Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses.

The impact of SARS-CoV2 vaccination in cancer patients remains incompletely understood given the heterogeneity of cancer and cancer therapies. We assessed vaccine-induced antibody response to the SARS-CoV2 Omicron (B.1.1.529) variant in 57 patients with B cell malignancies with and without active B cell-targeted therapy. Ancestral- and Omicron-reactive antibody levels were determined by ELISA and neutralization assays. In over one third of vaccinated patients at the pre-booster timepoint, there were no ELISA-detectable antibodies against either the ancestral strain or Omicron variant. The lack of vaccine-induced antibodies was predominantly in patients receiving active therapy such as anti-CD20 monoclonal antibody (mAb) or Brutons tyrosine kinase inhibitors (BTKi). While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the benefit was disproportionately evident in patients not on active therapy. Importantly, in patients with post-booster ELISA-detectable antibodies, there was a positive correlation of antibody levels against the ancestral strain and Omicron variant. Booster immunization increased overall antibody levels, including neutralizing antibody titers against the ancestral strain and Omicron variant; however, predominantly in patients without active therapy. Furthermore, ancestral strain neutralizing antibody titers were about 5-fold higher in comparison with those to Omicron, suggesting that even with booster administration, there may be reduced protection against the Omicron variant. Interestingly, in almost all patients regardless of active therapy, including those unable to generate detectable antibodies against SARS-CoV2 spike, we observed comparable levels of EBV, influenza, and common cold coronavirus reactive antibodies demonstrating that B cell-targeting therapies primarily impair de novo but not pre-existing antibody levels. These findings suggest that patients with B cell malignancies on active therapy may be at disproportionately higher risk to new versus endemic viral infection and suggest utility for vaccination prior to B cell-targeted therapy.

Immunological Insights Into the Therapeutic Roles of CD24Fc Against Severe COVID-19

BACKGROUNDSARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy. METHODSWe studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial (NCT04317040) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. FINDINGSTwenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8+ T cells, CD4+ T cells, and CD56+ NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity. INTERPRETATIONOur data demonstrates that CD24Fc treatment rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19. FUNDINGNIH

Co-author and Keyword Networks and their Clustering Appearance in Preventive Medicine Fields in Korea: Analysis of Papers in the Journal of Preventive Medicine and Public Health, 1991~2006 / 예방의학회지

OBJECTIVES: This study evaluated knowledge structure and its effect factor by analysis of co-author and keyword networks in Korea's preventive medicine sector. METHODS: The data was extracted from 873 papers listed in the Journal of Preventive Medicine and Public Health, and was transformed into a co-author and keyword matrix where the existence of a 'link' was judged by impact factors calculated by the weight value of the role and rate of author participation. Research achievement was dependent upon the author's status and networking index, as analyzed by neighborhood degree, multidimensional scaling, correspondence analysis, and multiple regression. RESULTS: Co-author networks developed as randomness network in the center of a few high-productivity researchers. In particular, closeness centrality was more developed than degree centrality. Also, power law distribution was discovered in impact factor and research productivity by college affiliation. In multiple regression, the effect of the author's role was significant in both the impact factor calculated by the participatory rate and the number of listed articles. However, the number of listed articles varied by sex. CONCLSIONS: This study shows that the small world phenomenon exists in co-author and keyword networks in a journal, as in citation networks. However, the differentiation of knowledge structure in the field of preventive medicine was relatively restricted by specialization.

Keywords Network Analysis of Articles in the North Korean Journal of Preventive Medicine 1997~2006 / 예방의학회지

OBJECTIVES: There are very few researches on North Korea's academic activities. Furthermore, it is doubtful that the available data are reliable. This study investigated research activities and knowledge structure in the field of Preventive Medicine in North Korea with a network analysis using co-authors and keywords. METHODS: The data was composed of the North Korean Journal of preventive medicine ranged from Vol. 1 of 1997 to Vol. 4 of 2006. It was the matrix of 1,172 articles by 1,567 co-authors. We applied R procedure for keywords abstraction, and then sought for the outcome of network forms by spring-KK and shrinking network. RESULTS: To comprehend the whole networks explicitly demonstrated that the academic activities in North Korea's preventive medicine were predisposed to centralization as similar as South Korea's, but on the other aspect they were prone to one-off intermittent segmentation. The principal co-author networks were formulated around some outstanding medical universities seemingly in addition to possible intervention by major researchers. The knowledge structure of network was based on experimentation judging from keywords such as drug, immunity, virus detection, infection, bacteria, anti-inflammation, etc. CONCLUSIONS: Though North Korea is a socialist regime, there were network of academic activities, which were deemed the existence of inducive mechanism affordable for free research. Article keywords has laid greater emphasis on experiment-based bacterial detection, sustainable immune system and prevention of infection. The kind of trend was a consistent characteristic in preventive medicine of North Korea having close correlation with Koryo medical science.