COVID-19: Who is immune without possessing an infection?

COVID-19: Who is immune without possessing an infection?
Image credit: Taiyou Nomachi/Getty Images

In blood samples donated before the start of the pandemic, scientists have discovered antibodies that respond to the current coronavirus. Some people may have at least a degree of preexisting immunity to the new virus, they say.

COVID-19 patient
Image credit: Taiyou Nomachi/Getty Images

In several regions around the world, the number of new COVID-19 cases is on the rise. But COVID-19 is not developed by any person who comes into contact with SARS-CoV-2, the new coronavirus.

Together with colleagues at University College London, both in the United Kingdom, a group of scientists from the Francis Crick Institute in London may have found a clue as to why certain people can fight better than others against SARS-CoV-2 infections.

Recently, their dissertation appeared in the journal Science.

Surprise discovery

Originally, the research team set out to develop a high-sensitivity test to detect SARS-CoV-2 virus antibodies.

This type of test can be used by scientists to determine whether a person has antibodies after getting COVID-19, which is a key piece of information for those attempting to determine how long immunity can last after infection with SARS-CoV-2.

The scientists used serum samples given by individuals who did not have COVID-19 as part of their work. In some of the samples, to their surprise, they found antibodies that responded to SARS-CoV-2.

The researchers explain a scientific hypothesis in their paper that exposure to some of the common human coronaviruses that can cause the common cold may lead to immunity against the other common human coronaviruses. They refer to this as immune cross-reactivity.

There are four different human coronaviruses that are seasonal, all of which often cause mild illness. The vast majority of individuals have an infection at some stage with at least one of these viruses.

Scientists now know that our bodies do not establish long-lasting immunity to these viruses, which is why a person can become infected more than once in their lifetime with a common human coronavirus.

But can previous exposure to a typical human coronavirus at least provide temporary protection against SARS-CoV-2?

Finding cross-reacting antibodies

In order to attach to and infect host cells, coronaviruses use a protein called the spike protein.

Prof. George Kassiotis, a senior author of the new study and the group leader of the Francis Crick Institute’s Retroviral Immunology Laboratory, explains how immune cross-reactivity can be provided by antibodies that recognize a part of the spike protein.

This coronavirus spike consists of two parts, or subunits, performing various jobs. The S1 subunit makes it possible for the virus to latch onto cells and is relatively diverse among coronaviruses, whereas the S2 subunit allows the virus to enter cells, and among these viruses it is more similar, he says. “Our work demonstrates that the S2 subunit is sufficiently similar for some antibodies to work against both common cold coronaviruses and SARS-CoV-2.”

In their study, in several collections of samples, Prof. Kassiotis and colleagues determined the levels of cross-reacting antibodies, most of which had been donated prior to the SARS-CoV-2 virus emergence.

The team found that 10 percent had cross-reacting antibodies in a group of 50 blood samples from pregnant people as of May 2018. Three had these antibodies in a separate cohort of 101 samples from May 2019.

The team analyzed 13 additional samples from adults who had recently had an infection with a common cold coronavirus in a further experiment. Of these, only 1 sample had antibodies that were cross-reacting.

Overall, 16 of 302 samples, or 5.29 percent, had SARS-CoV-2 cross-reacting antibodies, the authors report. The donors had a median age of 51 years.

But why did relatively few individuals have cross-reacting antibodies, given that common human coronavirus infections often occur?

This indicated that after each [common human coronavirus] infection in this age group, their emergence was not simply a common transient event,” the authors commented.” “Instead, given that virtually all adults have [common human coronavirus]-reactive antibodies, the rarity of SARS-CoV-2 cross-reactivity […] indicates additional requirements.”

One such criterion, they say, can include how often a person has a common human coronavirus infection. In children and teenagers, the incidence is greatest.

Children ‘more regularly exposed to other coronaviruses’

The team examined 48 blood samples from children and adolescents aged 1–16 years to look for a correlation between age and SARS-CoV-2 cross-reacting antibodies. The samples were all from before the pandemic.

Here, they found that 21 of the samples had cross-reacting antibodies, although these were only present in one sample in a different cohort of samples from people aged 25 years.

“Our findings suggest that children are much more likely than adults to have these cross-reactive antibodies. More research is needed to understand why this is, but it may be due to children being exposed to other coronaviruses more frequently says Kevin Ng, one of the lead authors of the study and a post-graduate student in the laboratory of Prof. Kassiotis.

“These higher levels we observed in children could also help explain why they are less likely to become severely ill with COVID-19. There is no evidence yet, however, that these antibodies prevent SARS-CoV-2 infection or spread.”

– co-lead study author Kevin Ng

“It is important to stress that there are still many unknowns that need more study,” Professor Kassiotis also weighs in. For instance, how is immunity to one coronavirus altered by exposure to another, exactly? ”

“Or, why does this activity decline with age? It is not the case that individuals who have had a cold recently should presume that they are immune to COVID-19, he adds.