April 8, 2020

expert reaction to preprint on antibody responses to the COVID-19 virus (SARS-CoV-2) in a group of recovered people in Shanghai

A preprint, posted on MedRxiv, reports on the antibody responses to the COVID-19 virus in a group of recovered people in Shanghai. 

Prof Richard Tedder, Visiting Professor in Medical Virology, Imperial College London, said:

“The recent manuscript from Wu and colleagues is the first detailed analysis of the development of neutralising antibodies in patients with Covid-19.  Samples were taken from a cohort of 175 individuals who had recovered from clinically-mild Covid-19 disease.  The ability of the sera to neutralise the infectivity of the virus was detectable early in the illness, usually between 10-15 days from the onset of the illness.  A small number of individuals, ten in total, apparently never produced detectable neutralising antibody at all.  Interestingly however, when it was detected, the level of neutralising antibody was higher in elderly patients and those with more raised markers of inflammation during the infection.  Also, once detectable the level of neutralising antibody appeared not to increase during the recovery phase.

“This may mean that besides conventional “neutralising antibody” other components of the serological response may benefit the patient.  The people studied here were 175 people with mild disease – people with severe disease who received convalescent plasma were excluded from the cohort.  The authors say that it is important that the presence of neutralising antibody is confirmed In the donor before their plasma is used.”

Prof Paul Hunter, Professor in Medicine, UEA, said:

“Although this paper is not yet peer-reviewed, it is an important and timely contribution.  What the authors have done is measure antibody levels against SARS-CoV-2 in 175 COVID-19 recovered patients who had mild symptoms.  The authors used a particularly sensitive and specific neutralising antibody test.  The main findings are:

“1. The antibody tests only became positive somewhere between 10 and 15 days after the onset of illness – this is not that surprising as this is the time that antibodies to many infections become positive.  It provides further evidence that if we do manage to role out antibody tests people should wait about 2 weeks after becoming ill to test themselves.

“2. The other main finding is that many people only have low (30%) or medium-low (17%) levels of antibody.  This has relevance to the current debate about antibody tests in the UK.  If many people only produce low levels of antibodies to SARS-CoV-2 then any community test would need to have high sensitivity.  This provides further insight about why community antibody tests in the UK have not yet been authorised for use.”

Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“Although not yet peer reviewed, this is a well written and methodologically sound study.  It provides a very useful set of data.

“The study is large (175 patients) and many patients were sampled repeatedly over the course of their illness.  It shows that the vast majority of patients developed virus neutralising antibodies (that might be expected to protect them against reinfection) within 10-14 days of onset of illness.  These antibodies were specific for this virus and did not neutralise SARS virus, for example.  A small number of people did not produce detectable neutralising antibodies but they all recovered, suggesting that there are other types of antibodies or other components of the immune response that can also fight the infection.  A simple antibody-binding assay (ELISA) was less specific (there was cross reaction with SARS virus) but levels of these antibodies correlated reasonably well with the neutralising antibodies suggesting that – at a population level – they may be an acceptable proxy for neutralising antibodies.  This is useful because ELISA assays are much quicker, cheaper and easier to scale up than assays for neutralising antibodies.

“Levels of all the antibodies analysed were higher in older individuals than in younger people and also correlated with markers of disease severity (CRP and lymphocyte count).  Although viral load data were not available (a major limitation of the study) this would be consistent with antibody levels being higher in those recovering from more severe disease, which may be due to higher viral loads.  Further limitations of the study are that no severely ill patients were included (so we don’t know whether they made neutralising antibody responses or not) and the follow up after discharge from hospital was quite short (two weeks) so it doesn’t tell us how durable these antibodies are.

“In summary, the results of this study are pretty much as one might expect for any respiratory virus, suggesting that there is nothing terribly unusual about the antibody response to the Covid-19 virus.  This is reassuring.”

Preprint (not a paper): ‘Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications’ by Fan Wu et al. is on medRxiv.  This work is not peer-reviewed. https://www.medrxiv.org/content/10.1101/2020.03.30.20047365v1

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19/

Declared interests

None received.