Intrahost viral evolution of SARS-CoV-2 infections in rheumatic versus hematological patients with severe iatrogenic immunosuppression
By
Emmanouil Karofylakis
Theodoros Loupis
Andromachi Blizou
Eleni Ntalaouti
Eirini Maria Stergioti
Giannis Vatsellas
Sotirios Tsiodras
Anastasia Antoniadou
Aggelos Banos
Konstantinos Thomas
April 30, 2026
Clinical Scorecard: Intrahost Viral Changes in SARS-CoV-2 Among Severely Immunosuppressed Patients with Rheumatic and Hematological Conditions
At a Glance
Category Detail
Condition COVID-19 in immunocompromised patients
Key Mechanisms Ongoing SARS-CoV-2 replication leading to intrahost genomic divergence and immune escape
Target Population Severely immunocompromised patients with rheumatic and hematological conditions
Care Setting Hospitalized patients with laboratory-confirmed COVID-19
Key Highlights
B-cell depleted patients are reservoirs for prolonged SARS-CoV-2 replication, leading to unique intrahost mutations. A positive correlation exists between duration of infection and intrahost single nucleotide variants (iSNVs) accumulation. No difference was noted in substitution rates between rheumatic and hematologic patients.
Guideline-Based Recommendations
Diagnosis
Laboratory-confirmed SARS-CoV-2 infection defined by positive nucleic acid amplification testing (NAAT).
Management
Monitor for relapsing COVID-19 in immunocompromised patients, especially those on B-cell depleting agents.
Monitoring & Follow-up
Weekly follow-up NP samples and monitoring of lymphocyte subpopulations in a subset of patients.
Risks
Increased risk of severe COVID-19 outcomes and mortality in patients with B-cell depletion.
Patient & Prescribing Data
Patients aged ≥ 18 years with laboratory-confirmed COVID-19 and criteria for immunosuppression.
Patients treated with B-cell depleting agents showed prolonged PCR positivity and delayed culture clearance.
Clinical Best Practices
Consider the risk of prolonged infection and unique mutations in severely immunocompromised patients. Implement close monitoring of COVID-19 progression in patients with prior B-cell depletion.
References