July 13, 2020

expert reaction to preprint on the duration of antibody response to SARS-CoV-2 infection

A preprint, an unpublished non peer reviewed paper posted on medRxiv, looked at the duration of antibody response to SARS-CoV-2 infection.

Prof Lawrence Young, Professor of Molecular Oncology, University of Warwick, said:

“This is the first comprehensive study of the longevity of antibody responses in both symptomatic and asymptomatic individuals infected with SARS-CoV-2.  This is a well-performed analysis which provides a thorough examination of different antibody responses to SARS-CoV-2.  It provides an important initial analysis but further studies with more recovered patients and asymptomatic individuals followed over longer time periods are required.  This will help to properly determine the longevity of the antibody response and what this means for the possibility of re-infection and the design of effective vaccines.

“It clearly demonstrates that in the majority of infected individuals antibody responses, including those that block virus infection (neutralizing antibodies), decline 60 days after the onset of symptoms.  Antibody responses were measured up to 94 days post onset of symptoms and in some individuals, particularly those with lower disease severity, the neutralizing antibody response became undetectable.  Nevertheless, the majority of infected individuals maintained some level of neutralizing antibodies after 60 days and in some asymptomatic healthcare workers high levels of neutralizing antibodies were detected.

“This is an important study that starts to define the longer-term dynamics of the antibody response to SARS-CoV-2.  It confirms what we already know about coronavirus infections in humans, that antibody responses can rapidly wane over time and that this can result in the ability of a previously infected individual to be re-infected.  However, previous studies on the so-called common cold seasonal coronaviruses suggest that re-infection is associated with less severe disease (colds) or no disease at all.  In both MERS and SARS-CoV infection neutralizing antibodies have been shown to wane over time but, even after a 2 years post-infection, the majority of individuals still maintain some, albeit, low level of antibodies.  We need further studies to determine the longevity of neutralizing antibodies beyond 3 months and whether these responses offer protection from re-infection.

“We also need to consider the other arm of the immune response, T cell-mediated immunity to SARS-CoV-2 which has already been shown to be present in recovered COVID-19 patients and to possibly be generated as a cross-reactive response to other coronavirus infections in individuals not exposed to SARS-CoV-2.  T cell responses to SARS-CoV-2 will be important in providing protection and, by analogy with other coronavirus infections, are likely to be maintained many years after initial infection.

“This study further emphasises the need for us to better understand what a protective immune response looks like if we are to develop an effective vaccine and reinforces the need for such a vaccine to generate a robust and durable antibody and T cell response to SARS-CoV-2.”

Dr James Gill, Honorary Clinical Lecturer, Warwick Medical School, and Locum GP, said:

“By assessing 65 patient samples, Seow et al confirm the established data that the strongest antibody response is linked to the severity of symptoms, although additional information as to whether this severity also correlates with viral load would have provide additional weight to their findings.

“The caution raised by Seow et al about the level of protection of antibodies in mild cases, can be considered, at this point to be reasonable.  Their initial findings of transient antibody titres and mild symptoms are supported by their sampling of hospital healthcare workers who have also tested positive.  Although again, further detail as to identifying if those staff members had previously been asymptotic is not made clear, but would not strongly detract from their note of caution.

“Antibody testing for COVID 19 has been seen by many as a psychological balm against the concerns of a possible infection.  Personally I have had several patients “so relieved” to find that they have tested positive for COVID-19 antibodies yet have also been surprised at these results having experienced no symptoms at all.

“As time has passed since the Sars-COV2 virus emerged, a degree of “Covid caution fatigue” appears to be developing.  Seow et al – whilst only in pre-print form – potentially give a warning shot to those who have been found to have antibodies to Covid yet have only had mild, if any symptoms.

“In the same way that these patients were surprised to have antibodies to COVID19, we should NOT be surprised if any protective benefit is mild, or at least transient.

“If you played the lottery and won £10, you wouldn’t immediately think that you had acquired increased natural luck, and used your life savings to buy further lottery tickets.

“Even those with a positive antibody test, especially those who cannot account for where they may have been exposed, should continue with to use caution, social distancing and appropriate mask use.”

Prof Mala Maini, Professor of Viral Immunology and Consultant Physician, UCL, said:

“This is a well-conducted study from a reputable group at Kings, which has not yet undergone peer-review.  It gives initial insights into the duration of antibodies to COVID-19 in the first few months after infection in 65 patients and 31 heath care workers.

“Importantly, the authors don’t just measure total levels of antibodies in the way many available tests do, they also measure the concentrations of neutralising antibodies, that is, the precise antibodies that are required for protection because they can cap the spikes on the virus to prevent it penetrating cells in our bodies.  What they found is that the level of these antibodies starts to wane within a couple of months after infection.  People who made a lot of neutralising antibodies in the first place – more commonly the case in those with severe infection – could still have good levels after 3 months.  But those who had mild infection and didn’t make many antibodies, could be left with undetectable levels by 3 months later.

“What are the implications of the study?  Even if you’re left with no detectable circulating antibodies, that doesn’t necessarily mean you have no protective immunity because you likely have memory immune cells (B and T cells) that can rapidly kick into action to start up a new immune response if you re-encounter the virus.  So you might well get a milder infection.

“We know from SARS infection (SARS-CoV-1) that T cells persisted many years longer than antibodies so we need to see whether that may also be the case after COVID-19.  Follow-up studies will tell us much more about the real-life level of protective immunity people who’ve had COVID-19 show when they re-encounter the virus.  But this study does reinforce the message that we can’t assume someone who has had COVID-19 can’t get it again just because they initially became antibody positive.  It also means a negative antibody test now can’t exclude you having had COVID-19 a few months ago.  And it suggests vaccines will need to be better at inducing high levels of longer lasting antibodies than the natural infection or that doses may need to be repeated to maintain immunity.”

Dr Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:

“This unreviewed preprint suggests that for a sizeable fraction of recovering SARS-CoV-2 infected individuals the resulting neutralising antibody response is only short-lived.  While this result is still very preliminary, with relatively low numbers of subjects followed for a limited period of time and without any information about responses following a second exposure to virus, confirmation could have very significant ramifications for our understanding of immunity to SARS-CoV-2 and vaccine development.  In addition it would suggest that we need to redouble our efforts to identify and develop novel therapeutic strategies, either by repurposing existing drugs or by performing new drug screens.”

Prof Daniel Altmann, Professor of Immunology, Imperial College London, said:

“This is a robust piece of work that helps in adding clarity to the emerging consensus on the nature of immunity to this very difficult infection.  It is especially helpful that unlike some studies, this study includes the demanding assays to looks carefully at true, functional, virus-neutralising antibody levels.  The answer, yet again, is that most people make them, but often they can wane rather rapidly, suggesting there could be little immunity to subsequent infection.  This offers a sobering message to any who think it would be worth taking chances for the sake of getting some immunity on board, those who hope we’ll emerge into a time where we’re rescued by herd immunity, and indeed, those who plan to reject our best current hope, in the form of effective vaccines.”

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“Whilst yet to be peer reviewed, the importance of this study is clear and the research has been rigorously undertaken.

“This work confirms that protective antibody responses in those infected with SARS-COV2, the coronavirus that causes COVID-19, appear to wane rapidly.  Whilst longer lasting in those with more severe disease, this is still only a matter of months.

“Similar short-lived responses are seen against other human coronaviruses that predominantly cause only mild illness, meaning that we can be re-infected as time goes by and outbreaks can adopt seasonality.  With the more serious, sometimes fatal, outcomes of SARS-COV2, this is troubling indeed.

“Vaccines in development will either need to generate stronger and longer lasting protection compared to natural infection, or they may need to be given regularly.  Whilst studies in primates show relatively weak responses that protect against severe disease but not infection itself or subsequent virus production, recent studies in pigs show that additional inoculations might improve outcomes.  It is also possible that other aspects of the immune response, such as T cells may provide protection.  It will also be important to understand what happens when patients with relatively recent infection are either re-exposed to the virus, or indeed become vaccinated.

“The implications of this study in terms of both managing the pandemic and the need for widespread education are broad-ranging.  First, herd immunity approaches, still callously promoted by some, are clearly non-viable.  Second, should a viable vaccine become available, it may require regular boosts or combination of different platforms to elicit the best possible protection.  Third, development of additional lines of antiviral therapies and/or drugs that lessen the severe inflammation in advanced COVID19 is essential to support future vaccination programmes.

“Finally, the troubling media reports around COVID19 parties, conspiracies, unfounded often dangerous therapies and politically motivated minimising of pandemic impact needs to be countered by widespread education and unified approaches to public health, such as that led by WHO.  We cannot afford to simply wait for vaccines or drugs and should make every effort to eliminate the virus using non-pharmaceutical approaches; the cost to life is already too high.”

Preprint (not a paper): ‘Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection’ by Jeffrey Seow et al.  This work is not peer-reviewed.

https://www.medrxiv.org/content/10.1101/2020.07.09.20148429v1

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www.sciencemediacentre.org/tag/covid-19

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None received.