June 18, 2020

expert reaction to study looking at the immune response of 37 asymptomatic people with confirmed SARS-CoV-2 infection

A study, published in Nature Medicine*, has looked at the immune response of 37 asymptomatic people with confirmed SARS-CoV-2 infection.

Prof Liam Smeeth, Professor of Clinical Epidemiology, London School of Hygiene and Tropical Medicine, said:

“This is an interesting study with important findings. Around one fifth of people infected developed no symptoms. The key important finding was that markers of likely immunity to SARS-CoV-2 reduced quite rapidly in many people. While this reduction was greater in those who never had symptoms, quite marked reductions were seen in some of those who had symptomatic COVID-19. This strongly suggests that immunity may well diminish within months of infection for a substantial proportion of people. We need larger studies with longer follow-up in more populations, but these findings do suggest that we cannot rely on people having had proven infections nor on antibody testing as strong evidence of long term immunity.”

Prof Charles Bangham FRS FMedSci, Chair of Immunology, Imperial College London, said:

“The paper by Long et al. makes the important observation that the antibody response to SARS-CoV-2 may diminish rapidly after infection, so negative serological results will need to be interpreted with caution.

“It is difficult to compare the duration of viral shedding between the asymptomatic and symptomatic groups in this study, because it is not clear when the individuals in each group became infected.  It is possible that those with symptomatic infection were detected sooner after acquiring the infection, precisely because the disease was clinically evident, so they might appear to clear the virus earlier than those with asymptomatic infection.

“A lower titre of antibody to SARS-CoV-2 may result from lower viral replication in the asymptomatic individuals, because the lower antigen load elicits a lower antibody response.  Lower viral replication is likely to result from a more efficient immune response to the virus.  Recently published papers suggest that asymptomatic individuals have a more efficient immune response to SARS-CoV-2 than those with COVID-19: see this review: https://royalsociety.org/-/media/policy/projects/set-c/set-c-immunology.pdf.  Therefore, caution should be taken in interpreting a lower antibody response as indicating a ‘weaker’ or less efficient immune response.

“For a full understanding of the immune response to SARS-CoV-2 in these individuals, it would be necessary to assay their T-lymphocyte responses to the virus as well as the antibody response.  The helper T cell response is necessary for an efficient antibody response, and the cytotoxic (CD8+) T cell response is necessary to eliminate the virus from the body.  In addition, the innate immune response, particularly the interferon response, is very important, especially during the first week of infection.”

Prof Danny Altmann, British Society for Immunology spokesperson and Professor of Immunology at Imperial College London, said:

“In this paper published today in Nature Medicine, Dr Long and colleagues have done a small but detailed study to compare SARS-CoV-2 immunity in symptomatic and asymptomatic people in the Wanzhou region of China during January-February. This is a really important question: much immunology data so far has come from analysing the sickest, hospitalised patients, but most people who have been more mildly affected will want to know whether this is likely to have conferred lasting, protective immunity. The study compares 37 symptomatic with 37 asymptomatic cases. The findings are interesting and confirm many points that have previously been proposed: the asymptomatic people, though PCR-positive, had lower amounts of virus. In line with this, they had also produced lower amounts of antibody. An important and potentially worrying point was that in many people, antibodies were already waning by 2-months, so that in the asymptomatic group, 40% had returned to baseline antibody levels at this time. Though this is quite a small sample, it is in line with some concerns that natural immunity to Coronaviruses can be quite short-lived.”

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

“These data are not surprising. The data are in line with several recently reported studies suggesting that those with mild or asymptomatic infections make a less robust antibody response to SARS-CoV-2 than those with more severe disease. It is not unusual for mild infections (of any cause) to induce a less florid immune response, indeed the immune system is designed to respond in a manner that is proportionate to the severity of the threat. The really interesting question, to which we don’t yet have an answer, is why some people develop such mild infections. It may be that they are genetically less susceptible to infection or that they have some pre-existing immunity due to prior infection with related seasonal coronaviruses.”

*Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections by Quan-Xin Long et al was published in Nature Medicine on Thursday 18 June.

DOI: https://doi.org/10.1038/s41591-020-0965-6

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

www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.