Marchegiani Greta, Carioti Luca, Coppola Luigi, Iannetta Marco, Alborghetti Leonardo, Malagnino Vincenzo, Benedetti Livia, Santoro Maria Mercedes, Andreoni Massimo, Sarmati Loredana, Alteri Claudia, Ceccherini-Silberstein Francesca, Bellocchi Maria Concetta
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Clinical Infectious Disease, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Viruses. 2025 Apr 8;17(4):540. doi: 10.3390/v17040540.
This retrospective study analyzed SARS-CoV-2 Omicron variability since its emergence, focusing on immunocompromised (IPs) and non-immunocompromised adult people (NIPs). Phylogenetic analysis identified at least five major Omicron lineage groups circulating in Central Italy, from December 2021 to December 2023: (a) BA.1 (34.0%), (b) BA.2 + BA.4 (25.8%), (c) BA.5 + BF (10.8%), (d) BQ + BE + EF (9.2%), and (e) Recombinants (20.2%). The BA.2 + BA.4 lineages were more common in IPs compared to NIPs (30.9% vs. 17.8%, respectively; = 0.011); conversely, Recombinants were less prevalent in IPs than in NIPs (16.0% vs. 27.1%, respectively; = 0.018). High-abundant single nucleotide polymorphisms (SNPs; prevalence ≥ 40%) and non-synonymous SNPs (prevalence ≥ 20%) increased during the emergence of new variants, rising from BA.1 to Recombinants (54 to 92, and 43 to 70, respectively, both < 0.001). Evaluating the genetic variability, 109 SNPs were identified as being involved in significant positive or negative associations in pairs (phi > 0.70, < 0.001), with 19 SNPs associated in 3 distinct clusters (bootstrap > 0.96). Multivariate regression analysis showed that hospitalization was positively associated with one specific cluster, including S686R and A694S in Spike and L221F in Nucleocapsid (AOR: 2.74 [95% CI: 1.13-6.64, = 0.025]), and with increased age (AOR:1.03 [95% CI: 1.00-1.06], = 0.028). Conversely, negative associations with hospitalization were observed for female gender and previous vaccination status (AORs: 0.34 [95% CI: 0.14-0.83], = 0.017 and 0.19 (95% CI: 0.06-0.63, = 0.006, respectively). Interestingly, the S686R SNP located in a furin cleavage site suggests its potential pathogenetic role. The results show how Omicron genetic diversification significantly influences disease severity and hospitalization, together with age, sex, and vaccination status as key factors.
这项回顾性研究分析了自SARS-CoV-2奥密克戎毒株出现以来的变异情况，重点关注免疫功能低下者（IPs）和非免疫功能低下的成年人（NIPs）。系统发育分析确定了2021年12月至2023年12月期间在意大利中部传播的至少五个主要奥密克戎谱系组：（a）BA.1（34.0%），（b）BA.2 + BA.4（25.8%），（c）BA.5 + BF（10.8%），（d）BQ + BE + EF（9.2%），以及（e）重组毒株（20.2%）。与NIPs相比，BA.2 + BA.4谱系在IPs中更为常见（分别为30.9%和17.8%；P = 0.011）；相反，重组毒株在IPs中的流行率低于NIPs（分别为16.0%和27.1%；P = 0.018）。在新变种出现期间，高丰度单核苷酸多态性（SNP；流行率≥40%）和非同义SNP（流行率≥20%）增加，从BA.1到重组毒株（分别从54个增加到92个，以及从43个增加到70个，两者P均<0.001）。评估遗传变异性时，鉴定出109个SNP参与了显著的正相关或负相关配对（phi>0.70，P<0.001），其中19个SNP在3个不同的簇中相关（自展值>0.96）。多变量回归分析表明，住院与一个特定的簇呈正相关，该簇包括刺突蛋白中的S686R和A694S以及核衣壳蛋白中的L221F（调整后比值比：2.74 [95%置信区间：1.13 - 6.64，P = 0.025]），并且与年龄增加相关（调整后比值比：1.03 [95%置信区间：1.00 - 1.06]，P = 0.028）。相反，观察到女性性别和既往疫苗接种状态与住院呈负相关（调整后比值比分别为：0.34 [95%置信区间：0.14 - 0.83]，P = 0.017和0.19 [95%置信区间：0.06 - 0.63]，P = 0.006）。有趣的是，位于弗林蛋白酶切割位点的S686R SNP表明了其潜在的致病作用。结果表明奥密克戎的基因多样化如何显著影响疾病严重程度和住院情况，同时年龄、性别和疫苗接种状态是关键因素。
