Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Why Does COVID-19 Disproportionately Affect the Elderly?

Version 1 : Received: 30 April 2020 / Approved: 30 April 2020 / Online: 30 April 2020 (22:38:53 CEST)

A peer-reviewed article of this Preprint also exists.

Mueller AL, McNamara MS, Sinclair DA. Why does COVID-19 disproportionately affect older people?. Aging (Albany NY). 2020; 12:9959-9981. https://doi.org/10.18632/aging.103344 Mueller AL, McNamara MS, Sinclair DA. Why does COVID-19 disproportionately affect older people?. Aging (Albany NY). 2020; 12:9959-9981. https://doi.org/10.18632/aging.103344

Abstract

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are of those over 65 years of age with a 23-fold greater risk of death. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes, obesity and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms. Here, we present the molecular differences between the young, middle-aged and elderly that may determine whether COVID-19 is a mild or life-threatening illness. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

Keywords

COVID-19; coronavirus; SARS-CoV-2; aging; immunosenescence; inflammaging; inflammation; cytokine storm; epigenetics; biological clock; sirtuin; glycome

Subject

Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Comments (1)

Comment 1
Received: 7 May 2020
The commenter has declared there is no conflict of interests.
Comment: If older people would take rapamycin to address dysregulation of mTOR and fisetin senolytic to reove excessive senescent cells, and take cbd oil with the appropriate broad spectrum of terpines, their immune systems would be biologically younger than their chronological age and they would either not get covid 19, or would handle with a less severe resu;lt. Marilyn Grashowa non scientist who takes good care of her health and total recovery from 2 cancers.There is plethora of excellent research on this from brilliant peopleread it. Also a very successful treatment by doctor(s) involved hydroxychloroquin and rapamycin.
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Comment 2
Received: 31 May 2020
Commenter: Martine Rothblatt
The commenter has declared there is no conflict of interests.
Comment: Great article. You say "Given the increasing
evidence that lower NAD+ levels in the lung and vascular endothelium contribute to poor
COVID-19 outcomes, NAD boosters, such as the NAD+ precursors NMN and NR [110],
have been suggested as first-line treatments against COVID-19, especially aged patients."

My question is, why not give NAD+ directly, such as sub-lingual, rather than via a precursor?
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