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Naslov:Respiratory microbiome alterations, coinfections and virus intra-host evolution in a persistently active SARS-CoV-2 infection
Avtorji:ID Boltežar, Lučka (Avtor)
ID Kogoj, Rok (Avtor)
ID Resman Rus, Katarina (Avtor)
ID Suljič, Alen (Avtor)
ID Bosilj, Martin (Avtor)
ID Knap, Nataša (Avtor)
ID Mali, Polonca (Avtor)
ID Tomažič, Janez (Avtor)
ID Avšič-Županc, Tatjana (Avtor)
ID Korva, Miša (Avtor)
Datoteke:.pdf PDF - Predstavitvena datoteka, prenos (1,75 MB)
MD5: 98575D8D5858133BC99271E535B897B4
 
URL URL - Izvorni URL, za dostop obiščite https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-025-11355-x
 
Jezik:Angleški jezik
Tipologija:1.03 - Drugi znanstveni članki
Organizacija:Logo UKC LJ - Univerzitetni klinični center Ljubljana
Povzetek:Background: Respiratory microbiome alterations, coinfections, and virus intrahost evolution are of great interest in persistently viable SARS-CoV-2 infections in the context of antiviral treatment and immune response. However, samples before, during, and after infection are seldom available to researchers. Therefore, there has been a significant lack of opportunities to comprehensively study microbiota homeostasis, coinfections, and virus intra-host evolution on the consensus and minor variants scale in response to antiviral treatments and patient immune response. Case presentation: A 63-year-old female patient with diffuse large B-cell lymphoma received multiple treatments for SARS-CoV-2 that remained active 169 days. Together, 32 respiratory and 19 serum samples were collected before, during, and after (- 398 to 233 days) COVID-19. Subsets were selected for virus viability testing by culture (20) and subgenomic (sg) RNA (20) measurement, intra-host evolution assessment (18), microbiome composition analysis (28), and coinfection identification (11). IgA/IgG and neutralizing anti-SARS-CoV-2 antibodies were measured 19 times throughout the infection. SARSCoV-2 lineage XBB.1.16.11 persisted and remained viable until 116 days post infection (PI) regardless of treatments. No sgRNA marker tested was suitable for virus viability prediction. IgG/IgA antibodies first appeared after 38 days, but the virus persisted regardless of multiple plasma treatments before neutralizing antibodies appeared (100 days PI) and finally cleared the virus 116 days PI. Consensus-level mutations fluctuated around 102.7 ± 4.0, and minor variants increased from six to 61 with a mutation rate of 4.9 × 10-3 per site per year, with the highest average number of mutations per gene length in S and E (0.013) with surges after every antiviral treatment. The transversion/transition ratio increased from 0.50 (day 0) to 0.57 (day 24) with a steady decrease to 0.48 (day 147). Mutational signature analysis showed dominance of C > T substitutions consistent with APOBEC antiviral enzyme activity. Upper respiratory microbiota showed three distinct profiles with varying α-/β-diversity and an association of Staphylococcus spp. with COVID-19. Conclusions: These findings further elucidate the dynamics of intra-host viral evolution and complexities of virus clearance in individuals with hematological malignancies and highlight the impact of antiviral treatments on the potential of virus variants emergence in longitudinally infectious patients due to delayed immune response.
Ključne besede:B-cell lymphoma, hematological malignancies, microbiome, prolonged SARS-CoV_2 infection, virus evolution, virus shedding
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Leto izida:2025
Št. strani:1-11 str.
Številčenje:Vol. 25, iss. 1, [article no.] 932
PID:20.500.12556/DiRROS-29154 Novo okno
UDK:616.9
ISSN pri članku:1471-2334
DOI:10.1186/s12879-025-11355-x Novo okno
COBISS.SI-ID:245172995 Novo okno
Opomba:Nasl. z nasl. zaslona; Opis vira z dne 7. 8. 2025;
Datum objave v DiRROS:22.04.2026
Število ogledov:97
Število prenosov:47
Metapodatki:XML DC-XML DC-RDF
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Gradivo je del revije

Naslov:BMC infectious diseases
Skrajšan naslov:BMC Infect Dis
Založnik:BioMed Central
ISSN:1471-2334
COBISS.SI-ID:2439444 Novo okno

Gradivo je financirano iz projekta

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P3-0083-2022
Naslov:Odnosi parazitskega obstajanja

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P3-0289-2019
Naslov:Značilnosti malignih neoplazem, pomembne za diagnozo ter napoved poteka bolezni in izida zdravljenja

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:J3-50101-2023
Naslov:Karakterizacija virusnih podvrst in mutacijskega podpisa virusa SARS-CoV-2 pri imunsko oslabelih bolnikih

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:I0-0022-2022
Naslov:Mreža raziskovalnih infrastrukturnih centrov Univerze v Ljubljani (MRIC UL)

Licence

Licenca:CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
Opis:Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:B-celični limfom, hematološke malignosti, mikrobiom, dolgotrajna okužba s SARS-CoV-2, razvoj virusa, izločanje virusa


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