Impact of COVID-19 Vaccination on Healthcare Worker Infection Rate and Outcome during SARS-CoV-2 Omicron Variant Outbreak in Hong Kong.

Immune escape is observed with SARS-CoV-2 Omicron (Pango lineage B.1.1.529), the predominant circulating strain worldwide. A booster dose was shown to restore immunity against Omicron infection; however, real-world data comparing mRNA (BNT162b2; Comirnaty) and inactivated vaccines' (CoronaVac; Sinovac) homologous and heterologous boosting are lacking. A retrospective study was performed to compare the rate and outcome of COVID-19 in healthcare workers (HCWs) with various vaccination regimes during a territory-wide Omicron BA.2.2 outbreak in Hong Kong. During the study period from 1 February to 31 March 2022, 3167 HCWs were recruited, and 871 HCWs reported 746 and 183 episodes of significant household and non-household close contact. A total of 737 HCWs acquired COVID-19, all cases of which were all clinically mild. Time-dependent Cox regression showed that, compared with two-dose vaccination, three-dose vaccination reduced infection risk by 31.7% and 89.3% in household contact and non-household close contact, respectively. Using two-dose BNT162b2 as reference, two-dose CoronaVac recipient had significantly higher risk of being infected (HR 1.69 p < 0.0001). Three-dose BNT162b2 (HR 0.4778 p< 0.0001) and two-dose CoronaVac + BNT162b2 booster (HR 0.4862 p = 0.0157) were associated with a lower risk of infection. Three-dose CoronaVac and two-dose BNT162b2 + CoronaVac booster were not significantly different from two-dose BNT162b2. The mean time to achieve negative RT-PCR or E gene cycle threshold 31 or above was not affected by age, number of vaccine doses taken, vaccine type, and timing of the last dose. In summary, we have demonstrated a lower risk of breakthrough SARS-CoV-2 infection in HCWs given BNT162b2 as a booster after two doses of BNT162b2 or CoronaVac.

Functional alterations of Lin-CD34+CD38+ cells in chronic myelomonocytic leukemia and on progression to acute leukemia.

The functional behavior of hematopoietic stem cell (HSC) and progenitors in chronic myelomonocytic leukemia (CMML) and on disease progression is little known. We performed cell proliferation, apoptosis, hematopoietic colony forming/replating and differentiation potential studies in the purified subpopulations of Lin(-)CD34(+)CD38(-) and Lin(-)CD34(+)CD38(+) cells from 16 CMML with 6 cases after acute myeloid leukemia transformation (AML-t). We observed an expansion of the hematopoietic progenitor pool (Lin(-)CD34(+) cells) in AML-t comprising mainly Lin(-)CD34(+)CD38(+) cells. The Lin(-)CD34(+)CD38(+) cells in AML-t displayed high proliferative activity, resistance to apoptosis, enhanced myeloid colony formation/replating ability and a complete dendritic cell (DC) differentiation block. Our findings suggest Lin(-)CD34(+)CD38(+) cells instead of Lin(-)CD34(+)CD38(-) cells could be the target(s) of secondary genetic lesions underpinning progression from CMML to AML, which have implications for the further study of the biology of leukemic transformation and the design of new strategies for the effective treatment of CMML.

Pentasomy 8q in therapy-related myelodysplastic syndrome due to cyclophosphamide therapy for fibrosing alveolitis.

Trisomy 8/8q is a common cytogenetic event in myelocytic malignancies, ranging from myelodysplastic syndrome (MDS) to acute myelocytic leukemia (AML) to blastic transformation of chronic myelocytic leukemia. Isochromosome 8q results in the same gene dosage effect. Duplication of i(8q), resulting in pentasomy 8q, has been reported only in two cases of AML. A patient with fibrosing alveolitis on prolonged cyclophosphamide treatment developed therapy-related MDS. Karyotyping, FISH, and CGH analysis showed a duplicated i(8q) among other complex abnormalities. The clinical features of 11 cases of myelocytic leukemia with pentasomy and hexasomy 8/8q were summarized. Compared with trisomy and tetrasomy 8, significant features included reduced median survival (90 days), treatment refractoriness (even with transplantation), monocytic differentiation, trilineage dysplasia, and radiation or toxin exposure. Increasing copy numbers of chromosome 8/8q may therefore be a marker of advanced leukemic evolution, exposure to toxins, underlying myelodysplasia, and an overall poor prognosis.