Covid-19 immunity and immunopathology – testing and mechanisms
Gitta Stockinger, Caetano Reis e Sousa, George Kassiotis, Adrian Hayday, Anne O’Garra, Samra Turajlic, Rupert Beale, Andreas Wack, Veni Papayannopoulos
How can we tell who’s already had the virus?
Most current tests for COVID-19 detect the presence of the virus by looking for its RNA component. It is also important to be able to identify the proportion of people who have been infected and cleared the virus, and may have some degree of immunity. This will help build scientific understanding of the outbreak and guide public health decisions.
The Crick/UCLH/UCL serology initiative has developed a blood test to indicate whether someone has been infected with SARS-CoV-2. Initial results suggest that this procedure has higher levels of accuracy than other tests. It also appears to be highly scalable, with the potential to carry out thousands of tests a day.
The test is based on the use of cells expressing the SARS-CoV-2 Spike protein being analysed by flow cytometry after exposure to sérum antibodies. The flow cytometry process detects binding of antibody to SARS-CoV-2 in patients’ blood. Importantly, a second stage of the process uses neutralisation tests to see how effectively the antibodies will stop the virus from being able to infect cells.
The Crick’s expertise in flow cytometry and neutralisation assays (tests that measure how effective different antibodies are at preventing infection), offer a high level of accuracy and provide powerful insights into patients’ immune response to infection.
The information from our tests could be used to quickly determine the effectiveness of candidate vaccines. It will also be used for research studies seeking to establish levels of infection across large groups of people and to find out how long immunity to SARS-CoV-2 might last.
Why are some cases much worse than others?
While many people with coronavirus experience mild symptoms, some end up in hospital and about 20% of these people will require critical care and possibly ventilation in an intensive care unit.
Patients who die of COVID-19 often succumb to pneumonia, leading to respiratory failure. Many of these patients are older or have existing health conditions, but doctors are also seeing younger, healthy individuals decline rapidly after infection.
Some of these patients suffer from overreactive immune responses. We need to understand the causes and consequences of excessive immune responses. Our researchers will use their substantial expertise in inflammation research, tissue repair and virology, to study why some people can’t get rid of the infection after a few days and why some people enter a type of ‘immune shock’ where inflammatory cells cause the body to shut down.
The Crick, King’s College London and Guy's and St Thomas' NHS Foundation Trust have built a high-throughput platform, looking at patient’s blood over time to see how our immune system responds to coronavirus, and if there are clues to whether someone might need additional treatment.
The team has previously run large studies monitoring how people’s immune systems respond to flu vaccines, and have developed new methods for tracking patients’ immune response. In the new platform, they are studying the differences in immune response between different groups of patients and examining how this relates to clinical outcome.
The results may be used by doctors to predict who will need intensive care and get them the treatment they need faster. A better understanding of our immune response could also aid in the development of treatments and vaccines.