Discussion
Tixagevimab/Cilgavimab, tixagevimab/cilgavimab
SYSTEMIC INFLAMMATORY RESPONSE, PROGRESSION
During COVID-19 pandemic, SARS-CoV-2 was rapidly acquiring new mutations with the wide spread of new variants among the world population. At the start of our research in September 2022, the Omicron variant consisted of 5 main sublineages, BA.1, BA.2, BA.3, BA.4, and BA.5 (According to our previous study from February 2022, when the epidemiological data suggested the beginning of the Omicron surge, the use of mAb Regdanvimab led to a significant decrease in the severity of clinical manifestations according to the Clinical Progression Scale (Despite the persistent virus-neutralising activity of tixagevimab/cilgavimab against the Omicron variant, it was still reduced by 22-fold compared to the Wuhan variant. The decrease of virus-neutralizing activity against Omicron is confirmed by literature data. Cao et al. reported that the activity of Bamlanivimab/Etesevimab, Casirivimab/Imdevimab, and Tixagevimab/Cilgavimab was significantly weakened against BA.2.12.1, BA.4, and BA.5 Omicron sublineages, while Sotrovimab was still active, but with reduced effectiveness (In our study, effective viral-neutralizing activity against the variants mentioned above was demonstrated by the negative results of PCR testing for SARS-CoV-2 RNA on Day 4 in the Tixagevimab/Cilgavimab groups being significantly more frequent than that in the Regdanvimab group (p < 0.017). PCR results in the Tixagevimab/Cilgavimab IV groups were 100% negative regardless of the dose used. It was also noted that the systemic inflammatory response, namely the levels of CRP and D-dimer, was significantly lower by Day 4 in the Tixagevimab/Cilgavimab 600 mg IV group than in other groups regardless of the concomitant anti-inflammatory therapy.Upon IM administration of Tixagevimab/Cilgavimab, there was no increase in nAb titers immediately after administration due to the pharmacodynamics of mAbs, unlike with the IV administration. The nAb testing in this study was performed one hour after the drug administration and then on Day 4. The concentrations of mAbs in the Tixagevimab/Cilgavimab groups one hour after the administration were higher in the IV groups than those in the IM group, and became equal by Day 4, which is consistent with publication data (