The first case of COVID-19 was diagnosed in St. Petersburg on March 2, 2020; the period of increase in the incidence lasted for 10 weeks, the maximum rates were recorded in mid-May, and subsequently there was a statistically significant decrease in the incidence.Objective: to determine the level and structure of community immunity to SARS-CoV-2 among the population of St. Petersburg during the period of intensive spread of COVID-19.Materials and methods. Selection of volunteers for the study was carried out through interviewing and randomization. The exclusion criterion was active COVID-19 infection at the time of the survey. 2713 people aged 1 to 70 years and above were  examined for the presence of specific antibodies to SARS-CoV-2. Antibodies were detected by enzyme immunoassay.Results and discussion. Studies have shown that in St. Petersburg, in the active phase of COVID-19 epidemic, there was a moderate seroprevalence to SARS-CoV-2, which amounted to 26 %, against the background of a high frequency (84.5 %) of asymptomatic infection in seropositive individuals who did not have a history of COVID-19 disease, positive PCR result and ARI symptoms on the day of examination. The maximum indicators of herd immunity were established in children 1–6 years old (31.1 %), 7–13 years old (37.7 %) and people over 70 years old (30.4 %). Differences in the level of seroprevalence in the age groups of 18–49 years are statistically significant. The highest level of seroprevalence was found among the unemployed (29.7 %), healthcare workers (27.1 %), education sector (26.4 %) and business sector personnel (25 %). In convalescents, COVID-19 antibodies are produced in 75 % of cases. In individuals with positive result of PCR analysis carried out earlier, antibodies are detected in 70 % of the cases. The results of the study of herd immunity to SARS-CoV-2 are essential to forecast the development of the epidemiological situation, as well as to plan measures for specific and non-specific prevention of COVID-19.

This study is a successor of our previous work concerning changes in the chemokine profile in infection that are associated with different SARS-CoV-2 genetic variants. The goal of our study was to take into account both the virus and the host immune system by assessing concentrations of cytokines in patients infected with different SARS-CoV-2 variants (ancestral Wuhan strain, Alpha, Delta and Omicron). Our study was performed on 340 biological samples taken from COVID-19 patients and healthy donors in the timespan between May 2020 and April 2022. We performed genotyping of the virus in nasopharyngeal swabs, which was followed by assessment of cytokines’ concentration in blood plasma. We noted that out of nearly 30 cytokines, only four showed stable elevation independently of the variant (IL-6, IL-10, IL-18 and IL-27), and we believe them to be ‘constant’ markers for COVID-19 infection. Cytokines that were studied as potential biomarkers lose their diagnostic value as the virus evolves, and the specter of potential targets for predictive models is narrowing. So far, only four cytokines (IL-6, IL-10, IL-18, and IL-27) showed a consistent rise in concentrations independently of the genetic variant of the virus. Although we believe our findings to be of scientific interest, we still consider them inconclusive; further investigation and comparison of immune responses to different variants of SARS-CoV-2 is required.

Background. Infection caused by SARS-CoV-2 mostly affects the upper and lower respiratory tracts and causes symptoms ranging from the common cold to pneumonia with acute respiratory distress syndrome. Chemokines are deeply involved in the chemoattraction, proliferation, and activation of immune cells within inflammation. It is crucial to consider that mutations within the virion can potentially affect the clinical course of SARS-CoV-2 infection because disease severity and manifestation vary depending on the genetic variant. Our objective was to measure and assess the different concentrations of chemokines involved in COVID-19 caused by different variants of the virus. Methods. We used the blood plasma of patients infected with different variants of SARS-CoV-2, i.e., the ancestral Wuhan strain and the Alpha, Delta, and Omicron variants. We measured the concentrations of 11 chemokines in the samples: CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and CX3CL1/Fractalkine. Results. We noted a statistically significant elevation in the concentrations of CCL2/MCP-1, CXCL8/IL-8, and CXCL1/IP-10 independently of the variant, and a drop in the CCL22/MDC concentrations. Conclusions. The chemokine concentrations varied significantly depending on the viral variant, leading us to infer that mutations in viral proteins play a role in the cellular and molecular mechanisms of immune responses.

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.

В декабре 2019 появилась информация о новом заболевании, этиологическим фактором которого оказался β-коронавирус SARS-CoV-2. В Ленинградской области первый случай COVID-19 выявлен 13 марта 2020 года. Период нарастания интенсивности эпидемического процесса продолжался 8 недель. Через один месяц после достижения максимального уровня заболеваемости было организовано исследование по определению серопревалентности к COVID-19 среди населения Ленинградской области. Работа проводилась в рамках проекта Роспотребнадзора по оценке популяционного иммунитета к вирусу SARS-CoV-2 у населения Российской Федерации с учетом протокола, рекомендованного ВОЗ. Содержание антител к SARS-CoV-2 определяли методом ИФА с использованием набора реагентов для анализа сыворотки или плазмы крови человека на наличие специфических иммуноглобулинов класса G к нуклеокапсиду вируса SARS-CoV-2 производства ФБУН ГНЦПМиБ Роспотребнадзора (г.Оболенск) в соответствии с инструкцией по применению. Результаты исследования показали, что коллективный иммунитет совокупного населения Ленинградской области составил 20,7%. Максимальный уровень коллективного иммунитета установлен у детей 1-6 лет (42,3%) и обследованных старше 70 лет (29,0%). Наибольший уровень серопозитивности, кроме детей и лиц старшего возраста, выявлен у безработных (25,1%). Наименьший уровень серопревалентности установлен в подгруппе госслужащих (12,8%) и подгруппе военных (16,7%). Показано, что при наличии контактов с больными COVID-19 риск инфицирования возрастает в 1,5 раза. После инфекции COVID-19 антитела вырабатываются в 82,1% случаев. У лиц с позитивным результатом ПЦР-анализа, полученным ранее, антитела выявляются в 82,8% случаев. Доля бессимптомных форм среди серопозитивных жителей Ленинградской области составила 86,9%. Результаты оценки популяционного иммунитета к вирусу SARS-CoV-2 у населения Ленинградской области свидетельствуют о том, что в период эпидемического подъема заболеваемости инфекцией COVID-19 сформировался средний уровень серопревалентности. После перенесенного заболевания у 18% лиц, антитела не выявляются. Значительная доля бессимптомных форм инфекции характеризует высокую интенсивность скрыто развивающегося эпидемического процесса. Полученные результаты необходимо учитывать при организации профилактических мероприятий, включая вакцинацию, и прогнозировании заболеваемости.

В конце 2019 – начале 2020 годов появились сообщения о вспышке инфекции, вызванной новым штаммом бета-коронавируса SARS-CoV-2, заболевание ВОЗ определила как coronavirus disease 2019 (COVID-19). В Санкт-Петербурге первый случай COVID-19 был диагностирован 2 марта 2020 г., период нарастания заболеваемости продолжался в течение 10 недель, максимальные показатели были зафиксированы в середине мая, в дальнейшем отмечалось статистически значимое снижение заболеваемости. Целью проведенного сероэпидемиологического исследования было определение уровня и структуры популяционного иммунитета к вирусу SARS-CoV-2 среди населения Санкт-Петербурга в период интенсивного распространения COVID-19. Отбор волонтеров для исследования проводили методом анкетирования и рандомизации путем случайной выборки. Критерием исключения была активная инфекция COVID-19 в момент анкетирования. На наличие специфических антител к SARS-CoV-2 обследовано 2713 человек. Возраст обследованных добровольцев варьировал от 1 года до 70 лет и старше. Результаты исследования показали, что в Санкт-Петербурге в активную фазу заболеваемости COVID-19 наблюдалась умеренная серопревалентность к SARS-CoV-2, составившая 26%, на фоне высокой частоты (84,5%) бессимптомной инфекции у серопозитивных лиц, не имевших в анамнезе перенесенного заболевания COVID-19, положительного результата ПЦР и симптомов ОРВИ в день обследования. Максимальные показатели коллективного иммунитета установлены у детей 1-6 лет (31,1%), детей 7-13 лет (37,7%) и лиц старше 70 лет (30,4%), различия с уровнем серопревалентности в возрастных группах 18-49 лет статистически значимы. В социально-профессиональной структуре населения наибольший уровень серопревалентности выявлен среди безработных (29,7%), работников здравоохранения (27,1%), образования (26,4%) и бизнеса (25%). У реконвалесцентов COVID-19 антитела вырабатываются в 75% случаев. У лиц с позитивным результатом ПЦР-анализа, проведенного ранее, антитела выявляются в 70% случаев. Результаты исследования о состоянии коллективного иммунитета к вирусу SARS-CoV-2 необходимы для разработки прогноза развития эпидемиологической ситуации, а также планирования мероприятий по специфической и неспецифической профилактике COVID-19.

COVID-19, an infection caused by the new coronavirus SARS-CoV-2, is associated with a number of pathophysiological mechanisms, mobilizing a wide spectrum of biomolecules, mainly, cytokines.The purpose of this study was to evaluate levels of multiple cytokines in blood plasma from the patients with COVID-19 during acute phase of the disease, and upon complete recovery. Samples of peripheral blood plasma of 56 patients with COVID-19, 69 convalescents and 10 healthy individuals were examined. Concentrations of 46 molecules, such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNα2, IFNγ, TNFα, TNFβ/ Lymphotoxin-α (LTA), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine, IL-1ra, IL-10, EGF, FGF-2/FGF-basic, Flt3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGF-AB/ BB, TGF-α, VEGF-A were measured via xMAP multiplexing technology. Significantly increased levels of 18 cytokines were found in blood plasma from COVID-19 patients during acute phase of the disease (as compared to control group), i.e., IL-6, IL-7, IL-15, IL-27, TNFα, TNFβ/Lymphotoxin-α (LTA), CCL2/MCP-1, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL9/MIG, IL-1rа, IL-10, M-CSF, GM-CSF, VEGF-A. We found a significant decrease of nearly all the mentioned cytokines in recovered patients, in comparison with those who had moderate, severe/extremely severe disease. Moreover, we revealed a significantly decreased level of 8 cytokines in plasma from convalescents, as compared with control group, i.e., IL-1α, IL-2, IL-9, IL-12 p40, IL-18, CCL22/MDC, Flt3 Ligand, TGF-α. Immune response caused by SARS-CoV-2 infection involves multiple cytokines, mostly, with pro-inflammatory effects. We have shown for the first time that the convalescence phase is characterized by significantly lower levels of cytokines which regulate cellular differentiation and hematopoiesis (in particular, lymphocytes, T-cells and NK-cells). Over acute phase of the disease, the levels of these cytokines did not change. We revealed a significant decrease of most plasma cytokines upon recovery as compared to acute phase. On the contrary, acute phase of the disease is accompanied by significant increase of both pro- and antiinflammatory cytokines in blood plasma.

Various immune cells as well as related cytokines are involved in immunopathogenesis of sarcoidosis and mechanisms of granuloma development. Currently, a role for chemokines in sarcoidosis has been extensively investigated, which is paralleled with a search for key molecules necessary for recruiting immune cells to intrusion site and granuloma formation as well as affecting outcome of the latter. Our study was aimed for determining level of plasma CCL17/TARC and CCL22/MDC chemokines in patients with sarcoidosis who received no immunosuppressive therapy is of high priority for clarifying some aspects in underlying immunopathogenesis as well as seeking out for secure clinical and laboratory criteria for assessing activity and disease prognosis. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CCL17 – 78.24 pg/ml vs 26.24 pg/ml, p < 0.001; CCL22 – 660.60 pg/ml vs 405.00 pg/ml, p < 0.001. Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CCL17 – 63% and 78%, CCL22 – 63% and 91%; in chronic sarcoidosis: CCL17 – 58% and 83%, CCL22 – 67% and 86%, respectively. In chronic sarcoidosis the levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), for CCL17 (r = 0.530; p = 0.003), for CCL22 (r = 0.446; p = 0.014). Patients with systemic lesions vs no systemic lesions (sarcoidosis of the respiratory system only) had significantly elevated CCL17 level: 102.82 pg/ml vs 32.72 pg/ml, p = 0.011. The concentration of chemokine CCL17 was significantly increased in patients with vs without signs of hepatomegaly: 130.73 pg/ml vs 51.60 pg/ml, p = 0.022. Levels of chemokines was significantly increased in patients with vs without ultrasound signs of splenomegaly comprising: for CCL17 – 249.18 pg/ml vs 46.87 pg/ml, p = 0.002; for CCL22 – 1271.40 pg/ml vs 660.63 pg/ml, p = 0.003. Thus, it should be noted that the peripheral blood plasma level of chemokines CCL17 and CCL22 may be used as additional prognostic markers in chronic sarcoidosis with varying scoring of clinical signs including with/without systemic disease manifestations.