Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

Pavel, Ana B.; Glickman, Jacob W.; Michels, James R; Kim‐Schulze, Seunghee; Miller, Rachel L.; Guttman‐Yassky, Emma

doi:10.3389/fgene.2021.706902

Cited by 67 publications

(71 citation statements)

References 33 publications

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“…For example, among the latest publications on this list, Pavel et al. ( 88 ) confirmed the association between Th2/Th1 cytokine imbalance and COVID-19 risk mortality; Singh et al. ( 89 ) confirmed the increase in serum inflammatory markers in COVID-19 patients; Mitamura et al.…”

Section: Discussionmentioning

confidence: 96%

“…These publications confirmed previous results in studies with different cohorts, populations, and settings and/or provided new serum biomarkers related to disease progression and symptomatology. For example, among the latest publications on this list, Pavel et al (88) Our study is the first to provide serum proteomic profiles of cohorts of SARS-CoV-2-infected recovered (hospital discharge), nonsevere (hospitalized), and severe (ICU) cases with increasing systemic inflammation in comparison with healthy individuals sampled prior to the COVID-19 pandemic. The results not only confirmed previous results but provided new serum biomarkers, BPs, and physiological disorders related to disease progression and symptomatology (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

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Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

et al. 2021

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The COVID-19 pandemic caused by SARS-CoV-2 challenges the understanding of factors affecting disease progression and severity. The identification of prognostic biomarkers and physiological processes associated with disease symptoms is relevant for the development of new diagnostic and therapeutic interventions to contribute to the control of this pandemic. To address this challenge, in this study, we used a quantitative proteomics together with multiple data analysis algorithms to characterize serum protein profiles in five cohorts from healthy to SARS-CoV-2-infected recovered (hospital discharge), nonsevere (hospitalized), and severe [at the intensive care unit (ICU)] cases with increasing systemic inflammation in comparison with healthy individuals sampled prior to the COVID-19 pandemic. The results showed significantly dysregulated proteins and associated biological processes and disorders associated to COVID-19. These results corroborated previous findings in COVID-19 studies and highlighted how the representation of dysregulated serum proteins and associated BPs increases with COVID-19 disease symptomatology from asymptomatic to severe cases. The analysis was then focused on novel disease processes and biomarkers that were correlated with disease symptomatology. To contribute to translational medicine, results corroborated the predictive value of selected immune-related biomarkers for disease recovery [Selenoprotein P (SELENOP) and Serum paraoxonase/arylesterase 1 (PON1)], severity [Carboxypeptidase B2 (CBP2)], and symptomatology [Pregnancy zone protein (PZP)] using protein-specific ELISA tests. Our results contributed to the characterization of SARS-CoV-2–host molecular interactions with potential contributions to the monitoring and control of this pandemic by using immune-related biomarkers associated with disease symptomatology.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

et al. 2021

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“…Recent findings have however shown that there is the presence of an immunosenescent phenotype which appears to be underpinned by elevated neutrophils-to-lymphocytes ratio (NLR) [ 208 ], and high IL-6 production [ 209 ], and is correlated to disease severity [ 210 ]. For example, a recent study has reported that a Th2/Th1 cytokine imbalance is correlated with a higher risk of mortality from COVID-19 [ 211 ]. Findings from another study have reported that biological age measure [on 42 biomarkers] captured using PhenoAge, as opposed to chronological age, is responsible for pushing the trends and correlations we are seeing with COVID-19 severity and age.…”

Section: The Potential Implications and Clinical Translation Of Senescence And Aging In Covid-19mentioning

confidence: 99%

Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

Lynch

Guo

Gibson

et al. 2021

Cells

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or “sendotypes”), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.

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“…With the shift from Th1 to Th2 CD4+ T cells in pregnant women, this carries unfavorable implications. For further evidence, Pavel et al discussed how the Th2/Th1 cytokine imbalance was found to be significantly higher in patients with known COVID-19 risk factors such as age (>40), sex (male), active smoking, as well as ACE2 expression and patients with asthma, leading to higher mortality risk [ 15 ].…”

Section: Implications Of Immune Modulation In Pregnancy and Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 and the Immune Response in Pregnancy with Delta Variant Considerations

Rangchaikul

Venketaraman

2021

Infectious Disease Reports

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As of September 2021, there has been a total of 123,633 confirmed cases of pregnant women with SARS-CoV-2 infection in the US according to the CDC, with maternal death being 2.85 times more likely, pre-eclampsia 1.33 times more likely, preterm birth 1.47 times more likely, still birth 2.84 times more likely, and NICU admission 4.89 times more likely when compared to pregnant women without COVID-19 infection. In our literature review, we have identified eight key changes in the immunological functioning of the pregnant body that may predispose the pregnant patient to both a greater susceptibility to SARS-CoV-2, as well as a more severe disease course. Factors that may impede immune clearance of SARS-CoV-2 include decreased levels of natural killer (NK) cells, Th1 CD4+ T cells, plasmacytoid dendritic cells (pDC), a decreased phagocytic index of neutrophil granulocytes and monocytes, as well as the immunomodulatory properties of progesterone, which is elevated in pregnancy. Factors that may exacerbate SARS-CoV-2 morbidity through hyperinflammatory states include increases in the complement system, which are linked to greater lung injury, as well as increases in TLR-1 and TLR-7, which are known to bind to the virus, leading to increased proinflammatory cytokines such as IL-6 and TNF-α, which are already elevated in normal pregnant physiology. Other considerations include an increase in angiotensin converting enzyme 2 (ACE2) in the maternal circulation, leading to increased viral binding on the host cell, as well as increased IL-6 and decreased regulatory T cells in pre-eclampsia. We also focus on how the Delta variant has had a concerning impact on SARS-CoV-2 cases in pregnancy, with an increased case volume and proportion of ICU admissions among the infected expecting mothers. We propose that the effects of the Delta variant are due to a combination of (1) the Delta variant itself being more transmissible, contagious, and efficient at infecting host cells, (2) initial evidence pointing to the Delta variant causing a significantly greater viral load that accumulates more rapidly in the respiratory system, (3) the pregnancy state being more susceptible to SARS-CoV-2 infection, as discussed in-depth, and (4) the lower rates of vaccination in pregnant women compared to the general population. In the face of continually evolving strains and the relatively low awareness of COVID-19 vaccination for pregnant women, it is imperative that we continue to push for global vaccine equity.

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Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

Cited by 67 publications

References 33 publications

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

SARS-CoV-2 and the Immune Response in Pregnancy with Delta Variant Considerations

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