COVID-19 PrEP for immunosuppressed patients: The time is now
For some time now, we have been discussing COVID-19 as two epidemics. One is the tragic and unnecessary epidemic among those unwilling to be vaccinated who are pushing our fragile health care system to the limit, unnecessarily spreading the infections throughout the community, including to the most vulnerable. The other is one of breakthrough infections in those who have done what they can to protect themselves by being partially or fully vaccinated.
I have previously commented that I am among this latter breakthrough epidemic, although I am fortunate that both myself and my wife, who are otherwise healthy, experienced mild COVID-19. While not fun, the vaccine did its job and we are fine. There is, however, a third epidemic that is not in the limelight, occurring among the 3% or so of the population who are immunosuppressed or otherwise unable to be immunized who are highly vulnerable to COVID-19, despite vaccinations.
Recent studies from Israel and the U.S. have demonstrated that among the few percent of breakthrough infections that wind up hospitalized with severe disease, approximately 30% to 40% have immunocompromising conditions, including autoimmune disease, transplantations, primary and secondary immunodeficiency states, cancer and other disorders that collectively limit their ability to mount a protective vaccine response.
The clinical outcomes of breakthrough infections in autoimmune patients can be severe and even fatal and have been recently documented. In our department at the Cleveland Clinic, we have unfortunately confirmed this and witnessed this clinically with fatal breakthrough infections, especially among those treated with B-cell depleting agents. Since we are unable to predict the end of the pandemic, I assert without hesitancy that strategies are needed now to mitigate risk in this vulnerable group.
Monoclonal antibodies have become a valuable tool in our armamentarium for patients with COVID-19 and have been granted emergency use authorization for patients early in their course with mild (non-hospitalized) infection. The data are clear that prompt therapy with such agents reduces the likelihood of hospitalization and death. This summer, the FDA revised and extended the EUA for REGEN-COV (casirivimab and imdevimab, administered together) beyond such treatment to include use as PEP or post-exposure prophylaxis for COVID-19 in adults and pediatric individuals who are unlikely to mount a robust response to vaccination and are at high risk for progression to severe disease. This preventive EUA also endorsed a lower dose ongoing regimen for these same vulnerable patients who are subjected to “repeated exposure.”
While most have interpreted this ongoing strategy for residents of endemic infected facilities (ie, nursing homes, jails, etc.), I asked immediately why this is not appropriate for these same immunosuppressed patients who must live their lives in this recent surge. This includes the teachers, bus drivers, health care workers, or anyone who really wants their life back but is unfortunate to be incapable of mounting a vaccine response that provides the reasonable assurances that the healthy vaccinated patient population enjoy.
Recently, AstraZeneca issued a press release regarding their combination monoclonal AZD7442, which is being investigated for both prevention and treatment demonstrating a significant protective effect in a study of more than 5,000 patients defined as having “increased risk for inadequate response to active immunization or having increased risk of SARS-CoV-2 infection.” Similar studies are underway for other monoclonals, as well.
At the Cleveland Clinic, we are organized around our Rheumatology-Infectious Disease Clinic and training program and have a unique vantage point of this third epidemic. We, like many other clinical immunologists – defined as any clinician engaged in the application of immunologic diagnostic and/or therapeutics – are already engaged in early battles to get ongoing COVID-19 PrEP approved for our patients.
I recognize that there are obstacles to instituting such a strategy, including our lack of standardized biomarkers for protective immunity. While regulatory agencies strongly advise against the use of serologic and cellular testing as an index of immunity in the general population, I would argue that there may be clinical merit of such in the most immunosuppressed patients. I assert that in patients with severe immunosuppression who are fully vaccinated, a complete absence of anti-S response is a source of clear concern.
In addition, while the costs of such a program are not insignificant, this is a relatively small part of our population in whom we are already investing large amounts of money for immune-based and other advanced therapeutics (ie, biologics, IVIG, etc.).
Coupled with the high costs of treating hospitalized COVID-19 patients – a likely outcome for those who didn’t mount immune responses following vaccination – the financial burden of this therapy would be comparatively small. I believe for many of my most severely immunocompromised patients (ie, patients on B-cell depleting agents, CVID, others) there are ample data to make these agents available on a compassionate use basis and the barriers should and must come down now. To delay further, particularly for the most vulnerable, will be fatal.