{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:25:30Z","timestamp":1777861530976,"version":"3.51.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Immunocompromised patients with B-cell depletion are at risk of ongoing SARS-CoV-2 replication that can lead to intra-host genomic divergence, immune escape during treatment and potentially emergence of novel variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective observational study including severely immunocompromised rheumatic and hematologic patients with laboratory-confirmed COVID-19. SARS-CoV-2 virome sequencing was performed on respiratory samples, followed by phylogenetic and intrahost single nucleotide variants (iSNVs) analysis. In a subset of patients, lymphocyte subpopulations were assessed by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-six patients were included (median age: 71 years, rheumatic disease: 50%, treated with B-cell depleting agent: 88%, prior COVID-19 infection: 68%, relapsing COVID-19: 65%, \u2265 3 vaccine doses: 68%). Twenty-two patients (85%) were hospitalized with 23% mortality. Three unique RdRP and 3CLPro gene mutations were identified with a prevalence &amp;lt; 0.1%, not known to confer antiviral resistance. We identified 30 mutations in the spike gene with prevalence &amp;lt; 0.1% or leading to a new N-glycosylation site. In patients with paired samples, we noticed a statistically significant iSNVs accumulation with an average substitution rate per site per day of 7 \u00d7 10\n                      <jats:sup>\u20136<\/jats:sup>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). We did not observe statistically significant difference in the substitution rates between rheumatic and hematologic patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In our cohort, a significant proportion of patients had relapsing COVID-19. Unique and rare mutations were detected mainly in the spike gene, whereas those in the polymerase and protease genes were not of known significance. We found a positive correlation of iSNVs accumulation with infection duration, without difference in substitution rates between rheumatic and hematologic patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1715096","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:23:24Z","timestamp":1777523004000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrahost viral evolution of SARS-CoV-2 infections in rheumatic versus hematological patients with severe iatrogenic immunosuppression"],"prefix":"10.3389","volume":"13","author":[{"given":"Emmanouil","family":"Karofylakis","sequence":"first","affiliation":[{"name":"4th Department of Internal Medicine, National and Kapodistrian University of Athens School of Medicine, Attikon University General Hospital","place":["Chaidari, 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