Microbiology Unit, DIMEC, Alma Mater Studiorum Università di Bologna, Bologna, Italy.
Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Virol J. 2024 Sep 3;21(1):210. doi: 10.1186/s12985-024-02483-y.
SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time.
SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time.
Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th.
Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients.
SARS-CoV-2 是导致当前全球大流行的罪魁祸首，新型变异株的不断出现威胁着脆弱人群，如免疫功能低下的患者。这类患者亚群似乎受到宿主内病毒变化的严重影响，因为病原体热衷于造成复制效率低下，影响受损的免疫系统，从而阻止病毒的有效清除。因此，这些患者可能是新的循环 SARS-CoV-2 变异株发展的最佳储库。本研究旨在调查随时间推移 SARS-CoV-2 阳性免疫功能低下患者的基因组变化。
对每位患者（患者 A 和患者 B）在不同时间点采集 SARS-CoV-2 阳性鼻咽拭子，提取后通过下一代测序（NGS）进行分析。检查所得序列以确定突变频率，描述病毒随时间的进化。
患者 A 为患有血液肿瘤的 53 岁患者，2022 年 5 月 28 日至 7 月 18 日持续感染 51 天。于 5 月 28 日、6 月 15 日和 7 月 4 日采集了 3 份确诊的 SARS-CoV-2 阳性样本。患者 B 为 75 岁血液肿瘤患者，持续感染 146 天。在以下时间点采集了 2 份确诊的 SARS-CoV-2 阳性样本：5 月 21 日和 8 月 18 日。
热图构建为两位患者提供了病毒随时间获得和/或丢失突变的证据，表明病毒在宿主内的基因组进化。此外，还观察到患者 B 中 SARS-CoV-2 谱系的突变多态性和变化。序列分析显示高突变模式变异性，反映了脆弱患者中病毒复制动力学的高度复杂性。
