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dcyphr | Compassionate Use of Remdesivir for Patients with Severe Covid-19

Abstract

Remdesivir is a nucleoside analog. Which means that its chemical structure imitates the chemical structure of a nucleotide. Nucleotides are how we store and transmit genetic information. SARS-CoV-2 uses this genetic language as well. To test Remdesivir it was given on a compassionate-use basis to patients hospitalized with confirmed COVID-19. A 9 day trial was conducted and the clinic data was collected for a one month period. This trial included severe cases of COVID-19 infection and compassionate-use of Remdesivir showed clinical improvements in 36 of the 53 patients (68%). Measurement of its efficacy requires future randomized, placebo controlled trials.


Background

Older patients and those with preexisting respiratory or cardiovascular related conditions appear to be at the greatest risk. Remdesivir is a prodrug of a nucleotide analogue. This means that Remdesivir is metabolized by the body into the active form of the chemical. This imitates a molecule called adenosine triphosphate. This will in turn inhibit viral RNA polymerases which are responsible for the eventual creation of viral proteins.


Methods

Patients accepted into the trial were required to have met several requirements. They needed to be confirmed positive, needed to have blood oxygen saturation of less than 94%, and several other blood tests. Blood tests, important patient values, and all adverse events were recorded daily.


Results

Interestingly, 75% of patients were men and the age range was 23 to 82 years, while the median age was 62 years. At baseline (before treatment) a majority of patients (64%) were receiving invasive ventilation. In comparison to patients receiving noninvasive ventilation, those receiving invasive ventilation tended to be older, were likely to be male, and a higher prevalence of coexisting conditions. After a median of 18 days after the first treatment, 68% of patients showed an improvement in the level of oxygen support required. It is notable that 75% of patients undergoing ECMO stopped receiving it. By day 28 after therapy the total number of patients showing clinical improvement was nearly 84%. A total of 32 patients (60%) reported adverse events during the therapy. Generally, adverse events were more common in patients who initially were receiving invasive ventilation. A total of 23% of patients had serious adverse events such as multiple organ system dysfunction, septic shock, acute kidney injury, and hypotension. 8% of patients discontinued use due to worsening of preexisting issues.


Discussion

To date no therapy has demonstrated efficacy for patients with COVID-19. This is purely a preliminary report that describes clinical outcomes with a small group of individuals, 53 patients total. Currently the researchers trials show the best preliminary results out of all therapies tested. The authors specifically note lopinavir-ritonavir. However, the researchers study took on much more serious condition patients and thus comparing the studies is largely unfounded. Kidney issues were observed during this short term therapy, but no clear evidence shows kidney toxicity as of yet. There are many shortcomings of this trial such as: small sample size, short follow up duration, missing data, lack of certain molecular info, or a randomized control group. This study suggests that remdesivir may have clinical benefit in patient with severe COVID-19.