Faculty of Science, Department of Microbiology, Mahidol University, Bangkok, Thailand.
Faculty of Medicine, Department of Microbiology, Universitas Airlangga, Surabaya, Indonesia.
PLoS One. 2024 Apr 3;19(4):e0301330. doi: 10.1371/journal.pone.0301330. eCollection 2024.
The ongoing COVID-19 pandemic has led to the emergence of new SARS-CoV-2 variants as a result of continued host-virus interaction and viral genome mutations. These variants have been associated with varying levels of transmissibility and disease severity. We investigated the phenotypic profiles of six SARS-CoV-2 variants (WT, D614G, Alpha, Beta, Delta, and Omicron) in Calu-3 cells, a human lung epithelial cell line. In our model demonstrated that all variants, except for Omicron, had higher efficiency in virus entry compared to the wild-type. The Delta variant had the greatest phenotypic advantage in terms of early infection kinetics and marked syncytia formation, which could facilitate cell-to-cell spreading, while the Omicron variant displayed slower replication and fewer syncytia formation. We also identified the Delta variant as the strongest inducer of inflammatory biomarkers, including pro-inflammatory cytokines/chemokines (IP-10/CXCL10, TNF-α, and IL-6), anti-inflammatory cytokine (IL-1RA), and growth factors (FGF-2 and VEGF-A), while these inflammatory mediators were not significantly elevated with Omicron infection. These findings are consistent with the observations that there was a generally more pronounced inflammatory response and angiogenesis activity within the lungs of COVID-19 patients as well as more severe symptoms and higher mortality rate during the Delta wave, as compared to less severe symptoms and lower mortality observed during the current Omicron wave in Thailand. Our findings suggest that early infectivity kinetics, enhanced syncytia formation, and specific inflammatory mediator production may serve as predictive indicators for the virulence potential of future SARS-CoV-2 variants.
持续的 COVID-19 大流行导致了新的 SARS-CoV-2 变体的出现，这是由于持续的宿主-病毒相互作用和病毒基因组突变。这些变体与不同程度的传染性和疾病严重程度有关。我们研究了六种 SARS-CoV-2 变体（WT、D614G、Alpha、Beta、Delta 和 Omicron）在 Calu-3 细胞（一种人肺上皮细胞系）中的表型特征。在我们的模型中，除了 Omicron 变体外，所有变体的病毒进入效率都高于野生型。Delta 变体在早期感染动力学和明显合胞体形成方面具有最大的表型优势，这可能有助于细胞间传播，而 Omicron 变体显示出较慢的复制和较少的合胞体形成。我们还发现 Delta 变体是最强的促炎生物标志物诱导剂，包括促炎细胞因子/趋化因子（IP-10/CXCL10、TNF-α 和 IL-6）、抗炎细胞因子（IL-1RA）和生长因子（FGF-2 和 VEGF-A），而这些炎症介质在感染 Omicron 时并没有显著升高。这些发现与以下观察结果一致，即在 COVID-19 患者的肺部中，Delta 波期间通常会出现更明显的炎症反应和血管生成活性，以及更严重的症状和更高的死亡率，而在泰国目前的 Omicron 波期间，症状较轻且死亡率较低。我们的研究结果表明，早期感染动力学、增强的合胞体形成和特定炎症介质的产生可能成为未来 SARS-CoV-2 变体毒力潜力的预测指标。
