scholarly journals Long-Term SARS-CoV-2 Specific Immunity Is Affected by the Severity of Initial COVID-19 and Patient Age

2021 ◽  
Vol 10 (19) ◽  
pp. 4606
Author(s):  
Margarethe Konik ◽  
Monika Lindemann ◽  
Markus Zettler ◽  
Lara Meller ◽  
Sebastian Dolff ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Patient Age ◽  
Factors Affecting ◽  
Humoral Immune ◽  
Specific Immunity ◽  
Cell Immunity ◽  
Patient Âgé

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients’ humoral immune responses to Spike (S) protein over the long-term, whereas the patients’ age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity.

scholarly journals Long-term follow-up of SARS-CoV-2 convalescents reveals distinct magnitude of spike-specific immunity after viral re-exposure and vaccination

2021 ◽  
Author(s):  
Percy Knolle ◽  
Nina Körber ◽  
Alina Priller ◽  
Sarah Yazici ◽  
Tanja Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Specific Immunity ◽  
Cell Immunity

Abstract Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is controlled by the host´s immune response1-4, but longitudinal follow-up studies of virus-specific immunity to evaluate protection from re-infection are lacking. Here, we report the results from a prospective study that started during the first wave of the COVID-19 pandemic in spring 2020, where we identified 91 convalescents from mild SARS-CoV-2 infection among 4554 health care workers. We followed the dynamics and magnitude of spike-specific immunity in convalescents during the spontaneous course over ≥ 9 months, after SARS-CoV-2 re-exposure and after BNT162b2 mRNA vaccination. Virus-neutralizing antibodies and spike-specific T cell responses with predominance of IL-2-secreting polyfunctional CD4 T cells continuously declined over 9 months, but remained detectable at low levels. After a single vaccination, convalescents simultaneously mounted strong antibody and T cell responses against the SARS-CoV-2 spike proteins. In naïve individuals, a prime vaccination induced preferentially IL-2-secreting CD4 T cells that preceded production of spike-specific virus-neutralizing antibodies after boost vaccination. Response to vaccination, however, was not homogenous. Compared to four individuals among 455 naïve vaccinees (0.9%), we identified 5/82 (6.1%) convalescents with a delayed response to vaccination. These convalescents had originally developed dysfunctional spike-specific immune responses after SARS-CoV-2 infection, and required prime and boost vaccination to develop strong spike-specific immunity. Importantly, during the second wave of the COVID-19 pandemic in fall/winter of 2021 and prior to vaccination we detected a surge of virus-neutralizing antibodies consistent with re-exposure to SARS-CoV-2 in 6 out of 82 convalescents. The selective increase in virus-neutralizing antibodies occurred without systemic re-activation of spike-specific T cell immunity, whereas a single BNT162b2 mRNA vaccination sufficed to induce strong spike-specific antibody and systemic T cell responses in the same individuals. These results support the notion that BNT162b2 mRNA vaccination synchronizes spike-specific immunity in all convalescents of mild SARS-CoV-2 infection and may provide additional protection from re-infection by inducing more rigorous stimulation of spike-specific T cell immunity than re-exposure with SARS-CoV-2.

scholarly journals Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Eliott Lafon ◽  
Gabriel Diem ◽  
Christina Witting ◽  
Viktoria Zaderer ◽  
Rosa Maria Bellmann-Weiler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Disease Progression ◽  
Color Flow ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cell Immunity ◽  
Antibody Titers ◽  
Anaphylatoxin C3a

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.

scholarly journals Interdependencies between cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination

2021 ◽  
Author(s):  
Moritz M Hollstein ◽  
Lennart Muensterkoetter ◽  
Michael P Schoen ◽  
Armin Bergmann ◽  
Thea M Husar ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Booster Vaccination ◽  
Antibody Avidity ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Cellular Immune

Background: Homologous and heterologous SARS-CoV-2-vaccinations yield different spike protein-directed humoral and cellular immune responses. However, their interdependencies remain elusive. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received homologous vaccination with Astra (ChAdOx1-S; AstraZeneca) or BNT (BNT162b2; Biontech/Pfizer) or heterologous vaccination with Astra/BNT. We assessed the humoral (anti-spike-RBD-IgG, neutralizing antibodies, antibody avidity) and cellular (spike-induced T cell interferon-y release) immune response in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Findings: Initial vaccination with Astra resulted in lower anti-spike-RBD-IgG responses compared to BNT (70+/-114 vs. 226+/-279 BAU/ml, p<0.01) at T1, whereas T cell activation did not differ significantly. Booster vaccination with BNT proved superior to Astra at T2 (anti-spike-RBD-IgG: Astra/BNT 2387+/-1627 and BNT/BNT 3202+/-2184 vs. Astra/Astra 413+/-461 BAU/ml, both p<0.001; spike-induced T cell interferon-y; release: Astra/BNT 5069+/-6733 and BNT/BNT 4880+/-7570 vs. Astra/Astra 1152+/-2243 mIU/ml, both p<0.001). No significant differences were detected between BNT-boostered groups at T2. For Astra, we observed no booster effect on T cell activation. We found associations between anti-spike-RBD-IgG levels (Astra/BNT and BNT/BNT) and T cell responses (Astra/Astra and Astra/BNT) from T1 to T2. There were also links between levels of anti-spike-RBD-IgG and T cell at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Interpretation: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses. Funding: Deutsche Forschungsgemeinschaft (DFG), ER723/3-1

scholarly journals Humoral Immunity to Adeno-Associated Virus Type 2 Vectors following Administration to Murine and Nonhuman Primate Muscle

2000 ◽  
Vol 74 (5) ◽  
pp. 2420-2425 ◽  
Author(s):  
Narendra Chirmule ◽  
Weidong Xiao ◽  
Alemseged Truneh ◽  
Michael A. Schnell ◽  
Joseph V. Hughes ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Neutralizing Antibodies ◽  
Cell Function ◽  
Capsid Proteins ◽  
Adeno Associated Virus ◽  
Blocking Antibody ◽  
Humoral Immune

ABSTRACT Adeno-associated virus (AAV) is being developed as a vector capable of conferring long-term gene expression, which is useful in the treatment of chronic diseases. In most therapeutic applications, it is necessary to readminister the vector. This study characterizes the humoral immune response to AAV capsid proteins following intramuscular injection and its impact on vector readministration. Studies of mice and rhesus monkeys demonstrated the formation of neutralizing antibodies to AAV capsid proteins that persisted for over 1 year and then diminished, but this did not prevent the efficacy of vector readministration. More-detailed studies strongly suggested that the B-cell response was T cell dependent. This was further evaluated with a blocking antibody to human CD4, primatized for clinical trials, in a biologically compatible mouse in which the endogenous murine CD4 gene was functionally replaced with the human counterpart. Transient pharmacologic inhibition of CD4 T cells with CD4 antibody prevented an antivector response long after the effects of the CD4 antibody diminished; readministration of vector without diminution of gene expression was possible. Our studies suggest that truly durable transgene expression (i.e., prolonged genetic engraftment together with vector readministration) is possible with AAV in skeletal muscle, although it will be necessary to transiently inhibit CD4 T-cell function to avoid the activation of memory B cells.

scholarly journals Activation or exhaustion of CD8+ T cells in patients with COVID-19

2021 ◽  
Author(s):  
Min-Seok Rha ◽  
Eui-Cheol Shin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Absolute Number ◽  
T Cell Memory ◽  
Checkpoint Receptors ◽  
Functional Analyses ◽  
Inhibitory Immune Checkpoint

AbstractIn addition to CD4+ T cells and neutralizing antibodies, CD8+ T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8+ T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8+ T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8+ T cells from patients with COVID-19. However, whether CD8+ T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8+ T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8+ T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8+ T cells and discuss long-term SARS-CoV-2-specific CD8+ T-cell memory.

scholarly journals SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2

2021 ◽  
Author(s):  
Junko S Takeuchi ◽  
Ami Fukunaga ◽  
Shohei Yamamoto ◽  
Akihito Tanaka ◽  
Kouki Matsuda ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Igg Antibody ◽  
Humoral Immune ◽  
Cell Responses ◽  
Cell Assays ◽  
Specific Igg

Background. The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. Methods. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted five surveys on day 1, day 15, day 29 (seven days after the second dose), day 61, and days 82-96 following the first dose. Results. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. Conclusions. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These early immune responses are sustained for approximately six-ten weeks following the second vaccination dose.

Factors predicting length of stay in patients hospitalized for acute parotitis

2020 ◽  
pp. jim-2020-001506
Author(s):  
Avinoam Markovich ◽  
Ohad Ronen
Keyword(s):  
Clinical Laboratory ◽  
Medical Center ◽  
White Cell Count ◽  
Acute Infection ◽  
Retrospective Chart Review ◽  
Significant Treatment ◽  
Patient Age ◽  
Factors Affecting ◽  
Patient Âgé ◽  
Length Of Hospitalization

Acute suppurative parotitis (ASP) is an acute infection of the parotid gland that necessitates hospitalization in some patients. The aim of this study was to evaluate clinical laboratory values including hydration, nutritional status, inflammatory markers and age, and to compare them with duration of hospitalization of patients with ASP. This is a retrospective chart review in a tertiary academic center. We investigated the factors affecting length of hospitalization in patients admitted to Galilee Medical Center with a diagnosis of ASP between 2010 and 2018. Of the 60 patients with ASP included in the study, 24 were male. The average age of patients was 60, ranging from 18 to 99. We found statistically significant correlations between length of hospitalization and patient age (r=0.3), C reactive protein (r=0.3), white cell count (WCC) at presentation (r=0.3), blood urea nitrogen to creatinine ratio (BUN:Cr) (r=0.2), and platelet levels at discharge (r=0.4). Examination of these factors on multivariate analysis found hospitalization duration was exclusively affected by patients’ level of dehydration as represented by BUN:Cr. Patient age, WCC levels at presentation, and platelet levels were not found to be statistically significant. Treatment and interventions should be planned accordingly.

scholarly journals Survival Associations between Patient Age and Treatment Modality in Olfactory Neuroblastoma: A Retrospective Population-Based Study

2021 ◽  
Vol 10 (12) ◽  
pp. 2685
Author(s):  
Andre J. Burnham ◽  
Phillip A. Burnham ◽  
Edwin M. Horwitz
Keyword(s):  
Treatment Modality ◽  
Age Groups ◽  
Olfactory Neuroblastoma ◽  
Population Based ◽  
Treatment Modalities ◽  
Long Term Outcomes ◽  
Patient Age ◽  
Population Based Study ◽  
Patient Âgé

Olfactory neuroblastoma (ONB) is a rare neuroepithelial-derived malignancy that usually presents in the nasal cavity. The rarity of ONB has led to conflicting reports regarding associations of patient age and ONB survival and outcome. Moreover, long-term outcomes of chemotherapy and other treatment modalities are speculated. Here, we aimed to compare survival outcomes across age groups through time and determine associations between treatment modality and survival. In this retrospective population-based study, we analyzed the SEER 2000–2016 Database for patients with ONB tumors. Using Kaplan–Meier survival analysis, a significant effect of age and cancer-specific survival (CSS) was observed; geriatric ONB patients had the lowest CSS overall. Generalized linear models and survival analyses demonstrated that CSS of the pediatric patient population was similar to the geriatric group through 100 months but plateaued thereafter and was the highest of all age groups. Radiation and surgery were associated with increased CSS, while chemotherapy was associated with decreased CSS. GLM results showed that tumor grade, stage and lymph node involvement had no CSS associations with age or treatment modality. Our results provide insight for future investigations of long-term outcomes associated with ONB patient age and treatment modality, and we conclude that survival statistics of ONB patients should be analyzed in terms of trends through time rather than fixed in time.

scholarly journals COVID-19: Mechanisms of Vaccination and Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 404 ◽  
Author(s):  
Daniel E. Speiser ◽  
Martin F. Bachmann
Keyword(s):  
Immune Responses ◽  
Clinical Management ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Public Life ◽  
High Affinity ◽  
Vaccination Strategies ◽  
Detailed Evaluation ◽  
Pros And Cons

Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

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