Depression, aging, and immunity: implications for COVID-19 vaccine immunogenicity

Ford, Bart N.; Savitz, Jonathan

doi:10.1186/s12979-022-00288-7

Cited by 14 publications

(13 citation statements)

References 180 publications

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“…43 In addition, depression requires careful observation because it increases the risk of complications after COVID-19 infection and reduces the immunogenicity of the vaccine. 44 Although the detailed feature and laboratory results of chest discomfort from this study were difficult to determine, the mRNA vaccine promotes the release of inflammatory cytokines, causing cardiovascular disorder. 45 Cardiovascular disorders such as myocarditis and acute myocardial infarction, including chest discomfort, can lead to SAEs after vaccination.…”

Section: Discussionmentioning

confidence: 89%

“…A study reviewing 11 psychiatric reaction case reports after COVID‐19 vaccination found that altered mental status, mania, depression, and functional neurologic disorder were reported 43 . In addition, depression requires careful observation because it increases the risk of complications after COVID‐19 infection and reduces the immunogenicity of the vaccine 44 . Although the detailed feature and laboratory results of chest discomfort from this study were difficult to determine, the mRNA vaccine promotes the release of inflammatory cytokines, causing cardiovascular disorder 45 .…”

Section: Discussionmentioning

confidence: 99%

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Signal detection of COVID‐19 vaccines adverse events using spontaneous reports from South Korea

Jeong

Chun

2023

Pharmacoepidemiology and Drug

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Purpose: Studies on the detection of COVID-19 vaccine signals in South Korea are insufficient. Therefore, to investigate adverse events (AEs) that might be associated with COVID-19 vaccines, signals were detected using spontaneous reports from South Korea. We compared the signals with the vaccine insert lists of the regulators in the four countries.Methods: Spontaneous reports from 62 sites were collected by the National Medical Center between January 2013 and May 2022. A descriptive analysis of AEs associated with COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, and Janssen) was performed, and the proportional reporting ratio, reporting odds ratio, and information component were calculated. We performed five analyses, with five cases and one control group.Results: During the study period, 68 355 cases were reported, of which 12 485 were COVID-19 vaccine AEs. Injection site pain (2198 cases, 17.6%), myalgia (1552 cases, 12.4%), headache (1145 cases, 9.2%), pyrexia (1003 cases, 8.0%), and fatigue (735 cases, 5.9%) were frequently reported. When comparing all COVID-19 vaccines with other viral vaccines, 20 signals were detected, of which cachexia, dyspepsia, abdominal discomfort, and mood swings were not listed on the vaccine inserts in all four countries. Overall, 20, 17, 29, and 9 signals were detected in vaccines developed by Pfizer, Moderna, AstraZeneca, and Janssen, respectively.Conclusions: Based on a disproportionate analysis of COVID-19 vaccine AEs using spontaneous reports from South Korea, different signals were detected for each vaccine manufacturer.adverse drug reaction reporting systems, COVID-19 vaccines, data mining, drug-related side effects and adverse reactions, pharmacovigilance Key Points• Analysis of spontaneous reports from South Korea revealed that injection site pain, myalgia, headache, and pyrexia were frequently reported AEs for the COVID-19 vaccines developed by Pfizer, Moderna, AstraZeneca, and Janssen, which was similar to the clinical trial results.• When all COVID-19 vaccines were compared with other viral vaccines, 20 signals were detected. Of these, cachexia, dyspepsia, abdominal discomfort, and mood swings were not listed on the vaccine inserts in South Korea, the United States, the United Kingdom, and Japan.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Signal detection of COVID‐19 vaccines adverse events using spontaneous reports from South Korea

Jeong

Chun

2023

Pharmacoepidemiology and Drug

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“…As the immune system ages, it undergoes senescence that may lead to a diminished response to vaccines (59). These alterations result in impaired immune functions, including limited germinal center responses, reduced numbers of naive cells, ampli ed memory cell populations, and increased in ammatory subsets of adaptive immune cells (60-63).…”

Section: Discussionmentioning

confidence: 99%

Kinetics of pro- and anti-inflammatory spike-specific T-cell responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: A prospective longitudinal study in Japan

Kakugawa,

Mimura,

Mimura-Kimura

et al. 2024

Preprint

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Background The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, this 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific T-cell responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. CD4 + T-cell responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions Older and severely frail individuals may exhibit diminished cell-mediated immune responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that of the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.

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“…The activation of the immune inflammatory cells may occur due to the microbial dysbiosis [ 14 ], but also due to the disturbed proteostasis, leading to an accumulation of misfolded proteins and cellular debris [ 15 ]. These fragments of cellular garbage may serve as ligands for certain pattern recognition receptors initiating pro-inflammatory signaling [ 16 ]. Thus, in combination with other contributing factors, both immunosenescence and inflammaging may lead to a poorer antiviral immune response and disturbed viral clearance and also to an increased risk of immune dysregulation [ 9 ].…”

Section: The Impact Of Immunosenescence and Inflammaging On The Immun...mentioning

confidence: 99%

“…The substantial sites of CMV localization were found in the brainstem, diencephalon, and basal ganglia [ 124 ], suggesting that CMV may itself or in combination with SARS-CoV-2 be responsible for CNS damage. Other studies found a depression-specific association of CMV with a reduced resting-state connectivity, white matter integrity, and gray matter volumes [ 125 – 127 ], indicating that CMV may induce structural and functional brain changes to a greater extent in elderly people with depression [ 16 ]. Thus, it is conceivable that a CMV infection may contribute to long COVID pathology by supporting immunosenescence, neuroinflammation, and by triggering persistent neurological symptoms, particularly in the older population.…”

Section: Potential Mechanisms That May Contribute To Long Covidmentioning

confidence: 99%

Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions

Müller

Benedetto

2023

Immun Ageing

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Advanced age is one of the significant risk determinants for coronavirus disease 2019 (COVID-19)-related mortality and for long COVID complications. The contributing factors may include the age-related dynamical remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. Both of these factors may induce an inflammatory milieu in the aged brain and drive the changes in the microenvironment of neurons and microglia, which are characterized by a general condition of chronic inflammation, so-called neuroinflammation. Emerging evidence reveals that the immune privilege in the aging brain may be compromised. Resident brain cells, such as astrocytes, neurons, oligodendrocytes and microglia, but also infiltrating immune cells, such as monocytes, T cells and macrophages participate in the complex intercellular networks and multiple reciprocal interactions. Especially changes in microglia playing a regulatory role in inflammation, contribute to disturbing of the brain homeostasis and to impairments of the neuroimmune responses. Neuroinflammation may trigger structural damage, diminish regeneration, induce neuronal cell death, modulate synaptic remodeling and in this manner negatively interfere with the brain functions.In this review article, we give insights into neuroimmune interactions in the aged brain and highlight the impact of COVID-19 on the functional systems already modulated by immunosenescence and neuroinflammation. We discuss the potential ways of these interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and review proposed neuroimmune mechanisms and biological factors that may contribute to the development of persisting long COVID conditions. We summarize the potential mechanisms responsible for long COVID, including inflammation, autoimmunity, direct virus-mediated cytotoxicity, hypercoagulation, mitochondrial failure, dysbiosis, and the reactivation of other persisting viruses, such as the Cytomegalovirus (CMV). Finally, we discuss the effects of various interventional options that can decrease the propagation of biological, physiological, and psychosocial stressors that are responsible for neuroimmune activation and which may inhibit the triggering of unbalanced inflammatory responses. We highlight the modulatory effects of bioactive nutritional compounds along with the multimodal benefits of behavioral interventions and moderate exercise, which can be applied as postinfectious interventions in order to improve brain health.

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Depression, aging, and immunity: implications for COVID-19 vaccine immunogenicity

Cited by 14 publications

References 180 publications

Signal detection of COVID‐19 vaccines adverse events using spontaneous reports from South Korea

Signal detection of COVID‐19 vaccines adverse events using spontaneous reports from South Korea

Kinetics of pro- and anti-inflammatory spike-specific T-cell responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: A prospective longitudinal study in Japan

Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions

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