Demystifying COVID-19: Understanding the Disease, Its Diagnosis. and Treatment

Ozgur Karcioglu, Selman Yeniocak, Mandana Hosseinzadeh

• Publisher: Bentham Science Publishers
• Year: 2021
• Print ISBN: 9781681087795
• eBook ISBN: 9781681087788
• Topic: Medicine
• Subtopic: Infectious Diseases

The management of COVID-19 is challenging due to the lack of clear information about the Sars-Cov2 and recommendations for specific treatment regimens. The scale of the pandemic has also exacerbated the situation, with health care systems under stress from the high volume of COVID-19 patients.In Demystifying COVID-19: Understanding the Disease, Its Diagnosis, and Treatment, medical experts explain many aspects about the COVID-19 pandemic, including guidelines to minimize risk of infection, diagnostic methods, treatment, real scenarios in the course of the disease and issues that need attention in specific patient groups. The book equips both general readers and healthcare professionals with key information required to understand COVID-19 and navigate a situation typical to a pandemic. Public health officials who wish to mobilize awareness campaigns for the benefit of the general public can also find value in the comprehensive information presented in this reference. Key Features: - 16 chapters covering several aspects of COVID-19 including risk management, clinical diagnosis and treatment, public health issues and vaccines- Unique Q&A format which presents easy-to-understand information for all types of readers- Presents basic clinical information- Provides information for the management of COVID-19 in special patients (patients with comorbidities, the elderly, newborns, children, and pregnant women)- Bibliographic References for further reading

Principles of Treatment

Ozgur KARCIOGLU

Abstract

It is well established that there is no ‘standard’ protocol for the treatment of COVID-19. The use of certain antiviral agents and antibiotics such as azithromycin has been concluded to be beneficial, and therefore, their use has been recommended. Namely, remdesivir and favipiravir may be the best potential antiviral drugs for the treatment of COVID-19. However, treatments should be tailored for every given patient in regard to the signs and symptoms, the severity of the disease, age and comorbid diseases, organ failures, phase of the disease, pregnancy status, and possible drug interactions.

The use of NSAIDs as an antipyretic, analgesic, and anti-inflammatory agents appears to be indicated in viral infections such as COVID-19, also during pandemic periods. There is no evidence to support NSAIDs not to be used in COVID-19 infections due to their side effects. NSAIDs are used after paracetamol, if necessary, to manage the symptoms of COVID-19.

Although it has been postulated that deficiencies of certain vitamins and minerals (e.g., vitamins C and D), multi-center, community-based, well-designed studies are necessary to clarify their relationship with COVID-19, especially before recommending them for treatment.

In brief, treatments should be individualized, and evidence-based principles must be followed.

Keywords: Antibiotics, Antivirals, COVID-19, NSAID, Pandemic, Treatment, Vitamin C, Vitamin D.

Antivirals

The sooner antiviral agents are started in the treatment of COVID-19, the more effective the treatment of the disease can be anticipated. Delayed antiviral therapy has previously been declared as an independent risk factor for long-term viral spread and detection of viruses and is also associated with grave outcomes (Wang et al, , 2018).

There is no established ‘standard’ protocol for the treatment of COVID-19. The use of certain antiviral agents has been concluded to be beneficial , and therefore,

their use has been recommended (Fig. 1). However, it is not recommended to use three or more antiviral drugs simultaneously (Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia. Trial Version 7).

Fig. (1))
The mechanism of action of favipiravir (T-705) against the virus. Favipiravir is incorporated into cells and transformed by host cells into favipiravir ibofuranosyl - 5 ′ - triphosphate (favipiravir - RTP). The triphosphate form, favipiravir-RTP, inhibits the activity of RNA-dependent RNA polymerase (RdRp) of RNA viruses. AO: Aldehyde oxidase; RMP: Ribosyl monophosphate

Antiviral agents that can be used in the management of COVID-19 were listed in Table 1.

Table 1 Antiviral Agents That Can Be Used in The Management of Covid-19.

I. Nucleotide Analogues
Favipiravir
Ribavirin
Remdesivir
Nafamostat
Nitazoxanide
Valipiravir
II. Neuraminidase inhibitors
Oseltamivir
Zanamivir
Peramivir
III. Lopinavir/ Ritonavir (Kaletra ® )
IV. Umifenovir (Arbidol ®)

Nucleotide Analogues (NA)

NA have different mechanisms of action, including lethal mutagenesis, specific or non-specific chain termination, and inhibition of nucleotide biosynthesis (Arabi et al, , 2018). Although some treatment options awaiting validation have been reported in the treatment of COVID-19, including various broad-spectrum antivirals such as valipiravir and remdesivir, there are currently no specific antiviral drugs that have been identified (Beigel et al, 2019; Li et al, 2020).

1. Favipiravir

Favipiravir (FPV) is an antiviral agent derived from pyrazine carboxamide 6-Fluoro-3-hydroxy-pyrazine-2-carboxamide. It acts by transforming favipiravir into ibofuranosyl-5′-triphosphate (T - 705 - RTP), which is its active metabolite by being ribosylated and phosphorylated in the cell (Furuta et al, 2017). T - 705 - RTP competes with purine nucleosides and interferes with viral replication by being incorporated into the viral RNA. Thus potentially inhibiting RNA-dependent RNA polymerase (RdRp) of RNA viruses (Fig. 1, Furuta et al, , 2005).

It is administered in COVID-19 with the thought that it shortens the time for relief of symptoms. It stops viral replication by inhibiting RNA polymerase on CoV (Mifsud et al, 2019; Wang et al, 2020). In a study conducted in China on its effectiveness in COVID-19 treatment, it was concluded that FPV is useful. FPV is administered 1600 mg twice a day on the first day and 600 mg in 2nd-14^th day. LPV / RTV was orally at 400/100 mg twice a day. Additionally, all participants received standard care. In this study, patients treated with FPV were reported to have faster viral clearance and better radiological recovery than patients treated with LPV / RTV. Diarrhea (5.71%) and liver-kidney damage (2.86%) were seen as side effects (Cai et al, 2020).

FPV is 54% bound to plasma proteins. The elimination half-life is about 2 to 5.5 hours, and the bioavailability rate is 97.6%. The mean Cmax is 51.5 µg / mL, the main volume of distribution is 15-20 L, and its metabolites are excreted by the kidneys. Use of FPV in patients with moderate renal impairment (GFR 30-60 ml / min) causes a 1.5-fold increase in Cmin compared to patients with normal renal

function; however, there is no data regarding its use in patients with GFR <30 mL / min (Joshi et al, 2020).

Posology

a) Treatment Dose:

1800 mg twice daily on day 1, followed by 600-800 mg twice daily for up to 14 days in mild to moderate COVID-19.

b) Prophylaxis: 1600 mg orally twice a day on day 1, then 2-25. 600-800 mg twice a day (NCT04448119) every day.

In order to determine the potential use and reliability of FPV and other antivirals in COVID-19, literature data evaluating the use of FPV in various databases were searched (Pilkington et al, 2020). Within the scope of this study, the data of 29 studies and 4299 patients and the side effects were examined The incidence of the compared side effects is shown in Table 2 below.

Table 2 Incidences of side effects (SE) attributed to oseltamivir, umifenovir, lopinavir / ritonavir and FPV.

-	FPV SE	Oseltamivir, Umifenovir, Lopinavir/Ritonavir SE
Grade 1-4 SE	28,2%	28,4%
SE that necessitates discontinuation of the drug	1,1%	1,2%
Serious SE	0,4%	0,4%
Gastrointestinal SE	8,7%	11,5%
Hyperuricemia	5,8%	1,3%

According to this study, it was concluded that FPV shows a favorable safety profile for total and serious side effects, and is safe and tolerable in short-term use.

In a study where 1798 articles were compiled to analyze the efficacy and safety of FPV in the treatment of COVID-19, the group who received FPV + standard care treatment, the control group who received other antivirals + standard care + supportive care (respiratory support, antibiotics, immunomodulators, and some herbal medicines) compared (Shrestha et al, , 2020). In this study, clinical recovery following treatment with FVP in COVID-19 patients, the time when RT-PCR turned negative after treatment, side effects during treatment, O₂ and mechanical ventilation requireme...

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• Contagion of the Pandemics: The Situation in the World
• How Can a Country Defeat COVID-19? Value of R0, Rt and Re
• Comorbid Diseases and COVID-19: COPD, Smoking, Obesity, Diabetes, Cancer, and Kidney Failure
• Risks and Losses of Healthcare Workers in the Pandemic Era
• What Kind of Disease is this? Signs and Symptoms, Predictors of Clinical Course and Management
• Diagnosis of COVID-19: Which Tests To Do? Laboratory and Radiological Adjuncts To Recognition
• Cardiovascular Disease, Myocarditis, Infarctions, And COVID-19
• Gastrointestinal Signs and Symptoms in the Course of COVID-19
• Is Our Psychology Affected By the Pandemic? How?
• COVID-19 and Our Brain: What's New?
• COVID-19 Pneumonia and ARDS: The Real Killer?
• Pregnancy, COVID-19, and Children: Dangerous Trio?
• COVID-19 and The Elderly: Is It Different From The Young?
• Principles of Treatment
• Critical Care in COVID-19
• Principles of Vaccination: Will it be the Definitive Solution?