Velasquez-Reyes Joseline M, Schaeffer Beau, Curry Scott R, Overbeck Victoria, Sher-Jan Cole, Taylor Bradford P, Turcinovic Jacquelyn, Kuppalli Krutika, Connor John H, Hanage William P
Program in Bioinformatics, Boston University, Boston, MA, USA; Department of Virology, Immunology, and Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA.
Lancet Microbe. 2025 Jul 11:101122. doi: 10.1016/j.lanmic.2025.101122.
People who are immunocompromised can develop persistent SARS-CoV-2 infections. Several viral mutations accumulated during the course of such persistent infections have also been observed in prominent variants of concern (VOCs). Here, we characterise persistent infection and viral evolution of SARS-CoV-2 lasting more than 750 days in a person with advanced HIV-1 infection.
Between March, 2021, and July, 2022, eight clinical specimens were collected from a person living with HIV, neither receiving antiretroviral therapy nor virally suppressed, and presumed to have been initially infected with SARS-CoV-2 in mid-May, 2020. Viral RNA was extracted from each swab and an amplicon-based sequencing approach was used for genomic analysis of SARS-CoV-2. Variable sites were characterised at the consensus and subconsensus levels, and phylogenetic tools were applied to analyse viral evolution. Publicly available SARS-CoV-2 sequences from GenBank were leveraged to contextualise our sequenced samples and identify any potential evidence of transmission.
Genomes formed a monophyletic cluster in the B.1 lineage. 68 consensus and 67 subconsensus single nucleotide variants were observed over the course of infection. The intrahost clock rate remained similar to that of the interhost rate in contemporaneous community sequences (6·74 × 10 [95% credible interval 5·05 × 10 to 8·54 × 10] substitutions per site per year vs 6·11 × 10 [5·54 × 10 to 6·66 × 10]). Mutations grouped into two distinct subpopulations present throughout infection. 10 non-synonymous mutations in the spike protein gene were at positions in common with those defining the omicron lineage (BA.1 or BA.2), of which nine were present before November, 2021. Nine of 18 substitutions present throughout infection were rare in online databases, suggesting a lack of long transmission chains descending from this individual.
Convergent SARS-CoV-2 evolution, both in and outside the spike protein, observed in this study suggests parallels with the evolutionary process leading to emergence of the omicron VOC. The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host. Our results underscore the importance of appropriate treatment to cure persistent SARS-CoV-2 infections and monitoring them to understand how mutations contribute to viral adaptation.
National Institute of General Medical Sciences of the National Institutes of Health, Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, MassCPR, and Morris Singer Foundation.
免疫功能低下的人可能会发生严重急性呼吸综合征冠状病毒2（SARS-CoV-2）持续感染。在这种持续感染过程中积累的几种病毒突变，在值得关注的主要变异株（VOCs）中也有观察到。在此，我们对一名晚期人类免疫缺陷病毒1型（HIV-1）感染者体内持续超过750天的SARS-CoV-2持续感染和病毒进化进行了特征分析。
在2021年3月至2022年7月期间，从一名未接受抗逆转录病毒治疗且病毒未得到抑制的HIV感染者身上采集了8份临床标本，推测该患者于2020年5月中旬初次感染SARS-CoV-2。从每份拭子中提取病毒RNA，并采用基于扩增子的测序方法对SARS-CoV-2进行基因组分析。在共识和亚共识水平上对可变位点进行了特征分析，并应用系统发育工具分析病毒进化。利用来自GenBank的公开可用SARS-CoV-2序列来关联我们测序的样本，并识别任何潜在的传播证据。
基因组在B.1谱系中形成一个单系簇。在感染过程中观察到68个共识单核苷酸变异和67个亚共识单核苷酸变异。宿主内的时钟速率与同期社区序列中的宿主间速率相似（每年每个位点6.74×10[95%可信区间5.05×10至8.54×10]个替换，而宿主间速率为6.11×10[5.54×10至6.66×10]）。突变分为在整个感染过程中存在的两个不同亚群。刺突蛋白基因中的10个非同义突变与定义奥密克戎谱系（BA.1或BA.2）的突变位点相同，其中9个在2021年11月之前就已存在。在整个感染过程中出现的18个替换中有9个在在线数据库中很罕见，这表明没有从该个体衍生出的长传播链。
本研究中观察到的SARS-CoV-2在刺突蛋白内外的趋同进化表明，与导致奥密克戎VOC出现的进化过程存在相似之处。推断没有后续感染可能表明在适应单一宿主的过程中传播能力丧失。我们的结果强调了适当治疗以治愈SARS-CoV-2持续感染并对其进行监测以了解突变如何促进病毒适应的重要性。
美国国立卫生研究院国家普通医学科学研究所、疾病控制与预防中心、国家过敏和传染病研究所、MassCPR以及莫里斯·辛格基金会
