1.1 Brief description of the disease
Coronavirus disease (COVID–19) is caused by a new coronavirus (CoV) [1] SARS-CoV–2 [2]. Previous outbreaks of CoVs include the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome (MERS)-CoV [2]. Like MERS CoV and SARS-CoV, the SARS-CoV–2 virus is a β coronavirus [1]. The β variant of the coronavirus is able to infect mammal [3]. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 as that for SARSCoV [3].
The SARS-CoV–2 mainly spreads through the respiratory tract [3], by droplets, respiratory secretions, and direct contact for a low infective dose [2]. The incubation period is 1–14 days and it is contagious during the latency period [3]. The symptoms of COVID–19 infection appear after an incubation period of approximately 5.2 days [2].
The COVID–19 may present with mild, moderate, or severe illness. The most common symptoms at the onset of COVID–19 illness are fever, cough (dry), fatigue, sore throat, nasal congestion, malaise, headache, muscle pain [1, 2, 4] chills, repeated shaking with chills, muscle pain, loss of taste or smell [1], and shortness of breath [3] other symptoms include sputum production, haemoptysis, diarrhoea, dyspnoea, and lymphopenia [2]. The severe clinical manifestations are severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and septic shock [4]. The elderly population and patients of all ages with underlying conditions are at higher risk [5]. Additionally, they are susceptible to infection and prone to serious outcomes, which may be associated with ARDS and cytokine storm [3].
The possibility of transmission before symptoms develop seems to be infrequent, although it cannot be excluded. Moreover, there are suggestions that individuals who remain asymptomatic could transmit the virus. The use of public health measures like social distancing, isolation and quarantine currently seems to be the best measures to contain this epidemic until effective vaccines and drugs become available [4].
The global pandemic of COVID–19 began in Wuhan, China, in December 2019, and has spread worldwide since then [6]. As of 05 May 2020, globally a total of 3.44 million confirmed cases (86,108 new) and 239,604 deaths (976 new) have been reported worldwide [7] in more than 200 countries [6].
1.2 Description of the intervention
Currently, no proven effective therapies for COVID–19 exist [6] and no vaccine is available [3]. The current treatments mainly focus on symptomatic and respiratory support [3]. Oxygen therapy represents the major treatment intervention for patients with severe infection. The strategies for addressing respiratory failure, include protective mechanical ventilation and high-flow nasal oxygen or non-invasive ventilation. Mechanical ventilation may be necessary in cases of respiratory failure refractory to oxygen therapy, whereas hemodynamic support is essential for managing septic shock [4]. Rescue treatment with convalescent plasma and immunoglobulin G is delivered to some critical cases based on their conditions [3].
The rapidly expanding knowledge regarding SARS-CoV–2 virology [6] and the previous experience of fighting SARS-CoV and MERS-CoV epidemic [3] has provided a significant number of potential drug targets [6]
As of 1st May–2020, a total of 1,829 clinical trials have been registered with the International Clinical Trials Registry Platform. Of which 626 are randomized trials (excluding Traditional Chinese medicine trials) and 319 of these are currently recruiting [8].
Various pharmacological treatments [9] are currently being tested for patients with COVID–19. Although no antiviral treatment for COVID–19 has been approved, several treatment strategies have been proposed [4]. Primarily, broad-spectrum antiviral drugs like nucleoside analogues and HIV-protease inhibitors that could attenuate virus infection are currently being tested until a specific antiviral becomes available [2]. The most commonly used pharmacological interventions currently being tested for COVID–19 are remdesivir, chloroquine, tocilizumab [4], lopinavir/ritonavir [2, 3, 6, 10] arbidol [3, 6, 10] darunavir [6, 10], favipiravir [6].
1.3 How the intervention might work
Many pharmacological interventions are being tried for the treatment of COVID–19 patients, here we have provided an example for one such promising agent currently being test in COVID–19 patients. Further intervention may be described in the review as appropriate.
Remdesivir (GS–5734) is one of the promising therapies currently being tested in COVID–19 patients [6]. Remdesivir is a nucleoside analogue prodrug [3] and shows broad-spectrum antiviral activity against several Ribonucleic Acid (RNA) viruses [3, 10]. It is an inhibitor of RNA polymerase with in vitro activity against multiple RNA viruses, including Ebola. It could be effective for both prophylaxis and therapy of HCoVs infections [4].
Pre-clinical studies experiments indicated that remdesivir can effectively reduce the viral load in lung tissue of mice infected with MERS-CoV, improve lung function, and alleviate pathological damage to lung tissue. This drug was positively tested in a rhesus macaque model of MERS-CoV infection [4]. It has potent in vitro activity against SARSCoV–2 and is currently being tested in ongoing randomized trials [6].
On 1st May–2020, remdesivir has been approved by the US Food and Drug Administration for emergency use in the treatment of hospitalized COVID–19 patients [11].
1.4 Why it is important to do this review
The elderly population and patients with underlying disease are at high risk of severe illness from COVID–19 [5]. The elderly patients are susceptible to greater frequency of decreased hepatic, renal, or cardiac function, and often have a concomitant disease or are on other drug therapy. All these conditions make COVID–19 patients more prone to experience adverse events (AEs) especially when various existing and novel pharmacological agent currently being tested in this population. For instance, consider the example of remdesivir; its pharmacokinetic is yet to be evaluated in patients with renal and hepatic impairment, in paediatric patients, and in the elderly patients (>65 years of age). Additionally, no adequate and well-controlled studies reporting the use of remdesivir in pregnant women have been conducted [12]. The limited clinical data and previous compassionate use of remdesivir make it imperative to assess AEs in COVID–19.
Additionally, in patients with COVID19, adverse effects may be exacerbated by combination therapy or viral infection because approximately 20% to 30% of patients have elevated transaminases at presentation with COVID–19. Also, one of the limitations of using repurposed agents is the tendency of these agents to cause acute toxicity. This is of utmost concern in patients at high risk for toxicity and in situations where AEs may preclude entry into clinical trials [6].