Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis
Coronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian p...
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2024-12-01
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| author | Asma Themlaoui Massimo Ancora Kais Ghedira Yosra Mhalla Manel Hamdoun Maroua Bahri Lamia Aissaoui Raihane Ben Lakhal Adriano Di Pasquale Cesare Camma Olfa Bahri |
| author_facet | Asma Themlaoui Massimo Ancora Kais Ghedira Yosra Mhalla Manel Hamdoun Maroua Bahri Lamia Aissaoui Raihane Ben Lakhal Adriano Di Pasquale Cesare Camma Olfa Bahri |
| author_sort | Asma Themlaoui |
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| description | Coronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian patients with hematological malignancies (40.5% with lymphoma and 37.8% with leukemia). In order to investigate the accumulation of viral mutations, we carried out genetic investigation on longitudinal nasopharyngeal samples using RT-PCR and whole-genome sequencing. Patients’ samples were collected until the RT-PCR results became negative. SARS-CoV-2 infection was symptomatic in 48.6% of cases with fever, and cough was symptomatic in 61% of cases; the mortality rate was estimated to be 13.5%. The duration of viral RNA shedding ranged from 7 to 92 days after onset; it exceeded 18 days in 79.4% of cases. An intermittent PCR positivity was observed in two symptomatic patients. Persistent PCR positivity, defined as the presence of viral RNA for more than 30 days, was found in 51.4% of cases. No significant differences were observed for age, sex, type of hematological malignancy, or COVID-19 evolution between this group and a second one characterized by non-persistent PCR positivity. Lymphopenia was an independent predictor of prolonged SARS-CoV-2 RNA detection (<i>p</i> = 0.04). Three types of variants were detected; the most frequent was the Omicron. Globally, the mean intra-host variability in the SARS-CoV-2 genome was 1.31 × 10<sup>−3</sup> mutations per site per year; it was 1.44 × 10<sup>−3</sup> in the persistent group and 1.3 × 10<sup>−3</sup> in the non-persistent group. Three types of mutations were detected; the most frequent were nucleotide substitutions in the spike (S) gene. No statistically significant difference was observed between the two groups as to the type and mean number of observed mutations in the whole genome and the S region (<i>p</i> = 0.650). Sequence analysis revealed the inclusion of one to eight amino acid-changing events in seventeen cases; it was characterized by genetic stability from the third to the twentieth day of evolution in six cases. For the two patients with intermittent PCR positivity, sequences obtained from samples before and after negative PCR were identical in the whole genome, confirming an intra-host evolution of the same viral strain. This study confirms the risk of persistent viral shedding in patients with hematological malignancies. However, persistence of PCR positivity seems to be correlated only with a continuous elimination of viral RNA debris. Additional studies based on cell culture analysis are needed to confirm these findings. |
| format | Article |
| id | doaj-art-9ea1c3415cc64287beaf384a009f15d1 |
| institution | Kabale University |
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| spelling | doaj-art-9ea1c3415cc64287beaf384a009f15d12025-01-24T13:52:23ZengMDPI AGViruses1999-49152024-12-011714610.3390/v17010046Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic AnalysisAsma Themlaoui0Massimo Ancora1Kais Ghedira2Yosra Mhalla3Manel Hamdoun4Maroua Bahri5Lamia Aissaoui6Raihane Ben Lakhal7Adriano Di Pasquale8Cesare Camma9Olfa Bahri10Laboratory of Microbiology and Biochemistry (LR16SP01), Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaNational Reference Centre for Whole Genome Sequencing of Microbial Pathogens: Database and Bioin-Formatic Analysis (GENPAT), Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise, 64100 Teramo, ItalyLaboratory of Bioinformatics, Biomathematics and Biostatistics (LR20IPT09), Pasteur Institute of Tunis, Tunis 1002, TunisiaLaboratory of Microbiology and Biochemistry (LR16SP01), Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaLaboratory of Microbiology and Biochemistry (LR16SP01), Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaHematology Department, Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaHematology Department, Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaHematology Department, Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaNational Reference Centre for Whole Genome Sequencing of Microbial Pathogens: Database and Bioin-Formatic Analysis (GENPAT), Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise, 64100 Teramo, ItalyNational Reference Centre for Whole Genome Sequencing of Microbial Pathogens: Database and Bioin-Formatic Analysis (GENPAT), Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise, 64100 Teramo, ItalyLaboratory of Microbiology and Biochemistry (LR16SP01), Aziza Othmana Hospital, University Tunis El Manar, Tunis 1068, TunisiaCoronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian patients with hematological malignancies (40.5% with lymphoma and 37.8% with leukemia). In order to investigate the accumulation of viral mutations, we carried out genetic investigation on longitudinal nasopharyngeal samples using RT-PCR and whole-genome sequencing. Patients’ samples were collected until the RT-PCR results became negative. SARS-CoV-2 infection was symptomatic in 48.6% of cases with fever, and cough was symptomatic in 61% of cases; the mortality rate was estimated to be 13.5%. The duration of viral RNA shedding ranged from 7 to 92 days after onset; it exceeded 18 days in 79.4% of cases. An intermittent PCR positivity was observed in two symptomatic patients. Persistent PCR positivity, defined as the presence of viral RNA for more than 30 days, was found in 51.4% of cases. No significant differences were observed for age, sex, type of hematological malignancy, or COVID-19 evolution between this group and a second one characterized by non-persistent PCR positivity. Lymphopenia was an independent predictor of prolonged SARS-CoV-2 RNA detection (<i>p</i> = 0.04). Three types of variants were detected; the most frequent was the Omicron. Globally, the mean intra-host variability in the SARS-CoV-2 genome was 1.31 × 10<sup>−3</sup> mutations per site per year; it was 1.44 × 10<sup>−3</sup> in the persistent group and 1.3 × 10<sup>−3</sup> in the non-persistent group. Three types of mutations were detected; the most frequent were nucleotide substitutions in the spike (S) gene. No statistically significant difference was observed between the two groups as to the type and mean number of observed mutations in the whole genome and the S region (<i>p</i> = 0.650). Sequence analysis revealed the inclusion of one to eight amino acid-changing events in seventeen cases; it was characterized by genetic stability from the third to the twentieth day of evolution in six cases. For the two patients with intermittent PCR positivity, sequences obtained from samples before and after negative PCR were identical in the whole genome, confirming an intra-host evolution of the same viral strain. This study confirms the risk of persistent viral shedding in patients with hematological malignancies. However, persistence of PCR positivity seems to be correlated only with a continuous elimination of viral RNA debris. Additional studies based on cell culture analysis are needed to confirm these findings.https://www.mdpi.com/1999-4915/17/1/46hematological malignanciesSARS-CoV-2 infectionwhole-genome sequencingviral shedding |
| spellingShingle | Asma Themlaoui Massimo Ancora Kais Ghedira Yosra Mhalla Manel Hamdoun Maroua Bahri Lamia Aissaoui Raihane Ben Lakhal Adriano Di Pasquale Cesare Camma Olfa Bahri Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis Viruses hematological malignancies SARS-CoV-2 infection whole-genome sequencing viral shedding |
| title | Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis |
| title_full | Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis |
| title_fullStr | Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis |
| title_full_unstemmed | Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis |
| title_short | Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis |
| title_sort | virological aspects of covid 19 in patients with hematological malignancies duration of viral shedding and genetic analysis |
| topic | hematological malignancies SARS-CoV-2 infection whole-genome sequencing viral shedding |
| url | https://www.mdpi.com/1999-4915/17/1/46 |
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