In China, in December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) caused an international outbreak of a respiratory illness called coronavirus disease 2019 [COVID-19](1). Since then, SARS-CoV-2 has spread globally, and COVID-19 has now been labeled a pandemic of international concern by the World Health Organization(2).
Coronaviruses are enveloped, positive-sense, single-stranded RNA virus genomes. The coronavirus encodes a nonstructural replicase polyprotein and structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N)(3–5). The S protein on the surface of SARS-CoV is the most common target for the development of vaccines and therapeutics(6).
There are about thirty types of coronaviruses infecting mammals, birds, and other animals. Only seven of them infect humans(4, 7). Four of them usually cause mild diseases such as the common cold (HKU1; OC43; 229E; and NL63), whereas MERS-CoV, SARS-CoV, and now SARS-CoV-2 are likely to cause more serious diseases(5, 7). The main transmission way of SARS-CoV is from human to human by respiratory droplets(8–10).
COVID-19 disease clinical presentation can be from subclinical infection with mild (self-limiting respiratory tract illness) to severe (progressive pneumonia, multiorgan failure, and death) (11–14). Massive alveolar damage and progressive respiratory failure are the cause of death in severe covid-19 disease (12). Patients having comorbidities like people with chronic lung disease, serious heart disease, chronic kidney disease, elderly (above 65 years), and immunocompromised people are suspected to have the severe disease(15).
As of November 04, 2020, there were 47,362,304 confirmed patients, 1,211,986 confirmed deaths, and 219 countries, areas, or territories with COVID-19 according to the World Health Organization(16).
The only anti-viral drug FDA approved is Remdesivir yet for the treatment of COVID-19 in hospitalized patients (aged ≥ 12 years and weighing ≥ 40 kg)(17). To control the growing COVID-19 pandemic, we rely on quarantine, isolation, and infection-control measures preventing the spread of disease as well as oxygen and mechanical ventilation as supportive care for infected patients(18). Currently, there are many drugs exist that are being under assessment for patients with COVID-19: example, Remdesivir (used to treat Ebola virus disease and Marburg virus infections), lopinavir and ritonavir (used to treat HIV/AIDS), chloroquine phosphate or hydroxychloroquine (used to treat malaria), tocilizumab (used to treat rheumatoid arthritis), corticosteroids, stem cells, and other types of interventions(19).
Several randomized clinical trials are underway. According to an online global COVID-19 clinical trial tracker available at www.covid19-trials.org, there are currently 2462 trials registered worldwide as about 20% of them are in the US.
Although the mortality rate is concerning, the high transmissibility of the disease is much more alarming. Even if a low percentage of patients need hospitalization, the rapid spread of the disease and a large number of people infected has overwhelmed the healthcare systems worldwide. To decrease the spread, severe social distancing measures, travel restrictions, closures of schools, and many businesses are taking an unprecedented socioeconomic and psychological toll. Therefore, COVID-19 has caused an enormous impact on people’s quality of life and posed far-reaching threats, especially to the economy, health, and the sustainability of healthcare systems(18).
There have been many efforts done to identify effective drug treatment for covid-19 but, evidence for effective treatment remains limited. It is, therefore, an urgent need of investigating the most effective drugs to slow the progression of the disease and unburden the health care systems. Although extraordinary efforts have been made on research regarding pharmacological interventions, none have proven most effective. Therefore, this systematic review and network meta-analysis aim to synthesize existing evidence to compare the efficacy and safety as well as identify the best drug among different anti-infectious drug categories for the treatment of mild to severe patients with COVID-19.