Abstract：
BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics.
METHODS: From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host.
RESULTS: Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts.
CONCLUSIONS: This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.
METHODS: From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host.
RESULTS: Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts.
CONCLUSIONS: This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.
摘要：
背景：SARS-CoV-2感染在免疫功能低下的宿主中比在免疫功能正常的患者中持续时间更长。长期感染与选择新型SARS-CoV-2突变的可能性更高相关，特别是在刺突蛋白中，疫苗和治疗的关键目标。
方法：从2020年12月至2022年9月，在巴黎两家医院诊断的444名免疫功能低下患者和234名医护人员的呼吸道样本对SARS-CoV-2呈阳性，法国,使用纳米孔技术进行全基因组测序分析。开发了自定义脚本以评估两组之间和宿主内部的SARS-CoV-2遗传多样性。
结果：大多数感染是SARS-CoV-2Delta或Omicron谱系。免疫功能低下患者感染的病毒遗传多样性明显高于对照组。在免疫受损个体测序的病毒中发现了微小的突变，随着疫情的进展，这成为了新的SARS-CoV-2变体的特征突变。两名患者共感染了Delta和Omicron变体。对免疫功能低下患者的随访显示，SARS-CoV-2基因组进化在上下呼吸道有所不同。
结论：这项研究发现，免疫功能低下患者的SARS-CoV-2感染与较高的遗传多样性有关，这可能导致新的SARS-CoV-2变体的出现，这些变体可能具有免疫逃避或不同的毒力特征。
方法：从2020年12月至2022年9月，在巴黎两家医院诊断的444名免疫功能低下患者和234名医护人员的呼吸道样本对SARS-CoV-2呈阳性，法国,使用纳米孔技术进行全基因组测序分析。开发了自定义脚本以评估两组之间和宿主内部的SARS-CoV-2遗传多样性。
结果：大多数感染是SARS-CoV-2Delta或Omicron谱系。免疫功能低下患者感染的病毒遗传多样性明显高于对照组。在免疫受损个体测序的病毒中发现了微小的突变，随着疫情的进展，这成为了新的SARS-CoV-2变体的特征突变。两名患者共感染了Delta和Omicron变体。对免疫功能低下患者的随访显示，SARS-CoV-2基因组进化在上下呼吸道有所不同。
结论：这项研究发现，免疫功能低下患者的SARS-CoV-2感染与较高的遗传多样性有关，这可能导致新的SARS-CoV-2变体的出现，这些变体可能具有免疫逃避或不同的毒力特征。
