Study raises questions over long-term COVID-19 immunity

Matt Woodley

29/06/2020 3:31:41 PM

Antibodies in previously infected patients dropped substantially after two to three months.

Picture of antibodies.
It is still unclear how critical antibodies are, or whether they are the only form of defence against COVID-19.

The study, which tracked 37 asymptomatic and 37 symptomatic patients from China’s Wanzhou District, found that more than 90% of both groups had steep declines in levels of SARS-CoV-2–specific immunoglobulin G (IgG) antibodies within 2–3 months of infection.
The dramatic reduction in IgG antibodies has created doubt over whether SARS-CoV-2 infection provides long-term protection against subsequent exposure to the virus, and could impact procedures for healthcare workers along with any future plans to issue ‘immunity passports’ for the disease.
Professor Dale Godfrey, Head of the Immunology laboratory at the Doherty Institute, told newsGP that while more time is required to properly measure the results, there is evidence from previous research into other coronaviruses that immunity typically does not last very long.
‘Antibodies will decline and that varies between infections for reasons that aren’t always that clear, but this is a fairly rapid decline, at least in some of those subjects,’ he said.
‘The plasma cells that make antibodies may still be present in high enough levels to be reactivated quickly, but you would prefer to have high levels of actual antibodies.’
The median percentage of decrease for IgG levels during the patients’ first eight weeks out of hospital was 71.1% and 76.2% in the asymptomatic group and symptomatic group, respectively. Reductions in neutralising antibody levels were also reported, and 40% of asymptomatic patients became seronegative in the eight weeks following release from hospital.
But Professor Godfrey said while SARS-CoV-2 has inhibitory proteins that shut down ‘a lot of our normal immune processes’, it remains unclear how critical antibodies are, or whether they are the only form of defence against COVID-19.
‘It is a worrying study and I can imagine people are thinking, “Oh god, we’re going to have this virus plaguing us year after year”, [but] I wouldn’t say that’s the situation just yet,’ he said.
‘Everything we know about the immune system and viruses suggests that antibodies normally play a key role, but that doesn’t necessarily mean they are the only factor in this equation.
‘We have lots of different parts of their immune system. There are T cells that don’t make antibodies – they find the infected cells directly – and there are innate immune cells that can also attack infected cells and antiviral factors that stop the virus from replicating.
‘The problem is that this is still very early days with a new and quite different infection, and so … we’re trying to work out what’s going on but we really don’t know the facts yet.’
Professor Stuart Tangye, Head of Immunity and Inflammation at the Garvan Institute, said there are conflicting studies regarding the antibody response to COVID-19 and believes it will be at least another six months before researchers have a clearer picture of post-infection immunity.
‘We just don’t have the kinetics yet, the longitudinal studies to track out long-term, how well an antibody can persist in virus positive individuals,’ he told newsGP.
‘That’s probably also going to be influenced by the severity of the disease, whether they were asymptomatic, or mild or severe, and there are probably other compounding factors.
‘If we are to infer from the SARS-CoV-1 data, I guess it’s not surprising that we are seeing this decline in antibodies more quickly than what we see for other classic viral infections and vaccinations.’
However, Professor Tangye said if the new latest report turns out to be accurate, it could have implications for efforts to produce a long-lasting COVID-19 vaccine.
‘Viruses are very clever. Viruses don’t want to be controlled, and they have all these ways of hiding themselves from the immune system or suppressing the immune system,’ he said.
‘But also keep in mind, influenza is not dissimilar [insofar as] we don’t make a great antibody response to influenza, [but] we have a new vaccine almost every year for it and the protection that it provides over that four-month winter period saves a lot of lives.
‘[Also] the strength of the T cell response very much lined up with the strength of the B cell response. So there is good evidence of antibody-mediated immunity and cell-mediated immunity correlating in these responses to the virus infection.’
Given the range of different immune responses the body can produce, along with the various methods researchers can use to develop vaccines, Professor Godfrey is still hopeful that immunologists will be able to produce a long-lasting form of protection against the virus.
University of Queensland researchers are aiming produce up to 100 million doses of a COVID-19 vaccine by the end of next year, while in the US Johnson & Johnson and AstraZeneca have both announced plans to produce billions of doses by early 2021.
But, should a long-term vaccine prove out of reach, Professor Tangye suggested other approaches – such as pharmacological inhibition of the virus, like what is currently used to manage HIV – could have a similar effect.
‘Combination antiretroviral treatments that target the virus have really revolutionised what being HIV-positive it means,’ he said.
‘People will still be pursuing those sort of antiviral, drug-therapeutic interventional approaches [for COVID-19] in order to have society go back to some sense of the new normal, and to buy us time to develop vaccines, of course, which will give you prophylactic protection.
‘I’d like to think that in a year’s time we will have … some type of passive immunotherapy that’s been engineered by producing very effective antibodies in the lab, which can then be transferred to high risk people or infected individuals.’
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Dr Ian Mark Light   30/06/2020 8:59:55 AM

The discovery of antivirals as in the great success in the treatment HIV Hepatitis C or the best time and dose for hyper immune immunoglobulin and the vaccines are the hope for the future .
Until then as many activities as possible outdoors where the virus is diluted and viral filtered ventilation systems is a path we ought take .

Dr Abid Ali Munir Ahmed Jamadar   30/06/2020 11:37:42 AM

Very insightful article.... Can any one tell me if this affects the use of Plasma therapy for Patient with active infection or on compassionate grounds as the number of antibodies are go down but still enough plasma cells still able to make antibodies in event of exposure to the virus. So should that be considered as an option of treatment?