Comparative assessment of efficacy and immunogenicity of Gam-COVID-Vac and CoviVac vaccines against SARS-CoV-2

The medical community is interested in the duration of immune protection and the level of specific antibodies (AB) that can pre-vent reinfection with SARS-CoV-2. Objective. To perform a comparative evaluation of efficacy and immunogenicity of Gam-COVID-Vac and CoviVac vaccines against SARS-CoV-2 in a prospective observational study. Material and methods. The following vaccines were used for the vaccination of subjects (n=3322) aged 18 years and older: Gam-COVID-Vac - 1,622 (48.8%) subjects (group I), CoviVac - 1,700 (51.2%) subjects (group II). Vaccinated subjects were fol-lowed up for 6 study visits: before the 1st component of the vaccine, before the 2nd component of the vaccine, 42 days, 3 months, 6 months, and 12 months after the 1st component of the vaccine. Immunoglobulin G (IgG) levels of AB to S protein were compared after the injection of Gam-COVID-Vac and CoviVac vaccines using an enzyme immunoassay. Statistical processing of the obtained data was performed using IBM SPSS Statistics v. 24 and MedCalc v. 20.104 software. Results. Group I subjects showed an increase in specific AB (IgG) levels to SARS-CoV-2 S protein from visit 1 to visits 2 and 3 (p<0.05). In more extended follow-up periods (visits 5, 6), AB levels in groups I and II did not differ significantly and remained sufficiently high by visit 6. Within one year of follow-up, the incidence of COVID-19 (confirmed by polymerase chain reaction) was significantly (p<0.01) lower in the Gam-COVID-Vac group (group I): 22.2% vs. 45.2% in the CoviVac group (group II). The maximum number of days (p<0.05) before the COVID-19 infection was observed in those vaccinated with Gam-COVID-Vac (221 days) compared to those immunized with CoviVac (159 days). Conclusion. The Gam-COVID-Vac vaccine is more effective against COVID-19 and induces a more rapid response of the hu-moral immune system than the CoviVac vaccine. However, the duration of the humoral immune response after administration of Gam-COVID-Vac and CoviVac was similar. Copyright © 2022, Media Sphera Publishing Group. All rights reserved.

The Fast Approval and Slow Rollout of Sputnik V: Why Is Russia's Vaccine Rollout Slower than That of Other Nations?

The emergence of the SARS-CoV-2 pandemic in the beginning of 2020 led to the deployment of enormous amounts of resources by different countries for vaccine development, and the Russian Federation was the first country in the world to approve a COVID-19 vaccine on 11 August 2020. In our research we sought to crystallize why the rollout of Sputnik V has been relatively slow considering that it was the first COVID-19 vaccine approved in the world. We looked at production capacity, at the number of vaccine doses domestically administered and internationally exported, and at vaccine hesitancy levels. By 6 May 2021, more first doses of Sputnik V had been administered abroad than domestically, suggesting that limited production capacity was unlikely to be the main reason behind the slow rollout. What remains unclear, however, is why Russia prioritized vaccine exportation. We provide three hypotheses that may contribute to explaining the slow domestic rollout: a generalized vaccine distrust among the Russian population, a desire to help less technologically advanced nations, and possible geopolitical incentives.

An ELISA Platform for the Quantitative Analysis of SARS-CoV-2 RBD-neutralizing Antibodies As an Alternative to Monitoring of the Virus-Neutralizing Activity.

Monitoring of the level of the virus-neutralizing activity of serum immunoglobulins ensures that one can reliably assess the effectiveness of any protection against the SARS-CoV-2 infection. For SARS-CoV-2, the RBD-ACE2 neutralizing activity of sera is almost equivalent to the virus-neutralizing activity of their antibodies and can be used to assess the level of SARS-CoV-2 neutralizing antibodies. We are proposing an ELISA platform for performing a quantitative analysis of SARS-CoV-2 RBD-neutralizing antibodies, as an alternative to the monitoring of the virus-neutralizing activity using pseudovirus or "live" virus assays. The advantage of the developed platform is that it can be adapted to newly emerging virus variants in a very short time (1-2 weeks) and, thereby, provide quantitative data on the activity of SARS-CoV-2 RBD-neutralizing antibodies. The developed platform can be used to (1) study herd immunity to SARS-CoV-2, (2) monitor the effectiveness of the vaccination drive (revaccination) in a population, and (3) select potential donors of immune plasma. The protective properties of the humoral immune response in hospitalized patients and outpatients, as well as after prophylaxis with the two most popular SARS-CoV-2 vaccines in Russia, were studied in detail using this platform. The highest RBD-neutralizing activity was observed in the group of hospitalized patients. The protective effect in the group of individuals vaccinated with Gam-COVID-Vac vaccine was 25% higher than that in outpatients and almost four times higher than that in individuals vaccinated with the CoviVac vaccine.

Microarray Profiling of Vaccination-Induced Antibody Responses to SARS-CoV-2 Variants of Interest and Concern.

Mutations in surface proteins enable emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to escape a substantial fraction of neutralizing antibodies and may thus weaken vaccine-driven immunity. To compare available vaccines and justify revaccination, rapid evaluation of antibody (Ab) responses to currently circulating SARS-CoV-2 variants of interest (VOI) and concern (VOC) is needed. Here, we developed a multiplex protein microarray-based system for rapid profiling of anti-SARS-CoV-2 Ab levels in human sera. The microarray system was validated using sera samples from SARS-CoV-2-free donors and those diagnosed with COVID-19 based on PCR and enzyme immunoassays. Microarray-based profiling of vaccinated donors revealed a substantial difference in anti-VOC Ab levels elicited by the replication-deficient adenovirus vector-base (Sputnik V) and whole-virion (CoviVac Russia COVID-19) vaccines. Whole-virion vaccine-induced Abs showed minor but statistically significant cross-reactivity with the human blood coagulation factor 1 (fibrinogen) and thrombin. However, their effects on blood clotting were negligible, according to thrombin time tests, providing evidence against the concept of pronounced cross-reactivity-related side effects of the vaccine. Importantly, all samples were collected in the pre-Omicron period but showed noticeable responses to the receptor-binding domain (RBD) of the Omicron spike protein. Thus, using the new express Ab-profiling system, we confirmed the inter-variant cross-reactivity of the anti-SARS-CoV-2 Abs and demonstrated the relative potency of the vaccines against new VOCs.

SAFETY of VACCINES AGAINST COVID-19 in PATIENTS with SPONDYLOARTHRITIS (PRELIMINARY D ATA)

Background: Patients with spondyloarthritis (SpA) probably have a high incidence of COVID-19. Vaccination remains one of the most effective methods of preventing infectious diseases. However, data on the safety of vaccines against COVID-19 in patients with SpA are few and relate to foreign vaccines that are not licensed in Russia. Objectives: To study the safety of COVID-19 vaccines in patients with SpA in real clinical practice. Methods: The study included 47 SpA patients (25-ankylosing spondylitis, 13-psoriatic arthritis, 9-undifferentiated SpA, 19 women, 28 men, age 42.3±11.6 years, duration of the disease 11.8±9.2 years)-the main group and 97 people without any immuno-infammatory rheumatic diseases (67 women, 30 men, age 43.7±13.1 years)-the control group. 20 patients received disease-modifying antirheumatic drugs (12-methotrexate, 8-sulfasalazine), 10-biological drugs (8-TNF-α inhibitors, 2-IL-17 inhibitors), 6-glucocorticoids, 1-tofacitinib, 12-only nonsteroidal anti-infammatory drugs, 8-did not receive therapy. In the main group, 40 patients were vaccinated with Gam-COVID-Vac (Sputnik V), 3-Covi-Vac and Sputnik Light, 1-EpiVacCorona (both components of the vaccine were received by 44 patients). In the control group 69 were vaccinated with Sputnik V, 15-CoviVac, 5-Sputnik Light and BNT162b2, 2-EpiVacCorona, 1-mRNA-1273. (91 participants received both components of the vaccine). All participants were interviewed by a research doctor with a unifed questionnaire, additional information was obtained from medical documentation. Results: The data obtained are refilected in the Table 1. Local adverse events (AEs) occurred relatively less frequently in patients with SpA than in the control group. After the introduction of the first component of the vaccine, there was a significant increase in the frequency of pain without restriction of movement and edema/hyperemia in the control group (p<0.001 and p=0.049, respectively), while after the introduction of the second component, a significant difference was registered only for the first indicated symptom (p<0.001). The most frequent systemic AEs were weakness, fever, arthralgia or myalgia, headache, and chills, which were significantly less common (p=0.008) in the main group after immunization with the first component. The proportion of SpA patients without any reactions was significantly higher after the introduction of the first component of the vaccine (59.6% and 29.9%, p<0.001), while after immunity with the second component there were no differences (59.1% and 44.0%, p>0.05). After complete immunization, the percentage of patients without any AEs was significantly higher in the main group than in the control (50.0% and 17.6%, p<0.001). There was no exacerbation of SpA or development of new autoimmune phenomena in the main group after full vaccination. Conclusion: According to preliminary data, the tolerability of vaccines against COVID-19 in patients with SpA is satisfactory. Further studies with an increased sample are needed to study the safety, immunogenicity and clinical efficacy of immunization against COVID-19 in patients of this cohort.

SAFETY of COVID-19 VACCINES in PATIENTS with RHEUMATOID ARTHRITIS (PRELIMINARY DATA)

Background: Patients with rheumatoid arthritis (RA) are at high risk of developing COVID-19. Vaccination should be an effective method of preventing this disease. However, vaccination may be unsafe in RA patients. At present, data on the safety of vaccines against COVID-19 in RA patients are few and relate to foreign vaccines that are not licensed in Russia. Objectives: To study the safety of COVID-19 vaccines in patients with RA in real clinical practice. Methods: The study included 131 RA patients (120 women, 11 men, age 53.8±13.9 years, duration of disease 11.5±9.2 years)-the main group and 121 people without any immuno-infammatory rheumatic diseases (87 women, 34 men, age 39.8±14.2 years)-the control group. 103 patients received disease-modifying antirheumatic drugs (54-methotrexate, 30-lefunomide, 10-hydroxychloroquine, 8-sulfasalazine, 1-mofetil mycophenolate), 68-biological drugs (58-rituximab, 5-TNF-α inhibitors, 4-abatacept, 1-tocilizumab), 64-glucocorticoids, 10-did not receive therapy. In the main group, 92 patients were vaccinated with Gam-COVID-Vac (Sputnik V), 21 with Sputnik Light, 16 with CoviVac, 2 with EpiVacCorona (110 patients received two components of the vaccine). In the control group, 91 were vaccinated with Sputnik V, 16 with Covi-Vac, 6 with BNT162b2, 5 with Sputnik Light, 2 with EpiVacCorona, 1 with mRNA-1273 (114 participants received two components of the vaccine). All participants were interviewed by a research doctor with a unifed questionnaire, additional information was obtained from medical documentation. Results: Local and systemic adverse events (AEs) were observed both in the main group and in the control group. After the introduction of the frst component of the vaccine, local AEs (pain/hyperemia/edema) were noted in 12.2% of RA patients and in 10.7% of the control group, after the introduction of the second component of the vaccine-in 9.1% and 11.4% of respondents, respectively (in both groups p>0.05). There was a signifcant difference between the main group and the control group in the frequency of pain at the injection site without restriction of movements both after the frst (24.4% and 40.5%, p=0.007) and after the second component (18.2% and 31.6%, p=0.021). The most frequent systemic AEs were weakness, fever, muscle or joint pain, headache, chills, which were observed in both groups after administration of both the frst and second components of the vaccine. There was a signifcant difference between the main group and the control group in the frequency of fever (16.8% and 39.7%, p<0.001), weakness (26.0% and 38.8%, p=0.029), muscle and joint pain (9.2% and 25.6%, p<0.001) after administration of the frst (but not the second) component of the vaccine. A signifcant difference was revealed between the main group and the control group in the number of patients with local and systemic AEs both after the introduction of the frst component of the vaccine (19.1% and 43%, p<0.001) and after the second (15.5% and 30.7%, p=0.007). After administration of the two components of the vaccine, a higher number of patients without any AEs were detected in the main group compared to the control group (32.7% and 18.4%, p=0.014). Exacerbation of RA and the emergence of new autoimmune phenomena in main group are not marked. Conclusion: According to preliminary data, the tolerance of vaccines against COVID-19 in RA patients is satisfactory. Further studies are needed to study the safety, immunogenicity and clinical efficacy of immunization against COVID-19 in patients of this cohort.

Association of humoral immunity status and thrombodynamics after vaccination with Gam-COVID-Vac and CoviVac.

The ongoing pandemic of coronavirus disease 2019 makes it important to study the immunogenicity, the duration of immune response, and the safety of existing vaccines. Aim. As part of a prospective observational study, to assess associations between levels of anti-Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) S protein IgG antibodies and thrombodynamics parameters in individuals vaccinated with Gam-COVID-Vac and CoviVac vaccines. Material and methods. The study included 137 people who completed the first 3 visits: 30 people received the Gam-COVID-Vac, 107 people -- CoviVac. The study participants underwent venous blood sampling before the introduction of the 1st and 2nd vaccine doses, as well as 42 days after the administration of 1st dose in order to quantify the level of IgG antibodies. At each visit, plasma hemostasis parameters were analyzed using a thrombodynamics test. Results. During the follow-up period, there was a clear increase in the level of anti-SARS-CoV-2 S protein IgG antibodies in both groups. At the same time, this increase over time was significantly greater in Gam-COVID-Vac group. There was no correlation detected between thrombodynamics test results and the levels of anti-SARS-CoV-2 S protein IgG antibodies. Conclusion. The data obtained demonstrate the ability of both vaccines to stimulate the production of anti-SARS-CoV-2 antibodies. However, immune response to Gam-COVID-Vac is much higher. The lack of correlation between thrombodynamics and the level of specific antibodies suggests that vaccination for COVID-19 with Gam-COVIDVac and CoviVac does not cause changes in plasma hemostasis and does not increase the risk of thrombosis. (English) [ FROM AUTHOR] Продолжающаяся пандемия новой коронавирусной инфекции (COVID-19, COronaVIrus Disease 2019) делает крайне актуальным изучение иммуногенности, длительности сохранения иммунного ответа и безопасности имеющихся вакцин. Цель. В рамках проспективного наблюдательного исследования изучить ассоциации между уровнем IgG к S белку коронавиру- са SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) и параметрами тромбодинамики у лиц, вакцинированных против SARS-CoV-2 вакцинами Гам-КОВИД-Вак и КовиВак. Материал и методы. В исследование включено 137 человек, кото- рые полностью прошли первые 3 визита: 30 человек получили вак- цину Гам-КОВИД-Вак, 107 человек -- КовиВак. У участников иссле- дования проводился забор венозной крови перед введением I-го и II-го компонентов вакцины, а также через 42 дня со дня введения I-го компонента с целью количественного определения уровня IgG к S белку. На каждом из визитов проводился анализ показателей плазменного гемостаза при помощи теста тромбодинамики. Результаты. В течение периода наблюдения отмечалась отчетли- вая динамика нарастания уровня IgG антител (АТ) к S белку в обеих группах. При этом увеличение уровня АТ в динамике было значи- тельно бóльшим в группе лиц, вакцинированных Гам-КОВИД-Вак. По результатам исследования плазменного звена гемостаза кор- реляционной связи между уровнями IgG АТ на каждом визите и па- раметрами тромбодинамики выявлено не было. Заключение. Полученные данные демонстрируют способность обеих вакцин стимулировать выработку АТ к SARS-CoV-2. Однако выраженность иммунного ответа на введение Гам-КОВИД-Вак значительно выше. Отсутствие корреляции между показателями тромбодинамики и уровня специфических АТ говорит о том, что вакцинация против COVID-19 вакцинами Гам-КОВИД-Вак и КовиВак не вызывает изменений плазменного гемостаза и не увеличивает риск тромбообразования. (Russian) [ FROM AUTHOR] Copyright of Cardiovascular Therapy & Prevention is the property of Silicea-Poligraf LLC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Thrombodynamics parameters in individuals vaccinated against SARS-CoV-2

During the ongoing COVID-19 pandemic, with a significant variety of available vaccines, it is crucial to consider their effects on the hemostasis system. Objective. To study thrombodynamics features of individuals vaccinated against SARS-CoV-2 with Gam-COVID-Vac and Covi-Vac vaccines in a prospective observational study. Materials and methods. Data from 99 vaccinated individuals who completed the first three visits were analyzed. Of these, 18 were vaccinated with Gam-COVID-Vac, and 81 with CoviVac. Venous blood was collected before injection of the components I and II of the vaccine and 42 days after administration of the component I to analyze thrombodynamics parameters using the Thrombo-dynamics Analyzer System T2 (Hemacore, Russia). Results. In the analysis of thrombodynamics test data, no significant differences were found between the Gam-COVID-Vac group and the CoviVac group at any of the three stages of the study. Moreover, no significant increase in any of the parameters from the visit 1 to visit 3 was observed in both groups. Conclusion. The obtained study data suggest that such plasma hemostasis parameters as stationary rate of clot growth and ini-tial rate of clot growth, lag-time, clot density and clot size, spontaneous clots formation time show no significant changes during 42 days after the component I of Gam-COVID-Vac and CoviVac vaccines injection. © 2021, Media Sphera Publishing Group. All rights reserved.

COLLECTIVE TRAUMA AND COVID-19: VACCINATION HESITANCY OVERCOMING BY MEANS OF EXAMINATION OF SIDE-EFFECTS OF VACCINES (COVAST-RU)

There is 15-year anniversary of Polytrauma journal in 2021. This is a high-quality periodical publication dedicated to various scientific and practical aspects of medicine of injuries on the basis of principles of evidence-based medicine. Agadzhanyan V.V., the founder and chief editor of the journal, professor, academician of RANS, maintains high level of publications. Congratulating the journal with this remarkable date, the author, who is proud for his cooperation with the editorial board, notes that activity of the journal has extended the term polytrauma in comparison with simple combination of severe mechanic injures. Unfortunately, 15th anniversary of the journal coincides with the third wave of the pandemic of the new coronavirus infection, which had led to the term collective trauma, i.e. global psychogenic influence of COVID-19. The article presents an analysis of the event of collective trauma in relation to healthcare workers, shows an association with the phenomenon of hesitancy of vaccination and declares the international observational study for active follow-up of side-effects of vaccines which will allow for the Russian Federation to objectify the data on efficiency and safety of the approved vaccines (Gam-COVID-Vak (Sputnik V), EpiVacCorona, CoviVac and Sputnik Light) as compared to foreign ones. Methods. The part of the three-stage international study, including the cross-sectional trial for testing of short-term side-effects of COVID-19 vaccines in healthcare workers. At the second stage, the side-effects of booster doses will be traced. At the third stage, the safety and efficiency will be studied. The validated self-administrated electronic questionnaire is used for collection of data. Results. The study protocol has been registered on ClinicalTrials.gov, with the identifier NCT04834869. The Russian Federation has connected to the study in July 2021. Conclusion. Vaccination hesitancy overcoming as manifestation of collective trauma in conditions of COVID-19 should be based on results, which will be presented in the Russian segment by CoVaST-RU - the first independent study of monitoring of side-effects of COVID-19 vaccines after booster doses, with estimation of long term safety and efficiency of the vaccines. © 2021 The Charity Fund of Clinical Center of Miners' Health Protection. All rights reserved.