Abstract
Context:
Following the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), researchers sought safe and effective treatment modalities. Remdesivir is currently being evaluated for clinical efficacy and safety in patients with COVID-19.
Objective:
To describe the clinical outcomes of COVID-19 patients following treatment with remdesivir at a community hospital.
Methods:
A retrospective review of medical records was conducted in August 2020 for all patients given remdesivir while hospitalized for severe COVID-19 between May 1 and August 19, 2020. A convenience sample of consecutive patients with treatment including remdesivir, antibiotics, convalescent plasma, dexamethasone, or a combination of multiple drugs was included in the analysis. Patients receiving remdesivir were administered a 5-day treatment course. Patients with a glomerular filtration rate of less than 30 mL/min, those with liver function tests 5 times the normal reference range, and those who were pregnant were excluded from treatment with remdesivir. Differences in between men and women were detected with χ2 and independent samples t tests. The degree to which presenting symptoms influenced patient outcomes was analyzed with a stepwise logistic regression.
Results:
Among the 76 patients who received remdesivir, the mean (95% confidence interval, CI) age was 63 years (59.8–66.2). Thirty-six (47.4%) were men and 40 (52.6%) were women. Forty-nine (64.5%) were White and 27 (35.5%) were nonWhite. The majority of patients (54; 71.1%) had at least 1 comorbid condition, with hypertension being the most common (43; 56.6%). The mean (95% CI) length of stay for patients who received remdesivir was 10.09 days (8.6–11.6) and the mean (95% CI) duration of oxygen therapy was 9.42 days (8.0–10.8). A total of 14 (18.4%) patients given remdesivir were admitted to the intensive care unit (ICU) with an mean (95% CI) length of stay of 9.29 days (5.6–13.0). Women administered remdesivir were more likely to be admitted to the ICU (11 [27.5%] vs 3 [8.3%]; P=.031). The mortality rate was 14 patients (18.4%), with no statistically significant difference observed between men (5; 13.9%) and women (9; 22.5%; P=.33). No significant difference was seen amongst sexes for duration of oxygen therapy (men, 8.0 days [6.2–9.8] vs women, 10.76 days [8.8–12.8]; P=.051) or length of stay (men, 8.61 days [6.7–10.5] vs women, 11.43 days [9.3–13.5]; P=.058). There was no statistically significant difference in pooled racial groups (White vs nonWhite) for in-hospital mortality, number admitted to the ICU, days spent in the ICU, duration of oxygen use, or length of stay.
Conclusion:
Remdesivir may show clinical efficacy for the treatment of severe COVID-19 in a community setting. 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.
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.
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%]).
Table 1.
Sample Patient Characteristics by Sex
Characteristic | All (n=76)a | Men (n=36; 47.37%)a | Women (n=40; 52.63%)a |
Ethnicity | | | |
White | 49 (64.5) | 24 (66.7) | 25 (62.5) |
Native American | 6 (7.9) | 1 (2.8) | 5 (12.5) |
Hispanic or Latino | 17 (22.4) | 8 (22.2) | 9 (22.5) |
Other | 4 (5.3) | 3 (8.3) | 1 (2.5) |
Patient presentation | | | |
Mean age, years (95% CI)b | 63 (59.8-66.2) | 63 (58.1-67.9) | 63 (58.3-67.7) |
Mean weight, kg (95% CI)b,c | 94.3 (87.8-100.8) | 102.7 (92.9-112.5) | 86.7 (78.7-94.7) |
Smokers | 19 (25.0) | 9 (25.0) | 10 (25.0) |
Fever | 55 (72.4) | 23 (63.9) | 32 (80.0) |
Cough | 61 (80.3) | 28 (77.8) | 33 (82.5) |
Altered smell | 9 (11.8) | 3 (8.3) | 6 (15.0) |
Altered taste | 7 (9.2) | 2 (5.6) | 5 (12.5) |
Diarrhea | 19 (25.0) | 9 (25.0) | 10 (25.0) |
Chest pain | 11 (14.5) | 6 (16.7) | 5 (12.5) |
Abdominal discomfort | 7 (9.2) | 4 (11.1) | 3 (7.5) |
Shortness of breath | 86.8 (66) | 33 (91.7) | 33 (82.5) |
Mean time from symptom onset, days (95% CI)b | 6.93 (5.8-8.1) | 7.7 (5.8-9.7) | 6.3 (5.1-7.5) |
Comorbid conditions | | | |
None | 22 (28.9) | 10 (27.8) | 12 (30.0) |
One | 24 (31.6) | 12 (33.3) | 12 (30.0) |
Two or more | 30 (39.5) | 14 (38.9) | 16 (40.0) |
Hypertension | 43 (56.6) | 24 (66.7) | 19 (47.5) |
Congestive heart failure | 7 (9.2) | 5 (13.9) | 2 (5.0) |
Type 2 diabetes | 31 (40.8) | 13 (36.1) | 18 (45.0) |
Chronic obstructive pulmonary disease | 13 (17.1) | 5 (13.9) | 8 (20.0) |
Outcomes | | | |
Mean duration of oxygen, days (95% CI)b | 9.42 (8.0-10.8) | 8.0 (6.2-9.8) | 10.8 (8.8-12.8) |
Number admitted to the ICUc | 14 (18.4) | 3 (8.3) | 11 (27.5) |
Mean ICU duration, days (95% CI)b,d | 9.29 (5.6-13.0) | 14.0 (3.6-24.4) | 8.0 (4.3-11.7) |
Mortality | 14 (18.4) | 5 (13.9) | 9 (22.5) |
Mean length of stay, days (95% CI)b | 10.09 (8.6-11.6) | 8.61 (6.7-10.5) | 11.43 (9.3-13.5) |
Table 1.
Sample Patient Characteristics by Sex
Characteristic | All (n=76)a | Men (n=36; 47.37%)a | Women (n=40; 52.63%)a |
Ethnicity | | | |
White | 49 (64.5) | 24 (66.7) | 25 (62.5) |
Native American | 6 (7.9) | 1 (2.8) | 5 (12.5) |
Hispanic or Latino | 17 (22.4) | 8 (22.2) | 9 (22.5) |
Other | 4 (5.3) | 3 (8.3) | 1 (2.5) |
Patient presentation | | | |
Mean age, years (95% CI)b | 63 (59.8-66.2) | 63 (58.1-67.9) | 63 (58.3-67.7) |
Mean weight, kg (95% CI)b,c | 94.3 (87.8-100.8) | 102.7 (92.9-112.5) | 86.7 (78.7-94.7) |
Smokers | 19 (25.0) | 9 (25.0) | 10 (25.0) |
Fever | 55 (72.4) | 23 (63.9) | 32 (80.0) |
Cough | 61 (80.3) | 28 (77.8) | 33 (82.5) |
Altered smell | 9 (11.8) | 3 (8.3) | 6 (15.0) |
Altered taste | 7 (9.2) | 2 (5.6) | 5 (12.5) |
Diarrhea | 19 (25.0) | 9 (25.0) | 10 (25.0) |
Chest pain | 11 (14.5) | 6 (16.7) | 5 (12.5) |
Abdominal discomfort | 7 (9.2) | 4 (11.1) | 3 (7.5) |
Shortness of breath | 86.8 (66) | 33 (91.7) | 33 (82.5) |
Mean time from symptom onset, days (95% CI)b | 6.93 (5.8-8.1) | 7.7 (5.8-9.7) | 6.3 (5.1-7.5) |
Comorbid conditions | | | |
None | 22 (28.9) | 10 (27.8) | 12 (30.0) |
One | 24 (31.6) | 12 (33.3) | 12 (30.0) |
Two or more | 30 (39.5) | 14 (38.9) | 16 (40.0) |
Hypertension | 43 (56.6) | 24 (66.7) | 19 (47.5) |
Congestive heart failure | 7 (9.2) | 5 (13.9) | 2 (5.0) |
Type 2 diabetes | 31 (40.8) | 13 (36.1) | 18 (45.0) |
Chronic obstructive pulmonary disease | 13 (17.1) | 5 (13.9) | 8 (20.0) |
Outcomes | | | |
Mean duration of oxygen, days (95% CI)b | 9.42 (8.0-10.8) | 8.0 (6.2-9.8) | 10.8 (8.8-12.8) |
Number admitted to the ICUc | 14 (18.4) | 3 (8.3) | 11 (27.5) |
Mean ICU duration, days (95% CI)b,d | 9.29 (5.6-13.0) | 14.0 (3.6-24.4) | 8.0 (4.3-11.7) |
Mortality | 14 (18.4) | 5 (13.9) | 9 (22.5) |
Mean length of stay, days (95% CI)b | 10.09 (8.6-11.6) | 8.61 (6.7-10.5) | 11.43 (9.3-13.5) |
×
Table 2.
Sample Patient Characteristics by Ethnicity
Characteristic | All (n=76)a | White (n=49; 64.47%)a | NonWhite (n=27; 35.53%)a |
Sex | | | |
Male | 36 (47.4) | 24 (49.0) | 12 (44.4) |
Female | 40 (54.8) | 25 (51.0) | 15 (55.6) |
Patient presentation | | | |
Mean age, years (95% CI)b | 63 (59.8-66.2) | 65.1 (61.3-68.9) | 59.3 (53.6-65.0) |
Mean weight, kg (95% CI)b | 94.3 (87.8-100.8) | 92.9 (86.3-99.5) | 96.9 (83.1-110.7) |
Smokers | 19 (25.0) | 14 (28.6) | 5 (18.5) |
Feverc | 55 (72.4) | 31 (63.3) | 24 (88.9) |
Cough | 61 (80.3) | 38 (77.6) | 23 (85.2) |
Altered smell | 9 (11.8) | 4 (8.2) | 5 (18.5) |
Altered taste | 7 (9.2) | 3 (6.1) | 4 (14.8) |
Diarrheac | 19 (25.0) | 16 (32.7) | 3 (11.1) |
Chest pain | 11 (14.5) | 9 (18.4) | 2 (7.4) |
Abdominal discomfort | 7(9.2) | 5 (10.2) | 2 (7.4) |
Shortness of breath | 66 (86.8) | 41 (83.7) | 25 (92.6) |
Mean time from symptom onset, days (95% CI)b | 6.93 (5.8-8.1) | 7.27 (5.7-8.8) | 6.33 (4.9-7.8) |
Comorbid conditions | | | |
None | 22 (28.9) | 14 (28.6) | 8 (29.6) |
One | 24 (31.6) | 14 (28.6) | 10 (37.0) |
Two or more | 30 (39.5) | 21 (42.9) | 9 (33.3) |
Hypertensionc | 43 (56.6) | 32 (65.3) | 11 (40.7) |
Congestive heart failure | 7 (9.2) | 6 (12.2) | 1 (3.7) |
Type 2 diabetes | 31 (40.8) | 18 (36.7) | 13 (48.2) |
Chronic obstructive pulmonary disease | 13 (17.1) | 9 (18.4) | 4 (14.8) |
Outcomes | | | |
Mean duration of oxygen, days (95% CI)b | 9.42 (8.0-10.8) | 8.92 (7.0-10.8) | 9.63 (7.7-11.6) |
Number admitted to the ICU | 14 (18.4) | 10 (20.4) | 4 (14.8) |
Mean ICU duration, days (95% CI)b,d | 9.29 (5.6-13.0) | 8.90 (4.4-13.4) | 10.25 (2.8-17.7) |
Mortality | 14 (18.4) | 8 (16.3) | 6 (22.2) |
Mean length of stay, days (95% CI)b | 10.09 (8.6-11.6) | 10.12 (8.1-12.1) | 10.04 (8.2-11.9) |
Table 2.
Sample Patient Characteristics by Ethnicity
Characteristic | All (n=76)a | White (n=49; 64.47%)a | NonWhite (n=27; 35.53%)a |
Sex | | | |
Male | 36 (47.4) | 24 (49.0) | 12 (44.4) |
Female | 40 (54.8) | 25 (51.0) | 15 (55.6) |
Patient presentation | | | |
Mean age, years (95% CI)b | 63 (59.8-66.2) | 65.1 (61.3-68.9) | 59.3 (53.6-65.0) |
Mean weight, kg (95% CI)b | 94.3 (87.8-100.8) | 92.9 (86.3-99.5) | 96.9 (83.1-110.7) |
Smokers | 19 (25.0) | 14 (28.6) | 5 (18.5) |
Feverc | 55 (72.4) | 31 (63.3) | 24 (88.9) |
Cough | 61 (80.3) | 38 (77.6) | 23 (85.2) |
Altered smell | 9 (11.8) | 4 (8.2) | 5 (18.5) |
Altered taste | 7 (9.2) | 3 (6.1) | 4 (14.8) |
Diarrheac | 19 (25.0) | 16 (32.7) | 3 (11.1) |
Chest pain | 11 (14.5) | 9 (18.4) | 2 (7.4) |
Abdominal discomfort | 7(9.2) | 5 (10.2) | 2 (7.4) |
Shortness of breath | 66 (86.8) | 41 (83.7) | 25 (92.6) |
Mean time from symptom onset, days (95% CI)b | 6.93 (5.8-8.1) | 7.27 (5.7-8.8) | 6.33 (4.9-7.8) |
Comorbid conditions | | | |
None | 22 (28.9) | 14 (28.6) | 8 (29.6) |
One | 24 (31.6) | 14 (28.6) | 10 (37.0) |
Two or more | 30 (39.5) | 21 (42.9) | 9 (33.3) |
Hypertensionc | 43 (56.6) | 32 (65.3) | 11 (40.7) |
Congestive heart failure | 7 (9.2) | 6 (12.2) | 1 (3.7) |
Type 2 diabetes | 31 (40.8) | 18 (36.7) | 13 (48.2) |
Chronic obstructive pulmonary disease | 13 (17.1) | 9 (18.4) | 4 (14.8) |
Outcomes | | | |
Mean duration of oxygen, days (95% CI)b | 9.42 (8.0-10.8) | 8.92 (7.0-10.8) | 9.63 (7.7-11.6) |
Number admitted to the ICU | 14 (18.4) | 10 (20.4) | 4 (14.8) |
Mean ICU duration, days (95% CI)b,d | 9.29 (5.6-13.0) | 8.90 (4.4-13.4) | 10.25 (2.8-17.7) |
Mortality | 14 (18.4) | 8 (16.3) | 6 (22.2) |
Mean length of stay, days (95% CI)b | 10.09 (8.6-11.6) | 10.12 (8.1-12.1) | 10.04 (8.2-11.9) |
×
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.
Table 3.
Stepwise Binomial Logistic Regression Model for Admission to the ICUa
Examination | B | Standard error | Wald X2 | Odds ratio (95% CI) | P value |
ICU admission |
Logistic regression step 1 |
Sex | 1.43 | 0.70 | 4.17 | 4.17 (1.06-16.43) | .041 |
Logistic regression step 2 |
Sex | 1.76 | 0.76 | 5.42 | 5.81 (1.32-25.52) | .020 |
Fever | 1.31 | 0.69 | 3.56 | 3.69 (0.95-14.35) | .059 |
Table 3.
Stepwise Binomial Logistic Regression Model for Admission to the ICUa
Examination | B | Standard error | Wald X2 | Odds ratio (95% CI) | P value |
ICU admission |
Logistic regression step 1 |
Sex | 1.43 | 0.70 | 4.17 | 4.17 (1.06-16.43) | .041 |
Logistic regression step 2 |
Sex | 1.76 | 0.76 | 5.42 | 5.81 (1.32-25.52) | .020 |
Fever | 1.31 | 0.69 | 3.56 | 3.69 (0.95-14.35) | .059 |
×
A limitation to the study is that only the charts of patients presenting to a single community hospital in Northern Arizona were reviewed. This could make our data less generalizable to other community hospitals across the country due to the study's primary location and the racial demographics of the area, as other community hospitals may not align to the demographics in Northern Arizona. Also, our retrospective sample size was small, which meant that we pooled diverse racial groups into a nonWhite classification to verify the outcomes associated with remdesivir among people of color. Further, treatment was selected at attending physician's discretion and numerous modalities were used during the study time period. Therefore, no comparisons could be made to a standard of care cohort and the exact treatment effect of remdesivir cannot be effectively determined based upon this retrospective chart review. Using multiple treatment modalities, including convalescent plasma and dexamethasone, could have altered the outcomes.
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.