Covid-19: Will new strains make the virus more difficult to control?

Variants from UK, South Africa and Brazil an increasingly menacing threat

 

Two factors are increasingly worrying as the world desperately tries to control ever increasing spread of Covid-19: The first is the almost unbearable strain on health services; the second is growing evidence new variants are playing an insidious role in undermining the ability to control the pandemic in spite of vaccination being rolled out.

Why is travel so worrying at present?

There may be some indications cases in Ireland may be plateauing due to the latest lockdown but three variants threaten to dominate across the globe. Because of this international travel, if improperly controlled, becomes the big facilitator of Coronavirus spread.

The Government is considering a stricter regime for inward bound travellers amid growing concern about new strains that are a lot more infectious.

This week it will consider all aspects of travel regulations in light of concerns about new Covid-19 strains from the UK, South Africa and Brazil – 1,500 people travelled from Brazil to Ireland in the past two weeks. More than 35,000 people travelled to Ireland from the UK over the Christmas period.

A stricter regime on inward-bound travellers to make it mandatory to quarantine for 14 days in a hotel as implemented in Australia and New Zealand is likely to be considered because it has been shown to work.

Current restrictions mean inward passengers must be in receipt of a negative PCR Covid test result, taken within 72 hours of departure, while the Government advises against all travel to and from countries in South America. Passengers from the UK, South Africa or any countries in South America are advised to self isolate (stay in your room) for the full period of 14 days following their arrival into Ireland.

Mandatory isolation would be difficult to implement legally, but it has been implemented elsewhere.

Scientists said mutations would occur and probably would be an insignificant threat. What has changed?

A virus changes to stop the immune system detecting it, and in most cases they are not any more troublesome than the original version. They are carried in what are known as variants, strains which are detectable by mapping their genetic make-up.

Viruses are constantly acquiring small changes in their genetic code. Usually, these mutations have no effect, but occasionally they will alter how the virus behaves – which is what may have happened with the UK, Brazilian and South African variants.

A variant took over completely across the world during the first phase of the pandemic last year, but did not mean an increase in virulence or more deaths on top of those already occurring.

Clearly, some variants are much more transmissible but not more virulent in terms of causing death. The critical issue is when other factors are added to the mix variants can become extremely problematic – as has happened over recent weeks.

What does this mean for public health policy and restrictions during the pandemic?

So opening up economies after lockdown; cold weather driving people indoors, and a lot of social mixing taking place over the holiday season in crowded restaurants and poorly ventilated homes coincided with the emergence of variants. It adds hugely to the complexity of the task – some clinicians would describe it as a “perfect storm”.

In such circumstances, there is a particular risk that a new variant will become dominant and exploit opportunities to spread when transmission of the virus is already very high.

All this means the quicker we get the vaccine into people, the better. At present, there is a real menace in the form of variants outstripping vaccines in some countries including Ireland, as more and more pressure is heaped on under-resourced health services, notably hospitals and their ICU units.

Which Covid-19 variants pose a threat?

The UK variant (known as B117) is the most menacing variant in terms of proven transmissibility across the northern hemisphere; it established a presence here in a matter of weeks.

B117 carries 14 defining mutations including seven in the spike protein that mediates entry of the virus into human cells. This is a relatively large number of changes compared with the many variants in circulation globally. Initial analysis in the UK found this variant could be up to 80 per cent more transmissible.

The bottom line is the new variant is a fitter virus with increased transmissibility achieved by binding more easily to host cells.

This variant first appeared in Kent. One study which followed a single immunocompromised patient, detected important changes in the virus each time the patient received plasma treatment, raising the possibility the antibodies it contained placed additional pressure on the virus to mutate. However, this is less likely to happen in people with healthier immune systems.

BII7 may have been prevalent in other regions/countries for some time but went undetected and was not sequenced genetically to identify its distinguishing characteristics.

The other variants of concern arose in South African (B1351), which has been confirmed in Ireland, and Brazil (P1), which has yet to be found here.

There are two new variants in Brazil; one that is rampant but of little concern, and P1 which is a lot more vexatious. It has three key mutations in the spike receptor binding domain (RBD) that largely mirror some of the mutations experts are worried about in the South African variant.

The coronavirus RBD is one of the main targets for our immune defences and also the region targeted by vaccines.

Like the South African variant, the Brazilian one carries a mutation in the spike protein called E484K, which is not present in the UK strain.

The E484K mutation has been shown to reduce antibody recognition, helping the virus to bypass immune protection provided by prior infection or vaccination.

Are there symptom differences for people infected by the new variants?

So far there is nothing to suggest this current range of dominant variants are giving rise to more serious disease or elevated mortality rates.

The one stand out feature seems to the occurrence of bigger “viral loads” when people become infected that are seen in swab samples obtained from the nose and the back of the throat and in blood – hence they spread illness more easily. Higher viral loads have been linked with worse Covid-19 outcomes.

People of all ages can be infected with both the new and old coronavirus variants and transmit them to other people, but primary-aged children appear less likely to do so – at least where older variants are concerned. Whether this also holds true for the new B117 variant is unclear.

So the symptoms to look out for remain the same, though the latest advice warns of some unexpected indicators too.

Most people are aware of the core symptoms of Covid-19: a fever, continuous cough, and loss of smell or taste.

Other common symptoms include headache, fatigue, sore throat, loss of appetite, shortness of breath and chillblains, while rashes are reported in around 8 per cent of adults. Older people may experience disorientation and confusion.

What are the best tactics to curb more aggressive variants?

Firstly, those same drilled-in control measures still apply; wear a face mask, wash hands and maintain social distancing. The problem is people are understandably tired and numbed by that rising cases/deaths curve, and there has been a breakdown in public behaviour, most obviously over the Christmas period.

The key message is: this virus cannot spread when households do not mix together, when social gatherings do not occur and when people stay at home for all but essential reasons.

The problem has been over the past six weeks, we have not being sustaining what we need to do, according to WHO head of emergencies Dr Mike Ryan, at a time that variants may change the rules of the game. In short, it may necessitate new strategic approaches implemented across the planet with better coherence, improved communications and greater involvement of communities.

Are different public health measures required to deal with the new variants?

US epidemiologist Dr Eric Feigl-Ding took to Twitter to say there may be a need for greater intensity of public health measures in Ireland, as the new UK variant becomes more prominent.

“It may mean we cannot ‘afford’ the leeway to keep schools open anymore that we could before,” he said.

“And we may need to switch to premium mask mandates,” Dr Feigl-Ding added, referring to masks such as FFP2 and N95, which offer higher levels of protection compared with cloth masks and basic medical masks.

If we are facing into a perfect storm, the odds on someone testing positive for coronavirus increase significantly, even in a household where there is a small number of people adhering to the standard measures – such are the levels of disease currently in circulation. Other evidence suggests variants are infecting groups in settings such as those in a nursing home or whole families a lot quicker.

In addition, infectious disease experts in the UK are concerned that the growing burden on hospitals may also mean more patients are discharged early, leaving other household members to pick up their care.

What should you do if you or a relative contract one of the new strains?

Keep your distance inside – wear a mask. Coronavirus spreads easily in household settings because of the length of time people tend to spend together in close proximity, but transmission isn’t inevitable.

People are most infectious from the first day of developing symptoms through to day five, though they may continue to shed virus after this.

However, a recent study found no live virus in any patient sample collected beyond nine days, so if someone is being discharged from hospital after severe Covid, they are extremely unlikely to remain infectious.

The virus is predominantly transmitted through respiratory droplets produced when people cough, talk or sneeze. These can be breathed in, but quickly fall to the floor, so during the early days of infection it pays to keep your distance – ideally two metres or more.

If possible, the infected person should wear a face covering, as should other household members. Used face coverings should be placed straight into the washing machine, where they can be washed with other items on a hot setting. Disposable masks should be double-bagged and stored for 72 hours, before being thrown away with other household rubbish.

The need to clean surfaces is more important than ever. Covid-19 can get onto people’s hands and faces, and subsequently contaminate other surfaces, including towels, bedding, plates, cups and cutlery. Hand washing and disinfecting frequently touched surfaces should therefore be a priority.

Ventilation is critical because the virus can linger in smaller airborne particles, so try to keep windows ajar – including windows in different rooms, to promote airflow. Because the virus can also be shed in faeces, remember to close the toilet lid during flushing, and keep ventilation fans running for longer. Ideally, the infected person should use a separate bathroom.

Have travel restrictions been successful in curbing new variants?

Travel restrictions are necessary but are an imperfect tool, while differences in measures between countries is compounding difficulties when it comes to curbing disease spread.

Dr Mike Ryan of WHO has called for a quicker and more targeted approach when it comes to curbs on movement. This, he suggested, should entail closer monitoring of emerging clusters and swift implementation of restrictions.

The key tool in this regard in genetic surveillance. He cited the effectiveness of the UCD virus reference laboratory in the Irish context. That capacity needed to be replicated in many other countries, he said.

Variants have been identified in countries with genome sequencing capabilities. It is very possible that these observations do not reflect the true distribution of variants, which could exist undetected elsewhere. We will know more as more genomes are generated and shared.

Will the current range of vaccines be robust enough to protect against emerging variants?

At the moment we don’t know. Though we should be reassured that vaccines stimulate a broad antibody response to the entire spike protein, so it is anticipated their efficacy will not be significantly hampered by mutations. This issue is the subject of intense research at present.

There is, however, evidence that other species of seasonal coronaviruses exhibit some ability to escape immunity over longer time periods. So we may need to update Covid-19 vaccines, as we do for influenza, to reflect variants in circulation at the time.

It’s too early to say if this will be the case now, but extensive genome sequencing, data sharing, and reporting of variants will inform these efforts. The good news is the new form of mRNA vaccines are remarkably versatile in being adaptable. Pfizer, for instance, has said it can within weeks adjust formulations to counter variants.

We don’t know yet whether the South African or Brazilian variants are vaccine resistant.

Vaccines are still likely to be effective as a control measure if coverage rates are high and transmission is limited as far as possible. But it will take another two or three months for the effects of the vaccination campaign to kick in.

Is there a risk a variant could increase risk of re

infection?

This is another area of intense research. There have been reports of people being reinfected with older coronavirus variants, but such reinfections appear to be rare.

Of some concern, Brazilian researchers have identified the P1 variant in a nurse who contracted Covid-19 previously, and the patient displayed worse symptoms. In most instances re-infection has entailed a weaker form of infection.

What we know about the new UK variant strongly suggests it remains sensitive to the immune response of the older variants and will be similarly sensitive to the immune response generated by the Pfizer-BioNTech and Oxford University-AstraZeneca vaccines.

Unfortunately there are remaining unknowns when it comes to Covid-19, so what are the key ones?

One year on, virologist Dr Connor Bamford of Queen’s University Belfast has spelt out the knowledge gaps. The first is how will SARS-CoV-2 evolve, adapt and change over the next year in the face of natural or acquired immunity through vaccination?

“Our treatments and public health measures will still work,” he noted in a piece published by theconversation.com, “but what about our vaccines? We continue to track, predict and understand SARS-CoV-2 evolution with regards to vaccine ‘escape’, and all our available evidence suggests it is minimal at best and that our current vaccine platforms are robust enough to withstand any changes if needed.”

We must also remain alert to the chance it will establish it itself in another species, such as mink.

Then there is the question of how SARS-CoV-2 will interact with the other viruses circulating in humans. The human respiratory tract is home to several viruses that circulate together – often in a single person.

“These viruses promote or impede the infection of other viruses. We now know that thanks to social distancing, the spread of most of our respiratory viruses, such as influenza and RSV, has been severely restricted. How will they ‘react’ when mitigation measures, such as social distancing, end?”

Finally, he suggested, we must identify the origin of Coronavirus to prevent the continued spill-over of SARS-CoV-2-like (or indeed other pathogenic coronaviruses) into humans.

“We know that SARS-CoV-2 probably emerged recently in south-east Asia and that ultimately the virus was in a horseshoe bat. But the biological and ecological steps it took to reach humans remain obscure,” he pointed out. Solving this puzzle will help safeguard our health for decades to come, in the same way as has been achieved for swine and avian flu infections.

The pandemic has shown science and scientists can and will deliver results, given the right financial and societal support, Bamford underlined. For the most part, they will collaborate and share data for the benefit of humanity.

How then, he asked, will we apply the lessons of Covid-19 to other serious problems, such as emerging infections, antimicrobial resistance and climate change?

Additional reporting: The Guardian

Other sources used: US Centers for Disease Control; Science Media Centre (London), thecoversation.com and HSE.ie

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