Navigating the Evolving SARS-CoV-2 Threat: Insights into Recent Omicron Subvariants and Co-Infections
- Ray Sullivan
- 8 minutes ago
- 3 min read
The SARS-CoV-2 pandemic may be behind us, but the virus continues its relentless evolution, posing ongoing challenges to public health. Research at the Center for Discovery & Innovation, led by Nadine Alvarez and David Perlin, sheds light on the immune evasion strategies and pathogenic potential of emerging Omicron subvariants, particularly in the context of co-infections with other prevalent respiratory viruses. The research employs a human bronchial airway epithelial cell (hBAEC) air-liquid interface model to mimic the lung epithelium, offering a physiologically relevant platform for investigation.
A key finding from this study underscores the diminished efficacy of current antibody-based interventions against newer Omicron subvariants. Commercial antibodies, including AM359b, casirivimab, and bebtelovimab, showed significantly reduced neutralizing activity against strains like JN.1 and its descendants. For instance, AM359b's neutralization capacity dropped below 50% for emerging strains starting with Omicron BA.5 and fell to less than 20% against EG.5.1. Similarly, casirivimab and bebtelovimab, while effective against the ancestral WA1/2020 strain, remained largely below 50% neutralization for most evolved Omicron subvariants. This aligns with real-world observations, such as the FDA's updates regarding bebtelovimab's reduced activity against BQ.1 and BQ.1.1 Omicron subvariants and the withdrawal of casirivimab for treatment and post-exposure prophylaxis due to its decreased potency against Omicron.
Moreover, human convalescent plasma samples collected in 2020 from unvaccinated donors, which had robust neutralizing activity against the ancestral WA1/2020 strain, provided little to no protection against Omicron JN.1 and its descendants (e.g., KS.1, LB.1, KP.2.3, KP.3.1.1, KP.3.1.4, and XDK.1). This highlights the remarkable adaptive capacity of SARS-CoV-2, particularly in its spike protein, where numerous amino acid substitutions directly impact the effectiveness of neutralizing antibodies and contribute to immune escape. Mutations like R346T, seen in LB.1 and KP.2 and their descendants, are linked to reduced neutralization. The study's observations emphasize the urgent need for updated vaccine compositions to re-establish immunity levels in the population.
Contrary to some previous reports suggesting milder disease with Omicron, this study reveals that recent Omicron subvariants JN.1 and KP.3.1.1 induced a more significant infection and cytopathic effect in hBAEC compared to the ancestral WA1/2020 strain. KP.3.1.1 notably caused a more pronounced cytopathic effect than its parental JN.1 and even surpassed the impact observed with WA1/2020. This enhanced infectivity was supported by higher viral loads detected in both apical and basolateral compartments of the hBAEC model.
The study also delved into the increasingly recognized phenomenon of co-infections, noting that SARS-CoV-2 often circulates alongside other respiratory viruses like Influenza A virus H1N1 (IFAV_H1N1) and Respiratory Syncytial Virus (RSV). A crucial finding was that co-infection of KP.3.1.1 with IFAV_H1N1 or RSV did not attenuate SARS-CoV-2 infectivity. Instead, it significantly exacerbated the pathogenic synergy in the lung epithelium. While co-infection with IFAV_H1N1 did not enhance apical SARS-CoV-2 infection compared to monoinfection, the combination with RSV showed a significant increase in SARS-CoV-2 infection levels. Microscopic analysis of co-infected hBAEC showed more severe epithelial damage, disorganization, and disruption of tight junctions, alongside a reduction in goblet cell marker, indicating compromised epithelial barrier integrity.
The research also profiled the host immunological response in hBAEC. It found that pro-inflammatory cytokines IL-6, IFN-β, and IL-10 were upregulated following SARS-CoV-2 monoinfection with recent Omicron subvariants, as well as during co-infection with IFAV_H1N1 and RSV. Interestingly, a polarized secretion of cytokines predominantly to the apical compartment was observed, suggesting a key role in modulating the hBAEC response to viral infections. While WA1/2020 induced a strong IFN-β response, which might explain its lower infectivity, the overall cytokine profiles in co-infections underscore a robust inflammatory response.
These findings offer vital new insights into the complex interplay between evolving SARS-CoV-2 Omicron subvariants and other respiratory viruses, especially regarding their impact on the human lung epithelium. The study's use of the hBAEC air-liquid interface model is particularly valuable, providing a highly relevant ex vivo system to understand viral behaviors and interactions, minimizing the need for animal models. The continued emergence of new subvariants with enhanced immune evasion and the potential for aggravated pathology during co-infections carry significant implications for therapeutic development and public health preparedness. These data reinforce the need for ongoing surveillance, deeper characterization of viral pathogenesis, and rapid adaptation of countermeasures to combat the ever-changing landscape of respiratory viral threats.
Alvarez N, Gonzalez-Jimenez I, Rasheed R, Goldgirsh K, Park S, Perlin DS. Genetic and Immunological Profiling of Recent SARS-CoV-2 Omicron Subvariants: Insights into Immune Evasion and Infectivity in Monoinfections and Coinfections. Viruses. 2025 Jun 27;17(7):918. doi: 10.3390/v17070918. PMID: 40733536; PMCID: PMC12300583.