SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant

Abstract

IntroductionIn November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta.MethodsClinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling.ResultsSevere Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics.DiscussionAlthough SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.

Morphology and Function of Red Blood Cells in COVID-19 Patients: Current Overview 2023

“…Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation [18,52]. This has previously been described in COVID-19 patients [10,53], especially when platelets are also activated [54][55][56]. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation [18,52].…”

“…Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation [18,52]. This has previously been described in COVID-19 patients [10,53], especially when platelets are also activated [54][55][56].…”

Does SARS-CoV-2 infect platelets?

“…Omicron is also found in platelets from severe patients, inducing selective autophagy. However, the mechanisms of intraplatelet processing of Omicron cargo differ from Delta, suggesting that S protein mutations modify virus-platelet interactions ( 52 ). Although several receptors on platelet surface ( Figure 1 ), besides ACE2, proposed for viral entry in platelets, due to the limited in vivo experimental evidence, further studies are required to substantiate these claims.…”

1,25‐Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS‐CoV‐2 spike protein via inhibiting integrin αIIbβ3 outside‐in signaling

“…29 Additionally, platelet hyperreactivity induced by Omicron subvariant infection may be associated with increasing platelet autophagy structures and inflammation. 30 Therefore, in our follow-up study, we will explore the effects of 1,25(OH) 2 D 3 on platelet function stimulated by spike protein from distinct variants.…”