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The COVID-19 Syndrome: One, Two, Three, or a Hundred Diseases......

Giovanni C Actis*

Emeritus Professor of Gastroenterology and Clinical Immunology, Turin General Hospitals, Turin, Italy

*Corresponding author: Giovanni C Actis, Emeritus Professor of Gastroenterology and Clinical Immunology, Turin General Hospitals, Turin, Italy, E-mail: actis_g@libero.it

Actis. CasesMed Res J 2020, Volume 2 Issue 1

Citation: Actis GC (2020) The COVID-19 Syndrome: One, Two, Three, or a Hundred Diseases....... CasesMed Res J 2(1): 19-21.

Copyright: © 2020 Actis GC, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: July 28, 2020 | Accepted: August 17, 2020 | Published: August 19, 2020

Abstract

We are now entering our 8th month of combat against the SARS-CoV-2, a previously unknown RNA coronavirus that allegedly causing a cluster of severe atypical pneumonias at the end of December 2019 in China, began to be identified and traced since then. After rapidly invading mainland China and a few other countries in sequence, this agent got the classification of pandemia, with the depending syndrome named COVID-19. This grading is now being supported by a toll of some 16 million infected, and 600,000 fatalities worldwide. One of the major problems is the lack of fully effective drugs, whereas several vaccine programs have still a long way to go. Peoples' fear, and massive job loss, is threatening to ignite social collapse, as a second disease within the first one. We hereby try to effectively unwrap a few qualifying points, to favor the designing of novel strategies.


Keywords: Covid-19 syndrome, manifold diseases, cytokine storm, Covid-19 psychological aspects


A bird's Eye Analysis

SARS-CoV-2 is a respiratory virus with an obvious tropism for the respiratory epithelia and alveoli. The incubation period is esteemed between a few, and 14 days. The fatality rate is 10-20%. The natural history of the SARS-CoV-2 disease may reveal two distinct phases: [1] the initial phase sustained by the cytopathic virus action, then followed by the inflammatory phase, in turn propelled by the irritant effect of the accumulating virus.


A Closer Analysis

Lung inflammation of SARS viruses is duly divided into two arms. A prodromic arm (innate response sustained by a front line of granulocytes), and the subsequent phase of acquired immunity handled by lymphocytes: the innate cells combat to grossly face and destroy the invader, the lymphocytes in the acquired immunity cycle, effect the immunologic reconstruction, building up of antigen-specific defense, and preparation of the antibody memory. As a point worth of crucial attention, in SARS immunity the timing of the two phases is essential for the inflammatory process to be implemented and then extinguished without remnants [2]. Loss of control of the innate phase could allow its undue prolongation, inhibition of the stabilization of an acquired antibody response, prolongation of attending lung damage, and eventual clinical failure, serologically marked by hyper-cytokinemia, and clinically by the known cytokine storm [3] and lung failure requiring the ICU. Interestingly, at the clinical level, this variegated response has been found to be linked to at least two features: gender, and age, with the male gender described as the carrier of the worst risk.


Analysis of Gender at COVID Risk

Males account for over 50% of the respiratory fatalities [4]; in historic flu pandemias (the last Hong-Kong infection) males needed hospital more than women; males do not respond well to pro-resolving lipid mediators, and exhibit a poorly diversified immune response; a key to understanding this puzzle may derive from reminding that most pro-inflammatory factors (including cytokines) are coded for on the X-chromosomes [5]. The only X-chromosome of males may fuel a monotonous poorly checked inflammation pattern. This is in contrast to women who statistically recover best from flu, and benefit from the stabilizing action of progesterone, and do not suffer from eventual polymorphisms of the conveyors of innate response, so-called toll-like receptors (TLR). To this end, females may benefit from their pair of X-chromosomes, of which one, incompletely silenced by methylation, confers flexible inflammatory reactions, deriving from a paternal/maternal mosaic [6].

Finally, that inflammation plays a crucial role in the ignition and evolution of COVID-19 is underscored by two further pieces of data. Pictures of otherwise unexplained vasculitis have been shown in conjunction with COVID, taking at times the appearance of specific heart vessel vasculitis (Kawasaki) or severe veno-occlusive disease requiring amputation [7]. Having set this, then more speculation can gain credit. Some investigators are now holding that the course and prognosis of the COVID-19 syndrome may most aptly be explained by taking the swings of the relevant COVID inflammation as the compass in the investigational search for a treatment. Thus, unchecked lung inflammation with alveoli damage seems to be the leading factor; we have proposed to materialize the culprits of this unbalance by pointing our finger toward males, who: 1) Control common flu much less than women, respond poorly to regulatory factors (pro-resolving mediators), and, their X-chromosomes code for most inflammatory mediators. 2) To lend a conclusive weight to such arguments, one could ask: can this hyperactive inflammatory bias of men be up- or down-regulated by extrinsic factors? The exciting answer seems to be positive. So-called Mediterranean Diets containing large components of anti-inflammatory factors [8,9] as borrowed from treatment schemes of autoimmune disorders, are being prescribed in COVID and post COVID, and study analysis is under way.


Psycho-Social factors in COVID

Mention of the role of the diet is lending us the chance to switch our attention to sociological matters, coherently with the multifaceted issues heralded in the title. The unexpectedly massive diffusion of severe COVID in the USA reminds us of the simple yet possibly crucial role played by the people's diet. The excessive introduction of elaborated meat and deep fried constituents can logically be suspected to be the one fostering factor of the uncontrolled inflammatory complications among the US cases of COVID-19; intriguingly, the excess diffusion of fatal COVID in the lower USA classes (latinos and Afro- Americans) reflects the known large consumption of junk inflammatory food by those ethnicities [10].

In the US, the COVID pandemia has turned into potentially deadly errors and wrong choices what previously was considered a hallmark of "mature capitalism".
For examples:
1) Trust on money has become more of greed;
2) Individual consideration has depended more and more on the individual's credit card;
3) Solidarity has rather become mistrust, mitigated at best by compassion and pity;
4) Each and all of the above has paradoxically generated hate and suspect towards the original founders of the fatherland, and some of their statues were destroyed before screaming crowds in a crazy scenario. Even more impressive, the medical insurance system, a hallmark of the American Institutions, has shown to be totally inadequate to cover the thousands of COVID affected patients, with people literally dying on the side-walk. This SARS pandemic has ruthlessly exposed the American frailties [11].

In Europe, depression and confusion have been the dominant tune [12]. People have witnessed almost passively the complete overturn of their individual and social lives: abolition of all working or leisure activity, cessation of all reciprocal interaction, which was totally replaced by a computer screen. At a difference to the ongoing "Phase 1" crisis in the USA with dying patients knocking at the ICU door, in most of the European states pandemia has become endemia: people are obliged to cohabitate with the virus, keeping alert for the signs of the next infection wave, and keeping at hand the phone number of the psychiatrist.

Even more worrying, Coronaviruses are keen at establishing their domicile with the hosts they happen to like. Those "lucky ones" might be forced to modify their immunity profile into a "corona-like" fashion. For example, bats after tiring periods of combat (pre-historic periods!) were finally forced to develop a down-graded edition of their response, for example by abating the reactivity of their inflammasomes, and ease Covid-19 acceptance [13]. Given the current state of Corona endemicity in many countries, and the pressure exerted by the bug, some investigators may righteously fear the eventual settlement of the SARS-CoV2 among our microbiota, making us the bats of the 21st century!!


Wrap-up Summary

Mankind has recently hit into a hitherto unknown variant of SARS Corona virus, which, as its distinctive attribute, can erratically induce fatal lung pathology if a peculiar condition ensues of erroneous take-over between the innate and adaptive response arms. Appalling virus invasiveness and forced lock-down measures are now undermining Western society all over, with a social/ financial damage that probably is manifold superior to the medical damage. In the absence of a cure/vaccine, people are invited to resist, and Authorities are plead to talk to people [14] to help all with this unprecedented endeavor.


References


1. Zhou F, Yu T, Du R, Fan G, Liu Y et al, (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China. a retrospective cohort study. Lancet 395: 1054-1062.

2. Manjili RH, Zarei M, Habibi M, Manjili MH (2020) COVID-19 as an acute inflammatory disease. J Immunol 205: 12-19.

3. Vaninov N (2020) In the eye of the COVID-19 cytokine storm. Nat Rev Immunol 20: 277.

4. Chen N, Zhou M, Dong X, Qu J, Gong F, et al. (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wu-han, China. a descriptive study. Lancet 395: 507-513

5. Libert C, Dejager L, Pinheiro I (2010) The X-chromosome in immune function: when a chromosome makes the difference. Nat Rev Immunol 10: 594-604.

6. Spolarics Z, Pena G, Qin Y, Donnelly RJ, Livingstone DH (2017) Inherent X-linked genetic variability and cellular mosaicism unique to females contribute to sex-related differences in the innate immune response. Front Immunol 8: 1456.

7. Goldman IA, Ye K, Scheinfeld MH (2020) Lower extremity arterial thrombosis associated with COVID-19 is characterized by greater thrombus burden and increased rate of amputation and death. Radiology. 202348.

8. Roopchand DE, Carmody RN, Kuhn P, Moskal K, Rojas-Silva P, et al. (2015) Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes 64: 2847-2858.

9. Zabetakis I, Lordan R, Norton C, Tsoupras A (2020) COVID-19: The inflammation link and role of nutrition in potential mitigation. Nutrients 12: 1466.

10. Costa CS, Del-Ponte B, Assuncao MCF, Santos IS (2018) Consumption of ultra-processed foods and body fat during childhood and adolescence, systematic review. Public Health Nutr 21: 148-159.

11. Farrell TW, Francis L, Brown T, Ferrante LE, Widera E et al, (2020) Rationing limited health care resources in the COVID-19 era and beyond: ethical considerations regarding older adults. J Am Geriatr Soc 68: 1143-1149.

12. Petzold MB, Bendau A, Plag J, Pyrkosch L, Mascarelli Maricic L, et al, (2020) Risk, resilience, psychological distress, and anxiety at the beginning of COVID-19 pandemic in Germany. Brain and Behavior.

13. Ahn M, Anderson DE, Zhang Q, Wah Tan C, Lee Lim B, et al, (2019) Dampened NLRP-3 inflammation in bats and implications for a special viral reservoir host. Nature Microbiol 4: 789-799.

14. Loder E. (2020) Getting it right in the pandemic. BMJ 370: m2637.