Current Pharmaco-therapeutic Approach on COVID-19 Admitted Patients in a Corona-dedicated Hospital in Khulna

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Introduction
Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Global Public Health Emergency.It began in Wuhan, China, in December 2019, and has now spread worldwide and declared as a global pandemic. 1,2ortality rates of Coronavirus Disease 2019 (COVID- 19) have been estimated to be 5-27% 2,3 which is more prevalent in vulnerable populations, including children, older people, pregnant women & patients with existing co-morbidities like DM, HTN, IHD, CVD, Asthma, etc. [1][2][3][4][5][6][7] No specific pharmacological treatment or vaccine has been invented against SARS-CoV-2 to save the people they cannot be approved to ensure a rapid and effective cure.WHO has given general guidelines for symptomatic management of COVID-19. 1,2,11,12he treatment may vary across countries.As such, the treatment of patients varies based on disease severity and consideration of underlying medical conditions. 2,13COVID-19 may range from asymptomatic and mild illness to severe illness.Bangladesh govt.has been established a national guideline for the management of COVID-19 published on 5th November 2020 where the six syndromes of COVID-19 have been categorized into mild, moderate, severe, and critical cases.Mild cases represent Influenza-like illness (ILI), moderate with pneumonia (CRB 65 score 0), patients with severe pneumonia, sepsis, and with ARDS, septic shock developed in those, considered as critical cases. 14Treatment guidelines are plotted below: 14 According to the guidelines symptomatic patients in risk groups (like DM, HTN, IHD, Prior Asthma/COPD/ILD patients, Known CKD, CLD, Known Malignancy, High-risk pregnancy, Obesity (BMI>25)) should be admitted in isolation ward and will be treated as follows: • Tab Paracetamol (500mg) In this study, we assessed pharmacological agents relevant to COVID-19-specific medications including remdesivir 15,16 , favipiravir 17 , systemic corticosteroids 2,18 , tocilizumab 19,20 and agents that may be used for supportive care in patients with COVID-19 including statins 21  other specific viruses 22 , anticoagulants 23,24 , inhalers/nebulizers 25 , proton pump inhibitors. 2 However, these drugs are employed due to their proven efficacy either individually or in combination, according to their national healthcare guidelines, though there is no specific drug available to treat the contagion. 9We aimed to explore the current therapeutic approaches in the treatment of COVID-19 in the inpatient settings.

Materials and methods
After

Results
Among all the recruited patients in the study group, male 170 (56.66%) were more affected than female 130 (43.33%).The majority of the participants were aged between 38 to 57 years (42.66%)followed by more than 57 years (35%) with fewer individuals in other age groups.Among the admitted patients majorities 205m(68.33%)have co-morbidities in which diabetes was the most common 67 (32.68%) and second most common was hypertension 51 (24.87%) followed by other comorbidities.Only 53 patients (17.66%) were vaccinated whereas maximum patients 247 (82.33%) were not vaccinated.All these demographic features are shown in Table 01.

Table 01: Demographic characteristics of the population
Out of 300 admitted patients in the hospital, 95 patients were treated as a mild case (31.66%), 142 patients as moderate (47.33%), 55 patients as severe(18.33%),and only 8 patients were admitted as critical case (2.66%) which is showed in Figure 01.Salbutamol & ipratropium bromide combination are used in the form of nebulization in all severe and critical patients.Each patient also received various supportive drugs with different percentages like bronchodilators, antihistamines, leukotriene receptor blockers, antiulcerants, paracetamol, anxiolytics, antiemetics, cough suppressants, immunity boosters like vitamin D, vitamin C, and zinc along with these drugs.Some other studies also revealed that remdesivir could be a promising antiviral and may be more widely available in the upcoming weeks. 2,8,11,13,15,16,29But it is varying with other studies where lopinavir/ritonavir was the preferred antiviral. 12,27,30Some studies showed that other antivirals like darunavir/ cobicistat, ribavirin, favipiravir, umifenovir, oseltamivir can play an important role in the treatment of COVID-19. 4,9,12,13,22,27,30few patients (severe &critical cases) received tocilizumab (9.52%) as monoclonal antibody, IL-6 receptor antagonist, which is FDA-approved to treat cytokine release syndrome.It may have a beneficial role in severe and life-threatening illness.13,11,19,20,30 In China a study done by Xu X. et al. reported that most of the patients who received only one dose of tocilizumab, 400mg was associated with clinical improvement and successful discharge.31 Almost all patients received steroids in different dosage forms.Budesonide, dexamethasone, methylprednisolone, and hydrocortisone are commonly used steroids using varying percentages in different categories of patients.Another study showed the uses of steroids in varying percentages.11 The WHO currently recommends against the routine use of corticosteroids in the treatment of patients with COVID-19, due to the potential for delayed viral clearance and other adverse effects such as avascular necrosis and psychosis.13 Almost all the admitted patients received antibiotics. Many of them gt more than one antibiotic.The consumption rate of moxifloxacin was more than other antibiotics.All the moderate, severe &critical cases received moxifloxacin (100%).Meropenem (100% in severe &critical cases) was the second most common antibiotic used followed by amoxicillin-clavulanic acid, and ceftriaxone.Some antibiotics used in the lowest percentage like piperacillin-tazobactam combination, ceftazidime, linezolid, etc.Some other clinical studies done by Hendaus M. A. et al., Chen T.et al., and Huang C. et al have shown positive therapeutic outcomes of antibiotic therapy.[32][33][34] Huang C. et al showed cephalosporins, carbapenems, and quinolones are good initial choices for COVID-19 patients.34 In our study, among 300 patients, all the moderate, severe & critical and mild cases with co-morbidity patients received LMWH and enoxaparin.To validate this finding, more forward-looking experiments are required.
Almost all the patients received bronchodilator agents.Among them, salbutamol & ipratropium bromide combination in nebulization form was broadly used (100% in moderate, severe & critical and 52.63% in mild cases).Secondly, methylxanthine derivatives doxophylline were also frequently used drugs.Patients got salmeterol & fluticasone combination and salbutamol in inhaler form in different percentages.Some other studies done by Lin K. J. et al. & Ari A. also found that bronchodilators may have a beneficial role in patients with different clinical categories of COVID-19. 2,25sides these drugs, physicians also prescribed antihistamines; fexofenadin, leukotriene receptor blocker; montelukast, antiulcerants;(omeprazole, esomeprazole), immunity booster agents like vitamin D and zinc along with these drugs with varying percentages.Some other symptomatic drugs include paracetamol, anxiolytics, antiemetics, cough suppressants (butamirate citrate, acetylcysteine, dextromethorphan), and pirfenidone with few percentages.A similar finding was found in another study conducted by Perveen R.A. et al. 8 Additionally some purposeful drugs like antidiabetic, antihypertensive, anti-asthmatic, antianginal, etc. were prescribed in patients with co-existing diseases.

Limitations & recommendations
Due to time constrain, there was evidence of inappropriate subgroup analysis like adults and children, different formulations, dosages and duration of drugs, etc.Furthermore, the study is needed to provide up-to-date insight into the current therapeutic approaches according to guidelines for the management of COVID-19 patients.

Conclusion
We concluded our study by addressing the pharmaco-therapeutic approaches where antiviral, LMWH, broad-spectrum antibiotic, corticosteroid and other symptomatic drugs were the mainstream treatment for different clinical categories of admitted COVID-19 patients.

Figure 01 :
Figure 01: Categories of the patient based on severity

Figure 02 :
Figure 02: Oxygen therapy in different categories of COVID patients , anti-infective agents like anti-biotics, anti-fungal and anti-viral drug for

Table 02
. Antivirals, monoclonal antibodies, steroids, antibiotics, and low molecular weight heparin were used mainly in critical, severe and some moderate cases.Mild cases with co-morbidities are also included under these supportive drugs.All categories were prescribed according to our national guidelines.Among antivirals, all the critical cases (100%) and 95.77% of moderate cases received remdesivir, whereas 4.(36.84% in mild cases, 88% in moderate cases, and 79.36% in severe & critical cases), was used in the highest percentages in all categories.Budesonide (90% in mild cases and 100% in severe & critical cases) was used commonly in the form of nebulization.Patients received

Table 02 : List of Drugs for supportive therapy in COVID-19 [
N.B: In most cases, the patient received more than one drug of the same group.So percentages were more than a hundred.]