike protein, which aids the virus in its effort to invade human cells.

The increased transmission of the UK variant is believed to be associated with a mutation called N501Y, which allows SARS-CoV-2 to bind more readily to the human receptor ACE2, the entry point for SARS-CoV-2 to a wide range of human cells.

This variant is now widespread in more than 70 countries, and has recently been detected in Australia.

While we commonly call it the “UK variant” (which it is), it’s also a strain because it displays different behaviours to the parental strain.

We’ve got lots more to learn

There is some confusion around how best to use these terms. Given all strains are variants (but not all variants are strains), it makes sense the term variant is more common. But when the science shows these variants behave differently, it would be more accurate to call them strains.

Pleasingly, the World Health Organisation and health departments in Australia appear to be using the terms correctly in the context of SARS-CoV-2.




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The big question everyone is asking at the moment is how the new variants and strains will affect the efficacy of our COVID vaccines.

The scientific community is uncovering more information about emerging mutations, variants and strains all the time, and leading vaccine developers are testing and evaluating the efficacy of their vaccines in this light.

Some recently licensed vaccines appear to protect well against the UK variant but recent data from Novavax, Johnson & Johnson and Oxford/AstraZeneca indicates possible reduced protection against the South African variant.

Health authorities in South Africa recently paused their rollout of the Oxford/AstraZeneca vaccine for this reason. However, its too early to tell what impact, if any, this will have on Australia’s vaccine plans.

The vaccine rollout in Australia will assess all information as it comes to light and ensure optimal available protection for the population.




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The Conversation


Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith University and Eugene Madzokere, PhD Candidate in Virology, Griffith University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Are vaccines already helping contain COVID? Early signs say yes, but mutations will be challenging


Maximilian de Courten, Victoria University; Maja Husaric, Victoria University, and Vasso Apostolopoulos, Victoria University

More than 130 million COVID vaccine doses have been administered worldwide already, according to the University of Oxford’s “Our World in Data” vaccination tracker.

Israel, the United Kingdom, the United States, the United Arab Emirates and China are leading this huge global effort.

COVID vaccines were initially tested and approved on their ability to reduce the severity of the disease.

However, the long-term goal of vaccination is to decrease infection rates and eliminate the virus.

Excitingly, early signs suggest vaccines are already helping drive down infection rates in some countries, including Israel and the UK.

In saying that, it’s early days, and some preliminary data suggest countries might have to update their vaccine strategies to deal with emerging variants of the virus.

Israel is leading the way

The US (43 million doses), China (40 million) and the UK (13 million) have administered the most doses in total.

However, these numbers don’t take into account population size, so looking at the number of doses injected per 100 people is more meaningful.

Here, the league table is currently topped by Israel, with around 67 vaccination doses administered per 100 people.

Almost 25% of the population are fully vaccinated with both doses. And all this in just five weeks.

Israel aims to vaccinate everyone over the age of 16 and reach at least 80% of its nine million people by May this year.

Reaching at least 70% of the population via vaccination (and/or natural infection) is needed for herd immunity for COVID, according to initial modelling by University of Chicago researchers in May last year.

However, given more infectious variants of the virus have emerged, we may need to vaccinate an even higher proportion of the population to reach herd immunity.

Infection rates are falling

So far, Israel is solely using the Pfizer/BioNTech vaccine. Interim reports from the country suggest the vaccine rollout is linked to a fall in infections in people over 60 years old.

It can be tricky to separate the effects of public health measures such as lockdowns versus the effects of vaccination.

But because the fall is most pronounced in older people who were first in line to receive the vaccine, data suggest this is also partly due to the vaccine, and not just the country’s current restrictions. A team of Israeli researchers found larger falls in infections and hospitalisations after the vaccinations than occurred during previous lockdowns.

Only 0.07% of the 750,000 over-60s vaccinated tested positive for COVID, according to Israeli Ministry of Health data released last week. And only 38 people, or 0.005%, fell ill and required hospitalisation. The chance of testing positive for COVID two weeks after receiving the first dose was 33% lower than in those not vaccinated.

The UK is also showing positive signs

The UK has administered 19.4 doses per 100 people. Around 13.2 million people (or one in five adults) have received the first dose, and 0.5 million have received the second dose.

It’s currently using both the Pfizer/BioNTech and Oxford University/AstraZeneca vaccines in its rollout.

The infection rate appears to be decreasing substantially. The current daily infection growth rate is falling by between 2-5%, and the R number is estimated to be between 0.7 and 1 (an R number of less than 1 means daily new cases will decrease over time).

However, it’s difficult to determine whether these numbers are due to the lockdown or vaccinations. It’s too early to tell whether vaccines are slowing transmission, but the signs are encouraging.

According to data from the Oxford/AstraZeneca vaccine group, released as a preprint with The Lancet last week and yet to be peer reviewed, its vaccine is showing signs of reducing transmission. The shot was associated with a 67% reduction in transmission among vaccinated volunteers in clinical trials in the UK.

It’s early days, but authors of the study suggest the vaccine may have a “substantial” effect on reducing rates of transmission in the future.

In saying that, preliminary data suggest it offers minimal protection against mild or moderate illness caused by the South African variant.




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What threatens the successful rollout of vaccines?

There are three main problems that might hinder the success of this global vaccination drive.

1. Vaccine development, manufacturing, distribution and delivery

The world’s population over the age of five is currently estimated at seven billion people. If we need to vaccinate at least 70% of them to achieve herd immunity, we need to reach around five billion people.

This is an enormous undertaking, so vaccine production and availability are crucial. Many countries face the massive challenge of producing or securing enough vaccines to immunise all their citizens.

Generally, wealthier countries that could afford to make advanced purchase agreements with vaccine producers — or who could manufacture a vaccine domestically — have been the first to start COVID vaccinations.

Unfortunately, partial vaccination of the world’s population won’t achieve herd immunity. One modelling study suggests if high-income countries exclusively acquire the first two billion doses without regard for vaccine equity, the number of COVID deaths could double worldwide.

2. Administering, monitoring, and reporting adverse effects

Vaccinating a large number of citizens quickly can’t be done with existing health institutions alone.

It’s urgent we enable alternative sites such as halls and sporting venues to be used as mass vaccination sites. We also need to allow a range of health professions such as medical students, public health officials and pharmacists to administer doses to help speed up the process.

And once vaccines have been administered, it’s crucial we monitor efficacy and report on any adverse effects, which will require additional resources.




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3. Vaccine effectiveness and virus mutation

The effectiveness of vaccines can be hindered by mutations of the virus. COVID variants originating in Brazil, South Africa, and the UK have triggered huge concern worldwide.

There’s early evidence some of our current crop of COVID vaccines respond less effectively to certain variants, though most of these data are preliminary and are still emerging.




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UK, South African, Brazilian: a virologist explains each COVID variant and what they mean for the pandemic


If vaccines become less effective, new vaccines will need to be developed either including a booster dose incorporating the region of the mutated virus, or reformulating existing vaccines to include the mutated strains.

This, however, isn’t uncommon — flu vaccines are required to be updated regularly in order to increase protective capacity against new mutated strains.The Conversation

Maximilian de Courten, Professor in Global Public Health and Director of the Mitchell Institute, Victoria University; Maja Husaric, Senior Lecturer; MD, Victoria University, and Vasso Apostolopoulos, Professor of Immunology and Pro Vice-Chancellor, Research Partnerships, Victoria University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

UK, South African, Brazilian: a virologist explains each COVID variant and what they mean for the pandemic


Kirsty Short, The University of Queensland

Australia has recently seen SARS-CoV-2 (the virus that causes COVID-19) escape several times from hotel quarantine, including in Brisbane, Perth and Melbourne.

These incidents have been particularly concerning because they involved people infected with “variants” of the virus.

But what exactly are these variants, and how concerned should we be?

What’s a variant?

Viruses can’t replicate and spread on their own. They need a host, and they need to hijack the cells of the host to replicate. When they replicate in a host, they face the challenge of duplicating their genetic material. For many viruses, this isn’t an exact process and their offspring often contain errors — meaning they’re not exact copies of the original virus.

These errors are referred to as mutations, and viruses with these mutations are called variants. Often, these mutations don’t affect the biological properties of the virus. That is, they don’t have any effect on how the virus replicates or causes disease.




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Some mutations can impair the virus’s ability to replicate and/or transmit. Variants with such mutations are quickly lost from the viral population.

Occasionally, however, variants emerge with an advantageous mutation, one that means it’s better at replicating, transmitting, and/or evading our immune system. These variants have a selective advantage (in biological terms, they are “fitter” than other variants) and may rapidly become the dominant viral strain.

There’s some concern we’re seeing a growing number of variants with advantageous mutations, contributing to the severity of the COVID-19 pandemic.

Here’s a look at the main three variants you might’ve heard about in the media.

The ‘UK variant’ — B.1.1.7

This variant was first detected in the United Kingdom towards the end of 2020. It has a large number of mutations, many of which involve the virus’ spike protein, which helps the virus invade human cells.

It has spread rapidly throughout the UK since it emerged, and to at least 70 other countries, including Australia.

The fact it has spread so rapidly, and quickly replaced other circulating variants, suggests it has some sort of selective advantage over other variants.

After examining the evidence surrounding the new variant, the UK New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) concluded it “had moderate confidence” the variant is substantially more infectious than other variants.

This may be the result of one of the mutations in the spike protein of the variant — a mutation called “N501Y”. One preprint manuscript, uploaded last month and yet to be peer reviewed, found N501Y is associated with increased binding of the virus to a receptor found on the surface on many of our cells, called “ACE2”. This could mean the variant is even more efficient at entering our cells.

Although initially the variant wasn’t associated with more severe COVID symptoms, more recent data have led NERVTAG to conclude there’s “a realistic possibility” that infection with the variant “is associated with an increased risk of death” compared with non B.1.1.7 viruses.

However, the group acknowledged there are limitations of the available data, and this remains an evolving situation.

The ‘South African variant’ — B.1.351

This variant was first detected in Nelson Mandela Bay, South Africa, in October 2020. Since then it has been found in more than 30 countries.

Similar to the UK variant, it quickly outcompeted other SARS-CoV-2 variants in South Africa. It now accounts for more than 90% of SARS-CoV-2 samples in South Africa that undergo genetic sequencing.

Like the UK variant, it also has the N501Y mutation in the spike protein, meaning it’s more efficient at gaining access to our cells to replicate. This may help to explain its rapid spread.

It also contains several other concerning mutations. Two of these, called “E484K” and “K417N”, are bad news for our immune system. They can reduce how well our antibodies bind to the virus (though this is also based on preprint data awaiting peer review).

But there’s no evidence yet to suggest the South African variant is more deadly than the original variants.

The ‘Brazilian variant’ — P.1

This variant was first detected in Japan in a group of Brazilian travellers in January 2021.

It’s now highly prevalent in the Brazilian state of Amazonas, and has been detected in countries including South Korea and the United States.

Like the South African variant, the Brazilian variant has the spike protein mutations N501Y, E484K and K417N (as well as numerous other mutations).

While there’s no evidence this variant causes more severe disease, there’s concern it has facilitated a wave of reinfections in Manaus, the largest city in Amazonas, which was thought to have reached “herd immunity” in October last year.

What does this mean for vaccines?

Major vaccine developers are testing the efficacy of their vaccines against these and other variants. Generally, the currently licensed vaccines protect relatively well against the UK variant.

But recent phase 2/3 data from both Novavax and Johnson & Johnson suggest reduced protection against the South African variant. The Oxford/AstraZeneca vaccine group also released data over the weekend suggesting its vaccine offers only minimal protection against mild-moderate disease caused by this variant.




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However, it’s important to recognise reduced protection doesn’t mean no protection at all, and that data are still emerging.

What’s more, numerous vaccine manufacturers are now investigating whether tweaks to the vaccines can improve their performance against the emerging variants.

The take-home message is that variants will emerge, and we need to closely monitor their spread. However, there’s every indication we’ll be able to adapt our vaccine strategies to protect against these and future variants.The Conversation

Kirsty Short, Senior Lecturer, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Why more contagious variants are emerging now, more than a year into the COVID-19 pandemic



Shutterstock/Lightspring

David Welch, University of Auckland; Jemma Geoghegan, University of Otago; Joep de Ligt, ESR, and Nigel French, Massey University

New variants of SARS-CoV-2 have now evaded New Zealand’s border protections twice to spread into the community.

In the most recent outbreak, which placed Auckland into an alert level 3 lockdown, there are three active community cases of the more infectious B.1.1.7 lineage.

While we have seen the virus mutate over the entire course of the pandemic, it was not until mid-December 2020 that variants with measurably different behaviour emerged.

There are several reasons for this, including the continued exponential rise in cases globally. Every COVID-19 case gives the virus a chance to mutate, and if the number of infections continues to rise, more new variants are likely to emerge.

Pressure to mutate

The genetic code of SARS-CoV-2 is a string of RNA of about 30,000 bases, or letters. When the virus enters our cells, it hijacks them to make thousands of copies of itself, but the copying process is not perfect.

Mistakes, or mutations, happen on average once every couple of weeks in any chain of transmission. Most are changes in a single letter and don’t result in a notable difference, but some will change the physical form of the virus, with possible knock-on effects to how the new variant behaves.




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We know about these variants thanks to the sequencing efforts from different countries and their open sharing of this knowledge. The variants that have arisen recently — known as B.1.1.7 (first identified in the UK), B.1.351 (identified in South Africa) and P.1 (identified in Brazil) — all have a large number of mutations that have physically altered the virus.

Graph showing the rise in new variants of the virus that causes COVID-19
This graph shows the frequency of SARS-CoV-2 sequences deposited on the global database GISAID (visualised by Nextstrain). The three ribbons at the bottom right correspond to variants P.1 (red, also known as 501Y.V1), B.1.1.7 (orange, also known as 501Y.V2), and B.1.351 (yellowy-orange, also known as 501Y.V1).
Nextstrain, CC BY-SA

A number of these changes are on the outside of the virus, in the spike proteins it uses to infect cells. Such changes can also undermine our immune system’s ability to detect these new versions of the virus when it has only seen the old version.

The most obvious reason why new variants have been emerging recently is that the number of global cases increased massively in the last quarter of 2020. There were about 35 million cases recorded worldwide in the first nine months of 2020, but it took just two months to double that number. We are well on the way to doubling that number again soon.

Evading rising levels of immunity

A second reason is that the virus is responding to immunity that has started to build up in the population. Our immune system plays an important role in driving which mutations survive and are transmitted.

The immune system is constantly trying to identify and kill the virus, which can only infect new people if it escapes detection. While mutations occur randomly, ones that lead to a more transmissible variant or those that escape our immune system are preferentially selected and more likely to persist.

The mutations that characterise B.1.1.7, B.1.351 and P.1 have been shown to spread faster (especially B.1.1.7) and initial evidence points to a difference in the immune response (though not in B.1.1.7).

Another indication that immunity plays a big role is that the B.1.351 and P.1 variants came to prominence in areas with large first waves of COVID-19 where the population developed higher levels of immunity.

Lights as a tribute to victioms of COVID-19 in Brazil
Special lighting will honour victims of COVID-19 during the cancelled carnival period in Rio de Janeiro.
Wagner Meier/Getty Images

P.1 was identified in Brazil where up to 70% of the population were infected during the first wave. B.1.351 quickly became the dominant strain in the Eastern Cape region of South Africa which was similarly hard hit.

The new variants could infect a greater number of people than the original wild type of the virus, which might infect only people who had never been infected before.

This is one of the reasons why historically herd immunity for a new virus has not occurred through “natural disease progression” but only through vaccination.




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The final part of the story is the fact that two of these variants (B.1.1.7 and P.1) differ by as many as 25 mutations from the closest known SARS-CoV-2 sequences. This is very unusual given that most viral sequences we see are within just a few mutations of others.

Such a rapid increase in diversity has been observed in chronic COVID-19 infections in immunocompromised hosts. Most people are ill for a week or two, but a few have to fight the disease for months. During that time, the virus continues to evolve, sometimes very quickly as a weakened immune system presents all sorts of challenges to the virus but fails to kill it off.

This kind of infection presents a “training ground” for the virus, as it continually adapts.

Will we see more new variants?

As long as the virus is around, it will continue to mutate. With vaccine protection and natural immunity in a growing number of people, there is greater pressure on virus variants that evade our immune defences.

The rate of new mutations varies greatly between viruses. The overall mutation rate of SARS-CoV-2 is about half that of the influenza virus and much slower than HIV. But the overall mutation rate doesn’t tell us everything. What really matters is the rate of mutations that physically alter the virus.

There is some early evidence this rate is about the same in SARS-CoV-2 as in influenza viruses. One reason for this is that SARS-CoV-2 has only recently jumped to people and is not yet “optimised” to spread in humans.

Essentially the original virus was only a few mutations away from better fitness, and there may be further easy changes that could make it even better adapted to humans. Once the virus is through this initial adaptation phase, there will be fewer opportunities for easy, fitness-improving changes and new variants may appear less frequently.

The variants that have been characterised so far are likely only a small subset of those in circulation. It is no coincidence they are known from countries with comprehensive sequencing programmes (notably the UK).

But the new variants are not the main driver of transmission globally. Most of the world is still susceptible to any variant of SARS-CoV-2, including the original version. The protective measures we have used successfully in Aotearoa to control the virus continue to work for any variant.

The best way to protect against all current variants and to prevent the emergence of further variants is to drive down the number of cases through ongoing control measures and vaccination.The Conversation

David Welch, Senior Lecturer, University of Auckland; Jemma Geoghegan, Senior Lecturer and Associate Scientist at ESR, University of Otago; Joep de Ligt, Science Lead Genomics & Bioinformatics, ESR, and Nigel French, Professor of Food Safety and Veterinary Public Health, Massey University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Why the COVID-19 variants are so dangerous and how to stop them spreading



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Michael Plank, University of Canterbury and Shaun Hendy

With new, more infectious variants of COVID-19 detected around the world, and at New Zealand’s border, the risk of further level 3 or 4 lockdowns is increased if those viruses get into the community.

These include a variant called B.1.1.7 that has spread very quickly within the UK, with other new variants now observed in South Africa and Brazil.

Changes in the genetic code of viruses like COVID-19 occur all the time but most of these mutations don’t have any effect on how the disease spreads or its severity.

These changes can be useful because they leave a signature in the virus’s genetic code that allows us to trace how the virus has spread from one person to another.




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But the new variant detected in the UK is more transmissible than the original virus that was dominant in 2020. That means it spreads more easily from one person to another.

The good news is it does not cause more severe illness or have a higher fatality rate than the original variant. Evidence so far suggests vaccines will still be effective against it.

But the bad news is because it spreads more easily, it has the potential to infect many more people, causing more hospitalisations and deaths as a result.

Why variants that spread more easily are so dangerous

The average number of people an infected person with COVID-19 passes the virus on to — the so-called R number — is 40%-70% higher with B.1.1.7 than the original variant.

As the graph below shows, the mathematics of exponential growth means that even a small increase in the transmission rate gets compounded over time, quickly generating enormous growth in the number of cases.

A variant like B.1.1.7 with a higher transmission rate is actually more dangerous than one with a higher fatality rate.

Sure, a 50% increase in the fatality rate would cause 50% more deaths. But because of exponential growth, shown in the graph, a 50% increase in transmissibility causes 25 times more cases in just a couple of months if left unchecked.

That would lead to 25 times more deaths at the original mortality rate.

How do we know the new variant is more transmissible?

The number of cases of the B.1.1.7 variant has risen rapidly relative to the original variant.

This can happen for a number of reasons. The new variant might simply happen to be present in a part of the country or group of people who are spreading the virus more rapidly for some other reason.

It could have become resistant to immunity, meaning it could more easily re-infect people who have already had COVID-19. Or it might cause people to become infectious more quickly.

Researchers in the UK used mathematical models to test these hypotheses.

They found the explanation that fitted best with the data was that the new variant really is more transmissible. And they estimated a person with the new variant infects 56% more people on average than a person with the original variant.

Contact tracing data from the UK also showed more of the close contacts of someone with the new variant go on to be infected.

A sign at an airport saying flights from UK cancelled after new COVID-19 variant discovered,
Some countries cancelled flights from the UK over fears of the new COVID strain.
Shutterstock/rarrarorro

Patients with the new variant have also been found to carry more of the virus. Together, this provides strong evidence the B.1.1.7 variant is between 40% and 70% more transmissible than the original variant.

The variants found in South Africa and Brazil share some of the same mutations as the B.1.1.7 variant. There is some evidence they may also be more transmissible or better able to evade immunity.

But there is more uncertainty about these variants, partly because the data quality isn’t as high as in the UK, which is very good at doing genome sequencing.

What does this mean for New Zealand’s border controls?

The new variants have been detected in many countries, including in people in New Zealand’s managed isolation facilities.

There have previously been several cases of people working in these facilities picking up infections from recent arrivals.

The more transmissible variants arriving at the New Zealand border increase the risks to these workers, who in turn have a higher chance of passing the virus onto others in the community, amplifying the risk of a community outbreak.

In response, the government says international arrivals will require a negative test in the 72 hours prior to departure. They will also be required to take an arrival day test when they get to New Zealand.

These measures provide an extra layer in our defences against COVID-19.

How can we manage the risk?

The new variants spread in the same way as the original one: through close contacts between people, especially in crowded or poorly ventilated environments.

This means all the tools we have developed to fight the virus will still work. These include testing, contact tracing, masks and physical distancing.

How face masks make a difference.

But any variant that is more transmissible has a higher R number. To control an outbreak, we need to bring the R number under 1 and so we may need to use more of these tools to achieve this.




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For example, in the Auckland outbreak in August 2020, alert level 3 was enough to contain and eventually eliminate the outbreak. Our analysis showed alert level 3 reduced R to about 0.7.

If we had a similar outbreak with the new variant, R could be 50% higher which would mean it is above 1. In other words, we would likely need to use alert level 4 to contain an outbreak, and it might take longer to eliminate the virus than it has previously.

To give our contact tracers the best possible chance of containing a new outbreak without needing alert level 3 or 4, we all need do our bit. This means looking for QR codes when out about and using the app to scan them, as well as turning on Bluetooth. And it means staying at home and getting tested if you feel sick.The Conversation

Michael Plank, Professor in Applied Mathematics, University of Canterbury and Shaun Hendy, Professor of Physics

This article is republished from The Conversation under a Creative Commons license. Read the original article.