Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in > 70 countries. Yet there is a shortage of data on this vaccine's performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in Kazakhstan. COVID-19-free participants (n = 82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays. We observed that most of the reported adverse events were mild-to-moderate injection site or systemic reactions, no severe or potentially life-threatening conditions were reported, and dose 1 appeared to be more reactogenic than dose 2. The seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization was 83% post-dose 1, increasing to 98% post-dose 2, with the largest relative increase observed in participants without prior COVID-19 exposure. Dose 1 boosted nasal S-IgG and S-IgA, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count. Overall, Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal. Thus, adjustments to the current vaccine dosing regimen are necessary to optimize immunization efficacy and cost-effectiveness. While Sputnik-V reactogenicity is similar to that of other COVID-19 vaccines, the induced alterations to the GRO/platelet axis warrant investigation of the vaccine’s effects on systemic immunology.
BACKGROUND:According to several authors, neutrophil extracellular traps (NETs) play an important role in the mechanisms of cancer development and metastatic processes, which allows them to be considered as a potential new target for the treatment of cancer.AIM:To investigate the presence of extracellular neutrophil traps in the blood of patients with cervical cancer on the background of the combined treatment.MATERIALS AND METHODS:The study was conducted in 28 patients with cervical cancer. Group 1 received only radiation therapy; Groups 2-radiation therapy with ftorafur; Group 3-radiation therapy with cisplatin. To determine the number of spontaneous extracellular neutrophilic traps in the blood of the examined individuals, we used a technique of I.I. Dolgushin and Yu.S. Andreeva.RESULTS:Peripheral blood neutrophils in 53.57% (33.87; 72.49) of cervical cancer patients showed the ability to generate NETs before treatment. The ability to form NETs was observed in neutrophils isolated from 66.67% (9.43; 99.16) patients of the Group 1. After radiation therapy with ftorafur, the ability of blood neutrophils to form NETs was observed in 50% (1.26; 98.74) of cervical cancer patients. After radiotherapy with cisplatin, 37.50% (15.20; 64.57) of patients were found to have NETs formationCONCLUSION:The ability to form NETs varied greatly after radiotherapy. The addition of chemotherapy drugs to radiation therapy did not increase the percentage of NETs in the blood of patients with cervical cancer but stimulated the appearance of basophil extracellular traps.
Background: Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in >70 countries. Yet there is a shortage of data on this vaccine's performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in a multi-ethnic cohort from Kazakhstan. Methods: COVID-19-free participants (n=82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays. Findings: Of the 73 and 70 participants retained post-dose 1 and 2, respectively, most (>50%) reported mild-to-moderate injection site or systemic reactions to vaccination; no severe or potentially life-threatening conditions were reported. dose 1 appeared to be more reactogenic than dose 2, with fatigue and headache more frequent in participants with prior COVID-19 exposure. After dose 2 nausea was more common in subjects without prior COVID-19. The combined S-IgG and S-IgA seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization titers was 83% post-dose 1', and increased to 98% post-dose 2', with the largest relative increase observed in participants without prior COVID-19 exposure. Nasal S-IgG and S-IgA increased post-dose 1, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count. Interpretation: Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal, suggesting that adjustments to the current vaccine dosing regimen may be necessary to optimize immunization efficacy and cost-effectiveness. Although Sputnik-V appears to have a reactogenicity profile similar to that of other COVID-19 vaccines, the observed alterations to the GRO/platelet axis call for further investigation of Sputnik V effects on systemic immunology. Funding: Ministry of Education and Science of the Republic of Kazakhstan.
COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence data are urgently needed to inform ongoing vaccination efforts and other strategies to mitigate the regional pandemic. Here, in a pilot serologic study we assessed the prevalence of SARS-CoV-2 antibody-mediated immunity in a multi-ethnic cohort of public university employees in Karaganda, Kazakhstan. Asymptomatic subjects (n = 100) were recruited prior to their first COVID-19 vaccination. Questionnaires were administered to capture a range of demographic and clinical characteristics. Nasopharyngeal swabs were collected for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)-reactive IgG and IgA and to assess virus neutralization. Pre-pandemic samples were used to validate the assay positivity thresholds. S-IgG and -IgA seropositivity rates among SARS-CoV-2 PCR-negative participants (n = 100) were 42% (95% CI [32.2–52.3]) and 59% (95% CI [48.8–69.0]), respectively, and 64% (95% CI [53.4–73.1]) of the cohort tested positive for at least one of the antibodies. S-IgG titres correlated with virus neutralization activity, detectable in 49% of the tested subset with prior COVID-19 history. Serologically confirmed history of COVID-19 was associated with Kazakh ethnicity, but not with other ethnic minorities present in the cohort, and self-reported history of respiratory illness since March 2020. Overall, SARS-CoV-2 exposure in this cohort was ~15-fold higher compared to the reported all-time national and regional COVID-19 prevalence, consistent with recent studies of excess infection and death in Kazakhstan. Continuous serological surveillance provides important insights into COVID-19 transmission dynamics and may be used to better inform the regional public health response.
At the present time, available views show our limited knowledge of the peculiarities of the functional status of neutrophils and their metabolism in patients with community-acquired pneumonia (CAP). The studying of changes of metabolic status of neutrophils can broaden our views about pneumonia pathogenesis and define datum points of therapeutic effect. Purpose of our research: to define oxidative stress activity and the level of oxidative modification of proteins of neutrophils in CAP patients. Materials and methods: neutrophils obtained from 23 patients with community-acquired pneumonia. Control group consisting of 19 healthy volunteers. The reactive carbonyl derivatives of proteins and advanced oxidation protein products were defined so as to assess the oxidative damage of proteins. The malondialdehyde and nitrite ions were assessed as being indicators of the oxidative stress. The neutrophils of CAP patients with moderate severity were characterized by a tendency of evidencing decreasing content of advanced oxidation protein products, along with the statistically important enhanced levels of carbonyl derivatives and nitrite ions, while their malondialdehyde status practically leveled off with the control and had only an insignificant trend towards growth. We have demonstrated the accumulation of carbonyl derivatives and nitrite ions in the peripheral neutrophils of CAP patients. These results give evidence of an oxidative misbalance in the cells which contributes to the aggravation of the disease.
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