Alcoholism as a risk factor for COVID-19: Boosting inflammatory response

Alcoholism is a condition associated with psychiatric and psychiatric problems, where the respiratory system is damaged through the mucociliary ladder mechanism and alveolar macrophage dysfunction. In the time COVID-19 has been observed a dramatic increase in alcohol consumption mediated by levels of anxiety and situations of confinement. In this work we analyze the relationship between alcoholism and SARS, especially with SARS-CoV-2, explained by a degradation of the host defenses of the respiratory epithelium by changing the barrier function, the discharge of cytokines and the functions of the cilia. All of them involved in the defense mechanism. of the lungs. This leads to a worse prognosis for patients precisely because of alcohol consumption. Based on this approach, alcoholism will exacerbate the consequences of COVID-19.


Introduction
Lives of a huge number of people had changed intensely when pandemic of severe acute respiratory syndrome corona virus 2 appeared in 2019. The outburst commenced in December 2019 from the Wuhan city of china and till March 2020, the WHO had announced it as a pandemic 1 . COVID-19 is an extremely contagious transferable disease, most frequently initiates muscular pain, fatigue, fever, dry cough and dyspnea. What differentiates this recent disease from others is its extremely quick spread and comparatively high death rate. This was endorsed in mid of the March 2020 when patients were documented in around 135 countries, approximately 12 weeks after the 1st case had appeared. On 1st March 2020, death rates extended >3.5 % in China and 1.5% in countries other than China 2 . The whole situation is certainly a catastrophe sensed by great numbers of individuals, leading to challenging psychological reactions. It requires substantial strength to re-adapt to an unidentified and ambiguous condition and how to deal with numerous distressing emotions, regular frustrations, and the outlook of a susceptible material presence to family and oneself. Because of the famous and recognized effects of impeding the nervous system, psychoactive ingredients including alcohol are utilized by numerous people in search of relief from anxiety, irritating or displeasing emotions, stress, or depression [3][4][5] . This entreats the query of whether the substantial escalations in sales of alcohol, observed in numerous countries are because of the pandemic when associated with the similar period in the preceding year. As an illustration, a study i.e. conducted in March 2020 by the Nielsen Company in United States of America establish 240% escalations in sales of alcohol by means of internet, counting wines by 66%, spirits by 75 percent, and beers by 42%. There have also been informations in press reporting amplified domestic brutality, which has long been related with alcohol misuse 6 . This is not merely a financial issue or a considerable one-time incident, however a compound and complicated experience disturbing billions of people all around the world in provinces for instance: political, medical, economic, geopolitical, religious, axiological, societal, cultural, and civilizational aspects. Hence, this includes nearly all regions in the existence of societies and individuals 7 .

Impact of COVID 19 pandemic on mankind
Right now the state of pandemic i.e. challenging mankind can be contemplated to be somewhat a multiple-stage complicated calamity, distressing the numerous facets of health, counting psychological health; in both individual and societal aspects 8 . Nevertheless the risk presented by the virus itself, numerous psychological issues may appears from the obligatory quarantine and lockdown together with the financial threats. Among other things the studies conducted upon animals have revealed the negative influence that loneliness has on enhancing stress levels in the body with both raised responsiveness to stress and neuroendocrine reactions 9 . All this can provoke a broad range of diseases of changing brutality, principally difficulties in concentrating, depression, anxiety, anger, insomnia, violence, and interpersonal clashes. The severity of these symptoms may at least in fragment be because of the degree and extent of the quarantine, a sensation of isolation, distress of infection, and approach to suitable or unsuitable facts and figures 10 . Existing evidence proposes the involvement of organ results from uninterrupted viralencouraged and cytokine arbitrated impairment 11 . In the attempt to generate a reaction to the entrance of SARS-CoV-2, there is a secretion of immune cells such as pro-inflammatory cytokines which frequently becomes amplified and originates fluctuating degrees of damage to the tissues. Raised pro-inflammatory cytokines for instance TNF-α, IL-6, IL-1, and interferon-γ have been linked with advanced severity of disease in COVID-19 12 . The pulmonary system is the principal system involved in COVID-19. Apart from general symptoms for instance sore throat, cough, and rhinitis; respiratory manifestation of acute respiratory distress syndrome (ARDS) o severe acute respiratory syndrome coronavirus (SARS) is the foremost reason of demise in corona virus disease-19 13 . Additionally, there is a proof that people who have survived from this deadly COVID-19 could progress post-recovery fibrosis in lungs 14 . The liver is similarly influenced by COVID-19. Indicators of hepatic injury for instance raised aminotransferases, bilirubin, and GGT (gamma-glutamyl transferase) have been establish to associate with severity of disease 15 . Though the particular mechanism of hepatic damage is not identified, there are assumptions that this is because of viral-arbitrated damage to cell as a consequence of the existence of angiotensin-converting enzyme 2 in cholangiocytes and cytokinepersuaded hepatic injury 16,17 . Moreover, hepatic damage could messed up with the usage of antiviral drugs used in the management of Corona virus disease-19 17 . Severe inflammation in muscles of pericardium, shock, arrhythmias, and cardiac failure have also been described as cardiac signs of COVID-19 8,18 . Because of the existence of angiotensin converting enzyme-2 in the heart, it is considered that both viral-arbitrated and cytokine-prompted damage are accountable for damage to the cardiac muscles 19 . Involvement of heart with or deprived of pulmonary failure has been linked in as much as forty percent of corona virus disease deaths 20 .

Alcoholism
Alcohol dependency, explains a state in which a person's societal role is diminished and they develop physical acceptance for alcohol and abstinence from it may cause withdrawal symptoms 24 . Abuse of Alcohol discusses about a form of consumption that originates adverse effects across one or more foremost domains of life (e.g. work or relationships). The lifetime incidence for depending upon alcohol ranges from country to country, fluctuating from 1.8-32.4%. In the USA, 8 to 14% of the people are dependent upon alcohol, and 50% of those who are dependent on alcohol are possibly to become alcohol addicts 25 . If genders are to be concerned, then males are more anticipated to be dependent upon alcohol and abuse alcohol as compare to female, though, there has been a progressive rise in consumption of alcohol in females with a decrease in the difference amid female and male alcohol intake from the past few years 25,26 . Similarly, younger grownups have the greatest frequency rates of alcohol dependence and abuse, with those amid the ages of 21-25 years being the most distressed 26 . Apart from the distinguishable environmental factors related with alcoholism, research projects have pointed at a prospective hereditary susceptibility in alcohol addicts. Progresses in the area of neurobiology's research have associated alcohol abuse with neural pathways by means of which hereditary susceptibilities to consumption of alcohol can be illuminated 25 . Study has revealed that 18 to 27 percent of male children born to parents who regularly consume alcohol develop complications with alcohol abuse even when raised by foster parents, in contrast with 6 percent of male kids from parents who are not alcoholic.
Research studies on monozygotic twins revealed that there were numerous comparisons in the consuming frequency of monozygotic twins than non-monozygotic twins 27 . In contrast with the popular belief that intake of alcohol in least quantities from time to time aids to prevent disorders for instance diabetes, dementia, cardiac disease and cognitive deterioration; numerous research studies have revealed that even modest consumption of alcohol contributes to more than sixty acute and persistent conditions of health [28][29][30] . Great number of health inferences of alcohol take place by means of mechanisms arising from other states of disease for instance carcinoma, hepatic ailments, high blood pressure, cardiac disease, violence, road accidents, and interpersonal clashes 28 .

Alcoholism and its effects on systems of the body and COVID 19
It would be anticipated that the negative effects of alcohol on the human body become intensified when associated with COVID-19 which correspondingly has multisystemic outcomes; and so far is in itself linked with a health response of community that persuades a big deal of psychological suffering and an enhanced probability of alcohol abuse, activating a vicious cycle. The harmful effects of alcohol on the pulmonary system have been defined in various research projects Among them one is compromised mucociliary stairway mechanism because of less sensitive cilia which is an significant adjustment for the eradication of particulate material, mucus and infectious agents from the airways has been documented 31 . This is associated with an enhanced risk of pulmonary infections. An compromised function of pulmonary cilia has also been related to other pulmonary ailments for instance asthma, COPD, bronchiectasis, and pulmonary abscess 32 . In persistent alcoholics, defense mechanism of host against infectious diseases are undermine.
Tight epithelial junctions of broncho-alveoli, an significant constituent of the innate immunity against infectious agents, are interrupted 33 . Additionally, alcoholism has been made known to cause dysfunction in alveolar macrophages 34 . The threat of ARDS has been establish to be three to four times greater in alcoholics in contrast with the common population 32 . An significant antioxidant, glutathione, has been revealed to be reduced in the alcoholic's alveolar epithelial substance 35 . Reduction in alveolar glutathione is also a distinctive discovery in acute respiratory distress syndrome which is the principal reason of demise in COVID-19 17,35 . Effects on heart in alcoholics depend on the extent of use, dosage, and distinct particularities of alcohol 36 extensive dosage and prolonged use of alcohol have been associated with harmful consequences on the heart 36 . Diseases of cardiac muscles in alcoholic is distinguished by cardiomegaly because of hypertrophy in heart wall, expanded chambers of heart, and interstitial fibrosis; all of which come up with decreased capacity of contraction, cardiac failure, and unexpected death of heart 37 . Other negative effects of prolonged alcoholism on the heart comprises of dyslipidemia, hypertension, and cardiac arrhythmias 38 . Hepatic disease is an significant cause of alcohol-associated morbidity and fatality, because alcohol is principally processed by liver cells 39 . In contrast, the frequency of hepatic injury amid patients of COVID-19 varies from 14.8-53%, described by disturbed LFTs 16 .
The development process of SARS-CoV-2 contagion can be defined in 2 stages: in the 1st stage, an early inherent defense happens in an effort to give pulmonary defense. Subsequently by a resulting 2nd stage of inflammation-related tissue damage. In vulnerable people, SARS-CoV-2 infection can advance to acute viral pneumonia and can lead to acute respiratory distress syndrome (ARDS). Acute respiratory distress syndrome is a diffuse, critical, inflammatory pulmonary damage that frequently needs mechanical air circulation. In reaction to such a "storm of cytokine", unrestrained hyperinflammation can cause a failure in multiple organs. It is identified about how substantial consumption of alcohol might affect in infection of COVID-19.
Whereas <15% of drunk alcohol go into the lung, exhalation is nevertheless an important process for elimination of alcohol, as demonstrated by the common utilization of the Breathalyzer test to consistently evaluate levels of blood alcohol 40 . Excessive consumption of alcohol deeply alters inherent and adaptive immunity of lungs, leading to cause greatest degrees of viral pneumonia 41 , RSV infection 42,43 , influenza A infection 44 , and microbial pneumonia [45][46][47] . In 1918 Spanish flu pandemic, substantial consumption of alcohol was identified as a risk factor for deprived consequences 48  Since production of alcohol is illegal in Iran, it is characteristically acquired by means of the black market. As a minimum 180 individuals in Iran expired by consuming black market alcohol that was adulterated with methyl alcohol, with more than 2500 looking for medical care 55 . The misconception that alcohol averts infection of COVID-19 encouraged the WHO (World Health Organization, 2020) and the NIAAA (National Institute on Alcohol Abuse and Alcoholism, 2020) to announce that excessive consumption of alcohol does not prevent or cease COVID-19. However it has a harmful effects on innate immunity of lungs 56 . It has extensively been identified that alcohol damages the capability of the pulmonary system to combat infection Furthermore, alcohol is barely identified as harmful substance for the health of lungs in contrast with other organs for instance the liver generally by the public.

Conclusion
Alcohol negatively affects nearly each and every cell of the pulmonary system and a lot of these alterations strongly put those who consume alcohol in large quantity at greater risk of developing COVID-19, more severe acute respiratory distress syndrome and pneumonia. Further extensive research is required to assist in understanding how to better manage those who consume alcohol or are addicts of alcohol with COVID-19.