When the body is first infected with SARS-CoV-2, the virus that causes COVID-19, the immune system goes to work to generate memory T and B cells that will fight the infection and give a “playbook” for how to fight the battle during subsequent infections. The memory B cells create antibodies that prevent the virus from reaching healthy cells. Memory T cells eliminate cells that have been infiltrated by the virus. But why do some people experience stronger and better “playbooks” than others?
What insights can be gleaned from individual immune responses in these first few days following infection that tell us about their immune protection against infection up to a year after being diagnosed with COVID?
To learn more, the Drexel News Blog checked in with Elias El Haddad, PhD, a professor in Drexel University’s College of Medicine. Haddad co-authored a recent study in the journal Nature Communications Biology, that looks at durability of immune responses in previously hospitalized COVID-19 patients for up to a year after they were discharged. Haddad also shares how these insights could improve future development of vaccines for COVID-19, the flu, and other diseases.
Haddad is also part of the National Institute of Allergy and Infectious Diseases “Immunophenotyping Assessment in a COVID-19 Cohort Study” (IMPACC), where Haddad is a principal investigator together with co-author Charles Cairns, MD, who is the principle investigator on the clinical project. Cairns is also the Walter H. and Leonore Annenberg dean of Drexel’s College of Medicine, senior vice president of medical affairs and senior vice president of Drexel Health Operations. The multicenter group has revealed other insights into the immunological aspects of care for hospitalized people with COVID-19.
Briefly share what your team did to learn about why some people have a more durable long-term immune response than others.
We wanted to know what early immune events in the first week of infection can tell us about how the immune response will behave long-term. Using data from roughly the first year of the pandemic in the United States, from May 2020 through March 2021, we collected long-term samples from 46 patients starting at the beginning of infection through their follow-up visits at the hospital up to a year later.
Every three months, the patients provided blood samples that measured antibodies, nose swabs and plasma to measure a type of white blood cell critical for the immune system known as peripheral blood mononuclear cells.
We found correlations between specific proteins, genes and cellular pathways and a more durable immune response up to a year after initial infection. For example, signaling proteins known as type-1 interferon and other messenger proteins (known as cytokines) that can regulate inflammation early upon infection are associated with a more durable long-term antibody response from the immune system, (including higher amounts of antigen specific B and T cells) and more neutralizing antibodies than those lacking a strong cytokine profile in the few days following a coronavirus infection.
When our team looked at memory responses, the cells that are ready to act if you got an infection again, we found that some of these cytokines that are associated with severe disease are also associated with a stronger memory immune response to COVID infection up to a year later. Although it’s an association due to a smaller sample size, these findings came through a multi-integration analysis. We looked at multi-omics analysis. We looked at protein and transcriptional profiles as well as multiplex flow cytometry.
Can takeaways from this paper be applied to other vaccines beyond COVID-19?
This is not only for COVID; it can be applied to other vaccines. We used COVID in the study as a model, but there’s a lot of vaccines like the flu vaccine where people need to be boosted every year. Of course this would need to be validated with future research, including phase one and phase two testing, but you can get information about a vaccine in the making, and get insights from the data about whether this vaccine can lead to a durable memory response.
What was most surprising about these findings?
I thought that the association between type one interferon signaling proteins and immune system durability is not fully surprising, but it’s a bit unexpected. We know these proteins are antiviral molecules associated with durability, and that they reduce viral load (which puts less stress on immune cells). That said, we found that the amount of interferon (too much causes the immune system to attack healthy tissue and generate less memory immunity) and timing of these responses makes a big difference. Regulating this type-1 interferon signaling and having the right balance, is also key for maximizing effectiveness of mRNA vaccination.
In addition, we found some cytokines that regulate inflammatory response to be associated with durability, which may surprise some people, as chronic inflammation is typically associated with poor health. There is an amount of inflammation that is supportive of an immune response. Too much inflammation where the immune system reacts too strongly early upon infection could be serious or even deadly, but these same cytokines at the right levels produce a robust long-term memory immune response.
Did you find any link between disease severity and quality or magnitude of memory T cell and B cell responses?
Severity of the disease is measured by multiple parameters, including hospital stay, respiration need and certain inflammatory protein in the blood. But we were looking at the molecular immune level to see how this is affecting immune response one year later. But we did not find any significant association between severity and durability. So in other words, if I got to the hospital and I spent one month of the hospital in the ICU and then you went to the hospital and stayed for 3 days and left. It doesn’t mean that you have a better memory response than me.
What is important is that there are certain components of the immune response in early events that can be associated with a durable memory and T-cell-response after one year.
How does this knowledge help in developing future vaccines?
If you are a company and you’re in a phase one or phase 2 trial and you’re looking at the first few days and you found that there are certain proteins that we found to be there (among study participants), then you would say, oh, that looks interesting and is worth looking at further to see if it produces a desired durable response.
Reporters interested in talking with Haddad should contact Greg Richter, an assistant director of media relations, at 215-895-2614 or gdr33@drexel.edu.
