Observational Studies on Remdesivir
Tested initially against Ebola, SARS-CoV and MERS-CoV [2],
Remdesivir has been used in the dose that was used during the Ebola
trials- 200 mg IV on day 1 followed by 100 mg for 9 days [8].
It was used in the first case of COVID-19 managed in the US [9],
showing presumably good response. The patient presented with a 4-day
history of fever and cough. On day 7 of hospitalization the patient
deteriorated and were then given IV Remdesivir under compassionate use
access with no adverse events observed on infusion [9]. Clinical
improvement followed the next day. However, the patient was also
concurrently given Paracetamol, Ibuprofen, Guaifenesin, Vancomycin and
Cefepime. This acts as a confounder and does not allow for
interpretation of the direct effect of Remdesivir on disease process.
Between January 20, 2020, and February 5, 2020 12 more patients were
infected with SARS-CoV2 [10]. Three of the patients received
Remdisivir on compassionate use access after deteriorating clinical
condition. The first signs of adverse effects were seen in this case
series as all patients experienced gastrointestinal symptoms (nausea,
vomiting, gastroparesis or rectal bleeding) after the initial dose.
However, treatment was not stopped until improvement in respiratory
symptoms, with all patients reporting resolution of symptoms by February
22, 2020[10]. However, the sample size is incredibly small and there
was no randomization, thus it is difficult to determine efficacy and,
importantly, efficacy in light of the reporting of adverse effects.
Gilead sponsored a study into patients who were given compassionate use
access of Remdesivir in critically unwell patients with COVID-19
[11]. A total of 53 patients- 22 were in the United States, 22 in
Europe or Canada, and 9 in Japan were observed in this study. 30
patients (57%) were receiving mechanical ventilation and 4 (8%) were
receiving extracorporeal membrane oxygenation at the start of
compassionate use. During follow-up (median-18 days), 36 patients (68%)
showed improvement in oxygen-support class. 17 of the 30 patients (57%)
on mechanical ventilation were extubated. 25 patients (47%) were
discharged, and 7 patients (13%) died. Among those receiving invasive
ventilation, mortality was 18% (6 of 34). It was 5% among those not
receiving invasive ventilation (1 of 19). [11] While 36 out of 53
(68%) showed clinical improvement, this study did not have a
comparative control arm, was on a very small cohort of patients and
crucially there was no adjustments for the level of care that each
patient received- providing the doorway for multiple confounders.