Coronavirus disease 2019 (COVID-19) has affected >700 million individuals, resulting in more than six million deaths worldwide (https://covid19.who.int/). At the beginning of the pandemic, several drugs were used experimentally to manage this infection due to the emergency situation, and since then, numerous studies regarding treatment strategies have been conducted (1). Current management approaches for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are based on the clinical course, the patient's risk factors and the availability of the agents (2).

The Food and Drug Administration (FDA) granted remdesivir as the first drug licensed for the treatment of severe COVID-19(3). Remdesivir belongs to the nucleoside analogues and serves as a competitive inhibitor of viral RNA-dependent RNA polymerase, exhibiting a broad spectrum of action against various RNA viruses (4,5). Remdesivir, provided to adult patients hospitalized for COVID-19-associated pneumonia as a 10-day (6) or 5-day (7) course, shortens the recovery time and allows for early clinical improvement, according to phase 3 studies. In another study, remdesivir was shown to decrease the likelihood of patients requiring high-flow supplementary oxygen and invasive mechanical ventilation, as well as the risk of 14-day mortality, when compared to the placebo (8).

COVID-19 is responsible for disproportionately high rates of mortality among the elderly, particularly those with multiple comorbidities (9-12). According to the PINETREE study, a 3-day remdesivir course administered within 7 days following symptom onset was found to be effective in decreasing the probability of hospitalization or mortality from any cause among outpatients who were at high risk of progression to severe disease due to comorbidities, including the elderly (13).

Apart from pivotal studies, limited real-world data supporting the effectiveness of early remdesivir therapy in decreasing the overall risk of hospitalization and disease progression in SARS-CoV-2 high-risk outpatients are currently available (14,15). In addition, real-life data focusing on the safety and effectiveness of early remdesivir among the elderly are limited. Considering the poor outcomes of COVID-19 in the elderly, providing real-world evidence on the safety and effectiveness of early remdesivir in this population is of utmost importance.

The present study aimed to assess the clinical features and outcomes of older adults (≥65 years of age) who received early remdesivir therapy in the outpatient setting during the predominance of the omicron variant of COVID-19.

In total, 143 patients (74 males, 51.7%) completed the prophylactic course and were enrolled during the research period, with a mean age of 77.38±8.29 years. The median time from symptom onset to the first dose of remdesivir was 1 day (range, 0-7 days). The median value of the Charlson Comorbidity Index (CCI) was 4 (range, 2-12). In total, 89 patients (62.2%) patients had >1 comorbidities. The most common comorbidities were arterial hypertension (65 patients, 45.5%) and cardiovascular disease, including ischemic stroke, acute myocardial infarction, coronary artery disease and arrhythmias (57 patients, 39.9%). Of the included patients, 118 (82.5%) patients were vaccinated with at least two doses. The characteristics of the study population are presented in Table I. No notable side-effects were observed from the prophylactic administration of remdesivir. In total, 6 patients (4.2%) were admitted to the hospital due to the progression of severe disease following the completion of the prophylactic course, and of these patients, 5 patients (out of 143 patients in total, 3.5%) succumbed to the disease within the study period. Of note, 4 patients succumbed due to COVID-19-associated pneumonia, 1 patient succumbed due to cardiac arrest after his hospitalization and 1 patient succumbed due to septic shock. As regards the risk factors for progression to severe disease and mortality among the non-survivors, 2 patients were suffering from haematological malignancy treated with B-cell depletion therapy, 1 patient was suffering from renal disease requiring haemodialysis, and the other 2 patients were unvaccinated.

In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR), 0.522; 95% confidence interval (CI), 0.278-0.981; P=0.043] and haematological malignancy (HR, 6.667; 95% CI, 1.114-39.89, P=0.038) were identified as predictors of progression to severe disease (Table II), and the albumin levels (HR, 0.806; 95% CI, 0.689-0.942, P=0.007), C-reactive protein-to-albumin ratio (CAR; HR, 1.768; 95% CI, 1.019-3.069; P=0.043] and hematological malignancy (HR, 0.150; 95% CI, 0.025-0.898; P=0.038) were identified as predictors of 28-day mortality (Table III).

The demographic characteristics and the levels of laboratory parameters of the patients who succumbed and the patients who were alive at 28 days are presented in Table IV.

In the PINETREE study, the probability of COVID-19-associated hospitalization or all-cause mortality was 87% lower in the remdesivir group compared to the placebo group during the first 7 days from symptom onset and with at least one underlying risk factor for progression to severe disease (13). Obesity, cardiovascular or cerebrovascular illness, diabetes mellitus, hypertension, immunodeficiency, mild or moderate chronic renal disease, chronic liver and respiratory disease, malignancy, or sickle cell disease were all considered risk factors in the PINETREE trial. However, diabetes mellitus, obesity and hypertension were identified as risk factors in the vast majority of enrolled individuals (62, 55 and 48%, respectively). The exclusion of vaccinated individuals, as well as the lack of patients with non-omicron variants, were the main limitations of that study that limited its applicability in everyday clinical practice (13).

Currently, a limited number of real-life studies have demonstrated that the early administration of remdesivir has a good safety profile and significantly reduces the risk of COVID-19 disease progression and mortality among high-risk patients in the era of the omicron variant (14,16-18). A recent study focused on non-hospitalized vaccinated high-risk patients and demonstrated that a 3-day course of remdesivir resulted in a 75% lower possibility of hospitalization and 95% of respiratory failure, with favourable outcomes in cases that required hospitalization (19). Previous studies have reported that an early 3-day course of remdesivir has an outstanding safety profile and may prevent disease progression among elderly patients infected with SARS-CoV-2 during hospitalization in palliative care and internal medicine wards (20,21). To the best of our knowledge, this is the first study focusing on real-life data from elderly outpatients with SARS-CoV-2 infection treated with a 3-day early course of remdesivir during the surge of the omicron variant. The results obtained from the 3-day early course of remdesivir in the present study cohort were notable, considering that during the predominance of the omicron variant, the majority of severe cases and in-hospital deaths occurred among individuals aged >65 years (22).

Recent studies have reported that early remdesivir treatment in solid organ transplant recipients is linked to a lower probability of hospitalization and/or mortality (18,23). Of note, in the presenst study, no disease progression or mortality was observed among elderly solid organ transplant recipients. This finding supports the findings of previous research indicating that immunosuppressive drugs used in solid organ transplantation may have a beneficial anti-inflammatory role and that the greater likelihood of COVID-19 progression in these individuals may be driven by other comorbidities, such as cardiovascular disease and diabetes mellitus (24,25).

According to a recent study on patients with haematological malignancies treated with various therapies, early treatment with remdesivir was associated with a failure rate of 3.4% (3/59 patients) (26). In the present study, among the elderly patients with haematological malignancies, the failure rate of early remdesivir administration was 15.4% (2/13 patients). In addition, two of the five deaths (40%) occurred in patients with haematological malignancies under B-cell depletion therapy. The continuing pandemic is a serious concern for patients treated with B-cell depletion therapy who exhibit clinical and virological evidence of SARS-CoV-2 infection that lasts >21 days and/or more than two episodes of acute respiratory syndrome, with a COVID-19 mortality rate of up to 60% (27,28).

Biomarkers such as NLR, CAR and albumin have all been reported as predictors of poor outcomes in patients with COVID-19 (29-31). To the best of our knowledge, the present study is the first to demonstrate the association of these specific inflammatory biomarkers with unfavourable outcomes among elderly patients receiving early remdesivir treatment, indicating the critical role of the nutritional and inflammatory state of these patients in the course of the disease.

The present study has some limitations which should be mentioned. The major limitation is the lack of a control group due to the prospective observational design and ethical issues. Secondly, this was a single-centre study. Thirdly, during the follow-up period, only a few events occurred that did not permit the performance of multivariable analysis in order to define independent factors associated with poor outcomes.

In conclusion, the safety and efficacy of prophylactic administration of a 3-day regimen of remdesivir for the prevention of severe COVID-19 disease in elderly patients are high. NLR, CAR ratio, albumin value and the presence of hematological malignancy are associated with poor outcomes.