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1.
Indian J Hematol Blood Transfus ; : 1-10, 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-2209544

ABSTRACT

Background: Immune dysregulation plays a key role in determining COVID-19 disease severity. We aimed to analyze the T cell activation profile in COVID - 19 cases and its predictive role in disease severity and outcome. Material & methods: This was a prospective observational pilot study from a tertiary care COVID-19 hospital. Peripheral blood samples obtained between the fifth and seventh day of COVID-19 illness, were subjected to lymphocyte subset analysis using multicolor flowcytometry using a single tube, 8 antibodies (CD45, CD19, CD3, CD4, CD8, CD38, HLADR, and CD56) analysis. Correlation between lymphocyte subset analysis and clinical profile was determined. Results: 26 patients including 11 with mild disease and 15 with severe disease were enrolled. The median age was 58 years (range: 33-81), with a male: female ratio of 1.36:1. Significant lymphopenia was observed in the severe group compared to the mild group (p < 0.02). The absolute numbers of CD3+, CD4+, CD8 + T cells, B cells, and NK cells were significantly reduced in the severe group as compared to the mild group (p < 0.05). In patients with severe disease, the proportion of CD8 + and CD4 + T cells were significantly higher than those in patients with mild disease (p = 0.0372). Using ROC analysis, a CD4:8 T cell ratio of ≥ 2.63 and an activated (CD38 + HLA-DR+) CD8 T cell proportion of > 15.85% of the total CD8 T cell population, significantly determined the severe disease category. Conclusions: Severe COVID-19 is associated with severe lymphopenia, altered CD4/CD8 ratio and markedly increased CD8 T cell activation profile. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01558-6.

2.
Frontiers in Immunology ; 13 (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-2215288

ABSTRACT

Understanding the T-cell responses involved in inhibiting COVID-19 severity is crucial for developing new therapeutic and vaccine strategies. Here, we characterized SARS-CoV-2 spike-specific CD8+ T cells in vaccinees longitudinally. The BNT162b2 mRNA vaccine can induce spike-specific CD8+ T cells cross-reacting to BA.1, whereas the T-cell receptor (TCR) repertoire usages decreased with time. Furthermore the mRNA vaccine induced spike-specific CD8+ T cells subpopulation expressing Granzyme A (GZMA), Granzyme B (GZMB) and Perforin simultaneously in healthy donors at 4 weeks after the second vaccination. The induced subpopulation was not maintained at 12 weeks after the second vaccination. Incorporating factors that efficiently induce CD8+ T cells with highly cytotoxic activity could improve future vaccine efficacy against such variants. Copyright © 2023 Nogimori, Suzuki, Masuta, Washizaki, Yagoto, Ikeda, Katayama, Kanda, Takada, Minami, Kobayashi, Takahama, Yoshioka and Yamamoto.

3.
Journal of Cell Science ; 135(13) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2214674
4.
In Vivo ; 37(1):70-78, 2023.
Article in English | EMBASE | ID: covidwho-2204978

ABSTRACT

Background/Aim: The manifestation and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections show a clear correlation to the age of a patient. The younger a person, the less likely the infection results in significant illness. To explore the immunological characteristics behind this phenomenon, we studied the course of SARS-CoV-2 infections in 11 households, including 8 children and 6 infants/neonates of women who got infected with SARS-CoV-2 during pregnancy. Material(s) and Method(s): We investigated the immune responses of peripheral blood mononuclear cells (PBMCs), umbilical cord blood mononuclear cells (UCBCs), and T cells against spike and nucleocapsid antigens of SARS-COV-2 by flow cytometry and cytokine secretion assays. Result(s): Upon peptide stimulation, UCBC from neonates showed a strongly reduced IFN-gamma production, as well as lower levels of IL-5, IL-13, and TNF-alpha alongside with decreased frequencies of surface CD137/PD-1 co-expressing CD4+ and CD+8 T cells compared with adult PBMCs. The PBMC response of older children instead was characterized by elevated frequencies of IFN-gamma+ CD4+ T cells, but significantly lower levels of multiple cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, and TNF-alpha) and a marked shift of the CD4+/CD8+ T-cell ratio towards CD8+ T cells in comparison to adults. Conclusion(s): The increased severity of SARS-CoV-2 infections in adults could result from the strong cytokine production and lower potential to immunomodulate the excessive inflammation, while the limited IFN-gamma production of responding T cells in infants/neonates and the additional higher frequencies of CD8+ T cells in older children may provide advantages during the course of a SARS-CoV-2 infection. Copyright © 2023 International Institute of Anticancer Research. All rights reserved.

5.
Indian Journal of Critical Care Medicine ; 27(1):52-56, 2023.
Article in English | EMBASE | ID: covidwho-2202497

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pneumonia and lymphopenia. We investigated the predictive value of T-lymphocyte subset absolute counts for outcomes following coronavirus disease-2019 (COVID-19)-associated acute respiratory failure (C-ARF). Patients and Methods: A retrospective chart review of adult patients with C-ARF was undertaken from 23 March 2020 to 20 November 2021 to obtain relevant data. Patients were divided into two groups based on survival. The T-lymphocyte subsets were determined by flow cytometric analysis. A binomial logistic regression was performed to ascertain factors affecting survival. Cut-off values to differentiate between survivors and non-survivors were identified with the receiver operating characteristic (ROC) analysis. Result(s): A total of 379 patients were analyzed. Age was negatively correlated with survival. Non-survivors had significantly lower T-lymphocyte subset absolute counts than survivors. Serum ferritin levels were significantly higher in non-survivors. Baseline lymphocyte (%) and a subset were predictive of survival in patients [lymphocyte (%) <5.65%, CD3+ <321 cells/microL, CD4+ <205 cells/microL, CD8+ <103 cells/microL]. Conclusion(s): Lower T-lymphocyte subsets were associated with higher mortality in patients with C-ARF. Monitoring trends may help in identifying patients at increased risk of poor outcomes. Copyright © The Author(s).

6.
Indian Journal of Critical Care Medicine ; 27(1):76, 2023.
Article in English | EMBASE | ID: covidwho-2202495
7.
Indian Journal of Critical Care Medicine ; 27(1):75, 2023.
Article in English | EMBASE | ID: covidwho-2202494
8.
Frontiers in Immunology ; 13 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2198910
9.
Frontiers in Immunology ; 13 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2198890

ABSTRACT

Background: The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination. Method(s): The aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNgamma, IL2 and TNFalpha T-cell production were evaluated, and T-cells were labelled "responding T-cells", those cells that produced at least one of the three cytokines of interest, and "triple positive T-cells", those cells that produced simultaneously all the three cytokines. Result(s): The cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165;CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703;at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022). According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNgamma-IL2-TNFalpha+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187;at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively). Conclusion(s): In pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT. Copyright © 2022 Dominelli, Zingaropoli, Tartaglia, Tortellini, Guardiani, Perri, Pasculli, Ciccone, Malimpensa, Baione, Napoli, Gaeta, Lichtner, Conte, Mastroianni and Ciardi.

10.
Frontiers in Immunology ; 13 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2198881

ABSTRACT

Introduction: Despite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome. Method(s): By combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals. Result(s): Based on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1beta, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors. Discussion(s): In conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes. Copyright © 2022 Chattopadhyay, Khare, Kumar, Mishra, Anand, Maurya, Gupta, Sahni, Gupta, Wadhwa, Yadav, Devi, Tardalkar, Joshi, Sethi and Pandey.

11.
Frontiers in Immunology ; 13 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2198878

ABSTRACT

Background: Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden. Method(s): We have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects. Finding(s): Higher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously in vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres. Interpretation(s): Our results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines. Copyright © 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders.

12.
Neurology ; 93(23 Supplement 2):S52-S53, 2022.
Article in English | EMBASE | ID: covidwho-2196693

ABSTRACT

Objective To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination. Background Anti-CD20 therapies attenuate humoral responses to vaccines. However, their effect on T cell responses is less clear. We examined B and T cell responses following COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs, e.g., autoimmune encephalitis, stiff person syndrome, etc.). Design/Methods MS and AIND patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses after a 3rd COVID-19 vaccination. Serum antibodies against the receptorbinding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD8 T cell responses, using activationinduced markers (AIM) and INF-gamma release assays (EUROIMMUN, Germany), were measured at various time points including prevaccination, post initial vaccination series, and 4 and 12 weeks after 3rd dose. Results Thirty-four MS and AIND participants are enrolled. Results for these patients (mean age 52 years-old, 79% female, 21 Pfizer, 13 Moderna) demonstrated attenuated RBD IgG antibody responses. However, a robust CD8 T cell response was observed, following a two-dose series, compared to non-immunosuppressed, age-matched vaccinated controls or unvaccinated with severe SARS-CoV-2 infection (p = 0.01). T cell response was sustained long-term (>12 weeks post 3rd dose) in all 11 anti-CD20 patients analyzed thus far. Collections are completed for all participants at 12 weeks and analysis to be completed by 05/15/22. Further analysis includes correlation of the INF- gamma release assay compared to RBD-CD8 T cell response detected by AIM assay. Conclusions Results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA after three doses but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.

13.
Virology Journal ; 19(1) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2196349

ABSTRACT

Background: Adaptive immune response has been thought to play a key role in SARS-CoV-2 infection. The role of B cells, CD4+T, and CD8+T cells are different in vaccine-induced immune response, thus it is imperative to explore the functions and kinetics of adaptive immune response. We collected blood samples from unvaccinated and vaccinated individuals. To assess the mechanisms contributing to protective immunity of CoronaVac vaccines, we mapped the kinetics and durability of humoral and cellular immune responses after primary and boost vaccination with CoronaVac vaccine in different timepoints. Material(s) and Method(s): We separate PBMC and plasma from blood samples. The differentiation and function of RBD-spcific CD4+T and CD8+T cells were analyzed by flow cytometry and ELISA. Antibodies response was analyzed by ELISA. ELISPOT analysis was perfomed to detected the RBD-spcific memory B cells. CBA analysis was performed to detected the cytokine immune profiles. Graphpad prism 8 and Origin 2021 were used for statistical analysis. Result(s): Vaccine-induced CD4+T cell responses to RBD were more prominent than CD8+T cell responses, and characterized by a predominant Th1 and weak Th17 helper response. CoronaVac vaccine triggered predominant IgG1 antibody response and effectively recalled specific antibodies to RBD protein after booster vaccination. Robust antigen-specific memory B cells were detected (p < 0.0001) following booster vaccination and maintained at 6 months (p < 0.0001) following primary vaccination. Vaccine-induced CD4+T cells correlated with CD8+T cells (r = 0.7147, 0.3258, p < 0.0001, p = 0.04), memory B cell responses (r = 0.7083, p < 0.0001), and IgG and IgA (r = 0.6168, 0.5519, p = 0.0006, 0.003) after vaccination. In addition, vaccine induced a broader and complex cytokine pattern in plasma at early stage. Conclusion(s): Taken together, these results highlight the potential role of B cell and T cell responses in vaccine-induced long-term immunity. Copyright © 2022, The Author(s).

14.
Circulation Conference: American Heart Association's ; 146(Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2194346

ABSTRACT

Overlap between the histopathologic changes of acute rejection and viral myocarditis presents a diagnostic dilemma. A 34 year-old female with a past medical history of postpartum cardiomyopathy and subsequent orthotopic heart transplant in December 2019, presented for routine surveillance heart biopsy seven months post-transplant. Her AlloMap was elevated and AlloSure was uptrending, concerning for rejection. Ten days prior to presentation, she tested positive for COVID-19 via polymerase chain reaction (PCR) testing. Her symptoms were fatigue and mild headache for two weeks prior to diagnosis. She did not seek medical attention for her symptoms and received no COVID-19 specific treatment. Endomyocardial biopsy showed grade 2R acute cellular rejection. Her echocardiogram was unchanged with normal left ventricular ejection fraction and right ventricular function. SARS-CoV-2 levels were measured by PCR of ribonucleic acid (RNA) isolated from the biopsy specimen and were undetectable. The patient was treated with two short courses of high dose prednisone which eventually abated her transplant rejection. The patient remained positive on PCR testing for COVID-19 for the next six months. Chest x-ray and computed tomography for follow up after COVID-19 infection showed no evidence of pulmonary fibrosis or superinfection considering ongoing immunosuppression for rejection. Our patient illustrates a case of concomitant COVID-19 infection and presumed transplant rejection, raising the question of whether the findings seen on immunohistochemistry were truly rejection or instead an elevated immune response due to COVID-19 infection. Given that our patient had a predominance of CD3+ T cells and less CD68+ macrophages (the former being more prominent in acute cellular rejection and the latter being more prominent in COVID-19 myocarditis), we are inclined to believe the former. (Figure Presented).

15.
Science ; 371(6528):477, 2021.
Article in English | EMBASE | ID: covidwho-2193389
16.
Open Forum Infectious Diseases ; 9(Supplement 2):S770-S771, 2022.
Article in English | EMBASE | ID: covidwho-2189959

ABSTRACT

Background. We studied immunological response against SARS-CoV-2 after two doses of vaccine in health care workers (HCW) at our Infectious Disease Unit Methods. We enrolled prospectively HCW without (group A) and with previous infection (group B). We collected peripheral blood at baseline (before the BNT162b2 vaccine), T1 (before the 2nd dose), T2 and T6 (after 1 and 6 months after of 2nd dose). The activation induced cell marker assay (AIM) was performed with CD4 and CD8 Spike peptide megapools (MPs). We evaluated the Stimulation Index (SI) as AIM+ stimulated cells/negative control (positive response SI >= 2). Quantitative antibodies (Abs) to Spike-1 protein (S) and to nucleocapside protein (N) were detected with an electrochemiluminescence immunoassay. We tested at T6 the responses to alpha, beta, gamma, delta and epsilon variants MPs.We used the linear mixed model with random intercept adjusted for age and sex to compare specific times to T0. To assess differences over time between groups the interaction with time was tested. Results. In group A 13/22 (59%) were female vs 5/7 (71%) group B, the mean age 40 vs 38 years, respectively. For CD4+ Spike the overall rate of change over time was significant at T1 (p=0.038) and at T2 (p< 0.001) vs T0 with a decreasing at T6 (p not significant) [Figure 1] with a trend of higher response in group A. In group B the CD8 + Spike reactivity increased at T1(p=0.037) and at T6 (p=0.005) vs T0. The interaction between SI and time was statistically significant at T1 (p=0.033);T2 (p= 0.046) and T6 (p=0.035) (mean values in group B higher than A). For overall population, the anti-S Abs significantly increased at T1 vs T0, T2 vs T0 and at T6 vs T0 [Figure 2A]. The group B at T6 retained a higher anti S response but the rate of change significantly differs between the two group (overall interaction: p< 0.001) [Figure 2B]. At T6 in both groups we found a high CD4+ T cells response to epsilon variant, even if not detected as circulant virus. Conclusion. The humoral response was persistent and increased in previous infected subjects. The CD4+T cells response after vaccination retained a response in uninfected subject, with an increasing trend and with a response to non-circulating variants. The vaccine could help the CD8+ T cells reactivity specific for Spike peptides.

17.
Open Forum Infectious Diseases ; 9(Supplement 2):S763, 2022.
Article in English | EMBASE | ID: covidwho-2189942

ABSTRACT

Background. COVID-19 (C-19) vaccines have demonstrated effectiveness in reducing SARS-CoV-2 related morbidity/mortality. The duration of protection in the general population is showing a waning immunity over time. Variable antibody responses to C-19 vaccines have been shown in persons living with HIV. We followed the anti-SARS-CoV-2 receptor biding domain (RBD) antibody titers, after 2 and 3 (booster) C-19 vaccinations, in US Veterans living with HIV (USVLH). Methods. Retrospective chart review of USVLH who had received C-19 vaccinations at Northport VAMC. Testing was done with the © Beckman Coulter enzyme immunoassay measuring total IgG antibody to the RBD, a critical target of neutralizing antibodies within the spike protein encoded in the mRNA vaccines. Titers were drawn after the 2nd and 3rd doses C-19 vaccines in variable timing. Demographic data, CD4+ T cell counts nadir and current, HIV viral load, comorbid conditions were reviewed. Results. We analyzed the SARS CoV-2 RBD IgG titers in 50 vaccinated USVLH. The median age is 65 years (range 36-75). 50% were Black, Caucasian 40%, Hispanic 10%. Risk factor for HIV infection, Heterosexual 52%, IVDU 18%, MSM 26%, needle stick 2%, blood transfusion 2%. The median CD4 nadir was 200/muL (5- 600), median current CD4 656 (174-1529). All USVLH were on HAART, 92% on INSTI-based therapy. 45 had undetectable HIV viral load (< 20), 5 had viremia from 22 to 563 copies. Medical conditions: diabetes 30%, CAD 18%, HTN 60%, COPD 8%, HLD 66%, smokers 18%. Six USV had C-19 prior to vaccination, and six had C-19 after vaccination with median 102 days (90-148) from last vaccine dose. Vaccines given: Janssen in 3 USVLH: Moderna (MOD)- 2 doses: 4;MOD-3 doses:5;Pfizer (PFZ)-2: 6;PFZ-3: 32. IgG titers decrease with time after 2nd vaccine dose and increase after booster dose. IgG titers checked after 2nd dose median days 120 (11-392) {titers: median 4.63 S/CO [0.17 - 53.66]}, 91 days (5-181) after 3rd dose {titers: median 16.22 [1.15-73.92]}. Titers were higher in MOD-2 vs. PFZ-2, median 25.7 vs. 4.63, P: 0.039, MOD-3 vs. PFZ-3 33.89 vs. 15.5, P: 0.117. No death due to C-19 was seen. SARS-CoV-2 RBD IgG titers in US Veterans living with HIV after 2nd dose of COVID vaccine. COVID-19 VACCINATED IN US VETERANS LIVING WITH HIV N=50 Conclusion. In a cohort of USVLH, well controlled on HAART, C-19 vaccinations produced a serologic response that decayed over time and increased after booster dose. MOD vaccine may have achieved higher titers than PFZ.

18.
Open Forum Infectious Diseases ; 9(Supplement 2):S504, 2022.
Article in English | EMBASE | ID: covidwho-2189813

ABSTRACT

Background. Benefit of COVID-19 vaccines is limited by need for freezing, high cost, requirement for multiple boosters, and waning immunity. An unmet need for safe and effective vaccines that can be quickly deployed worldwide during a pandemic exists. A barrier to developing scalable low-cost vaccines is the restricted access to vaccine- or adjuvant-formulations due to protection by intellectual property rights. This limits research to understand their mechanism of action and potential applicability towards vulnerable populations or emerging pathogens. Methods. We studied cellular and molecular mechanisms of action of adjuvant formulations developed for global open access in 4 distinct but complementary in vitro platforms that are human, age-specific, and enable the same individual to serve as control and test condition;generating data on adjuvant-induced responses in vitro that predict activity in vivo. Results. Whole blood assay that models magnitude of innate immune activation and identifies cell types activated showed that liposomal co-formulation of MPL +QS-21 activated monocytes and natural killer cells and induced cytokine production;tissue construct assay that models monocyte extravasation and autonomous differentiation into dendritic cells (DC) showed that only MPL+QS-21 co-formulation promoted CD14+ cells towards DC phenotype;monocyte-derived DC (MoDC) assay that interrogates immune activation type showed that MPL+QS-21 co-formulation in lipid nanoparticles promoted MoDC maturation by increasing CD40, CD86, CCR7 and HLA-DR expression and Th1-polarizing cytokine secretion;and dendritic cell-T cell interface assay that assesses potential of formulations to re-activate SARS-CoV-2 Spike antigen-specific T cells showed that only MPL+QS-21 coformulation enhanced activation of antigen-specific CD4+ and CD8+ T cells. Conclusion. Thus, human in vitro modeling provides new insight into the mechanism of action and synergistic effects of MPL+QS-21, and positions us to study them in vulnerable populations to assess potential age-specific application on vaccine development. Precision vaccinology coupled with global access may enable marked public health progress by accelerating, de-risking, and advancing affordable adjuvanted vaccines to the most vulnerable.

19.
Open Forum Infectious Diseases ; 9(Supplement 2):S465, 2022.
Article in English | EMBASE | ID: covidwho-2189747

ABSTRACT

Background. Data regarding cell-mediated immunological differences in children across COVID-19 clinical spectrum are limited. We prospectively investigated Spike-protein specific cellular immunity in children with symptomatic COVID-19 or MIS-C, by single cell cytokine expression profiling. Methods. PBMCs fromchildrenwithMIS-C, symptomaticCOVID-19 (onemonth after hospitalization) and healthy controls were isolated prospectively. Cell suspensions were divided into two quantitatively equal samples (a negative control-unstimulated and a positive-stimulated).Cells stimulationwas performed usingSARS-CoV-2 Spike antigenic peptidesmix (Peptivator SARS-CoV-2 Prot-S). Cells of each sample were stained with fluorochrome monoclonal antibodies against 8 surface markers (CD3, CD4, CD8, CD14, CD19, CD137, CD197, CD45RA) and 6 intracellular markers (IL-4, IL-2, IL-17, IFN-gamma, TNF-alpha, Granzyme B). Viability was assessed by 7AAD. Stained cell preparations were analysed using 13 colour Flow Cytometry (DX Flex, Beckman Coulter). Flow cytometric analysis was performed using Kaluza 2.1 Software. Results. Sixteen children (4 MIS-C, 8 post-COVID-19 and 4 healthy controls) were included in the study. The mean age (+/-SD) of the participants was 11.22 years (+/-3.48). Children with MIS-C had significantly higher mean (+/-SD) values of CD8+IFN-gamma/million CD3+ [226.68 (134.92) vs 45.43 (57.28);P: 0.033] and median (IQR) of CD8+IFN-gamma/ml [156.38 (184.13) vs 26.34 (82.36);P: 0.033] compared to symptomatic COVID-19 children. Compared to healthy controls, MIS-C patients had significantly higher median (IQR) values of CD4+IL-2/million CD3+ [923.12 (3777.95) vs 97.59 (71.71);P: 0.042] and CD4+IL-2/ml median (IQR) [626.33 (2744.98) vs 169.3 (173.91);P: 0.042]. No other significant differences were observed regarding other immunological markers in 3 study groups. Conclusion. IFN-gamma production by CD8+ T cells is highly expressed in children with MIS-C compared to hospitalized children one month after acute COVID-19 and could consist possible immunological biomarker. Further studies are needed in order to elucidate the pathophysiological basis of these findings.

20.
Open Forum Infectious Diseases ; 9(Supplement 2):S440, 2022.
Article in English | EMBASE | ID: covidwho-2189700

ABSTRACT

Background. Several studies reported an increased rate of indeterminate QuantiFERON-TB Gold Plus (QFT-P) assay results in patients with severe Coronavirus Disease (COVID)-19. Methods. Aim of the study was to longitudinally evaluate QFT-P responses in patients who survived COVID-19, with a previous indeterminate result. Results. We observed 223 patients with an indeterminate QFT-P assay among 949 patients hospitalized because of COVID-19 (23,5%) during 2020 and 2021. 36 patients among those with an indeterminate QFT-P assay were enrolled for reassessing the test. In 12 patients peripheral blood lymphocyte subsets were also reassessed. Considering disease severity, 30 were classified as severe and 6 as non-severe. Median age was 57,5 (interquartile range [IQR]: 49,5-63,8), with a prevalence of male sex (M/F: 24/12);median Charlson Comorbidity Index was 2 (IQR: 1-3). The second QFT-P assay was performed after at least 1 month from the first assay (median time 7 months, IQR: 5-12 months). All QFT-P assays gave a determined result: 2 positive (5.5%) and 34 negatives (94,4%). A statistically significant difference was observed after comparing the laboratory parameters at the time of the first and the second QFT-P assay: the absolute counts of total lymphocyte, total CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased (p< 0.001) while neutrophil absolute counts, neutrophil to lymphocyte (N/L) ratio, D-dimer,fibrinogen, ferritin, C-reactive protein (CRP) were significantly reduced (p< 0.0001). Concerning the QFT-P assay, interferon gamma (INF-gamma) production in the Mitogen-Nil, TB1-Nil and TB2-Nil conditions were significantly increased (p< 0.0001;p=0.0019;p=0.0205, respectively) (Table 1 and Figure 1). Conclusion. Once the acute phase of COVID-19 is resolved, inflammatory markers and peripheral blood leucocyte counts tend to normalize with an effective INF-gamma production after specific and nonspecific stimulation. All the 36 QFT-P showed a determinate result. Moreover, we observed 2 positive QFT-P assay, supporting the importance of retesting patients with indeterminate result to identify latent tuberculosis infection and monitor patients for possible reactivation because of the immunesuppression associated with COVID-19.

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