Mass General Brigham Study Highlights Varied Risk of Persistent COVID-19 Infection Among Immunocompromised Patients

• Patients who were severely immunocompromised were at greater risk of protracted disease and had a longer period in which they shed the virus, especially those with hematologic malignancy or transplant.
• While the sample size was limited, patients with mild/moderate immunosuppression had an intact immune response, comparable to control participants.

Individuals who are immunocompromised are at risk of worse COVID-19 outcomes and may have a less robust response to vaccination compared to non-immunocompromised individuals. But the term immunocompromised refers to a wide range of conditions, and not all patients in this category may be at equal risk. Researchers from Mass General Brigham studied a population of 56 immunocompromised individuals that included patients who were severely immunocompromised due to hematologic malignancies/organ transplant or auto-immune/B cell deficiency as well as non-severely immunocompromised patients. The team compared these groups to one another and to patients who were not immunocompromised.

They found that patients’ abilities to clear the virus differed by the extent of their immunosuppression. Patients who were immunocompromised due to a hematologic malignancy or organ transplant were most likely to have a chronic, prolonged infection. This finding suggests the importance of T cells in clearing SARS-CoV-2 infection, which has implications for patient monitoring and improved vaccine design. Participants who were severely immunocompromised also had a higher risk of developing resistance against therapeutic monoclonal antibodies.

“Providers and patients should be aware that protracted symptoms may mean persistent COVID-19 disease that requires additional testing and potential treatment,” said corresponding author Jonathan Li, MD, of the Division of Infectious Diseases at Brigham and Women’s Hospital.

Patients with a history of organ transplant or hematologic malignancy had the greatest delay in viral clearance; patients with B cell immunodeficiency had an intermediary risk; and the study’s 31 patients with mild, non-severe immunocompromise, such as those with autoimmune diseases receiving anti-tumor necrosis factor (TNF) treatment, had similar viral shedding dynamics to non-immunocompromised participants.

“While our sample size is limited, these results provide reassurance that most patients with mild/moderate immunosuppression (including those on B-cell depleting therapy) will be able to clear the virus during the acute phase of infection,” said Li.

Authorship: First author Yijia Li is a former BWH Infectious Disease Fellow and a current faculty member at University of Pittsburgh. Co-senior authors include Mark J. Siedner (MGH) , Amy K. Barczak (MGH), and Jacob E. Lemieux (MGH). Additional Mass General Brigham co-authors include Manish C. Choudhary (BWH), James Regan (BWH) , Julie Boucau (Ragon Institute), Anusha Nathan (Ragon Institute), May Yee Liew (MGH), Gregory E. Edelstein (BWH) , Yumeko Kawano (BWH) , Rockib Uddin (MGH) , Rinki Deo (BWH), Caitlin Marino (Ragon), Matthew A. Getz (Ragon), Zahra Reynold (MGH), Mamadou Barry (MGH), Rebecca F. Gilbert (MGH), Dessie Tien (MGH), Shruti Sagar (MGH, Tammy D. Vyas (MGH), James P. Flynn (BWH), Sarah P. Hammond (BWH), Lewis A. Novack (BWH), Bina Choi (BWH), Manuela Cernadas (BWH), Zachary S. Wallace (MGH) , Jeffrey A. Sparks (BWH), Jatin M. Vyas (MGH), Gaurav D. Gaiha (MGH). Additional co-authors include Tessa Speidel and Michael S. Seaman.

Disclosures: Hammond receives research funding from GSK and have served as an advisor to Pfizer. Jonathan Li is supported by a grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC. Yijia Li is a topic editor for DynaMed.

Funding: This work was supported by the National Institutes of Health (grant U19 AI110818, R01 AI176287), the Massachusetts Consortium for Pathogen Readiness SARS-CoV-2 Variants Program (MassCPR) and the Massachusetts General Hospital Department of Medicine.

Paper cited: Li, Y et al. “SARS-CoV-2 Viral Clearance and Evolution Varies by Type and Severity of Immunodeficiency” Science Translational Medicine DOI: 10.1126/scitranslmed.adk1599

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