Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?

Bajaj, Varnica; Gadi, Nirupa; Spihlman, Allison P.; Wu, Samantha; Choi, Christopher H.; Moulton, Vaishali R.

doi:10.3389/fphys.2020.571416

Cited by 394 publications

(376 citation statements)

References 186 publications

(521 reference statements)

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“…Moreover, immunosenescence occurs with aging, so we anticipated age to be a potential effect modifier in the relationship between mAb receipt and study outcomes. 14 Therefore, we planned a priori to select non-infused patients using propensity scores within age strata consistent with the EUA criteria: less than 55 years, 55 years to less than 65 years, and 65 years of age and older. 9 Patients receiving mAb infusion and the selected comparator patients across all age strata were then combined to constitute the study population.…”

Section: Methodsmentioning

confidence: 99%

Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection

Bariola

et al. 2021

Preprint

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Background: Monoclonal antibody (mAb) treatment may prevent complications of COVID-19. We sought to quantify the impact of bamlanivimab monotherapy on hospitalizations and mortality, as well as Emergency Department (ED) visits without hospitalization, among outpatients at high risk of COVID-19 complications. Methods: We compared patients receiving mAb to patients who met criteria but did not receive mAb from December 2020 through March 2021. The study population selection used propensity scores to match 1:1 by likelihood to receive mAb. The primary outcome was hospitalization or all-cause mortality within 28 days; the secondary outcome was hospitalization or ED visit without hospitalization within 28 days. Odds ratios (OR) calculation used logistic regression modeling including propensity score and mAb receipt predictors. Results: The study population included 234 patients receiving mAb and 234 matched comparator patients not receiving mAb. Patients receiving mAb were less likely to experience hospitalization or mortality (OR 0.31, 95% confidence interval [95%CI] 0.17-0.56, p=0.00001) and hospitalization or ED visit without hospitalization (OR 0.50, 95%CI 0.43-0.83, p=0.007). The impact of mAb was more pronounced in prevention of hospitalization (among all age groups, OR 0.35, 95%CI 0.19-0.66, p=0.001) than mortality or ED visit without hospitalization, and most strongly associated with patients age 65 years and older (primary outcome OR 0.28, 95%CI 0.14-0.56, p=0.0003). Conclusions: Bamlanivimab monotherapy was associated with reduction in the composite outcome of hospitalizations and mortality in patients with mild-moderate COVID-19. The benefit may be strongest in preventing hospitalization in patients ages 65 years or older.

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Section: Methodsmentioning

confidence: 99%

Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection

Bariola

et al. 2021

Preprint

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“…Several studies have suggested the significant reduction of immunologically important cells which provide adaptive immunity, such as T-cells in severe cases of COVID-19 [ 205 , 206 ]. Hence, T-cells in, for example, CD4 + and CD8 + cell populations have been found to be significantly declined compared to cells that provide innate immunity, such as macrophages and neutrophils in mild to severe cases of the SARS-CoV-2 infection [ 207 ].…”

Section: Response Rate Of Activated T-cell Types In Covid-19mentioning

confidence: 99%

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

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“…During development, dose optimization of the Moderna vaccine has been performed towards optimal protection of the elderly, exploring doses of 25, 50, 100 and 250ug, as the elderly show reduced immune response on vacccination[ 3 ]. Laboratory-assessed immunity levels typically exceeded those seen in the plasma of reconvalescent patients who have a protection of 83% for at least 5 months[ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Vaccination strategies for minimizing loss of life in Covid-19 in a Europe lacking vaccines

Hunziker

2021

Preprint

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BackgroundWe aimed at identifying vaccination strategies that minimize loss of life in the Covid-19 pandemic. Covid-19 mainly kills the elderly, but the pandemic is driven by social contacts that are more frequent in the young. Vaccines elicit stronger immune responses per dose in younger persons. As vaccine production is a bottleneck, many countries have adopted a strategy of first vaccinating the elderly and vulnerable, while postponing vaccination of the young.MethodsBased on published age-stratified immunogenicity data of the Moderna mRNA-1273 vaccine, we compared the established “one dose fits all” approach with tailored strategies: The known differential immunogenicity of vaccine doses in different age groups is exploited to vaccinate the elderly at full dose, while the young receive a reduced dose, amplifying the number of individuals receiving the vaccine early. A modeling approach at European Union scale with population structure, Covid-19 case and death rates similar to Europe in late January 2021 is used.ResultsWhen the elderly were vaccinated preferentially, the pandemic initially continued essentially unchecked, as it was dominantly driven by social contacts in other age groups. Tailored strategies, including regular dosing in the elderly but reduced dose vaccination in the young, multiplied early vaccination counts, and even with some loss in protection degree for the individual person, the protective effect towards stopping the pandemic and protecting lives was enhanced, even for the elderly.ConclusionProtecting the vulnerable, minimizing overall deaths and stopping the pandemic is best achieved by an adaptive vaccination strategy using an age-tailored vaccine dose.

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Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?

Cited by 394 publications

References 186 publications

Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection

Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Vaccination strategies for minimizing loss of life in Covid-19 in a Europe lacking vaccines

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