In this week’s Research Tracker we focus on immune responses to SARS-CoV-2 infections. In particular, what antibody testing shows about the prevalence of infections in communities, and whether prior infections with other coronaviruses helps or hinders immune responses to COVID-19.
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Large scale testing in Spain find 5% have antibodies to the coronavirus
Spain has tested over 60,000 people for antibodies to the coronavirus. While the results are not yet published, Spanish Ministers reported provisional results where 5% were found to have antibodies. If extrapolated this would be equivalent to 2.4 million people of their population having been infected (in mid-May Spain had only 274,000 reported cases). 2.5% of people who did not report COVID-19 symptoms were found to have the antibodies. On the other hand, 13% who tested positive for viral RNA did not have detectable antibodies. So some caution is required when extrapolating results. The testing continues for several more weeks.
Similar results found in Los Angeles
A smaller survey of 863 adults conducted in early April in Los Angeles and just published in the Journal of the American Medical Association found that just over 4% had antibodies. If representative of Los Angeles at the time of testing the researchers infer that many more people may have been infected than those reporting symptoms. However, the authors of this study acknowledge that there may be sampling bias because people self-selected to be tested.
Antibody tests are still improving
There were early concerns that many antibody tests were not accurate, and some studies were poorly designed. Antibody tests can over-estimate levels of infection if they are not very specific to the virus being tested. However, antibody tests for SARS-CoV-2 are improving, and there is close scientific scrutiny of screening studies. Further large scale antibody screening studies for SARS-CoV-2 are underway.
Potentially conflicting research results on the influence of earlier coronavirus infections on immune system responses
Three papers released in the last week examined how well immune system cells from people not infected with SARS-CoV-2 could react with proteins from the virus. Two reach similar conclusions, while the third, which had a stronger focus on children, proposes a different hypothesis. The research projects had different methods and objectives, so the results aren’t necessarily in conflict. But they do indicate the intricacies of immune system responses and the need for continued research. These research articles are summarised below.
Two recent studies suggest other coronavirus infections may confer some immunity to SARS-CoV-2
More detailed laboratory research into immune system responses to the virus is emerging. In the past week, a paper published in the journal Cell by a US group and a pre-print from a German research team reported similar results and reached similar conclusions. Testing blood samples from SARS-CoV-2 infected and uninfected people found that CD4 T lymphocytes from both these groups recognised the virus’ spike protein. CD4 T lymphocytes stimulate other cells in the immune system to fight infections. While the tests demonstrated stronger immune reactivity in the samples from infected people, both research teams suggested that previous infections with other coronaviruses (such as the common cold) may help the immune system recognise SARS-CoV-2 quicker. Further research is required to confirm this, and the extent, if any, of protection.
However, less exposure to other coronaviruses may allow the immune system to more effectively eliminate SARS-CoV-2
Research from the University of Melbourne, just released as a pre-print, tested antibodies against proteins from different coronaviruses (SARS-CoV-2, SARS-CoV-1, MERS, and human coronavirus). Samples from older healthy people showed stronger responses to human coronavirus. Antibodies from healthy young people (under 19) were more effective in targeting SARS-CoV-2 proteins than those from healthy adults 65 or older. The researchers propose that multiple rounds of exposure to coronaviruses (as experienced by adults) may result in slower immune responses to a novel coronavirus like SARS-CoV-2, while the less mature immune systems of children may be able to mount more targeted responses to new viruses.
Two studies in macaques indicate that there is at least short-term immunity following infection by SARS-CoV-2 and vaccines can protect against infection
Science has just published two studies from the same Harvard laboratory that demonstrate that macaques develop effective immune responses to SARS-CoV-2, and that DNA vaccines can provide protective immunity.
In the first study, nine rhesus macaques were experimentally infected with the virus. The virus replicated in the animals, they developed relatively mild COVID-19 symptoms and produced cellular and humoral immune responses to the infection. Thirty-five days later they were re-infected and all the macaques appeared to quickly reduce the levels of the virus and produce strong immune responses.
The second study developed six prospective DNA vaccines coding for different regions or lengths of the virus’ spike protein and tested these on macaques. All of the macaques showed an immune response to the vaccine they received. When subsequently infected with SARS-CoV-2, some animals had no detectable virus, while the others had viral levels significantly lower than controls. The vaccine containing the full length S protein was the most effective. This research will help in the development of vaccines for humans.
Science Media Centre immunity briefing and other COVID-19 resources
A document tracking emerging SARS-CoV-2 research is also available. This is updated with significant research results on a daily basis.