Author:
Inui Toshio,Kruglova Oksana,Martynenko Olga,Martynenko Kostiantyn,Tieroshyn Vadym,Gavrylov Anatoliy,Kubo Kentaro,Yamakage Hajime,Kutsyn Borys,Kubashko Alla,Veklych Zoryana,Terashima Yurika,Mette Martin,Kutsyna Galyna
Abstract
Abstract
Background
Targeting mucosal immunity of the gut, which is known to provide antigen processing, while avoiding excessive or unnecessary inflammation, was tested as a way to modulate COVID-19 severity.
Methods
Randomized open-label trial in 204 adults hospitalized with non-critical COVID-19 who received for 14 days in addition to standard of care (SOC) degalactosylated bovine glycoproteins formulations of either MAF capsules (MAF group) or M capsules (M group) or SOC only (control group).
Results
Median recovery time when patients did not require supplemental oxygen was 6 days in both study groups compared to 9 days in the control (MAF vs. control; P = 0.020 and M vs. control; P = 0.004). A greater reduction in mortality was seen in the MAF group compared to the control by day 14 (8.3% vs. 1.6%; P = 0.121) and by day 29 (15.3% vs. 3.2%; P = 0.020), and similarly in the M group by day 14 (8.3% vs. 2.9%; P = 0.276) and by day 29 (15.3% vs. 2.9%; P = 0.017). The proportion of those who had baseline absolute lymphocyte count (ALC) lower than 0.8 × 109/L was 13/63 (20.6%), 17/69 (24.6%), and 18/72 (25.0%) of patients in MAF, M, and control group respectively. Day 29 mortality among these lymphopenic patients was three times higher than for the intent-to-treat population (21% vs. 7%) and consisted in above subgroups: 2/13 (15%), 2/17 (12%), and 6/18 (33%) of patients. The decreased mortality in both study subgroups correlated with greater ALC restoration above 0.8 × 109/L level seen on day 14 in 91% (11/12) and 87.5% (14/16) of survivors in MAF and M subgroups respectively compared to 53.3% (8/15) of survivors in control subgroup. Incidences of any ALC decrease below the baseline level on day 14 occurred in 25.4% of patients in the MAF group and 29.0% of patients in the M group compared to 45.8% in control and ALC depletion by ≥ 50% from the baseline level consisted of 7.9%, 5.8%, and 15.3% of cases in these groups respectively.
Conclusion
This study showed that both study agents prevented ALC depletion and accelerated its restoration, which is believed to be one of the mechanisms of improved crucial clinical outcomes in hospitalized COVID-19 patients.
Trial registration
The trial was registered after the trial start in ClinicalTrials.gov NCT04762628, registered 21/02/2021, https://www.clinicaltrials.gov/ct2/show/NCT04762628.
Publisher
Springer Science and Business Media LLC
Reference6 articles.
1. Nagasawa H, Uto Y, Sasaki H, et al. Gc protein (vitamin D-binding protein): gc genotyping and GcMAF precursor activity. Anticancer Res. 2005;25(6A):3689–95.
2. Yamamoto N, Kumashiro R. Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of betagalactosidase of B cells and sialidase of T cells. J Immunol. 1993;151(5):2794–802.
3. Kuchiike D, Uto Y, Mukai H, et al. Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity. Anticancer Res. 2013;33(7):2881–5.
4. Uto Y, Kawai T, Sasaki T et al. Degalactosylated/Desialylated bovine Colostrum induces macrophage phagocytic activity independently of inflammatory cytokine production. Anticancer Res. (2015).
5. Mami, Ishikawa et al. A high-throughput quantitative assay system for macrophage phagocytic activity. Macrophage. 2018; 5: e1627. https://doi.org/10.14800/Macrophage.1627; 2018 volume 120.