T - Cell Responses Holds Up Against SARS - COVID - 2, New Study Finds

 By Prof. William. A. Haseltine.

There is remarkable news regarding the immune response to SARS-CoV-2. It is clear now that the virus mutates to evade the neutralizing antibody responses. There are new results that suggest that is not the whole story. When it comes to another arm of immunity, T-cell immunity, high response to one form of the virus means high response to them all. Here we will review what that might mean for the future of Covid-19.

In the months since SARS-CoV-2 variants came to the forefront of Covid-19 discussion, the average person is left with a number of questions. Will the vaccine my grandmother just received protect her from emerging strains? What about my previous infection during the summer? How long might that protection last?

Vaccines and prior infections confer antibodies, which are proteins produced by B-cells to counteract a specific antigen. Picture a custom couture tailored to you. The fabric aligns perfectly with every inch of your torso. An antibody is like a tailor-made protein that fits a specific pathogen, in this case, SARS-CoV-2. However, ample research indicates that these antibodies fade rather quickly over time, and may not protect as well against some variants. Though as it turns out, B-cells and antibodies are only half the adaptive immunity puzzle. 

The other piece is the T-cell. These are types of white blood cells in the immune system which act as the front-line soldiers against disease. Their purpose is to eliminate invading pathogens and clean up dead cellular debris. They do this by remembering past infections, waiting to encounter short amino acid sequences of the virus called peptides, then killing the virus when it reappears. Whereas antibodies are tailor-made proteins for a specific virus, T-cells attack a range of different pathogens, like a suit purchased off the rack. It may not quite fit exactly, but close enough will do and it will fit many others as well.

The T-cell is another tool in the arsenal against Covid-19, but the questions above must be translated in reference to this secondary weapon. Will T-cells protect against rapidly emerging variants of the virus that show signs of resistance to antibodies? Research from the La Jolla Institute of Immunology, led by Dr. Alessandro Sette and Dr. Shane Crotty, sought to illuminate these unknowns.

Their findings were encouraging. When exposing human T-cells from a wide range of hosts previously infected with Covid-19 to a number of SARS-CoV-2 variants, the T-cell response held up well. Responses decreased at most 30% relative to that cell’s response to the SARS-CoV-2 wild type. In some cases, such as the South Africa variant, T-cells produced a nearly equal response to the variant as the unmutated virus.

The same can be said for samples pulled from people vaccinated against Covid-19. Their T-cells responded in an equal or slightly decreased volume in comparison to the wild type. This is a major victory, confirming that T-cells have some effect in slowing mutated variants down, but to what extent?

There are strengths and weaknesses to the T-cell response. The strength, as shown by these researchers, is the blanket coverage they have over the variants. The virus is adaptive and mutative—changing over time. When we introduce antibodies specific to the virus, it has shown an ability to develop mutations to the receptor-binding domain, n-terminal domain, or elsewhere, that renders the antibody less effective. With T-cells, because everyone has their own unique hereditary set rather than one specific developed antibody from a vaccine or previous infection, the virus cannot adapt.

The weakness, however, is that T-cell responses to SARS-CoV-2 are limited. T-cells are not designed to prevent infection, only to kill the cells once they are in the body. The researchers confirm this by concluding that “while it is not anticipated that circulating memory T cells would be effective in preventing SARS-CoV-2 infection, it is plausible that they can reduce Covid-19 severity.”

Given all this, it may be the case that SARS-CoV-2 is allowing a certain level of T-cell response. Variants evolved while T-cells were present, prompting the idea that viruses are modulating the T-cell response to low enough levels for them to continue to spread. While mostly speculative, it seems possible that the virus could have regulatory influence on the T-cell.

Regardless, T-cell reactivity in the face of variant forms of SARS-CoV-2 is an unmitigated positive. The implication is that those vaccinated or previously infected will have at least some form of defense against newly circulating variants, even if they are capable of evading antibodies. This is much needed positive news in the face of the growing variant threat.

Quality Improvement within the hospital setting.

Root Cause Analysis Won’t Work If People Fear It

By Richard Guthrie | Thursday, January 16, 2020.

When I was a young staff member, I was involved in a medical error and participated in a root cause analysis (RCA). RCA is a process many health care systems use to learn how and why errors occurred.

Although it happened almost 30 years ago, the memory is so vivid that I remember the building it was in. I remember where I was sitting in the room.

My department chair and nursing supervisor were there. Many of the folks in the room were colleagues. As I recall, I considered everyone in the room a friend. In fact, one person was a very close friend.

It’s hard to describe unless you’ve been through it. It was difficult to answer the questions about what I had done wrong. I remember realizing I was talking about why I did things that I never thought I’d ever do, and I was saying these things in front of the people whose respect I wanted the most. It was embarrassing. I felt incompetent.

An Opportunity for Improvement

Years later, when I started in my role as Chief Quality Officer at Ochsner Health System five years ago, I was curious about our use of RCAs. After checking our records, I was surprised to learn we’d only done three the prior year.

So, I started asking around. After talking with a number of nurses and physicians, I found that many were terrified of RCAs.

People admitted that they sometimes made excuses — even calling in sick — to avoid attending one. From what I heard, the way RCAs were conducted felt psychologically unsafe for everyone involved. Given my own experience, I understood why a lot of people feared participating in them.

As if the lack of psychological safety weren’t bad enough, when I looked up what came of the three RCAs that had been done, I found the solution determined for all of them was simply “education.” That didn’t seem like a robust plan to prevent harm from happening again.

I realized we had a lot of work to do. We had an opportunity to do much better for our patients and our staff.

The Need for Something Better

In 2015, with support from The Doctors Company Foundation, the National Patient Safety Foundation (NPSF) convened a panel of experts to develop recommendations for improving how we learn from adverse events to reduce or eliminate future similar events. The panel found that processes like RCAs too often lacked a standardized approach, failed to identify systems-level causes, and did not institute good implementation follow-up. As a result, RCAs too often failed “to understand what happened, why it happened, and then take positive action to prevent it from happening again.” The panel renamed the process Root Cause Analyses + Actions (RCA2) to emphasize the need to specify clear responses to what is learned during an RCA.

Fortunately, about four months into my taking the role of CQO at Ochsner, I heard about RCA2. When I learned more about it, I knew it was the cure to what ailed us.

The Role of Empathy

For me, a huge difference between the old RCA and RCA2 is how interviews about adverse events are conducted one-on-one instead of in front of a group. It is still not pleasant to have made a near miss or a medical error that hurts a patient and then to have to talk about it. That’s never going to be easy, but having individual discussions as a way to gain a deeper understanding of what happened is better than the old way.

In addition to the psychological safety it offers the participants, it also helps us separate blameworthy behaviors from system issues. It is easy to focus on how a person did something wrong, but focusing on the individual is not going to solve our problem going forward.

Guided by empathy and a systems way of thinking, I believe RCA2 interviews yield far more useful information than the old types of RCA review. I encourage interviewers to remember that the staff involved in an adverse event are suffering. Even with a good peer support program like we have at Ochsner, the person or people involved are likely still struggling with the fact that they made an error that hurt (or could have hurt) someone.

Imagine you’re interviewing a tech who mistakenly used an empty syringe and injected an air embolism into a patient before a CT scan. The error led to the patient going into cardiac arrest. It’s easier for a peer who is part of the RCA2 workgroup to convey empathy one-on-one than in a room full of supervisors and other colleagues:

I know this is difficult. I could easily have made that mistake myself. I’m interviewing you today because I’m trying to learn what happened. I know you’re a good tech. What else did you have to focus on during that patient encounter? What was the workload that day? Were there any distractions? How can I better understand the situation so we can help make our system safer?

To me, RCA2 is at the junction between a culture of safety and robust process improvement. We want to keep people psychologically safe and report events to help us become safer for patients. We should use the tools available — including human factors engineering, change management, Lean, or Six Sigma, for example — to take what’s gleaned from an RCA2 process and turn it into actions.

We should use RCA2 to identify the system vulnerabilities that allowed harm to get all the way to a patient. When we create solutions for system defects, it not only prevents that single event from happening again, but it can prevent many other types of related events from happening and help us create a safer organization.