Joseph R, Marais G, Iranzadeh I, Alisoltani A, Hardie D, Davies M-A, Heekes A, Chetty N, Timmerman V, Hsiao N-Y, Williamson C
Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Department of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
J Virol. 2025 Sep 5:e0078025. doi: 10.1128/jvi.00780-25.
Ongoing viral evolution in immunocompromised individuals with persistent infection may facilitate the evolution of SARS-CoV-2 and emergence of variants of concern (VOC). This study was conducted in the Western Cape Province of South Africa where the HIV prevalence is around 8%, with limited information on the frequency of persistent SARS-CoV-2 infection, the pattern of evolution in these individuals, and if these variants contribute to the diversity of circulating viruses. This study investigated 75 individuals with two or more SARS-CoV-2 diagnoses at least one month apart. Of the 75, 13 were people living with Human Immunodeficiency Virus (PLWH) of which three were immunocompromised, 23 were HIV-negative, and the status of the remaining 39 was unknown. SARS-CoV-2 full-length genome sequence analysis identified 72 as reinfections with a distinct variant and 3 as persistent infections with B.1.1 (20B), B.1.1.459 (20B), and B.1.351 (20H) for 7, 4, and 3 months, respectively. All persistent infections were in severely immunocompromised PLWH with CD4+ T cell count below 30 cells/µL. We identified the emergence of uncommon mutations (global prevalence <0.01%) in SARS-CoV-2, together with permanent and/or transient non-lineage defining mutations with immune escape potential particularly in Spike (141-144del; 241-244del; D215G; E484K; Q498R; P681R; A701V). Some of these mutations were found in later VOCs including Omicron lineages (L18F; 141-144del; D215G; E484K; Q498R; P681R; A701V). Longitudinal viral sequences from these persistent infections provided insights into the evolutionary trajectory of SARS-CoV-2 and are suggestive of convergent evolution and host adaptation.
Unlike other respiratory viruses, SARS-CoV-2 has not yet established a seasonal pattern. Thus, resurgence and the emergence of novel variants including VOCs remain a concern. Ongoing SARS-CoV-2 replication in immunocompromised individuals may serve as reservoirs that could facilitate the emergence of mutations conferring transient and/or long-lasting immune escape potential and seed future outbreaks. Two of the five variants, Beta variant and Omicron variant, were first described in Southern Africa-a region with one of the highest rates of HIV infection globally. Targeted genomic surveillance in immunocompromised individuals including PLWH will provide insight into the evolutionary trajectory of SARS-CoV-2 and inform vaccine design that may help to circumvent resurgence.
免疫功能低下且持续感染的个体中正在进行的病毒进化可能会促进严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的进化以及令人担忧的变异株（VOC）的出现。本研究在南非西开普省开展，该省的人类免疫缺陷病毒（HIV）流行率约为8%，但关于SARS-CoV-2持续感染的频率、这些个体中的进化模式以及这些变异株是否促成了循环病毒的多样性的信息有限。本研究调查了75名至少间隔一个月有两次或更多次SARS-CoV-2诊断的个体。在这75名个体中，13名是感染人类免疫缺陷病毒者（PLWH），其中3名免疫功能低下，23名HIV阴性，其余39名的状态未知。SARS-CoV-2全长基因组序列分析确定72例为不同变异株的再次感染，3例为分别持续感染B.1.1（20B）、B.1.1.459（20B）和B.1.351（20H）达7个月、4个月和3个月。所有持续感染均发生在CD4 + T细胞计数低于30个细胞/微升的严重免疫功能低下的PLWH中。我们在SARS-CoV-2中发现了罕见突变（全球流行率<0.01%）的出现，以及具有免疫逃逸潜力的永久性和/或短暂性非谱系定义突变，特别是在刺突蛋白中（141 - 144缺失；241 - 244缺失；D215G；E484K；Q498R；P681R；A701V）。其中一些突变在后来的VOC中被发现，包括奥密克戎谱系（L18F；141 - 144缺失；D215G；E484K；Q498R；P681R；A701V）。来自这些持续感染的纵向病毒序列为SARS-CoV-2的进化轨迹提供了见解，并提示了趋同进化和宿主适应性。
与其他呼吸道病毒不同，SARS-CoV-2尚未建立季节性模式。因此，包括VOC在内的病毒卷土重来和新变异株的出现仍然令人担忧。免疫功能低下个体中正在进行的SARS-CoV-2复制可能成为储存库，促进具有短暂和/或持久免疫逃逸潜力的突变出现，并引发未来的疫情。五个变异株中的两个，即贝塔变异株和奥密克戎变异株，最初是在南非被描述的，南非是全球HIV感染率最高的地区之一。对包括PLWH在内的免疫功能低下个体进行针对性的基因组监测，将为SARS-CoV-2的进化轨迹提供见解，并为可能有助于避免疫情卷土重来的疫苗设计提供信息。
