Targeted COVID-19 Therapies in Immunosuppressed Patients

Volume 18, Issue 3

COVID-19 infection now carries a low risk of severe disease in otherwise healthy patients who are adequately vaccinated and boosted. The same cannot be said for immunosuppressed patients, who are vulnerable for a number of reasons.

First, these patients are less likely to mount a sufficient immune response to vaccination as a result of being on immunosuppression. Second, these patients are more vulnerable to severe disease if infected with COVID-19, as their immune systems are weakened by their immunosuppressant medications.

As such, these patients need access to targeted COVID-19 therapies when infected. However, limited data exists evaluating the effectiveness of contemporary COVID-19 therapies in immunosuppressed patients who become infected.

In this week’s issue of Talking Therapeutics, we explore 2 new papers (both of which I helped to author) that explore the use of targeted COVID-19 therapies in solid-organ transplant recipients.

Point 1: Paxlovid Works

The first paper explored the use of nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment in solid-organ transplant recipients infected with the BA.1 subvariant in New York City.

The rate of 30-day hospitalization or death was lower in patients treated with NR (n=28) or sotrovimab (n=51) vs those who received no COVID-19-specific treatment (n=75) (P = 0.009). Per this paper, “A total of 3 deaths occurred, all among patients who initially received no specific treatment prior to hospitalization.”

Overall, these findings support the use of NR (Paxlovid) for use in solid-organ transplant recipients who become infected with COVID-19. As reported in one of my previous columns, since NR retains its effectiveness against BA.5, we can comfortably extrapolate the findings of this paper to current practice.

Sotrovimab, on the other hand, does not retain efficacy against BA.5, so this data is less helpful in the current era. Which brings us to the second paper…

Point 2: Bebtelovimab Works

In the next paper, bebtelovimab (Beb) was evaluated in a cohort of 25 solid-organ transplant recipients who were infected during the BA.2 era.

Of these patients, only 1 patient was subsequently admitted to the hospital, and there were no fatalities related to COVID-19 infection. As I discussed in a previous issue, Beb retains efficacy against BA.5, so these findings are still relevant in the current era.

In summary, both Beb and NR are acceptable options for managing BA.5 infections in solid-organ transplant recipients. Beb has the advantage over NR with respect to drug interactions, as the latter can potentiate the toxicities of calcineurin inhibitors via inhibition of CYP3AR. On the other hand, Beb is a monoclonal antibody that has to be administered in an infusion clinic, so there are logistical hurdles to overcome when using this therapy.