Antivirals that directly target SARS-CoV-2 replication are believed to have the greatest effect when given early in the course of the disease1
COVID-19 is driven by the replication of SARS-CoV-21
When and how long viral replication occurs can vary significantly across patients.Age, underlying conditions,and vaccination status are some factors that can affect viral replication4,5
Viral replication can still occur later in the disease course, even during the inflammatory phase6
Immunosuppressive therapies (eg, corticosteroids) that modulate the inflammatory response may impair viral clearance and extend viral replication1,7
NIH recommendations include VEKLURY across a range of disease severity1
Select guidelines related to the use of VEKLURY and corticosteroids in adult patients hospitalized with COVID-19
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aCorticosteroids that are prescribed for an underlying condition should be continued.
bEvidence suggests that the benefit of VEKLURY is greatest when the drug is given early in the course of COVID-19 (eg, within 10 days of symptom onset).
cFor a list of risk factors, see the CDC webpage: Underlying Medical Conditions Associated With Higher Risk for Severe COVID-19.
dIf these patients progress to requiring HFNC oxygen, NIV, MV, or ECMO, the full course of VEKLURY should still be completed.
eConventional oxygen refers to oxygen supplementation that is not HFNC oxygen, NIV, MV, or ECMO.
fDexamethasone should be initiated immediately, without waiting until the second immunomodulator can be acquired. If other immunomodulators cannot be obtained or are contraindicated, use dexamethasone alone (AI).
gPreferred immunomodulator: PO baricitinib (AI); preferred alternative: IV tocilizumab (BIIa); additional alternatives (listed in alphabetical order): IV abatacept (CIIa), IV infliximab (CIIa).
hFor more information on using VEKLURY in people with immunocompromising conditions, see Special Considerations in People Who Are Immunocompromised.
iEg, those with a low Ct value, as measured by an RT-PCR result or with a positive rapid antigen test result.
jRecommended immunomodulators (listed in alphabetical order): PO baricitinib (BIIa) and IV tocilizumab (BIIa). If PO baricitinib and IV tocilizumab are not available or feasible to use, PO tofacitinib can be used instead of PO baricitinib (CIIa), and IV sarilumab can be used instead of IV tocilizumab (CIIa).
Strength of Recommendations: A=Strong recommendation for the statement; B=Moderate recommendation for the statement; C=Weak recommendation for the statement.
Evidence for Recommendation: I: High quality of evidence: 1 or more randomized trials without major limitations,* well-powered subgroup analyses of such trials, or meta-analyses without major limitations;
IIa: Moderate quality of evidence: Randomized trials and subgroup analyses of randomized trials that do not meet the criteria for a I rating; IIb: Moderate quality of evidence: Observational studies without major limitations†; III: Expert opinion.
VEKLURY is FDA approved across a spectrum of COVID-19 severity and can be used regardless of a hospitalized patient’s oxygen requirements8
*The rating may be lower than I in cases where trials have produced conflicting results.
‡This category also includes meta-analyses of observational studies.
Ct=cycle threshold; DEX=dexamethasone; ECMO=extracorporeal membrane oxygenation; HFNC=high-flow nasal cannula; LFO=low-flow oxygen; MV=mechanical ventilation; NIV=noninvasive ventilation; PO=oral; RT-PCR=reverse transcription–polymerase chain reaction.
Many eligible patients hospitalized with COVID-19 are missing the opportunity for guideline-based therapy with VEKLURY1,3
In a retrospective real-world study of more than 97,000 US patients who were hospitalized for COVID-19 and received dexamethasone within the first 2 days,
of patients not receiving supplemental oxygen at baseline (n=42,571) were treated with dexamethasone monotherapy (n=15,972) despite the NIH recommendation against its use with these patients. VEKLURY is the only recommended antiviral therapy for adult patients who are hospitalized for COVID-19 and do not require supplemental oxygen.
of patients receiving low-flow oxygen (n=35,768) were treated with dexamethasone monotherapy (n=13,234). The NIH guidelines recommend use of VEKLURY plus dexamethasone for most patients in this category.
“Many patients are being treated with dexamethasone monotherapy across the range of supplemental oxygen support, including patients with no oxygen support requirements, which goes against…guideline recommendations.”3
ACTT-1: VEKLURY reduced recovery time in patients hospitalized with COVID-191,2
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Median 10 days to recovery with VEKLURY vs 15 days with placebo; recovery rate ratio: 1.29 (95% CI, 1.12 to 1.49), P < 0.001
Primary endpoint was time to recovery within 29 days after randomization
Adverse reaction frequency was comparable between VEKLURY and placebo–all adverse reactions (ARs), Grades ≥3: 41 (8%) with VEKLURY vs 46 (9%) with placebo; serious ARs: 2 (0.4%)* vs 3 (0.6%); ARs leading to treatment discontinuation; 11 (2%)† vs 15 (3%).
Mortality in the overall population at Day 291,2:
Mortality at Day 29 was a prespecified secondary endpoint.
- Results in the overall population at Day 29 were not statistically significant; ACTT-1 was not powered to evaluate a difference in mortality in the overall population
In a post hoc subgroup analysis, VEKLURY reduced mortality rates at Day 29 in patients on low-flow oxygen at baseline by 70% vs placebo; HR: 0.30 (95% CI, 0.14 to 0.64).2,6
No difference was demonstrated in the other baseline oxygen status subgroups2,6
There was no adjustment to control for multiple testing in this post hoc analysis2
ACTT-1 study design: a randomized, double-blind, placebo-controlled, phase 3 clinical trial in hospitalized adult patients with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19, who received VEKLURY (n=541) or placebo (n=521) for up to 10 days. Recovery was defined as patients who were no longer hospitalized or hospitalized but no longer required ongoing medical care for COVID-19.1,2
*Seizure (n=1), infusion-related reaction (n=1).
†Seizure (n=1), infusion-related reaction (n=1), transaminases increased (n=3), ALT increased and AST increased (n=1), GFR decreased (n=2), acute kidney injury (n=3).
HR=hazard ratio.
Select study population characteristics1
Compared to nonreadmitted patients, readmitted patients:
- Were older: median 71 years vs 63 years
- Had more comorbidities: CCI ≥4: 36% vs 16%
- Were more likely to have NSOc (42% vs 39%) and less likely to be on low-flow oxygen (40% vs 42%)
- Were less likely to be treated with VEKLURY: 48% vs 57%
- Were more likely to have received corticosteroid monotherapy during index hospitalization: 38% vs 29%
Compared to non-VEKLURY patients, VEKLURY patients:
- Were younger: median 62 years vs 64 years
- Were more likely to have received some level of supplemental oxygen support (any supplemental oxygen support, 1-NSOc): 70% vs 48%
CCI=Charlson Comorbidity Index; NSOc=no supplemental oxygen charges.
Study considerations
Real-world studies should be interpreted based on the type and size of the source datasets and the methodologies used in order to mitigate potential confounding or bias. Real-world data should be considered in the context of all available data; results may vary between real-world studies
Strengths3
Large study population with COVID-19 diagnosis present on admission from a multicenter administrative database
Complements and builds on the findings from other RCTs and subsequent research over the evolution of the COVID-19 era
Two well-established methods were applied, PSM and IPTW, to balance inherently different groups due to confounding by indication; consistent results were obtained with the 2 methods
Limitations3
Potential for residual confounding due to imbalances in unmeasured variables between the treatment groups even after PSM
Data on time of symptom onset or time since first positive COVID-19 test were not available No vaccination data were available in the database
Patients from hospitals that did not report any charges for low-flow oxygen were not included in the NSOc group to ensure that data were from hospitals that uniformly report supplemental oxygen requirements
-
Data on antiviral use or any other treatment administered prior to hospitalization were unavailable, which may have led to residual confounding
IPTW=inverse probability of treatment weighting; PSM=propensity score matching; NSOc=no supplemental oxygen charges; RCT=randomized controlled trial.
Patients treated with VEKLURY had significantly reduced likelihood of COVID-19–related readmission1
Reduced likelihood of 30-day COVID-19–related readmission was observed with VEKLURY
Reduced likelihood of 30-day COVID-19–related readmission was observed with VEKLURY
In the overall cohort, patients treated with VEKLURY were 40% less likely to be readmitted for COVID-19 within 30 days; aOR: 0.60 (95% Cl, 0.58 to 0.62), P < 0.0001.
- 3.0% of VEKLURY patients vs 5.4% of non-VEKLURY patients experienced COVID-19–related readmission within 30 days
Reduction of 30-day COVID-19–related readmission with VEKLURY was consistently observed across variant periods and all supplemental oxygen requirements (May 2020 through April 2022)1
Patients treated with VEKLURY not requiring supplemental oxygen showed the greatest reduction in readmission—45% less likely to be readmitted
aOR=adjusted odds ratio; ECMO=extracorporeal membrane oxygenation; IMV=invasive mechanical ventilation; NIV=noninvasive ventilation.
Treatment with VEKLURY was associated with significantly reduced likelihood of all-cause readmission rates1
Reduced likelihood of 30-day all-cause readmission was observed with VEKLURY
Reduced likelihood of 30-day all-cause readmission was observed with VEKLURY
In the overall cohort, patients treated with VEKLURY were 27% less likely to be readmitted for any reason within 30 days; aOR: 0.73 (95% CI 0.72 to 0.75), P < 0.0001.
- 6.3% of VEKLURY patients vs 9.1% of non-VEKLURY patients experienced all-cause readmission within 30 days
30-day all-cause readmission across variant periods and by maximum oxygenation in index hospitalization (May 2020 through April 2022)1
- A statistically significant reduction in the likelihood of 30-day all-cause readmission was observed for all supplemental oxygen levels, except in the IMV/ECMO group, which did not meet statistical significance due to the low sample size of this group4
aOR=adjusted odds ratio; ECMO=extracorporeal membrane oxygenation; IMV=invasive mechanical ventilation; NIV=noninvasive ventilation.
Baseline characteristics: VEKLURY use at index hospitalization1
| Select characteristics | VEKLURY(n=248,785) | Non-VEKLURY(n=191,816) | |
|---|---|---|---|
| Median age (IQR), n | 62 (51-73) | 64 (52-76) | |
| Age group, % | |||
| 18-49 y | 23 | 21 | |
| 50-64 y | 33 | 29 | |
| 65+ y | 44 | 50 | |
| Maximum supplemental oxygenation support (highest level of oxygenation during the hospitalization), % | |||
| No supplemental oxygen charges | 30 | 52 | |
| Low-flow oxygen | 46 | 36 | |
| High-flow oxygen/NIV | 20 | 10 | |
| IMV/ECMO | 4 | 2 | |
| Variant period, % | |||
| Pre-Delta | 49 | 57 | |
| Delta | 34 | 23 | |
| Omicron | 17 | 20 | |
ECMO=extracorporeal membrane oxygenation; IMV=invasive mechanical ventilation; IQR=interquartile range; NIV=noninvasive ventilation.
Baseline characteristics: At index hospitalization by all-cause readmission within 30 days1
| Select Characteristics | Readmitted(n=33,217) | Nonreadmitted(n=407,384) | Overall(N=440,601) |
|---|---|---|---|
| Median age (IQR), n | 71 (60-80) | 63 (51-74) | 63 (51-74) |
| Age group, % | |||
| 18-49 y | 11 | 23 | 22 |
| 50-64 y | 24 | 32 | 31 |
| 65+ y | 65 | 45 | 47 |
| Gender, % | |||
| Female | 48 | 49 | 49 |
| Race, % | |||
| White | 73 | 69 | 70 |
| Black | 18 | 17 | 17 |
| Asian | 2 | 2 | 2 |
| Other | 7 | 12 | 11 |
| Ethnicity, % | |||
| Hispanic | 11 | 17 | 16 |
| Non-Hispanic | 79 | 73 | 73 |
| Unknown | 10 | 11 | 11 |
| CCI, % | |||
| 0 | 15 | 33 | 32 |
| 1-3 | 49 | 51 | 50 |
| ≥4 | 36 | 16 | 18 |
| Maximum supplemental oxygenation support (highest level of oxygenation during the hospitalization), % | |||
| No supplemental oxygen charges | 42 | 39 | 39 |
| Low-flow oxygen | 40 | 42 | 42 |
| High-flow oxygen/NIV | 16 | 16 | 16 |
| IMV/ECMO | 3 | 3 | 3 |
CCI=Charlson Comorbidity Index; ECMO=extracorporeal membrane oxygenation; IMV=invasive mechanical ventilation; IQR=interquartile range; NIV=noninvasive ventilation.
“Hospital readmission is a key marker of quality of care and increases the burden on patients.”
Explore real-world VEKLURY readmission data
This retrospective analysis examined the impact of VEKLURY on readmission rates for patients hospitalized due to COVID-19.
REAL-WORLD READMISSION DATA
Clinical insights on VEKLURY
Learn more about treatment with VEKLURY for your patients with a broad spectrum of COVID-19 severity.
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Important Safety Information
Important Safety
Information and Indication
Tap for Important Safety Information, including contraindication for history of clinically significant hypersensitivity to VEKLURY.
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (birth to <18 years of age weighing ≥1.5 kg, who are hospitalized, or not hospitalized, with mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Contraindication
- VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.
Warnings and precautions
- Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY; most reactions occurred within 1 hour. Monitor patients during infusion and observe for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time of up to 120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
- Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10x ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
- Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.
Adverse reactions
- The most common adverse reaction (≥5% all grades) was nausea.
- The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.
Dosage and administration
- Administration should take place under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible.
- Treatment duration:
- For patients who are hospitalized, VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
- For patients who are hospitalized and do not require invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended up to 5 additional days, for a total treatment duration of up to 10 days.
- For patients who are hospitalized and require invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
- For patients who are not hospitalized, diagnosed with mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset for outpatient use.
- Testing prior to and during treatment: Perform hepatic laboratory and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
- Renal impairment: No dosage adjustment of VEKLURY is recommended in patients with any degree of renal impairment, including patients on dialysis. VEKLURY may be administered without regard to the timing of dialysis.
Pregnancy and lactation
- Pregnancy: Available clinical trial data for VEKLURY in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following second- and third-trimester exposure. There are insufficient data to evaluate the risk of VEKLURY exposure during the first trimester. Maternal and fetal risks are associated with untreated COVID-19 in pregnancy.
- Lactation: VEKLURY can pass into breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VEKLURY and any potential adverse effects on the breastfed child from VEKLURY or from an underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
Indication
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (birth to <18 years of age weighing ≥1.5 kg), who are hospitalized, or not hospitalized, with mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Please see full Prescribing Information for VEKLURY.
Important Safety Information
Important Safety
Information and Indication
Tap for Important Safety Information, including contraindication for history of clinically significant hypersensitivity to VEKLURY.
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (birth to <18 years of age weighing ≥1.5 kg, who are hospitalized, or not hospitalized, with mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Contraindication
- VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.
Warnings and precautions
- Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY; most reactions occurred within 1 hour. Monitor patients during infusion and observe for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time of up to 120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
- Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10x ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
- Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.
Adverse reactions
- The most common adverse reaction (≥5% all grades) was nausea.
- The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.
Dosage and administration
- Administration should take place under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible.
- Treatment duration:
- For patients who are hospitalized, VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
- For patients who are hospitalized and do not require invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended up to 5 additional days, for a total treatment duration of up to 10 days.
- For patients who are hospitalized and require invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
- For patients who are not hospitalized, diagnosed with mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset for outpatient use.
- Testing prior to and during treatment: Perform hepatic laboratory and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
- Renal impairment: No dosage adjustment of VEKLURY is recommended in patients with any degree of renal impairment, including patients on dialysis. VEKLURY may be administered without regard to the timing of dialysis.
Pregnancy and lactation
- Pregnancy: Available clinical trial data for VEKLURY in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following second- and third-trimester exposure. There are insufficient data to evaluate the risk of VEKLURY exposure during the first trimester. Maternal and fetal risks are associated with untreated COVID-19 in pregnancy.
- Lactation: VEKLURY can pass into breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VEKLURY and any potential adverse effects on the breastfed child from VEKLURY or from an underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
Indication
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (birth to <18 years of age weighing ≥1.5 kg), who are hospitalized, or not hospitalized, with mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Please see full Prescribing Information for VEKLURY.
