Coronavirus disease 2019 (COVID-19) is an ongoing global fatal pandemic that emerged first in Wuhan, China, in December 2019 and has since spread worldwide. On 30th January, the world health organization declared it a" public health emergency of international concern." The disease causes severe manifestations ranging from multiple organ failure to death. There have been over 520 million confirmed COVID-19 cases worldwide since 18th May 2022, with 6 million deaths reported to the WHO (1). With no evidence of effective treatment, drastic non-therapeutic measures were implemented worldwide to control the spread of the infection, including cordon sanitaire, travel restrictions, and partial or even complete lockdown (2). Two years later, COVID-19 had disastrous consequences for the healthcare system. Despite the continuous dedicated clinical research and the number of vaccine doses exceeding 11 billion globally, a significant number of severe cases ended with death.
Throughout this unprecedented public health emergency, the pandemic has prompted research centers worldwide to investigate the efficacy of every available drug or to develop novel treatments(3). The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pertains to the Beta coronavirus family that comprises SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Consequently, every drug that demonstrated effectiveness in patients with MERS or SARS, in addition to broad-spectrum antivirals, was investigated in COVID-19 (4).
Remdesivir (RDV) is a broad-spectrum antiviral developed in 2009, initially to treat hepatitis C (HCV) and respiratory syncytial virus (RSV) but showed no marked effect. In 2015, it was repurposed and tested for Ebola virus disease (5). It is a prodrug administered intravenously and activated intracellularly into the active form, a ribonucleotide analog that inhibits the viral DNA-dependent RNA polymerase activity, decreasing the production of viral RNA and hindering its replication (6).
During the COVID-19 pandemic, in March 2020, the United States president announced the availability of RDV for "compassionate use." In addition, because there is no definitive cure, RDV has been approved or authorized for emergency use in approximately 50 countries to treat COVID19 (7). In May, The Food and Drug Authority (FDA) Authorized the Emergency Use of RDV in COVID-19 patients requiring hospitalization (8). Five months later, the drug was approved as "the first antiviral for the treatment of Covid-19" after three randomized controlled trials that demonstrated its effectiveness in improving recovery and reducing the average hospital stay among mild to severe COVID-19 (8–11).
In May 2020, the Egyptian COVID-19 treatment protocol introduced RDV to be used in severe and critically ill cases (12). Nevertheless, after the updated protocol in November, the drug's use was expanded to include severe and moderate cases in high-risk populations (13).
Surprisingly, on 15th October, the WHO Solidarity Trial (open-label global trial) published its interim results. The panel analyzed data from this trial, as well as three other randomized controlled trials. Data from over 7000 patients across the four trials were considered. The evidence indicated that there was no significant effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes (14,15).
However, the data from this trial have not undergone the rigorous review required to allow for constructive scientific discussion. RDV is a drug that is administered via intravenous infusion for five to ten days and costs around £2000.
In April 2022, The Food and Drug Authority (FDA) still authorized the Use of RDV as one of the options for COVID-19 hospitalized patients who require supplemental oxygen or oxygen through a high-flow device(8).
The guideline development group recognized that more research is needed, especially to provide higher certainty of the evidence for specific groups of patients. They supported continued enrollment in a trial evaluating RDV. New evidence supporting or refuting the need for RDV is imperative to guide Egyptian regulators' decision-making (16). Hence, our study aims to assess the impact of introducing RDV in treatment protocol on patient outcomes.
Specific aim: To compare the mortality rate, the hospital length of stay, and the need for MV before and after the introduction of RDV in moderate to severe COVID-19 patients. We hypothesized that introducing RDV will improve outcomes: reduce mortality rate, escalation to a higher level of care, the need for MV, and lower ICU and ward length of stay in moderate COVID-19 patients.