SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes

Nikolich‐Žugich, Janko; Knox, Kenneth S.; Rios, Carlos Tafich; Natt, Bhupinder; Bhattacharya, Deepta; Fain, Mindy J.

doi:10.1007/s11357-020-00186-0

Cited by 521 publications

(607 citation statements)

References 68 publications

Supporting

Mentioning

553

Contrasting

Unclassified

Order By: Relevance

“…Third, our model predicts that patients with higher immunopathology values are associated with longer infection clearance times, a prediction that is validated by recent clinical data suggesting that COVID-19 patients admitted to the ICU tend to take twice the clearance time compared to the non-ICU patients (30 days vs. 14 days) (39). Fourth, we demonstrate that the impaired ability of innate immune system to resolve the inflammation can drive cytokine-induced immunopathology; indeed, "being stuck in immune response" can be a hallmark of severe disease and possibly the death of the patient (37). Similar observations have been made for SARS-CoV and MERS-CoV (61); for instance, patients who died of SARS had higher levels of pulmonary pro-inflammatory cytokines (62).…”

Section: Discussionsupporting

confidence: 73%

“…Such a reduction would imply the set of cases where the resolution of inflammation by the innate immune system is inefficient. Such sustained innate immune system has been seen to be specific to non-survivors in SARS-CoV, suggesting that "being stuck in immune response" can lead to a severe disease phenotype (37). This lack of ability to resolve innate immune response and mount an efficient adaptive response is often an age-related change; this reason may at least in part explain higher susceptibility to the severe phenotype for elder population, ultimately leading to their death (37).…”

Section: Clinically Observed 'Severe' Phenotypes Of Covid-19mentioning

confidence: 99%

“…Such sustained innate immune system has been seen to be specific to non-survivors in SARS-CoV, suggesting that "being stuck in immune response" can lead to a severe disease phenotype (37). This lack of ability to resolve innate immune response and mount an efficient adaptive response is often an age-related change; this reason may at least in part explain higher susceptibility to the severe phenotype for elder population, ultimately leading to their death (37). Similarly, people with comorbidities such as obesity have heightened inflammatory levels at baseline (in the absence of infection), which could affect resolution in cases of inflammation (38).…”

Section: Clinically Observed 'Severe' Phenotypes Of Covid-19mentioning

confidence: 99%

See 2 more Smart Citations

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes

Sahoo

Hari

Jhunjhunwala

et al. 2020

Preprint

View full text Add to dashboard Cite

The disease caused by SARS-CoV-2 is a global pandemic that threatens to bring long-term changes worldwide. Approximately 80% of infected patients are asymptomatic or have mild symptoms such as fever or cough, while rest of the patients have varying degrees of severity of symptoms, with 3-4% mortality rate. Severe symptoms such as pneumonia and Acute Respiratory Distress Syndrome can be caused by tissue damage mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm. However, the mechanistic underpinnings of such responses remain elusive, with an incomplete understanding of how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinicopathological outcomes. Here, we use a dynamical systems approach to dissect the emergent nonlinear intra-host dynamics among virally infected cells, the immune response to it and the consequent immunopathology. By mechanistic analysis of cell-cell interactions, we have identified key parameters affecting the diverse clinical phenotypes associated with COVID-19. This minimalistic yet rigorous model can explain the various phenotypes observed across the clinical spectrum of COVID-19, various co-morbidity risk factors such as age and obesity, and the effect of antiviral drugs on different phenotypes. It also reveals how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe phenotypes. These results will help further the case of rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage simultaneously. Significance StatementThe SARS-CoV-2 pandemic has already infected millions of people, and thousands of lives have been lost to it. The pandemic has already tested the limits of our public healthcare systems with a wide spectrum of clinicopathological symptoms and outcomes. The mechanistic underpinnings of the resultant immunopathology caused by the viral infection still remains to be elucidated. Here we propose a minimalistic but rigorous description of the interactions of the virus infected cells and the core components of the immune system that can potentially explain such diversity in the observed clinical outcomes. Our proposed framework could enable a platform to determine the efficacy of various treatment combinations and can contributes a conceptual understanding of dynamics of disease pathogenesis in SARS-CoV-2 infections.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Clinically Observed 'Severe' Phenotypes Of Covid-19mentioning

confidence: 99%

Section: Clinically Observed 'Severe' Phenotypes Of Covid-19mentioning

confidence: 99%

See 1 more Smart Citation

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes

Sahoo

Hari

Jhunjhunwala

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…1 Until April 30, 2020, 185 countries/territories reported 3·2 million confirmed cases with 227,847 total deaths, 2 and the highest-burden has been placed in European and American countries. 1 Serious health, social and economic consequences of COVID-19 have been well-recognized, [3][4][5][6][7] especially among the elderly with comorbidities, homeless individuals, and also residents who face financial, mental, and physical hardships due to social distancing policies. 8 Given that COVID-19 is a new threat without any antiviral therapies or vaccines, current measures to mitigate this crisis depend heavily on the national and regional preparedness and responses.…”

Section: Introductionmentioning

confidence: 99%

Studies of Novel Coronavirus Disease 19 (COVID-19) Pandemic: A Global Analysis of Literature

Tran

Nguyen

et al. 2020

Preprint

View full text Add to dashboard Cite

An exponential growth of literature about novel coronavirus disease 19 has been observed in the last few months. This textual analysis of 5,780 publications extracted from the Web of Science, Medline, and Scopus databases was performed to explore the current research focuses and propose further research agenda. The Latent Dirichlet allocation was used for topic modeling. Regression analysis was conducted to examine country variations in the research focuses. Results indicated that publications were mainly contributed by the United States, China, and European countries. Guidelines for emergency care and surgical, viral pathogenesis, and global responses in the COVID-19 pandemic were the most common topics. There was variation in the research approaches to mitigate COVID-19 problems in countries with different income and transmission levels. Findings highlighted the need for global research collaboration among highand low/middle-income countries in the different stages of prevention and control the pandemic.

show abstract

“…As of June 1, 2020, the COVID-19 pandemic has infected over 6.3 million people and killed over 370,000 worldwide (https://coronavirus.jhu.edu/map.html). Its causative agent, the novel SARS-CoV-2, is an enveloped single stranded RNA virus that infects tissues including lung alveoli 1, 2 , renal tubules 3,4 , the central nervous system 5 , illeum, colon and tonsils [6][7][8] , and myocardium 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Differential expression of COVID-19-related genes in European Americans and African Americans

Singh

Wurtele

2020

Preprint

View full text Add to dashboard Cite

The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.

show abstract

SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes

Cited by 521 publications

References 68 publications

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes

Studies of Novel Coronavirus Disease 19 (COVID-19) Pandemic: A Global Analysis of Literature

Differential expression of COVID-19-related genes in European Americans and African Americans

Contact Info

Product

Resources

About