Leonard Calabrese, DO, on Managing the High-Risk Outpatient

Although the next phase of the COVID-19 pandemic is unpredictable, Leonard Calabrese, DO, believes there will likely be 2 separate pandemics — one among those who are unvaccinated and another among vaccinated patients being treated with immunosuppressive therapies, he said during the Interdisciplinary Autoimmune Summit April 21 session on “Immunologic Lessons From COVID-19.”

Dr Calabrese, professor of medicine and rheumatologist at Cleveland Clinic in Cleveland, Ohio, participated in a discussion panel on lessons learned during the pandemic with dermatologist Joel M. Gelfand, MD, MSCE, from the University of Pennsylvania, and gastroenterologist Stephen B. Hanauer, MD, FACG, from the Feinberg School of Medicine at Northwestern University in Chicago, Illinois.

“Not all immune-compromised patients are equal,” he explained. Patients who have received solid organ transplants have approximately twice the risk of breakthrough infection with COVID-19 after vaccination due to the multiple immunosuppressant medications they must take to prevent organ rejection. Patients with multiple sclerosis and those who are HIV-positive are also at higher risk.

Among patients with autoimmune illnesses, younger patients with few if any comorbidities are unlikely to become seriously ill if they do contract COVID-19. However, patients who are older, especially if they have comorbidities such as diabetes, hypertension, and obesity, are at significant risk of serious illness, hospitalization, and death if they become infected.

The medications that keep autoimmune illnesses controlled may be implicated in those risks.

“What do we as doctors do that might increase our patients’ risks?” Dr Calabrese asked. He noted that among the armamentarium of therapeutic agents now prescribed for autoimmune conditions, “rituximab is the elephant in the room.” This B-cell depleting agent, most often prescribed for treatment of rheumatoid arthritis (RA), creates “far and away” the greatest risk of exposing patients to serious illness, hospitalization, and death from COVID-19. Janus-kinase (JAK) inhibitors also appear to carry a higher risk of severe illness among patients with RA who contract COVID-19, along with high-dose corticosteroids.

For the most severely immunocompromised patients who are unlikely to mount a robust response to vaccine, pre-exposure prophylaxis (PrEP) should be offered, Dr Calabrese said. The US Food and Drug Administration (FDA) has given emergency use authorization (EUA) for a combination of the monoclonal antibodies tixagevimab and cilgavimab, with the trade name Evusheld, for PrEP of COVID-19.

Patients who received PrEP must not be currently infected with SARS-CoV-2 or have had recent exposure to anyone infected with the virus. In addition, PrEP candidates must be moderately to severely immune compromised due to a medical condition or immunosuppressive medication that could prevent them from mounting an adequate immune response to the vaccines. Patients who cannot take the vaccines due to a history of severe allergic reactions to the vaccines or its ingredients are also eligible for PrEP.

Evusheld has proved to reduce the risk of developing symptomatic COVID-19 by 77%, according to the FDA. Patients who are prescribed PrEP must commit to taking the therapy daily and having follow-up visits with their health care provider every 3 months.

For the effective management of immunocompromised patients, the strategy begins with an educated patient, he said. These at-risk patients must be able to recognize the signs and symptoms of COVID-19 and be aware of the urgency with which early treatment and prevention should be pursued. Patients should have ready access to and understand how to conduct at-home testing, know who to contact if they suspect they have COVID-19 or have a positive test, and if they have had a high-risk exposure.

Dr Calabrese noted, “We now have a toolbox of antivirals and monoclonal antibodies to work with as treatment for COVID-19.” The key monoclonal antibody drugs available are sotrovimab, for which the FDA granted an EUA last year, but which is not effective against the B.A2 variant, he explained, and bebtelovimab, for which an EUA was granted earlier this year. The latter is effective against omicron and other variants of concerns but must be given within a 7-day window of onset.

Antiviral therapy for COVID-19 consists of a combination of the oral agents nirmatrelvir and ritonavir, known as Paxlovid. This combination therapy must be started within 5 days of symptom onset, twice a day for 5 days. It can produce significant drug interactions and is contraindicated with a number of other medications, including statins, anticoagulants, and some antidepressants.   

Preventing and effectively treating COVID-19 among immunocompromised patients is vitally important, Dr Calabrese stressed. He noted, “There are now 10 million immunocompromised patients in the United States. Among patients on B-cell depletion who contract COVID-19, 40% end up hospitalized, and 10% die. No one knows what the next phase of this pandemic will be, but this virus is not going away.”

--Rebecca Mashaw

Calabrese, L. Updates in management of high-risk outpatients. Presented at: Interdisciplinary Autoimmune Summit. April 21, 2022. Virtual.