The global spread of SARS-CoV-2 points to unrivaled mutational variation of the virus, contributing to a variety of post-COVID sequelae in immunocompromised subjects and high mortality. Numerous studies have reported the reactivation of "sluggish" herpes virus infections in COVID-19, which exaggerate the course of the disease and complicate with lasting post-COVID manifestations CMV, EBV, HHV6). This study aimed to describe clinical and laboratory features of post-COVID manifestations accompanied by the reactivation of herpes virus infections (CMV, EBV, HHV6). 88 patients were recruited for this study, including subjects with reactivation of herpes viruses, 68 (72.3%) (main group) and 20 (27.7%) subjects without detectable DNA of herpesviruses (control group): 46 (52.3%) female and 42 (47.7%) male; median age was 41.4 ± 6.7 years. Patients with post-COVID manifestations presented with reactivation of EBV in 42.6%, HHV6 in 25.0%, and EBV plus HHV6 in 32.4%. Compared with controls, patients with herpes virus infections presented with more frequent slight fever temperature, headache, psycho-neurological disorders, pulmonary abnormalities and myalgia ( p < 0.01), activation of liver enzymes, elevated CRP and D-dimer, and suppressed cellular immune response ( p ≤ 0.05). Preliminary results indicate a likely involvement of reactivated herpes virus infections, primarily EBV infections in severe COVID-19 and the formation of the post-COVID syndrome. Patients with the post-COVID syndrome and reactivation of EBV and HHV6 infections are at high risk of developing various pathologies, including rheumatologic diseases.

Cytokines have been important mediators of the immunity and can be involved in numerous processes in the male genital tract including acting as immunomodulatory elements within the male gonad.The aims of this study were: 1) to detect pro- and anti-inflammatory cytokine levels in the control group and subgroups of infertile men; and 2) to set up the practical recommendations concerning determination of cytokine levels for the male infertility diagnosis.Observations were performed in a group of 82 men: healthy controls (n = 27) and infertile patients (n = 55). The male infertility group was further subdivided into patients with: varicocele (n = 22), idiopathic infertility (n = 13) and partners of couples with recurrent spontaneous abortion (RSA; n = 20). Semen analysis was determined following WHO criteria. The cytokine interleukin 1β (IL-1β), IL-6, IL-10, IL-18; tumor necrosis factor α (TNF-α), interferon g (IFN-g) and transforming growth factor β1 (TGF-β1) contents in serum and seminal plasma were determined by quantitative ELISA.An interesting marker of male infertility appears to be TGF-β1 (blood) significantly elevated in idiopathically infertile males and in the RSA group. Besides elevated TGF-β1 in a group of idiopathic infertility significantly elevated IL-10, IL-18, IFN-g (blood) and statistically decreased IL-1β while increased IFN-g were revealed in seminal plasma compared to healthy controls.We may postulate novel cytokine micropatterns for patients with different background of infertility. Therefore, circulating cytokines: IL-1β, IL-10, IL-18, TGF-β1, IFN-g and IL-1β, IFN-g and TGF-β1 in seminal plasma should be extended in evaluation of specific types of male infertility.

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Landomycin E (LE) is an angucycline antibiotic produced by Streptomyces globisporus.Previously, we have shown a broad anticancer activity of LE which is, in contrast to the structurally related and clinically used anthracycline doxorubicin (Dx), only mildly affected by multidrug resistance-mediated drug efflux. In the present study, cellular and molecular mechanisms underlying the anticancer activity of landomycin E towards Jurkat T-cell leukemia cells were dissected focusing on the involvement of radical oxygen species (ROS). LE-induced apoptosis distinctly differed in several aspects from the one induced by Dx. Rapid generation of hydrogen peroxide already at one hour drug exposure was observed in case of LE but not found before 24h for Dx. In contrast, Dx but not LE induced production of superoxide radicals. Mitochondrial damage, as revealed by JC-1 staining, was weakly enhanced already at 3h LE treatment and increased significantly with time. Accordingly, activation of the intrinsic apoptosis pathway initiator caspase-9 was not detectable before 12h exposure. In contrast, cleavage of the down-stream caspase substrate PARP-1 was clearly induced already at the three hour time point. Out of all caspases tested, only activation of effector caspase-7 was induced at this early time points paralleling the LE-induced oxidative burst. Accordingly, this massive cleavage of caspase-7 at early time points was inhibitable by the radical scavenger N-acetylcysteine (NAC). Additionally, only simultaneous inhibition of multiple caspases reduced LE-induced apoptosis. Both, a specific H 2 O 2 and an OH − scavenger (catalase and mannitol, respectively) effectively decreased LEinduced ROS production, but only partially inhibited LE-induced apoptosis. In contrast, NAC efficiently blocked both parameters. Summarizing, rapid H 2 O 2 generation and a complex caspase activation pattern contribute to the antileukemic effects of LE. As superoxide generation is HHS Public Access

OTHER ARTICLES PUBLISHED IN THIS SERIES Dying autologous cells as instructors of the immune system. Clinical and Experimental Immunology 2015, 179: 1-4. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks. Clinical and Experimental Immunology 2015, 179: 5-10. The effect of cell death in the initiation of lupus nephritis. Clinical and Experimental Immunology 2015, 179: 11-16 SummaryRecently we reported the first known incidence of antibodies possessing catalytic sialidase activity (sialidase abzymes) in the serum of patients with multiple myeloma and systemic lupus erythematosus (SLE). These antibodies desialylate biomolecules, such as glycoproteins, gangliosides and red blood cells. Desialylation of dying cells was demonstrated to facilitate apoptotic cell clearance. In this study we assessed the possibility to facilitate dying cell clearance with the use of F(ab)2 fragments of sialidase abzymes. Two sources of sialidase abzymes were used: (i) those isolated from sera of patients with SLE after preliminary screening of a cohort of patients for sialidase activity; and (ii) by creating an induced sialidase abzyme through immunization of a rabbit with synthetic hapten consisting of a non-hydrolysable analogue of sialidase reaction conjugated with bovine serum albumin (BSA) or keyhole limpet haemocyanin (KLH). Antibodies were purified by ammonium sulphate precipitation, protein-G affinity chromatography and size exclusion-high performance liquid chromatography (HPLC-SEC). Effect of desialylation on efferocytosis was studied using human polymorphonuclear leucocytes (PMN), both viable and aged, as prey, and human monocyte-derived macrophages (MoMa). Treatment of apoptotic and viable prey with both disease-associated (purified from blood serum of SLE patients) and immunization-induced (obtained by immunization of rabbits) sialidase abzymes, its F(ab)2 fragment and bacterial neuraminidase (as positive control) have significantly enhanced the clearance of prey by macrophages. We conclude that sialidase abzyme can serve as a protective agent in autoimmune patients and that artificial abzymes may be of potential therapeutic value.