SARS-CoV-2 in immunocompromised individuals

Abstract

Immunocompromised individuals and particularly those with hematologic malignancies are at increased risk for SARS-CoV-2-associated morbidity and mortality due to immunologic deficits that limit prevention, treatment, and clearance of the virus. Understanding the natural history of viral infections in people with impaired immunity due to underlying conditions, immunosuppressive therapy, or a combination thereof has emerged as a critical area of investigation during the COVID-19 pandemic. Studies focused on these individuals have provided key insights into aspects of innate and adaptive immunity underlying both the antiviral immune response and excess inflammation in the setting of COVID-19. This review presents what is known about distinct states of immunologic vulnerability to SARS-CoV-2 and how this information can be harnessed to improve prevention and treatment strategies for immunologically high-risk populations.

Keywords: B cell; COVID-19; SARS-CoV-2; T cell; anti-CD20; cancer; immunocompromised; infection; vaccination.

Figure 1

Investigating the immune response to COVID-19 at different states of immunity (A) States of relative immunologic vulnerability that potentially impact the immune response to COVID-19 infection and vaccination, stratified by underlying disease and/or treatment. (B) Specific immunocompromised states impact the natural trajectory of COVID-19 infection. Individuals with suppressed innate immunity (top) may experience a higher incidence of infection but intact adaptive immune responses enable efficient viral clearance. Patients with impaired adaptive cellular immunity (middle) demonstrate impaired acute viral clearance and have a high risk of death from acute infection. Conversely, patients with impaired adaptive humoral immunity (bottom) are relatively protected from acute infectious toxicity but have a high risk of prolonged viral shedding, viral rebound, and chronic infection.

Figure 2

A multifaceted approach to preventing, managing, and treating COVID-19 in the immunocompromised A multi-modal approach is required to limit COVID-19-associated morbidity in immunocompromised patients. This includes limiting the risk of infection via use of respirator-class masks (N95 or KN95), optimization tailoring of active and passive immunization strategies based on individual immunological vulnerabilities, including antibody therapy for patients with impaired humoral immunity and adjusting active vaccination strategies to promote broad and durable protection (#1). In addition, strategies for enhanced surveillance of high-risk patients, including access to at-home testing and facilitated early antiviral therapy, may limit the development of severe disease (#2). Finally, further investigations are required to improve immunomodulatory strategies to mitigate acute toxicity and promote long-term viral clearance and recovery in these individuals (#3–4).