Researchers from Inserm UMR1297, Université Toulouse-France, and Centre Hospitalier Universitaire de Toulouse-France have conducted a groundbreaking study shedding light on how the Omicron variant affects blood platelets and comparing it to the Delta variant. This study aimed to understand platelet behavior in severe COVID-19 patients infected with the Omicron variant and its implications for the virus-platelet interaction.
Platelets, tiny cellular elements, play a crucial role in maintaining normal hemostasis and responding to vascular injuries. In severe COVID-19 cases, platelet activation has been linked to thromboembolic events and exacerbated inflammatory responses. Despite the low presence of the primary receptor for SARS-CoV-2 in platelets, they have been shown to contain viral particles and can internalize the virus. SARS-CoV-2 infection also modifies the transcriptome of platelets, triggering an antiviral response.
The Omicron variant, characterized by a notable accumulation of mutations in the spike protein, has enhanced transmissibility potential. Initial reports suggested that Omicron induced milder symptoms compared to previous variants, but this study challenges that notion. The severity of Omicron-infected patients, as assessed by the Sequential Organ Failure Assessment (SOFA) score, was generally less severe than Delta-infected patients, but mortality rates remained high. Both patient groups showed elevated levels of pro-inflammatory cytokines, indicating persistent inflammatory responses.
The study analyzed several aspects of platelet behavior in Omicron-infected patients. Surface expression of key platelet glycoproteins indicated platelet activation, which was further supported by electron microscopy analysis. Soluble platelet activation markers were significantly increased in Omicron-infected patients compared to controls. Platelet hyporesponsiveness was observed in Omicron-infected patients, similar to severe Delta infection. Platelets from Omicron-infected patients exhibited elevated expression of IFITM3, an interferon-induced transmembrane protein that inhibits viral replication, but to a lesser extent than Delta-infected patients. Toll-like receptor (TLR) activation in platelets also differed between the two variants.
Viral-like particles were found within platelets from severe Omicron-infected patients, indicating the ability of the variant to infect and reside within platelets. The distribution of spike protein in platelets differed between the two variants, and the Omicron spike protein exhibited faster kinetics in activating signaling pathways compared to Delta. These observations highlight the distinct mechanisms of entry, processing, and platelet signaling induced by the two variants.
Understanding how platelets respond to different SARS-CoV-2 variants is crucial for deciphering their thrombotic potential and antiviral functions. These findings have implications for developing therapeutic strategies targeting the virus-platelet interaction. Ongoing research is essential to adapt our understanding of SARS-CoV-2’s interaction with the host immune system, including blood platelets, and to devise effective treatments and interventions to combat the evolving COVID-19 pandemic.