Remdesivir for the Treatment of Severe COVID-19: A Community Hospital's Experience

Since the coronavirus disease 2019 (COVID-19) pandemic began, more than 38 million people have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes it and more than 1,094,000 have died globally.¹ In the United States, more than 7.9 million patients have been infected with SARS-CoV-2, causing more than 217,000 deaths.¹ Based on the morbidity and mortality associated with COVID-19, researchers from across the globe are actively searching for safe and effective treatments for the disease.

Remdesivir (Gilead Sciences, Inc.) was granted an emergency use authorization by the US Food and Drug Administration (FDA) on May 1, 2020 for the treatment of hospitalized patients with severe COVID-19.² Remdesivir is a prodrug (a biological precursor that, when metabolized, forms the pharmacologically active drug) which forms an adenosine triphosphate analogue that inhibits viral RNA polymerase and replication.^3-5 Remdesivir has been shown to have broad spectrum activity against filoviruses (Ebola) and coronaviruses (SARS-CoV and Middle East respiratory syndrome coronavirus [MERS-CoV]).^3-5 Invitro and invivo research has demonstrated that remdesivir inhibits replication of SARS-CoV-2 within human airway epithelial cells and has verified its clinical and virologic efficacy in primate models.^6-8 In clinical trials, remdesivir administration has been shown to reduce the time to clinical improvement in patients with COVID-19, with very few side effects.^3-5 However, the majority of these trials have been conducted at large urban academic referral centers, which could make the results less generalizable to patients seen in a community setting. In this study, we report the outcomes of those admitted to a community hospital with severe COVID-19 who were given remdisivir.

Methods

Results

Of the 7246 patients assessed for enrollment, a total of 76 patients were included in the final analysis (Figure). Of patients who were hospitalized and received remdesivir, 36 (47.4%) were men and 40 (52.6%) were women; 49 (64.5%) were White and 27 (35.5%) were pooled into a nonWhite group (Table 2). The mean age of patients receiving remdesivir for severe COVID-19 was 63 years (95% CI, 59.8-66.2) and had a mean weight of 94.3 kg (95% CI, 87.8-100.8). The most common presenting complaint was shortness of breath (66 patients; 86.8%), followed by cough (61; 80.3%) and fever (55; 72.4%). The majority of patients had 2 or more comorbid medical conditions (30; 39.5%). Hypertension was the most common comorbid condition (43; 56.6%). There was no difference between men and women in the frequency of comorbid conditions (26 with comorbid conditions [72%]; 28 women [70%]).

Figure.

Flow chart demonstrating patient inclusion processes. A total of 7400 nasopharyngeal swabs for SARS-CoV-2 were performed at Kingman Regional Medical Center during the study period. Of the 433 patients testing positive for COVID-19 during that time, only 157 required hospitalization, with 76 meeting the clinical criteria for remdesivir administration under emergency use authorization.

The mean length of stay for patients who received remdesivir was 10.09 days (95% CI, 8.63-11.55), with the mean duration of oxygen therapy being 9.42 days (95% CI, 8.03-10.81). Men had a mean length of stay of 8.61 days (95% CI, 6.71-10.51), while women had a mean length of stay of 11.43 days (95% CI, 9.32-13.54; P=.058). Men also required fewer days of oxygen therapy compared with women (8.0 days and 95% CI, 6.16-9.84 vs 10.76 days and 95% CI, 8.75-12.77; P=.051). A total of 14 patients (18.4%) were admitted to the intensive care unit; these patients had a mean length of stay of 9.29 days (95% CI, 5.58-13). Women were more likely to be admitted to the intensive care unit (11 [27.5%] vs 3 [8.3%]; P=.031). Total in-hospital mortality included 14 patients (18.4%), with women accounting for 9 of those (11.8%). There were no adverse events reported in patients who received remdesivir.

In our pooled comparison by race, White patients had a mean age of 65.06 years (95% CI, 61.29-68.83) while the mean age of nonWhite patients was 59.26 years (95% CI, 53.53-64.99). NonWhite patients were more likely to experience fever (24 [88.9%] vs 31 [63.3%]; P=.017), while White patients experienced a higher incidence of diarrhea (16 [32.7%] vs 3 [11.1%]; P=.038). The majority of those admitted to the ICU were White (Table 2). There was no difference noted for mean days spent in intensive care unit between White and nonWhite patients (8.90 days and 95% CI, 4.42-13.38 vs 10.25 days and 95% CI, 2.77-17.73 days; P=.76) and no difference in mortality (8 [57.1%] vs 6 [42.9%]; P=.53). White patients had a mean length of stay of 10.12 days (95% CI, 8.1-12.14), vs 10.04 days (95% CI, 8.15-11.93) for nonWhite patients (P=.96). No difference was noted for the mean duration of oxygen therapy between White and nonWhite patients (8.92 days and 95% CI, 7.03-10.81 days vs 9.63 days and 95% CI, 7.67-11.59; P=.64)

Table 3 provides the results of the stepwise logistic regression for ICU admission. The variable accounting for the greatest predicative power toward ICU admission and entered in step 1 was sex. In step 2, a presentation to the emergency department with fever met statistical criteria for inclusion. Only sex (step 1, P=.041; step 2, P=.020) significantly predicted the odds of being admitted to the ICU. Accounting for the covariation of sex and fever increased the odds ratio of women being admitted to the ICU from 4.2 to 5.8. A similar analysis was completed for the outcome of mortality; however, no variable was statistically significant.

Discussion

This study contributes to the current literature on the efficacy of remdesivir for the treatment of severe COVID-19 by providing an account of its use at a community hospital. In our patient population, the mean number of days hospitalized (10.09) was longer than previously-reported median of 7 days following a 5-day course of remdesivir for the treatment of COVID-19.⁵ Mortality in our study (18.4%) was also higher than reported in previous literature when patients were treated with a 5-day course of remdesivir (8%).⁵ The exact reasons for these mean increased rates of mortality and length of stay are unclear, but could be directly related to a higher percentage of our study population having comorbid conditions such as hypertension (56.6%) as compared with the previous data (43%).¹¹ Previous literature has also shown that comorbid conditions are strongly correlated with COVID-19 disease severity and mortality.^12,13

Previous reports have shown that men infected with COVID-19 experience worse clinical outcomes than women¹⁴; men specifically have higher rates of hospitalization, intensive care admission, and mortality. Despite similar rates of comorbid conditions men in our study had lower rates of poor clinical outcomes, including lower mortality, intensive care admission, mean duration of oxygen therapy, and mean length of stay than women. Large randomized controlled trials will be needed to determine a true treatment effect of remdesivir for severe COVID-19 in the community setting.^5,11

Research has shown that people of color are disproportionally affected by COVID-19 and have worse clinical outcomes following treatment.^15-17 In our study, we documented no clinical difference between White and nonWhite patients who received remdesivir for severe COVID-19 in a community setting. This data is consistent with prior literature noting that there is no difference amongst racial groups for the rate of recovery from severe COVID-19 after being given remdesivir.⁴ Although no treatment effect could be determined with the lack of a placebo control group in this report, further studies should focus on the treatment effects of remdesivir amongst patients of different racial groups.

Conclusion

Remdesivir may show clinical efficacy for the treatment of severe COVID-19 in a community setting. This extends to both men and women; however, it may prove more effective among men. In this community-based observation study, there was no evidence to suggest a change in outcomes associated with remdesivir by patient race. Although this was a small-scale study with limited patients, it represents a point of reference for the use of remdesivir at other community hospitals.

Author Contributions

Drs Santarelli and Ashurst and Student Drs Lee and Caine provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; Drs. Santarelli, Ashurst, and Dietrich, Student Dr Lee, and nurse Schritter drafted the article or revised it critically for important intellectual content; all authors gave final approval of the version of the article to be published; and all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.