Health

Even mild coronavirus illness leads to antibodies: French study raises hope of immunity


Even people with mild symptoms of the coronavirus develop antibodies, according to a study that raises hopes that survivors do get immunity. 

Researchers analysed the blood of 160 medics who all had a mild form of Covid-19 and had not needed hospital care.

They found 99.4 per cent of the group had antibodies to the virus 13 days after their symptoms, which signals they have some form of protection against it.

The antibodies had the ability to ‘neutralise’ – or kill – the virus in tests, and appeared to grow stronger in the weeks after infection. 

The study did not look at blood samples any later than 40 days after symptoms, so it was not established how long antibodies last for.

Antibodies are a sign a person was infected by the coronavirus. But whether or not this protects a survivor from being re-infected has yet to be proven. 

Several countries, including the UK, have hung their hopes on tests that identify coronavirus antibodies to decide who is immune and can go back to work with so-called ‘immunity passports’.  

But the unsolved question regarding immunity has halted this idea and become one of the most contested issues during the pandemic. 

The French study comes after previous research revealed that mild Covid-19 patients have such low levels of antibodies they are barely detectable, which could mean they are often missed by antibody tests, or that person has weak immunity. 

A French study has shown even people with mild symptoms of the coronavirus develop antibodies, raising hope of immunity. Pictured: Women shopping in face masks in Paris

A French study has shown even people with mild symptoms of the coronavirus develop antibodies, raising hope of immunity. Pictured: Women shopping in face masks in Paris

The latest study was conducted at the Pasteur Institute, in Paris, where researchers screened the blood of 160 medics who had confirmed Covid-19

The latest study was conducted at the Pasteur Institute, in Paris, where researchers screened the blood of 160 medics who had confirmed Covid-19

The latest study was conducted at the Pasteur Institute, in Paris. The findings, which have yet to be peer-reviewed, have been published on MedRxiv.

Blood samples were taken from more than 160 staff at two hospitals in Strasbourg, eastern France, who became infected with Covid-19 early in March.

The cluster emerged after a ‘super-propagation’ event – linked to a five-day prayer and fasting gathering of the evangelical Christian Open Door church in Mulhouse, 70 miles (114km) from Strasbourg. 

Participants – doctors, nurses, dentists and other medics – were 32 years old on average, and anyone who was severely sick with the disease had been removed from the study. 

The researchers wanted to focus on patients with mild disease because there is little known about their immunity even though they make up to 80 per cent of cases, according to the World Health Organisation. 

Two separate antibody tests were used to look for antibodies. The first test was a commercially available one, which generally are less accurate.

The second test had been developed by the institute to identify antibodies, and the ability of those antibodies to neutralise the virus.

EVERY RECOVERED COVID-19 PATIENTS DEVELOPS ANTIBODIES – BUT THEY MAY NOT BLOCK THE INFECTION AGAIN

Most people who recover from the novel coronavirus generate at least some antibodies capable of neutralizing SARS-CoV-2, the first round of results from a new study suggest.

While many antibodies grab hold of the virus, only a few counteract the pathogen and prevent it from entering our cells. 

Researchers from Rockefeller University in New York City looked at 149 recovered patients and determined that the majority had a weak antibody response.

However, they found that every patient’s immune system seemed to be capable of generating the types of antibodies that neutralize the virus, just not particularly enough of them.     

‘This suggests just about everybody can do this, which is very good news for vaccines,’ Dr Michel C Nussenzweig, head of the Laboratory of Molecular Immunology at Rockefeller, said in a statement

‘It means if you were able to create a vaccine that elicits these particular antibodies, then the vaccine is likely to be effective and work for a lot of people.’

For the study, published on pre-peer review site bioRxiv.org, the team looked at 149 people who donated plasma at The Rockefeller Hospital in New York City over the course of five weeks. 

Convalescent plasma is the liquid portion of blood is taken from a recovered coronavirus patient, which contains antibodies and immune B-cells.

Participants had symptoms of the virus for about 12 days while infected, and their first symptoms occurred about 39 days before they donated plasma.

Researchers then mixed the plasma with a pseudo coronavirus and measured if or how well the virus would infect human cells in a petri dish. 

Most samples did not do very well at neutralizing the virus.

In fact, the neutralizing effect was undetectable in 33 per cent of donors. The investigators say this may be because their immune systems cleared the infection before antibodies could be produced.  

They found that the effect was very high among one percent of patients, so-called ‘elite donors.’

The team identified 40 antibodies that neutralized the virus, and focused on three that did so even at low levels. 

These antibodies bound to at least three sites on the spike protein found on the surface of the coronavirus that it uses to enter our cells.

Researchers now plan to clone these antibodies in hopes it will help patients with severe or life-threatening cases of the virus.

‘We now know what an effective antibody looks like and we have found similar ones in more than one person,’ Robbiani said. 

The first test, a rapid immunodiagnostic test, detected antibodies in 153 (95.6 per cent) of the samples.

The more robust test found antibodies in 159 (99.4 per cent) volunteers. It failed to detect antibodies in a 58-year-old man.

When looking at the antibodies’ ability to neutralise the virus, they appeared to grow stronger over time.

Neutralizing antibodies – which bind to the virus and inactivate it, rather than ‘tag’ it for other immune cells – were found in 79 per cent of samples 13-20 days after symptoms started. This rose to 98 per cent after 28-41 days. 

‘It is a fair assumption that the majority of individuals with mild Covid-19 generate neutralising antibodies within a month after onset of symptoms,’ Olivier Schwartz, one of the leading researchers, told the French newspaper Le Monde.

‘The neutralising activity is present much later than the appearance of antibodies and this is encouraging. 

‘Although not yet demonstrated, several lines of evidence suggest that the presence of neutralising antibodies may be associated with protective immunity for Sars-CoV-2 infection.’

Survivors of SARS, a coronavirus related to this one that died out in early 2000, have been found to have antibodies that are protective for two years. 

The evidence that mild Covid-19 patients elicit the production of antibodies has not always been positive. Some research has shown only patients with really severe disease develop antibodies, which may mean those who had mild forms are still vulnerable to infection again.   

A study of a similar size at Rockefeller University in New York City, published this week, also found that every patient’s immune system seemed to be capable of generating the types of antibodies that neutralize the virus – but sometimes in very weak amounts. 

For the study, published on pre-peer review site bioRxiv.org, the team looked at 149 people who donated blood plasma – which would contain antibodies.

Researchers then mixed the plasma with the spike protein of SARS-CoV-2 – which coats the virus – and measured if or how well the virus would infect human cells in a petri dish.   

 Most samples, which were collected 39 days after symptoms on average, did not do very well at neutralizing the virus.

 In fact, the neutralizing effect was undetectable in 33 per cent of donors. The investigators say this may be because their immune systems cleared the infection before antibodies could be produced. 

Antibodies are only one part of the picture – there are other parts of the immune system which are triggered by the virus, including T cells.

Health officials in several countries, including the UK, have hung their hopes on tests that identify coronavirus antibodies to decide who is immune and can go back to work. 

But getting the ball rolling on antibody testing has been a fiasco, not only because the science on immunity is full of holes, but because there have been obstacles in finding a test with enough reliability.  

Most antibody tests are fraught with inaccuracies, giving an incorrect result, which can be dangerous. 

Yesterday the Centers for Disease Control found antibody tests for Covid-19 may be wrong up to half of the time, and warned testing is not accurate enough for it to be used for any policy-making decisions.

NHS workers in the UK were confirmed to be getting antibody testing this week after a deal to buy 10million tests from manufacturers Roche and Abbott. 

These were planned to be rolled out to the public soon after – but there are concerns this will not go ahead.  

Health officials have banned people from buying the same tests online because they fear the results are too unreliable.

The ban affects Superdrug and Lloyds, which were just two companies offering the tests to people for a fee of £69 or more using the same equipment that are now being used for NHS staff.

The equipment is being used wrongly, officials say, because it takes blood from a finger prick sample – not someone’s veins, as been approved by the Government.

There has been no rapid home testing kit – which someone reads results on like a pregnancy stick – approved for use in the UK by health chiefs, despite promises back in March. 

ANOTHER testing shambles: Health chiefs ban public from buying the same antibody test they are rolling out for NHS workers 

Sam Blanchard, Senior Health Reporter for MailOnline

Health officials have banned people from buying at-home coronavirus antibody tests that use finger-prick blood samples because they fear the results are so unreliable.

The ban affects Superdrug, which is offering to test people for past infection with Covid-19 using the same equipment that are now being used for NHS staff.

The equipment is being used wrongly, officials say, because it only has Government approval when used with blood taken directly from someone’s veins, not their finger. Using the wrong type of blood sample makes it less reliable. 

The Medicines and Healthcare products Regulatory Agency (MHRA), which polices medicines and medical devices in the UK told firms and labs offering to test blood samples people take themselves to ‘temporarily stop providing this service’, warning they would take ‘enforcement action’ if businesses failed to abide by the rule.  

But health chiefs were today accused of ‘making the rules up as they go’, with critics calling the decision another failure in Britain’s testing fiasco, which has seen months of delays and wasted money in the bid to find near-perfect tests.

Public Health England officials last week approved the first two antibody tests, made by pharmaceutical giants Abbott and Roche, which both claim their machines and procedure are almost 100 per cent accurate when used with blood from a vein.

The NHS scheme – which began on Monday and is reserved for frontline workers – uses samples of blood taken by a needle in the vein collected by a nurse or a doctor, which are sent to a lab for testing and close to 100 per cent accurate.

Private firms jumped on PHE’s approval of those testing processes earlier this month to start selling their own tests, such as Superdrug – which quickly sold out of their £69 tests when they went on sale on Wednesday.

Confusingly, the lab-based equipment used to process the now-banned tests is the same as for the national scheme, but must be used in a certain way.

The decision by the MHRA – a branch of the Department of Health – only concerns tests which rely on people taking their own blood from their finger, not ones which use professional samples of vein blood.

It is unclear how many of these have been sold already but it is understood to affect thousands of people. Superdrug admitted only that it had received ‘strong demand’ for its tests.

Sources say officials only became aware of the antibody tests being used this way in the past few days – even though private firms across Britain have been selling blood kits for weeks online, some for more than £100 a time.

Antibody tests involve taking blood and looking for signs of past infection, which is indicated by the presence of antibodies from the immune system. Scientists have yet to prove this confers any form of immunity.

Abbott, the manufacturer of the test being used by Superdrug, is furious that its tests are being used with self-sampled blood, which was not its intended use. It has sold 800,000 of the tests to the NHS already.

It is not believed to be linked to a report issued yesterday by the US’s Centers for Disease Control and Prevention (CDC), which suggested that even highly accurate antibody tests may be wrong up to 50 per cent of the time when used for an uncommon virus. 

Abbott, one of the manufacturers of a Government validated test which is being used by Superdrug, is furious that its tests are being used with self-sampled blood, which was not its intended use. It has sold 800,000 of the tests to the NHS already

Abbott, one of the manufacturers of a Government validated test which is being used by Superdrug, is furious that its tests are being used with self-sampled blood, which was not its intended use. It has sold 800,000 of the tests to the NHS already

The highest performing antibody tests use high-tech machinery to try to produce a reaction between a blood sample and a part of the virus to see whether the person's immune system contains the substances needed to fight off the virus. Pictured: The Architect laboratory instrument that Abbott uses for its coronavirus test

The highest performing antibody tests use high-tech machinery to try to produce a reaction between a blood sample and a part of the virus to see whether the person’s immune system contains the substances needed to fight off the virus. Pictured: The Architect laboratory instrument that Abbott uses for its coronavirus test

Superdrug has said it will offer refunds to customers who bought its at-home tests. 

The high street retailer launched its service only a week ago – it had to stop selling them early because of overwhelming demand but has now been stopped in its tracks. 

A Superdrug spokesperson told MailOnline this evening: ‘We have contacted all our Covid-19 antibody testing service customers today to provide further information about the quality and safety of our Covid-19 antibody laboratory-based testing service. 

‘Our doctors continue to support our customers with interpreting and understanding their results. If a customer requests a refund then we will organise it for them.’

The MHRA has confirmed that it has the power to force companies to stop using the test – which it described as ‘non-compliance’ – if it needs to.

It said in a statement: ‘When we find instances of non-compliance, in the first instance, we act swiftly to ensure voluntary cooperation. 

‘In this case, service providers have voluntarily paused their services following discussions with the MHRA. We would only move to formal enforcement action where voluntary compliance was not successful.’  

Dr Simon Clarke, a cellular microbiology expert at the University of Reading, said taking the decision to block the testing this late in the day was ‘really odd’. 

At least half a dozen companies have already bought antibody tests and are selling them en masse to members of the public, many of whom are now unable to get results despite having paid for a private service. 

Dr Clarke said the Government was probably panicking that people receiving positive antibody results might believe they were immune to Covid-19 and get brave about breaking lockdown rules. 

He told MailOnline: ‘This is really odd. At least one of the tests validated by the Government is commercially available. 

‘Why they’re telling people not to use them; they don’t want people to be assuming that they’ve had the virus and are immune.

BRITAIN’S COVID-19 TESTING SHAMBLES: A TIMELINE

March 12: Professor Chris Whitty announced that widespread coronavirus testing of members of the public would come to an end. The outbreak was too large, officials have since admitted, and only hospital patients could be tested within capacity. 

March 19: Boris Johnson promised to get antibody tests ‘as simple as a pregnancy test’ available for people to use at home – this is still nowhere near a reality.

March 25: Public Health England’s Sharon Peacock said the UK had bought 3.5million antibody tests and was evaluating them with a view to getting them available ‘within days’ – they were all deemed useless and were never made available to the public.

April 2: Health Secretary Matt Hancock sets ambitious aim of carrying out 100,000 coronavirus tests every day by the end of the month. On April 1 the Government had done 10,412. 

April 3: Universities and private labs caused uproar in the ‘little ships’ fiasco when they revealed the Government had turned down their offers to help with swab testing, to check who had the disease at the time.

April 16: The New York Times reported that Britain had spent £16.5million on antibody tests that it no longer wanted to use.

May 1: Health Secretary Matt Hancock claimed the Government hit its 100,000-a-day test target, but it emerged that it had just mailed out 39,000 of them on that day and many of those may never have been returned or analysed. 

‘Them not wanting to think that way is probably right… but this should have been put to bed earlier.’ 

He said that taking the decision now shows ‘a lack of foresight that getting it wrong could cause problems’.  

At least two laboratories are known to have stopped processing as a result of the ‘guidance’ from the MHRA.

Professor Karol Sikora, a former World Health Organization cancer chief, took antibody testing into his own hands at the Rutherford Cancer Centres where he is medical director.

He told this website: ‘In Britain the testing is appalling. There seems to be no strategy and it changes by the day. They’re making it up as they go… 

‘It’s another failure. We shouldn’t have got to this point in the pandemic and not had a properly worked out testing strategy both for the virus and antibodies. It should have been sorted out at the beginning.’ 

The finger-prick tests have never been approved by the Government because they use a different type of blood to that which official tests have been validated on.

In the lab the tests use blood taken directly from a patient’s veins, while the home tests may use blood from capillaries, which are tiny vessels carrying oxygenated blood through the skin.

This blood, because it comes through a wound in the skin, is more likely to be contaminated by the time it reaches the test. 

Tissue fluid from parts of the body surrounding the blood vessels, or substances on the skin, may mix with the tiny amount of blood and make it more difficult for the test to filter it accurately.

Taking the blood properly is key – for example, the first drop of blood should not be used for the above reason – and unqualified people might be less likely to get a clean sample if doing it by themselves. 

ARE TESTS LESS RELIABLE WHEN FINGER BLOOD IS USED?

In the lab the tests use blood taken directly from a patient’s veins, while the home tests may use blood from capillaries, which are tiny vessels carrying oxygenated blood through the skin.

This blood, because it comes through a wound in the skin, is more likely to be contaminated by the time it reaches the test. 

Tissue fluid from parts of the body surrounding the blood vessels, or substances on the skin, may mix with the tiny amount of blood and make it more difficult for the test to filter it accurately.

Taking the blood properly is key – for example, the first drop of blood should not be used for the above reason – and unqualified people might be less likely to get a clean sample if doing it by themselves. 

Professor Sikora added: ‘The real problem is, if you’ve got this in the post and never done it before, the chances of you screwing it up are high – it’s just the way these things are designed. 

‘And people are nervous about pricking their fingers anyway. So there’s a lot of inconsistency.’

The finger-prick samples also only use a tiny amount of blood – usually just one or two drops – meaning there is more chance of the antibodies being missed.

Testing of Covid-19 patients has in the past revealed that some of them with the mildest illnesses have levels of antibodies in the blood that are so low they are barely detectable. 

Using a pure, larger blood sample from a deeper vein could increase the ability to detect these.

Professor Sikora added: ‘The real problem is, if you’ve got this in the post and never done it before, the chances of you screwing it up are high – it’s just the way these things are designed. 

‘And people are nervous about pricking their fingers anyway. So there’s a lot of inconsistency.’

The finger-prick samples also only use a tiny amount of blood – usually just one or two drops – meaning there is more chance of the antibodies being missed.

Testing of Covid-19 patients has in the past revealed that some of them with the mildest illnesses have levels of antibodies in the blood that are so low they are barely detectable. 

Using a pure, larger blood sample from a deeper vein could increase the ability to detect these.

After noticing rising numbers of pharmacies offering the home finger-prick tests the MHRA is now cracking down on these firms by urging them to stop. 

The tests remain legal and it is not clear whether the Government has any legal powers to stop the companies doing the testing anyway, but officials fear the results could be unreliable. 

People who bought the tests complained on Twitter that companies should not have been selling them in the first place if they weren’t approved. 

One user, Maneesh Juneja, tweeted: ‘I wonder if consumers like me who paid £69 for a covid-19 antibody test where they have already got a result back, will refund consumers now that the tests with finger prick blood sample method have to be validated by the MHRA?’

Another, Helen Ashby, said she had ordered a test and tweeted at online pharmacy Thriva: ‘Really shouldn’t have taken my order then!’

Ben Read said: ‘Stop selling coronavirus antibody kits until you are approved to sell them. Been given the run around for a test I purchased last week, supposedly blocked by MHRA guidance from April. Pretty deceitful.’ 

People who have bought tests have shown on Twitter that they were unhappy to be sold something not approved by the Government

People who have bought tests have shown on Twitter that they were unhappy to be sold something not approved by the Government

The Medicines and Healthcare products Regulatory Agency (MHRA) told MailOnline last night: ‘Patient safety and public health are our main priorities and it is in the interests of everyone for antibody tests to be as reliable and meaningful as they can be.

‘There are several UK providers of testing services who offer Covid-19 antibody testing using a fingerprick sample of capillary blood collected in a small container.

‘We are asking all providers of laboratory-based Covid-19 antibody testing services using capillary blood collected by a fingerprick to temporarily stop providing this service until home collection of this sample type has been properly validated for use with these laboratory tests.

CDC WARNS ANTIBODY TESTS ARE WRONG UP TO HALF THE TIME

Antibody tests for Covid-19 may be wrong up to half of the time, according to updated information from the Centers for Disease Control.

The CDC now warns antibody testing is not accurate enough for it to be used for any policy-making decisions, as even with high test specificity, ‘less than half of those testing positive will truly have antibodies’.

It urges caution with the test results as many false positives could lead people to believe they have an immunity to coronavirus and act accordingly.

Health care providers may need to test patients at least twice to give a more accurate reading, the new guidance posted to the CDC website adds.

Antibody studies, also known as seroprevalence research, are considered critical to understanding where an outbreak is spreading and can help guide decisions on restrictions needed to contain it.

There is currently a high level of inaccuracy in the testing, however, caused by how uncommon the virus is within the population.

If the infection has affected only a small number of people tested, it will have a magnified margin of error, the CDC explains.

It means that even a test with more than 90 per cent accuracy can still miss half the cases if only five percent of the population has been infected.

‘Use of unvalidated sample types may lead to unreliable results and as such we are working closely with the service providers, laboratories and test manufacturers to resolve the regulatory and patient safety issues.

‘People who have purchased one of these sampling kits, and received an antibody test result, should not consider the result to be reliable and should not take any action on it.

‘This does not affect rapid point of care tests or laboratory tests performed using venous blood.’

The way antibody tests work is that a blood sample is taken from a patient, either by  medical professional or by themselves, and that is posted off to a lab.

There, qualified technicians analyse the blood to look for antibodies for the coronavirus, which are immune system substances created when someone is infected with the virus.

People then receive a result in which the presence of antibodies – a positive result – indicates they have already had the virus, or the absence that they have not.

The lab analysis stage is now being blocked by the MHRA because the tests are being used with blood taken by the patient themselves.

The best-known company providing antibody tests, Superdrug, voluntarily stopped issuing its tests last week because of immense demand, so it could get through all the ordered samples.

It did not confirm whether the MHRA rule had affected its service.

A spokesperson said: ‘We have been contacted by the MHRA and are in ongoing discussions with them about Covid-19 laboratory-based testing services and the updated guidance provided by Abbott.

‘We are also contacting all our Covid-19 antibody testing service customers today to provide further information about the quality and safety of our Covid-19 antibody laboratory-based testing service. We are updating them on our current position together with inviting them to contact us directly if they’d like further information or if they have any questions or concerns.

HOW CAN ACCURATE TESTS BE INACCURATE?

Antibody tests with what could be considered a high level of accuracy can still produce large margins of error if only a small proportion of a population has been infected. 

A 95% specific test, for example, will always produce five false positive results from a group of 100 people.

Even if it is sensitive enough to detect all the people who have genuinely had the disease, it will still return five false positives, and the effect this has on the results of a survey can be large if the number of true positives is low.

If the prevalence of antibodies is low – for example, only 5% of people in the group have had the illness – the results could end up half wrong. The 95% test, in that situation, would be expected to return 10 positives – five of them right, five of them wrong.

This means the functional accuracy of the test, known as its true predictive value, is only around 50%.

The effect of these false positives is magnified if the prevalence of the virus in the population is low, and less noticeable if the prevalence is high.

For example, if 30% of the population have been infected, those five false positive results would be counter-balanced by 30 true positives, making the test more like 85 per cent accurate.

A more specific test can reduce this effect; by comparison a 99.9% specific test would return one wrong result per thousand – 100 per million. 

Lloyds Pharmacy is also believed to have been affected by the decision but did not confirm this.

Andy Sloman, a managing director at the company, said: ‘We are working closely with our partners and regulators and have taken the decision to temporarily pause the LloydsPharmacy Online Doctor COVID-19 antibody testing service pending further guidance.

‘The health and safety of customers is our top priority, particularly during such a difficult and uncertain time. 

‘We are following the developing advice and guidance on COVID-19 antibody tests from the government and medical professionals closely.’

Professor Ian Jones, a virologist at Reading university, said: ‘In general I am in favour of freedom of choice as long as there is full information given on the reliability of the test performed.

‘After all, you can buy any number of totally useless products sold under the vitamin or “immune health” type banner and the Government does nothing.

‘It’s worth noting that part of Germany’s success in dealing with the epidemic was because of a commercial testing drive, in that case for active infections. 

‘The problem with centralisation is that it cannot cope with the numbers and that any teething troubles affect all samples. 

‘A disseminated system at least avoids this. It seems to me the issue is lack of accurate information about which kits are acceptable and which providers are offering them. Then people can choose.’

A Department of Health spokesperson said: ‘The Government is working to develop scalable solutions for at home antibody testing. Our experts are clear that an unreliable test is worse than no test.

‘We strongly discourage organisations and individuals purchasing their own unvalidated antibody tests.’ 



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