Compassionate Use of Remdesivir for Patients with Severe Covid-19

Original: NEJM April 10, 2020

Author(s): Grein J, Ohmagari N, Shin D et al

Reviewer: Stylianos Loukides, e-Learning Director

Published: 12 Apr, 2020

Infection with SARS COV-2 has become a worldwide pandemic. Clinical manifestations of the disease are quite variable. We have asymptomatic patients, patients with mild symptoms and patients with severe pneumonia who require hospitalization or/and admission to ICU. Older people and those with pre-existing chronic diseases are groups at risk. At the moment no effective treatment exists. Several attempts are on the way in order to find proper and effective treatment interventions.

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has broad-spectrum activity against members of several virus families, including forms of coronaviruses. Additionally it has shown in vitro activity against SARS-CoV-2.

In the current study, using a cohort of patients hospitalized for severe infection from Covid-19, the authors wanted to determine whether the administration of remdesivir was related with positive outcomes. Requirements for Remdesivir administration were the following: An oxygen saturation of 94% irrespective of oxygen support, a creatinine clearance above 30 ml per minute and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than five times the upper limit of the normal range. No other investigational drugs were permitted. The treatment plan [10 days] was the following: A loading dose of 200 mg intravenously on day 1, plus 100 mg daily for the following 9 days.

61 patients were initially recruited. 40 (75%) received the full 10-day course of remdesivir, 10 (19%) received 5 to 9 days of treatment, and 3 (6%) fewer than 5 days of treatment. 34 received invasive ventilation. 75% had pre-existing conditions.

After receiving the first dose of remdesivir, 36 patients (68%) showed an improvement in the category of oxygen support, whereas 8 of 53 patients (15%) showed worsening. Seven (six receiving IV) of the 53 patients (13%) died after the completion of remdesivir treatment. Age and serum creatinine were contributable factors in mortality assessment. 60% of patients reported AE. 23% had serious adverse event like multiple-organ-dysfunction syndrome, septic shock, acute kidney injury, and hypotension. All Severe AE were reported in patients who were receiving invasive ventilation at baseline.

Five important points:

  • Improvement in oxygen-support status was observed in 68% of patients, and overall mortality was 13%. These findings are better compared to previously reported for lopinavir–ritonavir.
  • We have to identify variables that drive responsiveness.
  • We need a more proper design and a larger population in order to strengthen the above results.
  • Safety still remains a significant issue.
  • Finally, early administration even in milder forms still remains a challenging hypothesis.
Respiratory critical care
Respiratory digests
Respiratory infections