SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19

Abstract

The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are also discussed.

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ARTICLE TYPE: Review
Title: SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19
Ligen Yu *a, Mohd Khanapi Abd Ghani b, Alessio Aghemo c, Debmalya Barh d, Matteo Bassetti e, Fausto Catena f, Gaetano
Gallo g, Ali Gholamrezanezhad h, Mohammad Amjad Kamal i, Amos Lal j, Kamal Kant Sahu k, Shailendra K Saxena l, Ugo
Elmore m, Farid Rahimi n, Chiara Robba o, Yuanlin Song p, Zhengyuan Xia q, Boxuan Yu r
a Talent Recruitment and Career Support (TRACS) Office, Nanyang Technological University, N2.1 B4-01, 76 Nanyang Drive, Singapore
637331
b Biomedical Computing and Engineering Technologies (BIOCORE) Applied Research Group, Faculty of Information and
Communication Technology, Universiti Teknikal Malaysia Melaka, Durian Tunggal 76100 Melaka, Malaysia
c Humanitas Research Hospital IRCCS, Rozzano, Italy
d Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, WB-721172, India; and Departamento
de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901,
Brazil
e Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Policlinico San Martino Hospital – IRCCS, Genoa,
Italy
f Azienda Ospedaliero - Universitaria di Parma, Parma, Italy
g University of Catanzaro, Catanzaro, Italy
h Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
i 7 Peterlee Place, Hebersham, NSW 2770, Australia
j Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA 55902
k Huntsman Cancer Centre, University of Utah, USA
l Center for Advanced Research, King George's Medical University (KGMU), Lucknow - 226003, India
m Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute University, Milan, Italy
n Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Ngunnawal and
Ngambri Country, Canberra, ACT 2600, Australia
o Anesthesia and Intensive Care, Policlinico San Martino, Largo Rosanna Benzi 15, 16100 Genova, Italy
p Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, P.R.China, 200032
q Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
r School of Computer Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798
*Address correspondence to LG Yu at the Talent Recruitment and Career Support (TRACS) Office, Nanyang Technological University, N2.1
B4-01, 76 Nanyang Drive, Singapore 637331, Singapore; Tel: ++65-6592-3248; E-mail: mlgyu@ntu.edu.sg
Abstract: The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions
of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular
disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author’s
keywords was carried out, and searched for possible links between various coronavirus studies over

2 Current Medicinal Chemistry, 2022, Vol. 0, No. 0 Yu et al.
the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition,
malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to
each other. Based on these findings, we hypothesized that the human immune system is a multilevel
super complex system, which employs multiple strategies to contain microorganism infections and
restore homeostasis. It was also found that the behavior of the immune system is not able to be
described by a single immunological theory. However, one main strategy is “self-destroy and rebuild”,
which consists of a series of inflammatory responses: 1) active self-destruction of
damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus,
invading microorganisms’ clearance could be only a passive bystander response to this destroy–rebuild
process. Microbial infections could be self-limiting and promoted as an indispensable essential
nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge
resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state
in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible
coping strategies to mitigate COVID-19, including vaccination, are also discussed.
CONSENT FOR PUBLICATION
Not applicable.
FUNDING
None.
CONFLICT OF INTEREST
Dr. Ligen Yu is the Section Editor of the Journal of CMC.
Acknowledgements
The authors are grateful to Dr. Melvin Hayden (MD, Professor at the University of Missouri, USA), Dr Jamie
Cunliffe (www.morphostasis.org.uk), Dr. Marcello Candelli (Catholic University of Sacred Heart of Rome,
Italy), Dr. Danilo Buonsenso (Fondazione Policlinico Universitario A, Italy), Dr. Susanna Esposito,
(University Hospital of Parma, Italy), and Dr. Sushil Kumar Middha (Maharani Lakshmi Ammanni College
For Women, India) for reading and providing insightful comments to this manuscript.

SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19 Current Medicinal Chemistry, 2023, Vol. 0, No. 0 3
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