ABSTRACT
Objective. To evaluate some parameters of the psychosomatic state, cytokine levels (IL-6, IL-8, IL-17A), and free radical status (levels of nitrates and nitrites, antioxidant plasma activity) in convalescent patients after severe COVID-19. Patients and methods. We examined 64 patients who had severe COVID-19 and underwent either a 30-35-day course of inpatient rehabilitation after their discharge from a hospital for infectious diseases or a 60-65-day course of outpatient rehabilitation at the Ambulatory Center of Nalchik, Clinical Hospital No 1. Results. We surveyed patients after severe COVID-19 and found that they required a long rehabilitation. Many of them reported asthenic syndrome, psycho-emotional disorders, and other complaints upon discharge from the hospital. Serum levels of proinflammatory cytokines remained high in patients after severe COVID-19 even 30-35 days following their discharge (p < 0.05). Serum levels of IL-6, IL-8, nitrites, and nitrates remained elevated on days 60-65 following discharge (p < 0.05), despite comprehensive therapy in a rehabilitation department. Plasma antioxidant activity was reduced, whereas IL-17A level normalized by this time. Conclusion. Our findings suggest that currently used rehabilitation measures for COVID-19 are insufficient. Adequate rehabilitation of convalescent COVID-19 patients requires proper monitoring of their immune system condition, as well as new effective methods for immune correction and restoration of their psychoemotional status after the acute phase of the disease.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Cancer patients, particularly those receiving B cell-depleting therapy for lymphoid malignancies, are at risk of prolonged SARS-CoV-2 infection, poorer clinical outcomes, and delayed initiation or disruption of cancer-directed therapy (Lee at al., 2022, Clark et al., 2021). We first studied T-cell mediated response to the Wuhan strain of SARS-CoV-2 in a cohort of 69 patients with hematologic and solid cancers, including 18 patients who received prior B-cell depleting therapy. Patients with prolonged COVID-19 clearance, defined by a positive PCR test for longer than 30 days, had a broad but poorly converged CD8+ dominant response and a lacking CD4+ response. To conduct this analysis, we performed bulk T-cell receptor (TCR) sequencing of 121 blood samples and tracked over time TCR repertoire statistics such as clonality, convergence, breadth, and depth of COVID-19-associated TCRs during the active and convalescent periods of COVID-19 infection. These SARS-CoV-2-associated TCRs were identified leveraging immunoSEQ T-MAP database (Snyder et al., 2020), a set of TCR sequences derived from COVID-19 patients and experimentally identified as responsive to MHC Class I and II epitopes from the Wuhan SARS-CoV-2 strain using the multiplex identification of TCR antigen assay (Klinger et al., 2015). To extend our TCR repertoire analysis to other SARS-CoV-2 variants, including Omicron, we developed a deep learning (DL) method to predict TCR specificities for new SARS-CoV-2 epitopes. This DL approach also permits the identification of SARS-CoV2-responsive TCRs private to an individual. Combining this DL approach with our TCR statistics methodology, we studied the dynamics of T-cell response to COVID-19 vaccinations in a cohort of 50 patients with cancer and analyzed TCR repertoire characteristics associated with different degrees of COVID-19 severity in a cohort of 42 cancer patients who contracted the Omicron. Understanding cellular response to novel infections is critical for patient care in the context of cancer, and our novel DL-based approach can leverage existing datasets to analyze and track response to emerging viral strains.
ABSTRACT
Introduction. Coronavirus infection is associated with severe endotheliopathy, thromboinflammation and immunothrombosis leading to excessive release of von Willebrand factor (vWF) multimers from Weibel-Palade bodies, which can affect activity of ADAMTS-13 metalloproteinase (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and the ADAMTS-13/vWF axis previously shown by us to be altered in non-pregnant women with severe COVID-19. Aim(s): to study a clinical role of hemostasis activation particularly ADAMTS-13/vWF axis in pregnant women after COVID-19. Materials and Methods. A prospective case-control study was conducted with pregnant women (n = 135) divided into 3 groups: group 1 included 45 women with prior COVID-19 during pregnancy, group 2 - 45 women in the acute phase of the infection during pregnancy, group 3 - 45 healthy pregnant women. The level of vWF and ADAMTS-13 was assessed in all patients. Results. The concentration of vWF antigen (vWF:Ag) in the acute period of the disease in pregnant women with COVID-19 was significantly higher compared to the control group (p < 0.001). ADAMTS-13 level in pregnant women after COVID-19 did not differ from that of in control group, while vWF level was significantly higher in 66.7 % (30/45). The ADAMTS-13/vWF ratio was increased and significantly differed both in pregnant patients during the acute period of the disease (p < 0.001) and pregnant women after infection (p = 0.0002) compared with the control group. Conclusion. Our results show that endotheliopathy was prominently manifested in pregnant women with COVID-19 and persisted for several months after disease. The ADAMTS-13/vWF ratio determines the pathway functioning, the risk of microcirculation disorders and clinical complications.Copyright © 2023 Vestnik Sankt-Peterburgskogo Universiteta, Yazyk i Literatura. All rights reserved.
ABSTRACT
Today, medical rehabilitation is undergoing significant transformation. The new system built around the biopsychosocial model includes assessment of physical constraints and rehabilitation diagnosis, determination of rehabilitation potential, formulation of goals and objectives of individual interventions, development of rehabilitation plans, and progress evaluation. All of these rehabilitation components can be implemented using a personalized, problem-oriented, multidisciplinary approach, which is now being actively introduced into clinical practice. The current pandemic of the novel coronavirus infection has demonstrated that medical rehabilitation is crucial for convalescents. However, its principles and techniques have not been fully elaborated yet. This review describes the current state of medical rehabilitation of children with or after infectious diseases and identifies its avenues and prospects.Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.
ABSTRACT
Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023
ABSTRACT
The aim of the study was to assess the frequency of symptoms of post-COVID syndrome by means of a questionnaire among medical university employees. Material and methods. From March 2021 to February 2022, an anonymous online survey was conducted at the A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation. Only 313 fully completed questionnaires were selected for analysis. Results and discussion. A wide range of asthenic, infectious-inflammatory, respiratory, cardiovascular, neuropsychiatric, gastroenterological and dermatological symptoms were noted both during the peak period and during the convalescence of COVID-19. According to the subjective data of respondents, for more than 3 months, various symptoms associated with deterioration of health after recovering from a new coronavirus infection persisted in 25.9% of cases. Within 3-6 months after the illness and more than 6 months, 44.6% and 55.4% of respondents noted the presence of symptoms of post-COVID syndrome, respectively. During the analysis, it was found that with an increase in the volume of lung damage according to CT data, there was a tendency to increase the proportion of respondents with a long-term (more than 6 months) persistent symptoms of post-COVID syndrome from 20% with CT score 0, up to 29% with CT score 1-2 and up to 58% with CT score 3-4. In this regard, apparently, it is necessary to develop additional screening programs as part of the medical examination of COVID-19 patients. Conclusion. SARS-CoV-2 infection causes a wide range of symptoms both during the period of the disease and during the period of convalescence. Attention should be paid to the need for a targeted survey of patients who have undergone COVID-19 to identify the manifestations of post-COVID syndrome and conduct their medical examination with the participation of a multidisciplinary team.Copyright © Eco-Vector, 2022.
ABSTRACT
Background: T cells play an essential role in SARS-CoV-2 immunity, including in defense against severe COVID-19. However, most studies analyzing SARSCoV- 2-specific T cells have been limited to analysis of blood. Furthermore, the role of T cells in SARS-CoV-2 immunity in pregnant women, which are at disproportionately higher risk of severe COVID-19, is poorly understood. Method(s): Here, we quantitated and deeply phenotyped SARS-CoV-2-specific T cells from convalescent women (n=12) that had mild (non-hospitalized) COVID-19 during pregnancy. Endometrial, maternal blood, and fetal cord blood specimens were procured at term, which ranged from 3 days to 5 months post-infection. SARS-CoV-2-specific T cells were deeply analyzed by CyTOF using a tailored phenotyping panel designed to assess the effector functions, differentiation states, and homing properties of the cells. Result(s): SARS-CoV-2-specific T cells were more abundant in the endometrium than in maternal or fetal cord blood. In a particularly striking example, in one donor sampled 5 months after infection, SARS-CoV-2-specific CD8+ T cells comprised 4.8% of total endometrial CD8+ T cells, while it only reached 1.4% in blood. Endometrial SARS-CoV-2-specific T cells were more frequently of the memory phenotype relative to their counterparts in maternal and fetal cord blood, which harbored higher frequencies of naive T cells. Relative to their counterparts in blood, endometrial SARS-CoV-2-specific T cells exhibited unique phenotypic features, including preferential expression of the T resident memory marker CD69, inflammatory tissue-homing receptor CXCR4, and the activation marker 4-1BB. Endometrial T cells were highly polyfunctional, and could secrete IFNg, TNFa, MIP1b, IL2, and/or IL4 in response to spike peptide stimulation. By contrast, their counterparts in blood preferentially produced the cytolytic effectors perforin and granzyme B. Conclusion(s): Polyfunctional SARS-CoV-2-specific T cells primed by prior exposure to the virus are abundant and persist in endometrial tissue for months after infection. These cells exhibit unique phenotypic features including preferential expression of select chemokine receptors and activation molecules. Compared to their blood counterparts, the effector functions of these cells are more cytokine-driven and less cytolytic. The long-term persistence of these cells in the endometrium may help protect future pregnancies from SARS-CoV-2 re-infection.
ABSTRACT
Background: A significant portion of individuals experience persistent symptoms months after SARS-CoV-2 infection, broadly referred to as Long COVID (LC). Although the frequencies of subsets of SARS-CoV-2-specific T cells have been shown to differ in individuals with LC relative to those with complete recovery, a deep dive into phenotypic and functional features of total and SARSCoV- 2-specific T cells from individuals with LC has yet to be performed. Method(s): Here, we used CyTOF to characterize the phenotypes and effector functions of T cells from LIINC cohort. The median age was 46, the cohort was 55.8% female, and 9/43 had been hospitalized. Participants were reported a median of 7 LC symptoms at 8 months. SARS-CoV-2-specific total antibody levels were also measured in concurrent sera. Manual gating was used to define T cell subsets, SPICE analyses for polyfunctionality, T cell clustering for phenotypic features, and linear regression for correlation. Permutation tests, Student's t tests, and Welch's t test were used for statistical analysis. Result(s): SARS-CoV-2 total antibody responses were elevated in the LC group (p=0.043), and correlated with frequencies of SARS-CoV-2-specific T cells in those without LC (r=0.776, p< 0.001) but not those with LC. While the frequencies of total SARS-CoV-2-specific CD4+ and CD8+ T cells were similar between individuals with and without LC, those from individuals without LC tended to be more polyfunctional (co-expressing IFNgamma, TNFalpha, IL2, and/or MIP1beta). CD4+ T cells from individuals with LC harbored higher frequencies of Tcm (p=0.003), Tfh (p=0.037), and Treg subsets (p=0.0412), and preferentially expressed a variety of tissue homing receptors including CXCR4 and CXCR5 (p=0.037). SARS-CoV-2-specific CD4+ T cells producing IL6, albeit rare, were observed exclusively among those with LC (p=0.016). In addition, participants with LC harbored significantly higher frequencies of SARS-CoV-2-specific CD8+ T cells co-expressing exhaustion markers PD1 and CTLA4 (p=0.018). Conclusion(s): Long COVID is characterized by global phenotypic differences in the CD4+ T cell compartment in ways suggesting preferential migration of these cells to inflamed mucosal tissues. Individuals with LC also harbor higher numbers of exhausted SARS-CoV-2-specific CD8+ T cells, potentially implicating viral persistence. Finally, our data additionally suggest that individuals with LC may uniquely exhibit an uncoordinated T cell and antibody response during COVID-19 convalescence.
ABSTRACT
The question on the duration and effectiveness of post-infection vs post-vaccination SARS-CoV-2 immunity remains in the focus of numerous studies. The aim of the work was to examine the duration of maintained post-infection and post-vaccination SARS-CoV-2 immunity as well as formation of hybrid (vaccination after infection) and breakthrough (repeated disease or disease after vaccination) immunity in the context of an ongoing COVID-19 pandemic. 107 adults with mild or moderate COVID-19 3-18 months after the disease and 30 subjects vaccinated twice with the Sputnik V vaccine were examined 1-6 times. Antibodies against SARS-CoV-2 virus were determined by ELISA on the "SARSCoV-2-IgG quantitative-ELISA-BEST" test systems. The antibody avidity was measured by additional incubation with and without denaturing solution. Mononuclear cells were isolated from blood by gradient centrifugation, incubated with and without coronavirus S-protein for 20 hours, stained with fluorescently labeled antibodies, and the percentage of CD8highCD107a+ was counted using FACSCanto II cytometer. It was shown that in the group of convalescent and vaccinated subjects, the level of virus-specific antibodies decreased more deeply in individuals with initially high humoral response, but 9 months later the decrease slowed down and reached a plateau. The antibody avidity rose up to 50% and persisted for 18 months. Cellular immunity in recovered patients did not change for 1.5 years, while in vaccinated patients it gradually decreased 6 months later, but remained at detectable level. After revaccination, a significant increase in the level of antibodies, avidity up to 67.6% and cellular immunity returned to the initial level were noted. Hybrid immunity turned out to be significantly higher than post-infection and post-vaccination immunity. The level of antibodies increased to 1218.2 BAU/ml, avidity - to 69.85%, and cellular immunity - to 9.94%. Breakthrough immunity was significantly higher than that after the first disease. The level of antibodies rose to 1601 BAU/ml, avidity - up to 81.6%, cellular immunity - up to 13.71%. Using dynamic observation of four COVID-19 convalescents, it has been shown that in the context of the ongoing pandemic and active coronavirus mutation, natural boosting occurs both asymptomatically and as a result of a mild re-infection, which prevents disappearance of SARS-CoV-2 humoral and cellular immunity.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
The COVID-19 pandemic has altered people's lifestyles around the world. Prevention of recurrent episodes of the disease and mitigation of its consequences are especially associated with effective post-COVID-19 rehabilitation in patients. The aim of the study was to evaluate the effects of the drug Likopid (glucosaminylmuramyl dipeptide, GMDP) for post-COVID-19 rehabilitation in patients. Material and methods. Patients who recovered from mild to moderate COVID-19 (n=60, mean age 54+/- 11.7 years) were randomized into the observation group (n=30, 15 men and 15 women) who received 2 courses of Licopid (1 mg twice a day) and the comparison group (n=30, 15 men and 15 women). Analysis of the phenotypic and functional characteristics of the innate immune cellular factors was carried out before the start of immunomodulatory therapy, immediately after the end of the course, and also after 6 months observations. In order to assess the quality of life of all patients, we used the SF-36 Health Status Survey and the Hospital Anxiety and Depression Scale questionnaires. Results. During assessing the effect of immunomodulatory therapy on the parameters of innate immunity of patients at the stage of rehabilitation after COVID-19, an increase in the protective cytolytic activity of CD16+ and CD8+Gr+ cells, as well as a persistent increase in TLR2, TLR4 and TLR9 expression was found, which indicates the antigen recognition recovery and presentation at the level of the monocytic link of the immune system. The use of GMDP as an immunomodulatory agent resulted in an 8-fold reduction in the frequency and severity of respiratory infections due to an increase in the total monocyte count. As a result of assessing patients' quality of life against the background of the therapy, a positive dynamic in role functioning was revealed in patients. In the general assessment of their health status, an increase in physical and mental well-being was noted during 6 months of observation. The comparison group showed no improvement in the psychoemotional state. Discussion. The study demonstrated the effectiveness of GMDP immunomodulatory therapy in correcting immunological parameters for post-COVID-19 rehabilitation in patients. The data obtained are consistent with the previously discovered ability of GMDP to restore impaired functions of phagocytic cells and induce the expression of their surface activation markers, which in turn contributes to an adequate response to pathogens. Conclusion. The study revealed that the correction of immunological parameters with the use of GMDP in COVID-19 convalescents contributed not only to a decrease in the frequency and severity of respiratory infections, but also to an improvement in the psycho-emotional state of patients, and a decrease in anxiety and depression.Copyright © Eco-Vector, 2023. All rights reserved.
ABSTRACT
Background: Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Method(s): We obtained cross-sectional paired blood and lung biopsy samples from patients (n=30) undergoing lung resection for various reasons and assigned them to one of four groups: I.) uninfected unvaccinated individuals (n=5), II.) unvaccinated long-term SARS-CoV-2 convalescent individuals (between 6.0-10.5 months post-infection;n=9), III.) uninfected and long-term vaccinated individuals (between 6.0-7.7 months after the second or third dose;n=10), and IV.) uninfected and short-term vaccinated individuals (between 1.3-1.8 months after the third or fourth dose;n=6). We determined the presence of SARS-CoV-2-specific CD4+ and CD8+ T cells in blood and lung samples after exposure of cells to M, N, and S peptide pools, followed by flow cytometry to detect TRM cells expressing interferon (IFN)gamma and/or CD107a, as a degranulation marker. Result(s): We found that the frequency of CD4+ T cells secreting IFNgamma in response to S-peptides was variable but detectable in blood and lung up to 8 months after mRNA vaccination. Moreover, the IFNgamma response of CD4+ T cells in the lung of mRNA-vaccinated patients was similar to the response found in convalescent patients. However, in mRNA-vaccinated patients, lung responses presented less frequently with a TRM phenotype compared to convalescent infected individuals and, strikingly, polyfunctional CD107a+ IFNgamma+ TRM were virtually absent in vaccinated patients. Conclusion(s): mRNA vaccines might induce memory responses within the lung parenchyma in some patients, potentially contributing to the overall disease control. However, the robust and broad TRM response established in convalescent-infected individuals may offer advantages at limiting disease if the virus is not blocked by initial mechanisms of protection, such as neutralization. Our results warrant investigation of mucosal vaccine-induced resident T cell responses in establishing superior site-specific protective immunity.
ABSTRACT
Objective. To evaluate some parameters of the psychosomatic state, cytokine levels (IL-6, IL-8, IL-17A), and free radical status (levels of nitrates and nitrites, antioxidant plasma activity) in convalescent patients after severe COVID-19. Patients and methods. We examined 64 patients who had severe COVID-19 and underwent either a 30-35-day course of inpatient rehabilitation after their discharge from a hospital for infectious diseases or a 60-65-day course of outpatient rehabilitation at the Ambulatory Center of Nalchik, Clinical Hospital No 1. Results. We surveyed patients after severe COVID-19 and found that they required a long rehabilitation. Many of them reported asthenic syndrome, psycho-emotional disorders, and other complaints upon discharge from the hospital. Serum levels of proinflammatory cytokines remained high in patients after severe COVID-19 even 30-35 days following their discharge (p < 0.05). Serum levels of IL-6, IL-8, nitrites, and nitrates remained elevated on days 60-65 following discharge (p < 0.05), despite comprehensive therapy in a rehabilitation department. Plasma antioxidant activity was reduced, whereas IL-17A level normalized by this time. Conclusion. Our findings suggest that currently used rehabilitation measures for COVID-19 are insufficient. Adequate rehabilitation of convalescent COVID-19 patients requires proper monitoring of their immune system condition, as well as new effective methods for immune correction and restoration of their psychoemotional status after the acute phase of the disease.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Introduction: COVID-19 is a disease with gaps in its knowledge. It is required to explore its clinical manifestations over time and consequences for performance in the working population. Objective(s): To identify the clinico-epidemiological characteristics and the fitness to work in health workers convalescing from COVID-19. Material(s) and Method(s): A prospective longitudinal study was carried out on health workers in Havana. The population consisted of 40 workers who attended the COVID-19 convalescent consultation and were followed up in May 2022. Result(s): Dyspnea (18.8 %), insomnia (18.8 %), and arthralgia (12.5 %) persisted at the end of the year. Hypertension, obesity and bronchial asthma were the main comorbidities. In addition, 100 % of workers were fit for work. Conclusion(s): PostCOVID-19 symptoms deceased considerably 8 months after the onset of the disease;dyspnea, arthralgia, and insomnia persisted at the end of the year.Copyright © 2022 Universidad de Ciencias Medicas de La Hab. All rights reserved.
ABSTRACT
The aim is to examine dynamics of avidity maturation of IgG antibodies against SARS-CoV-2 RBD depending on the type of immunization (vaccination or infection), as well as on the duration and frequency of immunization. Materials and methods. The study was performed on two sample cohorts collected at two time points during COVID-19 pandemic. The first cohort (group No. 1) consisted of 87 samples of blood sera obtained from COVID-19 convalescents in the period from March to September 2020. The second cohort included 204 samples obtained in September 2021 from two patient groups. Group No. 2 (n = 64) - patients immunized with a full course of Gam-Covid-Vac, group No. 3 (n = 140) - COVID-19 convalescent patients and subjects vaccinated with Gam-Covid-Vac ("hybrid immunity"). Results and conclusion. The dynamics of avidity maturation for SARS-CoV-2 RBD IgG antibodies depending on the method and frequency of immunization, showed that the most effective immunity was formed in COVID-19 convalescent patients and subjects vaccinated with a full course of Gam-Covid-Vac. The "hybrid" immunity showed not only a significantly higher (compared with groups No. 1 and No. 2) level of IgG antibodies (median 228 BAU/ml vs 75 or 119 BAU/ml, p < 0.001), but also a higher level of avidity (IA 90.5% vs 54.5 and 76.6, respectively, p < 0.001, 4M urea). In the test for assessing the avidity index with the denaturing agent 8M urea in patients with "hybrid immunity", the median level of IA was 25% versus 14.8% and 16% in COVID-19 convalescents and vaccinated subjects (p < 0.001), only in 8 patients IA was higher than 50%. While comparing a single infection of COVID-19 with a full course of Gam-Covid-Vac, it was shown that vaccination leads to higher IgG levels (median values in groups 119 and 75 BAU/ml, p < 0.001) and to a higher avidity index (median 76.6% vs 54.5%). Thus, the more rapid induction of high-avidity antibodies was in vaccinated individuals at early stages of immunization (up to 4 months), during the period when IgG avidity maturation has not yet been completed. Our results showed that during this period vaccination leads to production of antibodies with avidity index at median level of 82% versus 36% in COVID-19 convalescents at similar time point.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Introduction. Coronavirus infection is associated with severe endotheliopathy, thromboinflammation and immunothrombosis leading to excessive release of von Willebrand factor (vWF) multimers from Weibel-Palade bodies, which can affect activity of ADAMTS-13 metalloproteinase (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and the ADAMTS-13/vWF axis previously shown by us to be altered in non-pregnant women with severe COVID-19. Aim(s): to study a clinical role of hemostasis activation particularly ADAMTS-13/vWF axis in pregnant women after COVID-19. Materials and Methods. A prospective case-control study was conducted with pregnant women (n = 135) divided into 3 groups: group 1 included 45 women with prior COVID-19 during pregnancy, group 2 - 45 women in the acute phase of the infection during pregnancy, group 3 - 45 healthy pregnant women. The level of vWF and ADAMTS-13 was assessed in all patients. Results. The concentration of vWF antigen (vWF:Ag) in the acute period of the disease in pregnant women with COVID-19 was significantly higher compared to the control group (p < 0.001). ADAMTS-13 level in pregnant women after COVID-19 did not differ from that of in control group, while vWF level was significantly higher in 66.7 % (30/45). The ADAMTS-13/vWF ratio was increased and significantly differed both in pregnant patients during the acute period of the disease (p < 0.001) and pregnant women after infection (p = 0.0002) compared with the control group. Conclusion. Our results show that endotheliopathy was prominently manifested in pregnant women with COVID-19 and persisted for several months after disease. The ADAMTS-13/vWF ratio determines the pathway functioning, the risk of microcirculation disorders and clinical complications.Copyright © 2023 Vestnik Sankt-Peterburgskogo Universiteta, Yazyk i Literatura. All rights reserved.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic in 2020 is one of the worst catastrophic events in human history. A number of therapeutic modalities have been utilized in order to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the majority of them failed to demonstrate a beneficial clinical effect. Among the anti-COVID-19 agents being investigated, the convalescent plasma collected from recovered donors has gained a growing interest. Convalescent plasma has been employed for over a hundred years to treat severe acute viral infections when a vaccine or a specific antiviral treatment was not yet available. In this narrative review, we summarize the literature data on the use of convalescent plasma during previous viral outbreaks and pandemics, including influenza viruses, coronaviruses other than SARS-CoV-2 and Ebola virus. A literature search, using the Medline and PubMed electronic database, was performed to retrieve publications on the use of convalescent plasma in previous viral epidemics. In conclusion, the available literature data suggest the safety profile of convalescent plasma and its potential benefit in treating emerging viral infectious diseases. In addition, these data retrieved from previous viral epidemics provide a solid rationale for the employment of plasma from convalescent donors also in COVID-19 patients.Copyright © 2021 AME Publishing Company. All rights reserved.
ABSTRACT
Background: Hybrid immunity is more protective than vaccination or prior infection alone. To understand the formation of hybrid immunity, we studied how SARS-CoV-2 mRNA vaccines interact with T cell memory by tracking spike (S) specific T cells in cohorts of hospitalized (n = 19) or non-hospitalized (n = 34) COVID-19 convalescents. We hypothesized that S-reactive CD4 and CD8 T cells would increase in response to serial vaccine doses and reflect prior immune exposure at the clonal level. Method(s): After vaccination, we stimulated PBMCs from 12 participants (8M/4F) with peptides spanning S. Activated cells (CD69+CD137+) were sorted and CD4/CD8 phenotype linked with paired TRB-TRA sequences at single cell resolution. S-reactive TRB sequences were mapped within 4-6 serial blood and post-booster nasal TRB repertoires to evaluate S-reactive CD4 and CD8 T cell clonotypic kinetics spanning convalescence to boost. PBMCs from 53 participants were sequenced with the ImmunoSEQ assay to evaluate S-reactive TRB breadth using a database of S-assigned TRB sequences (Adaptive Biotechnologies), comparing S-reactive TRB diagnostic breadth by hospitalization status (Wilcoxon test). Result(s): SARS-CoV-2 mRNA vaccination provoked strong T cell clonal expansion in most participants. At 8-12 months after infection, each primary mRNA dose increased the abundance and diversity of S-specific T cells. Clonal and integrated expansions were larger in CD8 than in CD4 T cells. At the convalescent time point, we observed greater diagnostic S-reactive CD4 T cell breadth in hospitalized vs. non-hospitalized patients (p< 0.01). CD4 T cell S breadth was again higher in previously hospitalized persons after the 2nd primary (p=0.02) and booster (p< 0.01) doses, suggesting that diverse CD4 T cell memory after severe infection leads to increased repertoire diversity after vaccination. S-specific T cells with identical TCRs were detectable in blood and the nasal mucosa, with specificity confirmed using a TRA/TRB transgenic T cell with the matching receptor. Conclusion(s): Although both S-specific CD8 and CD4 T cell memory are established by prior infection, S-specific CD8 T cells predominated in blood after primary vaccination, with some clonotypes showing up to 1000-fold expansion across 1-2 mRNA doses. Vaccine-reactive CD8 clonotypes were present at the barrier nasal site after booster mRNA dosing. Severe disease imprinted a highly diverse S-reactive CD4 repertoire persisting through vaccination.
ABSTRACT
Background: Neurocognitive symptoms are common in acute as well as convalescent (post-acute sequelae of COVID-19 [PASC]) COVID-19, but mechanisms of CNS pathogenesis are unclear. The aim of this study was to investigate cerebrospinal fluid (CSF) biomarker evidence of CNS infection, immune activation and neuronal injury in convalescent compared with acute infection. Method(s): We included 68 (35% female) patients >=18 years with CSF sampled during acute (46), 3-6 months after (22) SARS-CoV-2 infection or both (17), and 20 (70% female) healthy controls from longitudinal studies. The 22 patients sampled only at 3-6 months were recruited in a PASC protocol. CSF N-Ag was analyzed using an ultrasensitive antigen capture immunoassay platform (S-PLEX SARS-CoV-2 N Kit, Meso Scale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF beta2-microglobulin (beta2M)], IFN-gamma, IL-6, TNF-alpha neurofilament light (NfL), and total and phosphorylated tau. Log-transformed CSF biomarkers were compared using ANOVA (Tukey post-hoc test). Result(s): Patients sampled during acute infection had moderate (27) or severe (19) COVID-19. In patients sampled at 3-6 months, corresponding initial severity was 10 (mild), 14 (moderate), and 15 (severe). At 3-6 months, 31/39 patients reported neurocognitive symptoms;8/17 patients also sampled during acute infection reported full recovery after 3-6 months. CSF biomarker results are shown in Figure 1. SARS-CoV-2 RNA was universally undetectable. N-Ag was detectable only during acute infection (32/35) but was undetectable in all follow up and control samples. Significantly higher CSF concentrations of beta2M (p< 0.0001), IFN-gamma (p=0.02), IL-6 (p< 0.0001) and NfL (p=0.04) were seen in acute compared to post-infection. Compared to controls, beta2M (p< .0001), IL-6 (p< 0.0001) and NfL (p=0.005) were significantly higher in acute infection. No biomarker differences were seen post-infection compared with controls. No differences were seen in CSF GFAp, t-tau or p-tau. Conclusion(s): We found no evidence of residual infection (RNA, N-Ag), inflammation (beta2M, IL-6, IFN-gamma, TNF-alpha), astrocyte activity (GFAp) or neuronal injury (NfL, tau) 3-6 months after initial COVID-19, while significantly higher concentrations of several markers were found during acute infection, suggesting that PASC may be a consequence of earlier injury rather than active CNS damage. CSF beta2M, IL-6, IFN-gamma and NfL were significantly lower after 3-6 months than during acute COVID-19 and not different from healthy controls. (Figure Presented).
ABSTRACT
Background: T cells play a critical role in the adaptive immune response to SARS-CoV-2 in both infection and vaccination. Identifying T cell epitopes and understanding how T cells recognize these epitopes can help inform future vaccine design and provide insight into T cell recognition of newly emerging variants. Here, we identified SARS-CoV-2 specific T cell epitopes, analyzed epitope-specific T cell repertoires, and characterized the potency and cross-reactivity of T cell clones across different common human coronaviruses (HCoVs). Method(s): SARS-CoV-2-specific T cell epitopes were determined by IFNgamma ELISpot using PBMC from convalescent individuals with mild/moderate disease (n=25 for Spike (S), Nucleocapsid (N) and Membrane (M)), and in vaccinated individuals (n=27 for S). Epitope-specific T cells were isolated based on activation markers following a 6-hour peptide stimulation, and scRNAseq was performed for TCR repertoire analysis. T cell lines were generated by expressing recombinant TCRs in Jurkat cells and activation was measured by CD69 upregulation. Result(s): We identified multiple immunodominant T cell epitopes across S, N and M proteins in convalescent individuals. In vaccinated individuals, we detected many of the same dominant S-specific epitopes at similar frequencies as compared to convalescent individuals. T cell responses to peptide S205 (amino acids 817-831) were observed in 56% and 59% of individuals following infection and vaccination, respectively, while 20% and 19% of individuals responded to S302 (a.a. 1205-1219) following infection and vaccination, respectively. For S205, a CD4+ T cell response, we confirmed 8 unique TCRs and determined the minimal epitope to be a 9mer (IEDLLFNKV). While TCR genes TRAV8-6*01 and TRBV30*01 were commonly utilized across the TCRs, we did identify TCRs with unique immunogenetic properties with different potencies of cross-reactivity to other HCoVs. For S302, a CD8+ T cell response, we identified two unique TCRs with different immunogenetic properties that recognized the same 9mer (YIKWPWYIW) and cross-reacted with different HCoV peptides (Figure 1). Conclusion(s): These data identify immunodominant T cell epitopes following SARS-CoV-2 infection and vaccination and provide a detailed analysis of epitope-specific TCR repertoires. The prospect of developing a vaccine that broadly protects against multiple human coronaviruses is bolstered by the identification of conserved immunodominant SARS-CoV-2 T cell epitopes that cross react with multiple other HCoVs.
ABSTRACT
BACKGROUND: The current COVID-19 pandemic mainly affects the respiratory system;however, with the increase in cases worldwide, there is evidence of compromise at the cardiovascular level, which can manifest as acute myocardial infarction, myocarditis, pericarditis, myopericarditis, heart failure, cardiogenic shock, vasculitis, deep vein thrombosis, pulmonary embolism, ischemic stroke, acute arterial insufficiency, arrhythmias, and sudden death. CLINICAL CASE: A 70-year-old male patient who simultaneously presented multisystemic thrombosis manifested by cerebral vascular event, pulmonary thromboembolism, acute myocardial infarction and acute arterial insufficiency in the context of SARSCoV-2 pneumonia. CONCLUSION(S): In patients with COVID-19 there is a high thrombogenic potential secondary to blood stasis, hypercoagulability and endothelial dysfunction, which worsens the prognosis and increases mortality, mainly in patients who require ICU stay, so an adequate thromboprophylactic or anticoagulant scheme and follow-up in the convalescent phase must be provided to detect sequelae associated with COVID-19.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.