scholarly journals Antibody and T cell memory immune response after two doses of the BNT162b2 mRNA vaccine in older adults with and without prior SARS-CoV-2 infection

2021 ◽  
Author(s):  
Julie Demaret ◽  
Benedicte Corroyer-Simovic ◽  
Enagnon Kazali Alidjinou ◽  
Anne Goffard ◽  
Jacques Trauet ◽  
...  

We quantified S1-specific IgG, neutralizing antibody titers, specific IFNγ secreting T cells and functionality of specific CD4+ and CD8+ T cells in 130 young adults (median age 44.0 years) and 106 older residents living in a long-term care facility (86.5 years) after 2 doses of BNT162b2. Three months after the first injection, humoral and cellular memory responses were dramatically impaired in the 54 COVID-19-naive older compared to the 121 COVID 19 naive younger adults. Notably, older participants' neutralizing antibodies, detected in 76.5% (versus 100% in young adults, P < 0.0001), were ten times lower than the younger's antibody titers (P < 0.0001). Antibody and T cell responses were greater among the 52 COVID 19-recovered than among the 54 COVID-19-naive older adults (P < 0.0001). Our study shows that 2 doses of BNT162b2 does not guarantee long-term protection against SARS-CoV-2 in the older. An additional dose should be considered to boost their specific memory response.

2021 ◽  
Vol 12 ◽  
Author(s):  
Julie Demaret ◽  
Bénédicte Corroyer-Simovic ◽  
Enagnon Kazali Alidjinou ◽  
Anne Goffard ◽  
Jacques Trauet ◽  
...  

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants’ neutralizing antibodies were 10 times lower than the younger’s antibody titers (p &lt; 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ+ and IFNγ+IL-2+TNFα+ cells among specific CD4+ T cells, and the frequency of specific CD8+ T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults (p &lt; 0.0001 and p = 0.0018, respectively). However, COVID-19-recovered older participants (n = 51) had greater antibody and T-cell responses, including IFNγ+ and IFNγ+IL-2+TNFα+-specific CD4+ T cells (p &lt; 0.0001), as well as TNFα+-specific CD8+ T cells (p &lt; 0.001), than COVID-19-naive older adults. We also observed that “inflammageing” and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4+ and CD8+ T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.


2012 ◽  
Vol 37 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Navita Viveky ◽  
Lynda Toffelmire ◽  
Lilian Thorpe ◽  
Jennifer Billinsky ◽  
Jane Alcorn ◽  
...  

Vitamin–mineral supplementation may offer older adults health and cognition-related benefits but overuse may contribute to polypharmacy. We examined the prevalence of supplement usage in long-term care facility (LTC) residents (≥65 years of age). As cognition may be affected by nutrition, we also examined use in those with diagnosis of dementia and those with no dementia diagnosis. The prevalence of supplement usage and overall “pill count” from pharmaceutical use was assessed in 189 LTC residents and a subsample of 56 older adults with dementia diagnosis, respectively. Participants were residing in an LTC facility of a mid-size metropolitan area during 2009. The average use of supplements was 1.0 per day for all residents, with 35% taking vitamin D supplements, 20% multivitamins, and 26% calcium. Supplement use was similar (p ≥ 0.05) for those with dementia diagnosis (53%, average 2.0 per day) and for those without such diagnosis (45%, average 2.2 per day). Usage ranged between 1–6 supplements per day. In both of these groups, ∼73% of users were taking vitamin D. The number of prescribed medications ranged from 4 to 24 (average 10.2) in a subsample of residents whose supplement intake was 0 to 6 (average 2). These findings suggest an overall low rate of supplement use, with no significant differences (p ≥ 0.05) in use between residents with and without dementia diagnosis. However, some residents were at risk for supplement overuse.


Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1027
Author(s):  
Nima Taefehshokr ◽  
Sina Taefehshokr ◽  
Bryan Heit

The current coronavirus disease 2019 (COVID-19) pandemic, a disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was first identified in December 2019 in China, and has led to thousands of mortalities globally each day. While the innate immune response serves as the first line of defense, viral clearance requires activation of adaptive immunity, which employs B and T cells to provide sanitizing immunity. SARS-CoV-2 has a potent arsenal of mechanisms used to counter this adaptive immune response through processes, such as T cells depletion and T cell exhaustion. These phenomena are most often observed in severe SARS-CoV-2 patients, pointing towards a link between T cell function and disease severity. Moreover, neutralizing antibody titers and memory B cell responses may be short lived in many SARS-CoV-2 patients, potentially exposing these patients to re-infection. In this review, we discuss our current understanding of B and T cells immune responses and activity in SARS-CoV-2 pathogenesis.


2015 ◽  
Vol 90 (5) ◽  
pp. 2208-2220 ◽  
Author(s):  
Srinika Ranasinghe ◽  
Damien Z. Soghoian ◽  
Madelene Lindqvist ◽  
Musie Ghebremichael ◽  
Faith Donaghey ◽  
...  

ABSTRACTAntigen-specific CD4+T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+T cells and, to a lesser extent, gp41-specific CD4+T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies.IMPORTANCEOne of the earliest discoveries related to CD4+T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4+T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4+T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4+T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection.


2006 ◽  
Vol 18 (1) ◽  
pp. 47-73 ◽  
Author(s):  
Philippe Landreville ◽  
Annick Bédard ◽  
René Verreault ◽  
Johanne Desrosiers ◽  
Nathalie Champoux ◽  
...  

Background: Aggressive behavior (AB) is common in institutional settings. It is an important issue because of its consequences on both the person manifesting such behaviors and their caregivers. Although there are numerous studies assessing non-pharmacologic strategies to manage AB in older adults, no extensive review of the literature is available. This review synthesizes the current knowledge on the effectiveness of non-pharmacological interventions in institutional settings.Method: Papers describing the assessment of a non-pharmacological intervention to manage AB in which participants were at least 60 years old and living in a long-term care facility were selected mainly by searching various databases.Results: A total of 41 studies were identified and included in the review. These studies mainly use quasi-experimental designs and include less than 30 participants. Sixty-six percent (27/41) of the studies report either a statistically or behaviorally significant reduction of AB as a result of a non-pharmacological intervention. Staff training programs and environmental modifications appear to be the most effective strategies.Conclusion: Non-pharmacological interventions seem effective for managing AB. Future studies on the effectiveness of these interventions need to be more rigorous. Development in this field needs to be based on knowledge regarding the determinants of AB in older adults.


2021 ◽  
Vol 12 ◽  
Author(s):  
Izabela Siemińska ◽  
Kazimierz Węglarczyk ◽  
Marcin Surmiak ◽  
Dorota Kurowska-Baran ◽  
Marek Sanak ◽  
...  

The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells with regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor cells (LDNs/PMN-MDSCs). These cells have been described in both infections and cancer and are known for their immunosuppressive activity. In the case of COVID-19, long-term complications have been frequently observed (long-COVID). In this context, we aimed to investigate the immune response of COVID-19 convalescents after a mild or asymptomatic course of disease. We enrolled 13 convalescents who underwent a mild or asymptomatic infection with SARS-CoV-2, confirmed by a positive result of the PCR test, and 13 healthy donors without SARS-CoV-2 infection in the past. Whole blood was used for T-cell subpopulation and LDNs/PMN-MDSCs analysis. LDNs/PMN-MDSCs and normal density neutrophils (NDNs) were sorted out by FACS and used for T-cell proliferation assay with autologous T cells activated with anti-CD3 mAb. Serum samples were used for the detection of anti-SARS-CoV-2 neutralizing IgG and GM-CSF concentration. Our results showed that in convalescents, even 3 months after infection, an elevated level of LDNs/PMN-MDSCs is still maintained in the blood, which correlates negatively with the level of CD8+ and double-negative T cells. Moreover, LDNs/PMN-MDSCs and NDNs showed a tendency for affecting the production of anti-SARS-CoV-2 S1 neutralizing antibodies. Surprisingly, our data showed that in addition to LDNs/PMN-MDSCs, NDNs from convalescents also inhibit proliferation of autologous T cells. Additionally, in the convalescent sera, we detected significantly higher concentrations of GM-CSF, indicating the role of emergency granulopoiesis. We conclude that in mild or asymptomatic COVID-19 convalescents, the neutrophil dysfunction, including propagation of PD-L1-positive LDNs/PMN-MDSCs and NDNs, is responsible for long-term endotype of immunosuppression.


Author(s):  
José-Manuel Ramos-Rincón ◽  
Máximo Bernabeu-Whittel ◽  
Isabel Fiteni-Mera ◽  
Almudena López-Sampalo ◽  
Carmen López-Ríos ◽  
...  

Abstract Background COVID-19 severely impacted older adults and long-term care facility (LTCF) residents. Our primary aim was to describe differences in clinical and epidemiological variables, in-hospital management, and outcomes between LTCF residents and community-dwelling older adults hospitalized with COVID-19. The secondary aim was to identify risk factors for mortality due to COVID-19 in hospitalized LTCF residents. Methods This is a cross-sectional analysis within a retrospective cohort of hospitalized patients≥75 years with confirmed COVID-19 admitted to 160 Spanish hospitals. Differences between groups and factors associated with mortality among LTCF residents were assessed through comparisons and logistic regression analysis. Results Of 6,189 patients≥75 years, 1,185 (19.1%) were LTCF residents and 4,548 (73.5%) were community-dwelling. LTCF residents were older (median: 87.4 vs. 82.1 years), mostly female (61.6% vs. 43.2%), had more severe functional dependence (47.0% vs 7.8%), more comorbidities (Charlson Comorbidity Index: 6 vs 5), had dementia more often (59.1% vs. 14.4%), and had shorter duration of symptoms (median: 3 vs 6 days) than community-dwelling patients (all, p&lt;.001). Mortality risk factors in LTCF residents were severe functional dependence (aOR:1.79;95%CI:1.13-2.83;p=.012), dyspnea (1.66;1.16-2.39;p=.004), SatO2&lt;94% (1.73;1.27-2.37;p=.001), temperature≥37.8ºC (1.62;1.11-2.38; p=.013); qSOFA index≥2 (1.62;1.11-2.38;p=.013), bilateral infiltrates (1.98;1.24-2.98;p&lt;.001), and high C-reactive protein (1.005;1.003-1.007;p&lt;.001). In-hospital mortality was initially higher among LTCF residents (43.3% vs 39.7%), but lower after adjusting for sex, age, functional dependence, and comorbidities (aOR:0.74,95%CI:0.62-0.87;p&lt;.001). Conclusion Basal functional status and COVID-19 severity are risk factors of mortality in LTCF residents. The lower adjusted mortality rate in LTCF residents may be explained by earlier identification, treatment, and hospitalization for COVID-19.


Gerontology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Roberta Causa ◽  
Diego Almagro-Nievas ◽  
Mario Rivera-Izquierdo ◽  
Nicolás Benítez-Muñoz ◽  
Begoña López-Hernández ◽  
...  

<b><i>Background:</i></b> Older adults living in long-term care facilities (LTCFs) are at increased risk for severe outcomes from COVID-19 and were identified as a priority group in COVID-19 vaccination strategies. Emerging evidence suggests vaccine effectiveness in LTCF populations, but data about median and long-term durability of immune response after vaccination are still limited. <b><i>Objectives:</i></b> In this study, we assessed the humoral response to BNT162b2 mRNA COVID-19 vaccine 3 months after the second dose, in a cohort of 495 residents aged ≥65 years from 11 LTCF in Granada, Spain. <b><i>Method:</i></b> Between April 19 and April 30, 2021, we measured anti-SARS-CoV-2 Spike IgG to evaluate the humoral vaccination response. Antibody titers were reported in binding antibody units (BAU/mL). Bivariate and multivariate logistic regression models were performed to investigate the impact of age, sex, underlying health conditions, and prior COVID-19 infection on the antibody levels. <b><i>Results:</i></b> Over 96% of the participants developed an adequate humoral response. We detected higher antibody titers in previously infected individuals, compared with those previously uninfected (<i>B</i>: 1,150.059 BAU/mL, <i>p</i> &#x3c; 0.001). Moreover, we found a significant inverse association between age and antibody levels (<i>B</i>: −7.943 BAU/mL, <i>p</i> &#x3c; 0.05). This negative age-dependent response was more noticeable among residents over 85 years old. In contrast, baseline health conditions and cognitive status were not associated with different antibody levels. <b><i>Conclusions:</i></b> These findings support monitoring COVID-19 vaccination response trend in older adults, in order to optimize future disease prevention and control strategies in this vulnerable population.


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