March 01, 2022
3 minute read
Sparks J. COVID Breakthrough in IMIDs. Presented at Basic and Clinical Immunology for the Busy Clinician; February 26, 2022. (virtual meeting).
Disclosures: Sparks claims to be a consultant for Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead Sciences, Inova Diagnostics, Janssen, Optum and Pfizer; and grant/research support from Bristol Myers Squibb.
An evolving definition of “fully vaccinated” has made it difficult to assess the usefulness and success of COVID-19 vaccines in patients with immune-mediated inflammatory diseases, a presenter noted here.
At the start of the COVID-19 vaccine era, breakthrough infections were considered rare, Jeffrey Sparks, MD, MMSc, associate physician at Brigham and Women’s Hospital and Harvard Medical School, told attendees at the Basic and Clinical Immunology Symposium for the Busy Clinician Symposium. “It was thought that vaccines would eliminate COVID, but that has not been the case,” he said. “No vaccine is perfect.”
What is now known is that vaccines can help prevent serious illness, hospitalization and death. Sparks noted that the products used succeeded in this.
However, a number of factors can impact the effectiveness of the vaccine, according to Sparks.
Even in people without immune-mediated diseases, differences in immunity can have an impact. Additionally, structural factors such as product manufacturing, transportation, and storage can create variability in response. “Sometimes an intramuscular vaccine can be given subcutaneously, which can impact the response,” Sparks added.
Another factor is timing, according to Sparks. A breakthrough infection is described as “a positive test 14 days or more after full immunity”, but there is often uncertainty as to when the exposure actually occurred.
All of these factors affect anyone vaccinated. But, of course, the problems are compounded in patients with immune-mediated diseases. “The obvious thing with IMIDs is that the definition of fully vaccinated has changed,” Sparks said.
At first it was defined as two doses. But then there was stimulation, and there was mixing and matching with mRNA and other approaches. Sorting out when, exactly, a person can be defined as fully vaccinated is nebulous. This, in turn, has made it difficult to study so-called breakthrough infections. “Literature hasn’t caught up with that,” Sparks said.
The presentation then covered some well-established data regarding impaired humoral and adaptive immunity in people with IMID. Sparks described issues ranging from organ damage to the impact of immunosuppressive drugs like B-cell depletion therapies. “Most patients make antibodies, but to a lesser extent than healthy controls,” he said. -he declares.
All of this, in turn, translates into clinical outcomes. A first study published in 2021 in Annals of rheumatic diseases, reported 16 breakthrough infections in patients with IMID, observing that drugs impacting humoral immunity – rituximab (Rituxan, Genentech), mycophenolate mofetil, tacrolimus and methotrexate among them – were present in most cases. Six of the 16 patients died. “It showed that breakthrough infections can be symptomatic and severe,” Sparks said.
Similar data were seen in EULAR case series and results from the Global Rheumatology Alliance database.
If there is a key caveat in interpreting these results, it is that many of the studies were conducted during delta or previous surges. “Then omicron came along, and it’s a whole new ball game,” Sparks said.
As the omicron decreases and the next variant may or may not emerge, Sparks stressed that ongoing studies to determine when to stop and restart immunomodulatory drugs based on COVID-19 vaccination are needed. .
Sparks closed looking to the future. There is hope that an intranasal vaccine could be a welcome addition to the current arsenal, he said. The nose-to-lung path may be different from the arm-to-lung path, leading to more robust immunity in patients with IMID. They could alter which parts of the immune system are activated and how quickly the immune response moves through the body.
“Intranasal vaccines provide greater mucosal immunity, while intramuscular vaccines provide less mucosal immunity,” he said.
Also looking to the future, Sparks suggested that the next phase of COVID-19 vaccination in patients with IMID should take a different approach. “Perhaps there is a shift towards preventing the severity of infection rather than preventing the infection itself,” he said.