Risk of Severe COVID-19 in Four Immunocompromised Populations: A French Expert Perspective

Infect Dis Ther. 2025 Apr;14(4):671-733. doi: 10.1007/s40121-025-01124-3. Epub 2025 Mar 18.

Abstract

Immunocompromised patients are disproportionately impacted by severe disease, hospitalization, and mortality associated with coronavirus disease 2019 (COVID-19). To optimize the management of these patients in clinical practice, we convened an expert panel to review current evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine responses and severe COVID-19 in immunocompromised populations. We identified four main immunocompromised groups-solid organ transplant recipients, patients receiving allogeneic hematopoietic stem cell transplantation or chimeric antigen receptor (CAR) T cell therapy, patients treated for hematologic malignancies, and patients treated for inflammatory diseases-who mount suboptimal humoral responses to SARS-CoV-2 vaccination and are at increased risk of severe COVID-19-related outcomes. A wide range of risk factors were associated with reduced vaccine responses and/or poor outcomes, most commonly older age, comorbidities, and the type and number of immunosuppressive therapies. We believe that early identification and close monitoring of these at-risk patients, plus regular booster vaccinations, prophylactic monoclonal antibody therapy, non-pharmacologic prevention measures, prompt antiviral treatment, and other risk mitigation strategies, are critical to protect against SARS-CoV-2 infection and severe COVID-19.

Keywords: Allogeneic hematopoietic stem cell transplantation; COVID-19; Chimeric antigen receptor (CAR) T cell therapy; Hematologic malignancy; Hospitalization; Immunocompromised patients; Immunosuppressive therapy; Mortality; Solid organ transplant; Vaccination.

Plain language summary

Although most people will fully recover from COVID-19, people who are immunocompromised are less able to fight the infection and more likely to be hospitalized or die from severe COVID-19. To improve the prevention and treatment of COVID-19 in immunocompromised people, 10 experts from France met to discuss the latest medical research in this area. The experts focused on four main groups of immunocompromised people: (1) people receiving organ transplants; (2) people receiving stem cell transplants or T cell therapy; (3) people being treated for blood cancers; and (4) people being treated for inflammatory diseases (such as rheumatoid arthritis). These groups of immunocompromised people are less likely to be protected after COVID-19 vaccination and more likely to develop severe forms of COVID-19. Immunocompromised people who are most at risk of severe COVID-19 are older people, people with pre-existing medical conditions (such as diabetes, obesity, and heart, lung, or kidney disease), and people being treated with immunosuppressants. The experts agreed that it is important to quickly identify these people in the clinic, so they can receive COVID-19 booster vaccines every 6 months. For people unable to build up their immunity after vaccination, antibody treatments can also be used to prevent COVID-19 infection. In immunocompromised people with COVID-19, the experts recommend using antiviral therapies (such as nirmatrelvir/ritonavir or remdesivir) to prevent COVID-19 from becoming severe. In addition to other measures (such as mask wearing and social distancing), these strategies will help to protect immunocompromised people against severe COVID-19.

Publication types

  • Review