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COVID-19 and Immunocompromise
COVID-19 in Patients With Immunocompromise: An Ounce of Prevention Is Worth a Pound of Cure

Released: November 17, 2022

Expiration: November 16, 2023

Alicia Lichvar
Alicia Lichvar, PharmD, MS, BCPS, BCTXP
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Key Takeaways

  • COVID-19 prevention is key in patients with immunocompromise.
  • Vaccine responses vary in patients with immunocompromise.
  • Monoclonal antibodies can be used as COVID-19 pre-exposure prophylaxis in patients with immunocompromise, but efficacy wanes as SARS-CoV-2 variants evolve.

Patients with immunocompromising conditions and/or taking immunocompromising medications are a vulnerable population in the setting of COVID-19. According to the National Institutes of Health, people who qualify as being moderately or severely immunocompromised include those who:

  1. Are receiving active treatment for solid tumor and/or hematologic malignancies
  2. Have hematologic malignancies associated with poor responses to COVID-19 vaccines or an increased risk of severe COVID-19, regardless of the treatment status for the hematologic malignancy
  3. Have had a solid organ transplant and/or an islet transplant requiring immunosuppression
  4. Are receiving or have received CAR T-cell therapy or a hematopoietic stem cell transplant and are within 2 years of these therapies
  5. Have a moderate or severe primary immunodeficiency
  6. Have advanced or untreated HIV infection
  7. Are receiving active treatment with high-dose corticosteroids, alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, and/or biologic agents that are immunosuppressive or immunomodulatory

Clinical outcomes in this patient population when infected with COVID-19 are complex and continue to evolve as new SARS-CoV-2 variants, treatment options, and preventive strategies emerge.

In general, patients with immunocompromise have a higher risk of hospitalization or death from COVID-19 than those who do not. Older age, chronic kidney disease, cardiovascular disease, and other comorbidities compound the risk in this vulnerable patient population. Prevention of COVID-19 is critical in ensuring optimal outcomes in patients with immunocompromise.

COVID-19 Prevention Strategies: A Focus on Pre-Exposure Prophylaxis
Without question, vaccination is a key element in COVID-19 prevention and mitigation in patients with immunocompromise. However, not all individuals with immunocompromise can mount an appropriate response to COVID-19 vaccination. Pre-exposure prophylaxis with the monoclonal antibody combination tixagevimab plus cilgavimab is an additional measure that can be employed in these patients given the lack of optimal immunologic response to the available vaccines.

PROVENT
Tixagevimab plus cilgavimab binds to nonoverlapping portions of the SARS-CoV-2 spike protein, preventing the virus from interacting with the human angiotensin-converting enzyme 2 receptor. Issuance of the Emergency Use Authorization was based on results of the unpublished (at the time of issuance) double-blind trial PROVENT. In total, 5197 unvaccinated adults who were at elevated risk due to age, a predefined comorbidity (which included obesity, chronic obstructive pulmonary disease, immune compromise, and history of severe adverse reaction to vaccines), or their residential or occupational status were randomized to receive tixagevimab plus cilgavimab or placebo.

At a median follow-up of 83 days, symptomatic COVID-19 occurred in 8 patients (0.2%) who received tixagevimab plus cilgavimab and 17 (1.0%) who received placebo (relative risk reduction RRR: 76.7%; 95% CI: 46.0%-90.0%). Similar results were observed in a post hoc analysis at a median follow-up of 6.5 months (0.3% vs 1.8%; RRR: 82.8%; 95% CI: 65.8%-91.4%). At a 6-month follow-up, there were no severe or critical COVID-19 events in the monoclonal antibody group compared with 5 in the placebo group. However, only 3.2% of patients enrolled were receiving immunosuppressive therapies, and only 0.4% had an immunosuppressive medical condition.

Observational Study in Immunocompromise
Since then, more data have emerged in this niche population of patients with immunocompromise. In an observational study by Nguyen and colleagues, 1112 patients with immunocompromise were assessed after receiving tixagevimab plus cilgavimab as pre-exposure prophylaxis. Reasons for immunosuppression included being a transplant recipient (56.7%), hematologic malignancy (37.5%), rituximab for autoimmune disease (11.3%), other immunosuppressive treatment (2.4%), and primary immune deficiency (2.1%).

COVID-19 infection was confirmed in 49 (4.4%) patients >5 days after tixagevimab plus cilgavimab administration. Of those with breakthrough infection (n = 49), 43 (88%) had a mild to moderate form of COVID-19, and 6 (12%) had a moderate to severe form. Patients with moderate to severe COVID-19 were less likely to have received early therapies than patients with mild forms (53.5% vs 16.7%, respectively), and 2 (4%) patients died from COVID-19.

Study in Kidney Transplant
In another study, 860 fully vaccinated kidney transplant recipients were evaluated after receiving tixagevimab plus cilgavimab between December 23, 2021, and March 7, 2022. During the study period, omicron BA.1 was the dominant variant for a portion of the time before BA.2 became predominant. The cohort consisted of patients with vaccine-induced immunization (33.5%), patients who received passive immunity with tixagevimab and cilgavimab (47.9%), and patients with insufficient immunization response (18.6%). All patients who received tixagevimab plus cilgavimab received 2 doses of tixagevimab 150 mg plus cilgavimab 150 mg. Of note, 267 patients in the group who received tixagevimab plus cilgavimab had prior receipt of casirivimab plus imdevimab.

During this study, 113 patients (13.1%) contracted COVID-19. Of those, 75.2% were symptomatic, and 18.5% required hospitalization. Eight patients (7.1%) necessitated ICU admission, and 5 (4.4%) died from COVID-19. Infection occurrence was significantly higher in those with insufficient vaccine response (vaccine responder group: 10.1%; tixagevimab plus cilgavimab group: 6.8%; vaccine nonresponder group: 35.0%; P <.001). All 5 COVID-19 deaths occurred in patients with insufficient vaccine response in the absence of tixagevimab plus cilgavimab administration.

Evolving Landscape of COVID-19
On October 3, 2022, the FDA released information stating that not all of the emerging COVID-19 variants are neutralized by tixagevimab plus cilgavimab, and the FDA updated its Fact Sheet for Healthcare Providers with this warning. This may alter the utility of tixagevimab plus cilgavimab as pre-exposure prophylaxis in the evolution of the COVID-19 pandemic, but time and data will be needed to fully elucidate this impact. Currently, no monoclonal antibody therapies are authorized for postexposure prophylaxis.

Patients with immunocompromise are a vulnerable group in the era of COVID-19, and although COVID-19 treatment options are available for these patients, prevention strategies are paramount. Vaccine responses can vary across this population, and tixagevimab plus cilgavimab is the only monoclonal antibody combination available for pre-exposure prophylaxis. Although breakthrough infection can occur after tixagevimab plus cilgavimab administration, these infections occurred less frequently and less severely in those who received the treatment compared with those who did not, especially in those who are unvaccinated or with insufficient vaccine response.

How tixagevimab plus cilgavimab will be used in the setting of new SARS-CoV-2 variants remains to be seen, so vigilant COVID-19 testing in the setting of any COVID-19 symptoms should be performed regardless of vaccination or tixagevimab plus cilgavimab receipt.

Your Thoughts?
Should all patients with immunocompromise receive tixagevimab plus cilgavimab regardless of vaccination status? Join the conversation by posting a comment below.