INTRODUCTION:

Coronaviruses (CoVs) belong to the Coronaviridae family, and usually cause mild acute respiratory illnesses or “common cold”. In December 2019, pneumonia cases of unknown etiology were reported in China. Within a few weeks, the cause of these cases appeared to be a novel coronavirus (CoV). This novel virus shares around 96% with bat-CoV RaTG13 and around 80% sequence similarity with the SARS-CoV. Hence, it was given the name SARS-CoV-2, and the disease it causes was called coronavirus infectious disease 2019, or shortly COVID-19 ¹.

Coronavirus can cause human respiratory tract infection or animal intestinal infection. The process of virus infection requires the participation of receptors on the surface of the host cell membrane. When an infected person coughs, droplets containing the virus spread out, the virus could infect the new person when droplets enter into their nose or mouth. When we breathe air flows through our mouth and nose, and down our airways and inclaster are air filled sacs. The air sacs are surrounded by tiny blood vessels. Oxygen from the lungs passes into the blood stream to get the tissues throughout our body, and carbodioxide is breathed out. Covid-19 is a disease caused by virus called SARS-CoV2 ².

The virus infects cells on your airways by attaching to ACE-2 and other molecules on themselves. The virus uses ACE-2 as a door to get inside of the cell and make more copies of the itself, the virus and our immune system reaction due at the inflammation, damages the air sacs, causing them discard and different or filled with fluid. These block some oxygen from passing of our lung into the blood stream. As blood oxygen levels falls make sure as you are breath. In some cases a ventilator or other support may be needed. Inflammation fights our body from infection, but in some people with the Covid-19, it seems to go into our drive³.

Treatment of Covid-19:-

The most common symptoms of Covid-19 are a fever, coughing, and breathing problems. Unless if the symptoms are mild you can most likely treat at home the way you would for cold or flu. At home corona virus treatment is:- If your symptoms are mild enough that you can recover at home you should:- Rest, stay home, Drink fluids, Monitor, Ask your doctor about over-the-counter medicines that may help, like acetaminophen to lower your fever. The important thing is to avoid infect other people, especially those who are over 65, who have other health problems.

If your case is severe, members of medical staff will check signs that the illness is causing more serious problem. They might:- Check the levels of oxygen in your blood with a clip on finger monitor, putting a 6-inch cotton swab up both sides of your nose for about 15 seconds. Give you a chest x-ray or CT-scans. In very serious cases, doctors will connect you to a machine that can breathe for you called a ventilator. You may also get fluids through a tube or IV in your arm to keep you from getting dehydrated.

Doctors may give you a antiviral medicine called remdesivir. Remdesivir is the first drug approved by the FDA for treatment of hospitalized Covid patient over the age of 12. Doctors might also give medication to thin your blood and prevent clots. Clinical trials are under way for other medicatios, including tocilizumab, which has been used to treat autoimmune conditions and an inflammatory condition called cytokine release syndrome. The FDA has resclinded its emergency authorization for the use of hydroxychloroquine or chloroquine to treat people who are hospitalized with Covid-19 amid serious concerns about their safety and how well they worked against the virus. Dexamethasone, a common steroid medication, can help people who are hospitalized with severe Covid-19 complications⁴.

Comorbidities:-

Diabetes with Covid-19:-

People with diabetes are inclined to get infections due to impaired phagocytic cell capabilities. Further, several other factors increase the risk of COVID-19 in diabetic patients. An elevated level of ACE-2 receptors found to be causally related to diabetes by Mendelian randomization analysis; this might prejudice people with diabetes to SARS-CoV-2 infection. Furin is a type 1 membrane-bound protease expressed in high levels in diabetic patients. This proprotein convertase involved in the entry of the virus inside the host cell by decreasing the SARS-CoV-2 dependency on human proteases.

The SARS-CoV-2 spike (S) protein attach to the ACE-2 receptors is activated by the enormous furin levels. This pre-activation of S protein allows the viral entry into the cell and escapes from the human immune system. Hence, a dysregulated immune response with increased ACE-2 receptors and furin expression may lead to a higher lung inflammation rate and lower insulin levels. The convenient entry of virus leads to a life-threatening situation for diabetic patients⁵.

COPD with Covid-19:-

COVID-19 illness can lead to the development of hypoxemia in 15–20% of the patients, which require ventilator support in adverse conditions. The transition in the inflammatory response, microbiome imbalance, weak immunity, continual mucus production, use of respiratory corticosteroids, and structural damages are involved in establishing COPD. COPD and other chronic disorders were also associated with SARS (1.4%) and MERS (13%) infections.[20] Although earlier studies did not report a high number of COVID-19 cases with COPD, the expression of ACE-2 receptors is increased in this disease, contributing to the establishment of severe symptoms among COVID-19 individuals, including structural damage to lungs, weak immunity and hyper mucous production. COPD observed in 50–52.3% of the total ICU admitted COVID-19 cases, lead to high mortality among these patients with increased mucous production and blockage of air passages⁶.

COPD with Covid-19:-

Although earlier studies did not report a high number of COVID-19 cases with COPD, the expression of ACE-2 receptors is increased in this disease, contributing to the establishment of severe symptoms among COVID-19 individuals, including structural damage to lungs, weak immunity and hyper mucous production. COPD observed in 50–52.3% of the total ICU admitted COVID-19 cases, lead to high mortality among these patients with increased mucous production and blockage of air passages⁷

Liver disease and Covid-19:-

Liver injuries and abnormal liver biochemistry were reported in SARS, MERS, and now in COVID-19 infections. It implies that there is a relationship between abnormal liver enzyme secretion and coronavirus infection. ACE-2 receptors present on liver cells mediate the entry of SARS-CoV-2 inside the liver cells. Among the COVID-19 cases, 43.4% found with the abnormal secretion of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH). However, no patient observed with the characteristic intrahepatic cholestasis or hepatic failure. Another study reported that 39.1% of COVID-19 patients’ exhibit elevated ALT and AST levels, and 6% have increased bilirubin levels.

Around 29% of the COVID-19 patients demonstrate liver injury and develop severe complications during later stages of infections. Besides abnormal liver function tests in COVID-19, elevated enzymes may also be released from cardiac and body muscles. The changes in blood chemistry usually return to normal without significant hepatic morbidity. The liver damage is presented as a temporarily raised level of ALT and AST without hepatic failure in most of the patients; however, this could be detrimental in severe cases of COVID-19. Psychological stress, systemic inflammatory response, drug toxicity, and preceding hepatic diseases could be the underlying mechanisms of liver damage in SARS-CoV-2 infection. Currently, it is not evident that the SARS-CoV-2 is associated with hepatocellular damage or intrahepatic cholestasis pathophysiology⁸.

Asthma and Covid-19:-

It is known for almost 18 years that asthmatic people are more prone to develop viral infections. If left uncontrolled, these viral infections can develop severe symptoms. People with asthma have a delayed innate antiviral immune response and impaired secretion of IFN-λ, which makes people more susceptible to develop severe complications. Asthma, along with other pulmonary chronic diseases, were associated with SARS (1.4%) and MERS (13%), which induced severe symptoms.

Based on history, it is assumed that asthma could be among a potent risk factor of COVID-19; however, we did not find any specific evidence of SARS-CoV-2 in asthmatic patients. A comparative analysis of critical and non-critical COVID-19 patients in Wuhan revealed no significant association of SARS-CoV-2 with asthma and other self-reported allergies, such as food allergy, atopic dermatitis, and allergic rhinitis. However, the risk of developing severe disease in COVID-19 patients is associated with asthmatic smokers, particularly geriatric individuals. Though asthma is not directly associated with COVID-19 infections, people with other complications and respiratory diseases are more likely to become entangled during asthma⁹.

HIV and Covid-19:-

A strain of CoV OC43 was isolated from HIV positive patients in 2003, and COVs have a firm history in HIV patients. People suffering from HIV infection have a high risk of developing COVID-19 disease because of the compromised immune system. After the first report of HIV affected patient positive for SARS-CoV-2, it was presumed that HIV infection is vulnerable comorbidity with COVID-19 infection. However, no significant correlation observed between HIV positive individuals having COVID-19 infections.

As the outbreak expands, few more cases of COVID-19 were reported in HIV patients; nevertheless, all patients had mild disease without ICU admissions. There is no correlation between HIV and COVID-19 was observed in Thailand, which is one of the most HIV affected areas. Formerly, it was also speculated that antiretroviral drugs have potent activity against SARS-CoV-2, which could be a reason behind fewer cases of SARS-CoV-2 in HIV patients ¹⁰.

Adverse Drug Reactions:-

The most common adverse events related to lopinavir/ ritonavir are gastrointestinal adverse effects such as diarrhoea, nausea, and vomiting. But other serious adverse reactions such as AKI, respiratory failure, or secondary infection were not observed in patients treated with lopinavir/ritonavir ¹¹.

Corticosteroids could induce psychiatric adverse reactions. Corticosteroid-induced psychosis mostly occurs as a dose dependent adverse effect but idiosyncratic psychotic reactions were also observed. Since acute psychotic features might occur in older patients who have had a stroke¹². Corticosteroid consumption could induce mood changes such as anxiety, agitation, and depression. Generalized anxiety disorder, agitation, and depression are common post-stroke complications ¹³.

Hydroxycholoroquine consumption may resulted into cardiac toxicity varied between trials: RECOVERY defined the outcome as new major arrhythmias (supraventricular tachycardia, ventricular tachycardia or fibrillation or atrioventricular block requiring intervention), two studies as new arrhythmias and one study as new arrhythmias or cardiac arrest. The remaining studies did not provide details about cardiac toxicity definition. Hydroxychloroquine probably increases the risk of diarrhoea when compared to standard care or placebo. The certainty of the evidence was moderate because of imprecision as the optimal information size (OIS) was not met¹⁴.

Remdesivir may have little or no effect on acute kidney injury when compared to placebo. The certainty of the evidence was low because of serious imprecision and serious indirectness (studies used change in serum creatinine rather than patient-important measures of acute kidney injury like renal replacement therapy requirement)^15-17.

Tocilizumab might cause vascular disorders such as hypertension. Also, it could induce nervous system disorders such as headache, demyelinating disorders, leukoencephalopathy with cognitive impairment, and peripheral neuropathy. A serious adverse effect reported with tocilizumab is increasing the risk of fungal and bacterial infections which should be considered in Covid-19 patients ^18-20.

CONCLUSION: -

Covid-19 is the viral disease, so it can spread through the contamination and contacting with each other, in human being. SARS-CoV-2 infection may induce a wide spectrum of illnesses, with patient conditions range from being asymptomatic to severely ill. Indeed, various clinical symptoms with multi-organ involvement related to COVID-19 infection have been reported.

Comorbidities are normally occurred in a people above the age of 35 years, according to that the treatment has been given to the patients and the Adverse drug reactions of that treatment or medications has been reported qualitatively and quantitatively. A huge amounts of clinical trials and investigations have been done in various countries and are going on too with the multiple developments.

The actual 99-100% effective vaccine has not been developed till yet, further research study still going on specially in different age group people, lactating or pregnant women, comorbid patients, etc. ‘In case of comorbid patients, if the patient is in severe condition like the hypertension, having the heart attack or heart pumping is lower or patient having the immunocompromise condition means having the chemotherapy or having a kidney failure then death adversely affects the Covid-19 infections’.

REFERENCES: -

1. Gl J Med. 2020 May 22; NEJMo a 20 203-212 https://www.narayanahealth.org/blog/how-comorbidiities-impacts-coronavirus/

2. Wang, H. et al. SARS coronavirus entry into host cell through a novel clathrin and caveolae- independent endocytic pathway. Cell Res. 18, 290-301 (2008).

3. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069. doi: 10.1001/jama.2020.1585.

4. Web MD Medical Reference Reviewed by Branilda Nazaria, MD on January 26, 2021.

5. Fernandez C., Rysa J., Almgren P., Nilsson J., Engstrom G., Orho-Melander M. Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality. J Intern Med. 2018;284(4):377–387. doi: 10.1111/joim.12783

6. Yin Y., Wunderink R.G. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018;23(2):130–137. doi: 10.1111/resp.13196.

7. Fang L., Karakiulakis G., Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8(4):e21. doi: 10.1016/s2213-2600(20)30116-8.

8. Uhlen M., Fagerberg L., Hallstrom B.M., Lindskog C., Oksvold P., Mardinoglu A. Tissue-based map of the human proteome. Science. 2015;347(6220) 514-523 doi: 10.1126/s

9. Contoli M., Message S.D., Laza S.V., Edwards M.R., Wark P.A., Bartlett N.W. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12(9):1023–1026. doi: 10.1038/nm1462.

10. Pene F., Merlat A., Vabret A., Rozenberg F., Buzyn A., Dreyfus F. Coronavirus 229E-related pneumonia in immunocompromised patients. Clin Infect Dis. 2003;37(7):929–932. doi: 10.1086/377612.

11. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382 (19):1787–1799. doi:10.1056/NEJMoa2001282 57.

12. Campbell R, Tycon L, Pruskowski J. Corticosteroid-Induced Psychiatric Symptoms# 323. J Palliat Med. 2017;20(3):298–299. doi:10.1089/jpm.2016.0475

13. Ou G, Bressler B, Galorport C, et al. Rate of corticosteroid-induced mood changes in patients with inflammatory bowel disease: A prospective study. J Can Assoc Gastroenterol. 2018;1(3):99–106. doi:10.1093/jcag/gwy023

14. Jun C, Liu D, Li L, et al. A preliminary study of hydroxychloroquine sulfate in patients with common 2019 coronavirus disease (COVID-19). Journal of Zhejiang University 2019; 49:215-226

15. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19-Final Report. 416-427 N En

16. Koryürek ÖM, Kalkan G. Tocilizumab: a new alternative therapy in dermatology. 912-933 Immunomodulatory Immunosuppressive Drugs Dermatol.

17. Rohane S.H., Makwana A. G., 2017. A Review on Hydrazone, the fascinating field of investigational in medicinal chemistry. Asian J Res. Chem. 10,417-30.

18. Rohane S. H., Makwana A. G., 2019. In silico study for the prediction of multiple pharmacological activities of novel hydrazone derivatives. Ind J. Chem. Sec-B. 58, 387-402.

19. Rohane S. H., Makwana A. G., 2020. Synthesis and in vitro antimycobacterial potential of novel hydrazones of eugenol. Arab J. Chem. 13, 4495-4504.

20. Rohane S. H., Aware D. V., 2021. A Role of Herbal Drug as an Immunity Booster during Covid-19 Pandemic. AJPRes. 11(3), 206-211.

Received on 11.08.2021 Modified on 03.09.2021

Asian J. Research Chem. 2021; 14(6):451-454.

DOI: 10.52711/0974-4150.2021.00079