Effect of multiple apheresis platelet donation on platelet indexes and aggregation rate in platelet donors / 中国输血杂志

【Objective】 To investigate the effect of multiple apheresis platelet donation on platelet indexes and aggregation function in platelet donors, and to analyze the relationship between platelet indexes and their relationship with platelet aggregation rate. 【Methods】 A total of 83 platelet donors were randomly selected from Foshan Central Blood Station from September 2021 to October 2022, and were divided into control group (n= 9, first-time platelet donors or donors with the time interval from the last platelet donation >1 year) and study group (n= 74, repeat platelet donors or donors with the time interval from the last platelet donation ≤ 1 year) according to the times of blood donation. The study group was divided into 4 subgroups: 2-5 times group, 6-10 times group, 11-15 times group and 16 times group. The platelet count(Plt), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), and maximum platelet aggregation rate (MAR) before donation in each group were detected and analyzed. 【Results】 There were no significant differences in Plt, MPV, PDW, P-LCR and MAR between the subgroups and the control group (P>0.05), and there were no significant differences in Plt, MPV, PDW, P-LCR and MAR between each subgroup (P>0.05) .There was a positive correlation between Plt and MAR in blood donors (P<0.05), and the correlation coefficient was 0.445. MPV, PDW and P-LCR were negatively correlated with MAR (P<0.05), and the correlation coefficients were -0.282, -0.233 and -0.217, respectively. Plt was negatively correlated with MPV, PDW and P-LCR (P < 0. 05), and the correlation coefficients were -0.399, -0.307 and -0.339, respectively. MPV, PDW and P-LCR are positively correlated with each other. The correlation coefficient between MPV and PDW was 0.792, that between MPV and P-LCR was 0.863, and tthat between PDW and P-LCR was 0.817. 【Conclusion】 There was no significant effect of multiple platelet donations on Plt, PDW, MPV, P-LCR and MAR in blood donors. Plt has the most significant impact on MAR among platelet indexes of platelet donors.

Neutralization of Omicron BA.4/BA.5 and BA.2.75 by Booster Vaccination or BA.2 Breakthrough Infection Sera

Many new Omicron sub-lineages have been reported to evade neutralizing antibody response, including BA.2, BA.2.12.1, BA.4 and BA.5. Most recently, another emerging sub-lineage BA.2.75 has been reported in multiple countries. In this study, we constructed a comprehensive panel of pseudoviruses (PsVs), including wild-type, Delta, BA.1, BA.1.1, BA.2, BA.3, BA.2.3.1, BA.2.10.1, BA.2.12.1, BA.2.13, BA.2.75 and BA.4/BA.5, with accumulate coverage reached 91% according to the proportion of sequences deposited in GISAID database since Jan 1st, 2022. We collected serum samples from healthy adults at day14 post homologous booster with BBIBP-CorV, or heterologous booster with ZF2001, primed with two doses of BBIBP-CorV, or from convalescents immunized with three-dose inactivated vaccines prior to infection with Omicron BA.2, and tested their neutralization activity on this panel of PsVs. Our results demonstrated that all Omicron sub-lineages showed substantial evasion of neutralizing antibodies induced by vaccination and infection, although BA.2.75 accumulated the largest number of mutations in its spike, BA.4 and BA.5 showed the strongest serum escape. However, BA.2 breakthrough infection could remarkably elevated neutralization titers against all different variants, especially titers against BA.2 and its derivative sub-lineages.

Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages

The SARS-CoV-2 Omicron variant has been partitioned into four sub-lineages designated BA.1, BA.1.1, BA.2 and BA.3, with BA.2 becoming dominant worldwide recently by outcompeting BA.1 and BA.1.1. We and others have reported the striking antibody evasion of BA.1 and BA.2, but side-by-side comparison of susceptibility of all the major Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are urgently needed. Using VSV-based pseudovirus, we found that sera from individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV) showed very weak to no neutralization activity, while a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) markedly improved the neutralization titers against all Omicron variants. The comparison between sub-lineages indicated that BA.1.1, BA.2 and BA.3 had comparable or even greater antibody resistance than BA.1. We further evaluated the neutralization profile of a panel of 20 mAbs, including 10 already authorized or approved, against these Omicron sub-lineages as well as viruses with different Omicron spike single or combined mutations. Most mAbs lost their neutralizing activity completely or substantially, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, reflecting their antigenic difference. Taken together, our results suggest all four Omicron sub-lineages threaten the efficacies of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters to combat the emerging SARS-CoV-2 variants.

Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera form convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists 7 of 8 authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.