Inclusive Review on Existing Treatment and Management Modalities for COVID-19

Abstract

COVID 19 is widely regarded as one of the worst pandemics of the twenty-first century. The World Health Organization (WHO) named the viral infection caused by the new coronavirus (COVID-19), which was first reported in December 2019, as severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV2), and it became a cause of death for many all over the world. As a result, a unique inquiry and clinical trial to find a solution for this catastrophic pandemic disease is under way. To manage and eradicate the disease, effective vaccinations and antiviral therapies are urgently needed. There were no treatments or vaccines available for this fatal virus at first, but several medications that are used to treat other diseases are now being used to treat Covid19. Remdesivir has been licenced for therapy since it has shown to shorten hospital stays. Corticosteroids reduced mortality in patients requiring oxygen supplementation or mechanical ventilation. The purpose of this review is to make readers aware of the possible efficacy and availability treatment for this viral infection.

1. Introduction

Covid-19 which is also known as novel coronavirus pneumonia firstly encountered in Wuhan, China in December 2019. The WHO Emergency committee declared a global health emergency on 30 January 2020 based on the growing case rates of covid-19 at Chinese and international locations [1]. This virus spread was so rapid that after 2 weeks from the first case diagnosed, 1000 patients were tested positive and the number of positive cases reached over 30,000 and 2500 deaths by 18, March 2020 [2].

The rate at which transmission of nCoV19 among the human is increasing than SARS CoV1 and MERS CoV, one of the group of international committee on taxonomy of virus (ICTV) named as coronaviridae study group (CSG) renamed as SARS CoV2, while WHO named as Coronavirus disease 2019 (COVID-19) [3]. Structurally SARS CoV2 contains single strand RNA [4] of which two third part of RNA is located in open reading frame (ORF) which include polyproteins and non-structural protein for viral cycle [3]. There are other structural protein which are encoded by ORF’s like spike glycoprotein (S), enveloped protein (E), matrix protein (M) and nucleocapsid protein (N). S protein of virus attached to host cell’s receptor is present on the angiotensin converting enzyme 2 (ACE2) [5] from which SARS CoV2 passes through the mucous membrane of respiratory tract from which it enter to lungs then to systemic circulation through which it could target organ such as heart, brain, renal, lungs, GIT [3]. Then after entering into the cell, it gets replicated using protein such as chymotrypsin(proteases) and RNA polymerase.

The number of COVID-19 cases in second wave was much higher than the first wave of COVID-19. There were several factors responsible for the same. There are some clear distinctions between the first and second waves which are shown in Table 1. Paediatric and younger people, as well as older people, got infected in the second wave. COVID 2nd wave symptoms were extremely varied [6].

	First wave	Second wave
Causative organism	SARS-Cov-2 virus	Various mutants of SARS-Cov-2 virus
Knowledge about the disease	Less	More knowledge
Symptomatology	Mostly related to respiratory system	New symptoms like Gastrointestinal etc.
Presentation	More severe	Less intense
Shortness of breath	Fewer cases with breathlessness	Much more cases with breathlessness
Age profile of the patients	Elder patients widely affected	Effect seen more in younger patients
Comorbidities	Patients with comorbidities affected more	Less
Drug availability	Acute shortage and black marketing	Available in the hospitals and pharmacies
Health care workers	They were lesser trained, not vaccinated and afraid of acquiring infection	More trained increased Lesser fear to acquire infection Mostly vaccinated
Bed capacity	Limited	Enhanced
Ventilator beds	Less than 25,000	Increased to more than 50,000
Laboratory testing	Only one laboratory in January 2020	More laboratories in Private and Government center
PPE	Scarcity	Plenty 1 million PPE produced
Vaccine	Not available	Approved vaccines available
Treatment affordability	Increased test price Increased treatment cost and PPE	Markedly reduced test price Reduced treatment cost and PPE
Oxygen requirement to the patient	Less	More
Requirement of mechanical ventilation	Less	More
Disease Spread	Slower	Much faster
Plasma Therapy	Limited	Much more
Death rate	Higher	Lower
Positivity rate	Lower	Much higher

Table 1.

Differences between the first and the second wave of COVID-19 in India.

From an Indian standpoint, things moved slowly initially, with the first cases showing in February 2020. The lockdown had its drawbacks, in that it controlled the disease to a certain level in the hopes of a few treatments fighting against the virus. Hydroxychloroquine, azithromycin, favipiravir, an antiviral, and ivermectin, an anthelminthic, were being used during the start of the pandemic in India [7].

The majority of COVID-19 patients had mild-to-moderate symptoms and were treated by qualified clinicians outside of the hospital. In India, a typical COVID-19 prescription contains azithromycin, doxycycline, ivermectin, hydroxychloroquine, vitamin C, vitamin D, zinc, acetylcysteine, and budesonide inhalation or dexamethasone [8].

Despite not being indicated for COVID-19 by any major standards, the antiviral favipiravir became India’s best-selling medicine in April 2021. Despite the advice of most international expert panels, anticoagulants like rivaroxaban were prescribed in outpatient settings, even for patients with no elevated thrombotic risk. Antibiotics with a broad spectrum of action are introduced under the pretence of treating secondary infections [8].

There has never been a poly-prescription of the mentioned medications previously. It’s unclear how these pharmaceuticals interact with one another (or with medications administered for pre-existing problems). It becomes difficult to tell whether a new symptom is caused by COVID-19 progression, an adverse drug reaction, or a new consequence [8].

Due to structural similarities of SARS CoV2 to HIV, Hepatitis B, C the drugs used for the treatment of Hepatitis C virus [4] i.e. remdesivir is also used in SARS CoV2 as antiviral agents. Hence nucleoside analogues HIV proteases inhibitors (also RNA Polymerase) may be useful in COVID 19. On the other hand the second antiviral drug used in COVID treatment is FAVIPIRAVIR which is a purine based analogue [9] and RNA dependent RNA polymerase (RdRp) inhibitors which will inhibit RdRp for transcription and replication of viral genomes [3]. An another purine nucleoside analogue ribavirin, inhibits the activity of enzyme IMPDH [9] (Inosine-5-monophosphate dehydrogenase) which leads to the suppression of the cellular DNA and mRNA which lead to suppression of protein synthesis, due to deceased level of the intracellular guanosine triphosphate pool.

Apart from this other two methods were also used for hindering the replication which included immune modulation where convalescent plasma therapy was used [10] and viral entry inhibition which was achieved by drug hydroxychloroquine (HCQ) [9]. Hydroxychloroquine and chloroquine which are anti-malarial agents with anti-inflammatory activities, can produce immune modulatory effect too, therefore a useful option for COVID 19 management. HCQ is known to demonstrate high potency inhibition of SARS CoV 2 virus in invitro studies. Besides this, corticosteroids also showed a tendency to reduce or prevent the systemic inflammation seen in COVID 19 patients [9]. Additionally many other drugs have also been selected for managing COVID 19 infection like Azithromycin (as antibiotics) lopinavir-ritonavir, interferon (antiviral drugs) multivitamins (vitamin D, vitamin C, and zinc) [3, 4, 9]. The supportive treatments included non-pharmacological approaches.

The C reactive protein and serum albumin have shown independent prognostic marker along with the age, maximum body temperature, smoking status and respiratory failure [11]. The immune response of the patients is weakened by inadequate nutrition. This shows that the nutritional derangements should be systematically managed in patients suffering from coronavirus. Besides giving the medicines or drugs when the patient’s body is not responding to medications the other therapy used was convalescent plasma therapy where the plasma from recovered patients was ejected out and given to the infected one [12]. Vaccination helped to improve the immune system of individuals [13].

The review emphasis on the comprehensive overview on various treatment modalities available for the management of Covid-19.

2. Drug treatment options available for Covid-19 treatment and management

2.1 Drug treatment for Mild to moderate Covid-19 infection

2.1.1 Molnupiravir

Molnupiravir is an orally accessible prodrug of the nucleoside analogue -D-N4-hydroxycytidine and is a broad-spectrum antiviral (NHC). In replicating coronaviruses, molnupiravir or NHC can promote G to A and C to U transition mutations [14].

Mechanism of action: NHC circulates systemically after molnupiravir dosing and is phosphorylated intracellularly to NHC triphosphate. Viral RNA polymerase incorporates NHC triphosphate into viral RNA, which then misdirects viral polymerase to incorporate either guanosine or adenosine during viral replication. As a result, detrimental mistakes accumulate throughout the viral genome, rendering the virus non-infectious and unable to replicate [15].

Adverse effects: Diarrhea, Dizziness and Nausea [16].

Other indications: NA.

2.1.2 Azithromycin

Azithromycin is a broad-spectrum macrolide antibiotic with a protracted half-existence and tremendous tissue penetration. It is mostly used for the remedy of respiration, enteric and genitourinary infections and can be utilized in desire to different macrolides for a few sexually transmitted and enteric infections. Azithromycin has extra immunomodulatory consequences and has been utilized in continual respiration inflammatory illnesses for this purpose [17].

Mechanism of action: Azithromycin has antiviral action against SARS-CoV-2 and may act at various stages of the viral cycle. Its immunomodulatory features include the capacity to reduce cytokine production, maintain epithelial cell integrity, and prevent fibrosis in the lungs [18].

Adverse effects: QTc prolongation has been linked to torsade’s de pointes and polymorphic ventricular tachycardia, rarely hepatotoxicity [18].

Other indications: Community-acquired pneumonia, in relation to its activity against Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis. Treatment of other upper respiratory diseases, like acute otitis media and acute reoccurrence of chronic obstructive pulmonary disease [19].

2.1.3 Favipiravir

Favipiravir is an oral medication that was authorized in Japan in 2014 for new and re-emerging pandemic influenza. Favipiravir (prodrug) is a purine base analogue that undergoes intracellular phosphoribosylation to become active favipiravir ribofuranosyl-5B triphosphate (favipiravir-RTP).

Mechanism of action: Favipiravir is integrated into the nascent viral RNA via the error-prone viral RdRp, resulting in viral mutagenesis and chain termination. The presence of RdRp in many types of RNA viruses allows favipiravir to have a broader spectrum of antiviral activity. Favipiravir-RTP acts as a mutagen after RNA viral inclusion, allowing it to avoid coronavirus repair machinery. Overall, favipiravir-RTP has a beneficial effect on SARS-CoV-2 by inducing a cytopathic effect, which reduces the number of viral RNA and infectious particles, as well as increasing the frequency of mutation [20].

Adverse effects: Abnormal liver function tests, psychiatric symptom reactions, digestive tract reactions and raised serum uric acid [3].

Other indications: RNA viruses such as resistant influenzas virus, arenaviruses, Bunyaviruses, floviruses, Rift Valley Fever, Yellow Fever, West Nile, Western equine encephalitis, foot-and-mouth disease virus, norovirus and avian influenza [3].

2.1.4 JAK-STAT inhibitors

As cytokines are clearly important in the fight against viral infections, the hyperinflammatory conditions caused by the SARS-CoV-2 infection due to the cytokine storm.

Mechanism of action: STAT proteins with SH2 domains are inactive and restricted to the cytoplasm in unstimulated cells. STAT proteins use SH2 domains to bind to the phospho-tyrosine that includes receptor sequences after cytokine receptor stimulation. Furthermore, JAK-induced phosphorylation of STAT proteins at cytokine type receptors results in STAT protein dimerization. STATs can translocate inside the nucleus and trigger apoptosis, immunological modulation, cell cycle differentiation, and gene transcription due to their dimerization.

Adverse effects: Ruxolitinib: Purpuric lesions on the skin of limbs and erythrodermic rashes in 2 SARS-CoV-2 patients.

Long term use of Baricitinib: Serious infections and thromboembolic events in patients.

Tofacitinib: Abdominal pain, acne vulgaris, anemia, angioedema, diarrhea, dehydration, dyspepsia, headache, hepatotoxicity, hyperlipidemia, hepatitis, lymphoma, lymphopenia, nausea, neutropenia, pulmonary embolism, rashes, vomiting, blood clots, GI perforations [21].

Other indications: Rheumatoid arthritis, Psoriatic arthritis, Ulcerative Colitis, Chron’s disease, Alopecia areata, Vitiligo, Psoriasis, Atopic dermatitis [22].

2.2 Drug treatment for severe Covid-19 infection

2.2.1 Remdesivir

Remdesivir (RDV), also known as GS-5734, is a monophosphoramidate prodrug and adenosine nucleoside analogue that is converted to GS-441524, the active form [3].

Mechanism of action: Remdesivir inhibits viral RNA-dependent RNA polymerase (RdRp), which is involved in viral genome replication. When remdesivir is metabolized by the host cells into its pharmacologic active analogue, adenosine triphosphate (GS-443902), it competes with ATP for integration by the RdRp complex into the nascent RNA strand, resulting in the cessation of RNA synthesis and reducing viral replication [23].

Adverse effects: Hypotension, arrhythmias, and cardiac arrest, Dyspnea, Acute respiratory failure, acute respiratory distress, pneumothorax, pulmonary embolism, Anemia, lymphopenia, Hyperglycemia, Pneumonia, septic shock, Elevated lipase, nausea, vomiting, diarrhea, constipation, poor appetite, gastroparesis, and lower GI bleeding, Acute kidney injury or worsening of underlying chronic kidney disease, hypernatremia, hypokalemia, Headache, lightheadedness, Rash, contact dermatitis, pruritus, Delirium, Pyrexia, insomnia, multi-organ dysfunction and DVT.

Other indication: Ebola Virus [24].

2.2.2 Dexamethasone

Dexamethasone is a corticosteroid with anti-inflammatory and immunosuppressive properties that is used to treat a variety of illnesses [25].

Mechanism of action: It works by blockade of inflammation pathways, vasodilation and immune cell migration [26].

Adverse effects: Hyperglycemia, secondary infections, psychiatric effects, avascular necrosis [25].

Other indications: Allergic states, GIT disorders, Hematologic disorder, Renal disorders [25].

2.2.3 Selinexor

Selinexor, a selective inhibitor of nuclear localization compound that structures exportin 1 (XPO1) and compels nuclear concentration and initiation of oncogenic proteins, inhibits transcription factor nf B, and reduces oncoprotein messenger RNA translation, could be a new treatment option for myeloma that has resisted current treatments [27].

Mechanism of action: The severe pulmonary inflammation associated with COVID-19, as well as high levels of cytokines such as IL6, IL1, IFNg, and others, is one of the most essential features of the virus. Selinexor has shown substantial anti-inflammatory effect by inhibiting Nuclear Factor kB (NF-kB), resulting in decreases in all of these cytokines and is helpful especially for COVID-19 patients who are hospitalized [28].

Adverse effects: Blurred vision, Cataract was reported as the most widespread side effect [29]. Nausea, vomiting, diarrhea, constipation, weight loss. Loss of appetite. Extreme tiredness. Difficulty falling asleep or staying asleep. Headache. taste changes. Easy bleeding or bruising, fatigue, pale skin, or shortness of breath, fever, cough, chills, or other signs of infection, seeing things or hearing voices that do not exist, confusion, double vision and increased sensitivity to light and glare [30].

Other indications: Selinexor is indicated for the remedy of relapsed or refractory a couple of myelomas in aggregate with dexamethasone. Patients need to have acquired as a minimum four previous treatments and feature sickness that’s refractory to least proteasome inhibitors, as a minimum immunomodulatory agent, and an anti-CD38 monoclonal antibody [31].

2.2.4 Nitric oxide

In the cardiovascular and immune systems, nitric oxide plays a significant pathophysiological role. NO works as a selective pulmonary vasodilator to promote oxygenation and lessen pulmonary vascular resistance [32].

Mechanism of action: NO has the ability to act as a vasodilator and immunological regulator. As a vasodilator, it works as a selective pulmonary vasodilator to improve oxygenation and reduce pulmonary vascular resistance, as a bronchial/airway dilator to promote oxygen inhalation, as a vascular anticoagulant to prevent blood clotting and excessive platelet activation [33].

Adverse effects: Blurred vision, dizziness, faintness, or light-headedness. Sweating, Unusual exhaustion or weakness. Incidence not known: bluish lips or skin, Chest discomfort, Difficult or labored breathing, Dizziness, Tightness in the chest, Trouble breathing [33]. Clinical adverse effects of iNO include the following: Worsening heart failure, Hypotension, Pulmonary vasospasm, Methemoglobinemia [34, 35].

Other indications: Pulmonary Hypertension in Infants, Chronic Lung Disease in the Infant [34]. Improve oxygenation and reduce the risk of extracorporeal membrane oxygenation in term and near-term infants with hypoxic respiratory failure and clinical and/or echocardiographic signs of pulmonary hypertension [35].

2.2.5 Paxlovid

Ritonavir-Boosted Nirmatrelvir. Nirmatrelvir is an orally absorbed protease inhibitor that inhibits MPRO, a viral protease that cleaves the two viral polyproteins required for viral replication. It has shown antiviral activity against all known coronaviruses that infect people [36].

Mechanism of action: Paxlovid is made up of two drugs: nirmatrelvir, which stops the virus from replicating by inhibiting a SARS-CoV-2 protein, and ritonavir, which slows down the breakdown of nirmatrelvir and allows it to stay in the body for longer at higher concentrations [37].

Adverse effects: Diarrhea, Altered or impaired sense of taste, Muscle aches, Increased blood pressure [38].

2.3 Supportive treatments for Covid-19 infection

2.3.1 Paracetamol

Paracetamol, often known as acetaminophen, is a pain reliever and fever reducer commonly used for mild to moderate pain and discomfort. This medicine has been prescribed to alleviate the symptoms of COVID-19 infection, which include fever, body aches, and headaches. Patients with these symptoms may find relief with paracetamol, but it is not a treatment for COVID-19 [39].

Adverse effects: Itchy, red, swollen, blistered, or peeling skin, wheezing, chest or throat tightness, difficulty breathing or speaking, swelling of the mouth, face, lips, tongue, or throat [40].

2.3.2 Vitamin D

It has the ability to function autocrinally in a local immunologic environment. Vitamin D has the ability to influence both innate and adaptive immune responses. Vitamin D deficiency has been linked to increased autoimmunity and susceptibility to infection. As immune cells in autoimmune diseases are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with autoimmune disease may extend beyond the effects on bone and calcium homeostasis [41].

Mechanism of action: Vitamin D receptors are found on B cells, T cells, and antigen-presenting cells, among other immune cells. Because these cells may generate the active vitamin D metabolite, vitamin D has the potential to manipulate innate and adaptive immune responses [42].

Adverse effects: Some side effects of taking too much vitamin D include weakness, dry mouth, nausea, vomiting, and others. Taking vitamin D for long periods of time in doses higher than 4000 IU (100 mcg) daily is possibly unsafe and may cause very high levels of calcium in the blood [43].

Other indications: Osteoporosis, Hypoparathyroidism, Vitamin D resistant Rickets, Familial Hypophosphatemia [44].

2.3.3 Vitamin C

Vitamin C levels in serum and leukocytes are depleted during the acute stage of infection owing to increased metabolic demands. Vitamin C supplementation at a high dose aid in the normalization of serum and leukocyte vitamin C levels. Vitamin C has a number of pharmacological properties, including antiviral, anti-oxidant, anti-inflammatory, and immunomodulatory activities, making it a promising treatment choice for COVID-19 [45].

Mechanism of action: Vitamin C, also known as ascorbic acid, is a water-soluble nutrient that is vital for human health. Immune responses rely heavily on ascorbic acid. As an antioxidant, vitamin C plays a vital homeostatic role. It has been shown to have direct virucidal activity as well as increase interferon production. Both the innate and adaptive immune systems have effector mechanisms. Vitamin C inhibits NF-B activation, which reduces reactive oxidative species (ROS) and inflammation. While SARS-CoV-2 suppresses the expression of type-1 interferons (the host’s main antiviral defense), ascorbic acid increases the expression of these important host defense proteins [46].

Adverse effects: Nausea, vomiting and diarrhea, Heartburn, Stomach cramps or bloating, Fatigue and sleepiness, or sometimes insomnia, Headache, Skin flushing. Vitamin C supplements taken orally, especially in large doses, might produce kidney stones. The use of oral vitamin C supplements in excess of 2000 milligrams per day for an extended period of time raises the risk of serious side effects [47].

Other indication: Assisting in the protection and maintenance of cells. Maintaining healthy skin, blood vessels, bones and cartilage. Assisting in the healing of wounds [48].

2.3.4 Zinc

Zinc is a trace mineral, which means it is only needed in minute amounts by the body, yet it is required for almost 100 enzymes to carry out critical chemical reactions. It plays an important role in the formation of DNA, cell development, protein synthesis, tissue repair, and immune system support [49].

Mechanism of action: Zn supplementation has the ability to increase innate and humoral antiviral immunity, as well as restore reduced immune cell activity or improve normal immune cell function, especially in immunocompromised or elderly patients. When used with normal antiviral therapy, Zn has been shown to have a synergistic effect in patients with hepatitis C, HIV, and SARS-CoV-1. Physical processes such as virus adhesion, infection, and uncoating are primarily responsible for Zn′s effectiveness against a variety of viral species. Zn may also protect or stabilize the cell membrane, which may help to prevent the virus from entering the cell [50].

Adverse effects: Indigestion, Diarrhea, Headache, Nausea, Vomiting [51].

Other indications: Zinc can be used to treat zinc deficiency, diarrhea, and Wilson disease. Acne, diabetes, anorexia, burns, and a variety of other conditions are all treated with zinc. Several scientific evidence supports its usage in the treatment of some of these conditions [52].

Additionally, supplemental oxygen therapy is provided to patients with Severe Covid and respiratory distress, hypoxemia, or shock. Oxygen therapy at 5 L/min and titrate flow rates to reach target SpO2 ≥ 90% in non-pregnant adults and SpO2 ≥ 92–96% in pregnant patients. NIV/HFNC (Helmet or face mask interface depending on availability) should be used in patients with increasing oxygen requirement, if work of breathing is increasing.

Intubation should be prioritized in patients with high work of breathing /if NIV is not tolerated., presence of hemodynamic instability, altered mental status or multi-organ failure. Ventilatory management carried out according to protocol [53].

3. Standard treatment according to MoHFW for different severities of COVID-19 infection

MoHFW (Ministry of Health and Family Welfare) is a government ministry in India that is responsible for health policy [53]. It is also in charge of all government-sponsored family planning programmes in India. As a member of the Council of Ministers, the Minister of Health and Family Welfare has cabinet rank.

The standard treatment given by MoHFW for different severities is given below.

Drug treatment for patients with mild cases:

1. Tab Paracetamol for fever and if fever is not controlled with a maximum dose of Tab. Paracetamol 650 mg QDS, then consult a doctor and they may prescribe drugs like non-steroidal anti-inflammatory drug like for example Tab.Naproxen 250 mg twice a day.

2. Tab Ivermectin (200 mcg/kg OD) for 3–5 days (avoid in pregnant and lactating women)

3. Tab Hydroxychloroquine (400 mg BD for 1 day, followed by 400 mg daily for next 4 days, unless contraindicated)

4. Inhalational Budesonide (given via inhalers with spacer at a dose of 800 mcg BD for 5–7 days) only to be given if symptoms (fever and/or cough) are persistent beyond 5 days of disease onset.

5. Systemic oral steroids not required in mild severity. If symptoms are persistent beyond 7 days (persistent fever, worsening cough etc.) consult the doctor for treatment with low dose oral steroids.

6. Continue the medications for other co-morbidities.

Drug Treatment for patients with moderate cases:

1. Antipyretic (Paracetamol) for fever and pain,

2. Anti- tussives for cough

3. Adequate hydration should be ensured

4. Oxygen Support: Target SpO2: 92–96% (88–92% with COPD patients). The device chosen for administering oxygen depends on the severity of hypoxia and work of breathing.

5. Anticoagulants: Prophylactic dose of Un-Fractionated Heparin (UFH) or Low Molecular Weight Heparin (LMWH) (e.g., enoxaparin 0.5 mg/Kg body wt per day SC). Consider UFH in ESRD.

6. Anti-inflammatory or immunomodulatory therapy: IV Methylprednisolone 0.5–1 mg/kg OR IV Dexamethasone 0.1–0.2 mg/kg for a duration of 5–10 days. Switch to oral therapy if the patient’s health is improving.

7. Antibiotics should be prescribed only when clinical suspicion of bacterial infection. Those who develop infection, consider empiric antibiotic therapy as per local antibiogram.

8. Continue the medications for other co-morbidities.

Drug treatment for patients with severe cases:

1. Symptomatic treatment with paracetamol,

2. Antitussives for cough

3. When no evidence of shock use of conservative fluid management in patients to maintain euvolemia.

4. Respiratory support according to the requirement.

5. Anti-inflammatory or immunomodulatory therapy: IV Methylprednisolone 1–2 mg/kg IV in two divided doses (or 0.2–0.4 mg/kg of dexamethasone) usually for 5–10 days.

6. Anticoagulants: Prophylactic dose of Un-Fractionated Heparin (UFH) or Low Molecular Weight Heparin (LMWH) (e.g., enoxaparin 0.5 mg/Kg body wt per day SC). Consider UFH in ESRD.

To conclude, these are the drugs that are used in India for the treatment of mild, moderate and severe covid infection. For mild-moderate infection, Molnupiravir, Azithromycin, JAK-STAT Inhibitors and Favipiravir. For severe covid infections, drugs like Remdesivir, Paxlovid, Nitric Oxide, Selinexor and Dexamethasone. Common treatment includes Nutritional and Vitamin Supplements, Paracetamol and Zinc. Additionally,Nitazoxanide, Niclosamide, Rintatolimod, Bencentinib, Plitidepsin, VIR-2703, Emetine hydrochloride, AT-527, Trabedersen, Stannous protoporphyrin, Antroquinonol, Apilimod dimesylate, Brilacidin, Infliximab, Abatacept, Cenicriviroc, Interleukin-1 inhibitors, Interleukin-7 inhibitors are drugs under trial for the treatment for COVID 19 infection. As per the latest data from WHO, the total confirmed cases since the pandemic started till May end 2022 are 43,147,530 and the total deaths accounts to 524,539 [54].