In this retrospective single-center data analysis including hospitalized PCR confirmed COVID-19 patients during the delta and omicron wave, who received remdesivir for treatment, early remdesivir administration was associated with a significantly lower probability for need of high flow oxygen therapy and a lower risk for ICU admission, after adjusting for age, sex, vaccination status, and viral variant. Patients who received remdesivir on day 4 or later after first symptoms had a 2–3 time higher chance to need high flow oxygen therapy and a more than 4‑fold higher risk to be admitted to the ICU. Furthermore, the risk for clinical progression seemed to have doubled in patients who received remdesivir after day 4 of symptom onset and there was a trend for an increased need for any oxygen therapy.

The relationship between early administration of remdesivir and a favourable clinical outcome of hospitalized patients has previously been shown in randomized trials. Beigel et al. showed that patients who received remdesivir within the initial 10 days after symptom onset had a higher rate ratio for recovery, than those who received it after the first 10 days, suggesting a more beneficial outcome when remdesivir was administered early [17]. A retrospective multi-center study from Spain suggested that the administration of remdesivir in the first five days was associated with a lower probability of ICU admission [24]. The meta-analysis conducted by the WHO Solidarity Trial Consortium indicated a more favourable outcome when remdesivir was administered during the early stages of disease progression, in patients who did not require supplemental oxygen or only needed low flow oxygen [11], also suggesting a more favourable outcome when started early.

In non-hospitalized PCR confirmed SARS-CoV‑2 patients with risk of disease progression Gottlieb et al. showed that early (median was day 5 since symptom onset) outpatient treatment with remdesivir was linked to a significant reduction in hospitalization or death [22]. Rajme-Lopez et al. were able to demonstrate similar results when remdesivir was given early (median was day 3 since symptom onset) for outpatient treatment [25].

To our knowledge, this is the first study that has undertaken an analysis of the timing of remdesivir administration in hospitalized patients during both the delta and omicron waves. The early initiation of remdesivir treatment is linked to better outcomes, while administering it at a later stage in disease appears to be associated with a higher likelihood of unfavourable outcomes. This could be attributed to delayed hospitalization, where patients who arrive later may already be in an advanced disease stage, resulting in inferior results. Moreover, these patients may not have been provided with the option of earlier outpatient remdesivir treatment due to potential logistical challenges associated with outpatient intravenous administration of the drug.

This becomes particularly crucial when oral nirmatrelvir/ritonavir is contraindicated due to organ failure, potential drug interactions, symptoms persistence for more than five days or need for hospitalization. Patients at risk of disease progression often take medications that interact with nirmatrelvir/ritonavir [18]. Thus making the prescription process challenging. For instance, organ transplant recipients under immunosuppressants like tacrolimus require close monitoring by specialists if considering nirmatrelvir/ritonavir for SARS-CoV‑2 [26]. If nirmatrelvir/ritonavir is not feasible, treatment with intravenous remdesivir is a viable alternative with fewer drug interactions. Therefore, the identification of high-risk individuals and the prompt initiation of remdesivir are of significant importance in hospitalized and outpatient settings.

However, physicians might be more reluctant to prescribe remdesivir as early as possible, because even if intravenous remdesivir can be stored at room temperature and does not require special infusion settings, its administration might be challenging in certain healthcare settings as providing consecutive intravenous doses over 3 to 5 days could pose logistical difficulties. A viable alternative for an early treatment start might be oral remdesivir agents. For example VV116, a deuterated remdesivir hydrobromide with oral bioavailability, has shown non inferiority to nirmatrelvir–ritonavir to the time to sustained clinical recovery, with fewer safety concerns [27].

This study possesses several limitations due to its retrospective nature, including data incompleteness and potential recruitment biases, which may introduce unknown confounders. Additionally, the absence of a control group not receiving remdesivir restricts the conclusions to the comparison between early and late remdesivir administration, making it challenging to evaluate remdesivir’s overall efficacy in COVID-19 treatment. Moreover there was an overrepresentation of the early group with a higher proportion in Omicron cases and vaccinated individuals, both associated with milder disease progression. In addition the late group scored higher on the WHO Clinical progression scale upon admission, suggesting a poorer health status at baseline. These factors may have contributed to a confounding bias in the analysis, despite attempts to adjust the data for vaccination status and virus variant. Furthermore, data was collected during the Delta and early Omicron waves, whereas the current predominant variant is Omicron XBB. In addition, this was a single-center study conducted in Vienna, and results may vary in other settings and countries. Since this study exclusively examined hospitalized patients, there is a potential for an overrepresentation of sicker individuals, which could have influenced the observed outcomes, possibly leading to a less favourable overall outcome.