Infectious Diseases I
| (3) | Anti–IL-6 monoclonal antibody siltuximab |
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| (4) | Bruton tyrosine kinase inhibitors (e.g., acalabrutinib, ibrutinib, zanubrutinib) |
Antiviral therapy
Remdesivir
| (a) | Nucleotide prodrug of adenosine analog that binds to viral RNA polymerase, terminating |
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RNA transcription and inhibiting viral replication. Initially developed to treat MERS
| (b) | FDA-approved as Veklury for adult and pediatric (12 years or older and weighing at least |
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40 kg) patients hospitalized with COVID-19
| (1) | Dosage: 200 mg intravenously once, then 100 mg intravenously daily for 5 days; 10 |
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days’ duration can be considered in patients with no clinical improvement after 5 days
| (2) | Precautions include patients with baseline liver dysfunction, particularly those with |
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elevated alanine aminotransferase.
| (c) | Recommended in hospitalized patients who require supplemental oxygen with or without |
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corticosteroids or those patients at high risk for decompensation or immunocompromised.
| (1) | Should only be used in combination with corticosteroids in patients requiring high- |
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flow oxygen; not recommended in patients requiring MV or ECMO because benefit is
uncertain in subgroups of more severely ill patients.
| (2) | If supplies are limited, prioritize use for patients not requiring high-flow oxygen; not |
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recommended in patients requiring MV or ECMO.
| (d) | To date, the largest published, placebo-controlled trial is the Adaptive COVID-19 Treatment |
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Trial (ACTT-1), which compared remdesivir with placebo in 1063 patients hospitalized
with COVID-19 and receiving standard of care.
| (1) | Primary outcome was the time to recovery within 28 days, defined as the first day |
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of clinical improvement to categories 1–3 on an ordinal scale ranging from 1, not
hospitalized, return to usual care; to 3, hospitalized, not requiring supplemental
oxygen; to 8, death. All patients had scores of 4–7 at enrollment. At baseline, 197
patients (18.5%) required high-flow supplemental oxygen (score of 6), and 292 (25.6%)
required MV or ECMO (score of 7).
| (2) | Patients receiving remdesivir had a shorter time to recovery (median 11 days vs. 15 |
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days; rate ratio 1.32; 95% CI, 1.12–1.55; p<0.001). Among patients with baseline scores
of 6 and 7, rate ratios for time to recovery were 1.20 (95% CI, 0.79–1.81) and 0.95 (95%
CI, 0.64–1.42), respectively.
| (3) | Rate ratio for 14-day mortality among all patients was 0.70 (95% CI, 0.47–1.04), with |
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the greatest treatment effect in the largest patient subgroup (n=421) with a baseline
score of 5 (rate ratio 0.22 [95% CI, 0.08–0.58]). Corresponding rate ratios among
patients with baseline scores of 6 and 7 were 1.12 (95% CI, 0.53–2.38) and 1.06 (95%
CI, 0.59–1.92), respectively.
| (4) | Adverse effects were generally similar between groups. |
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| (e) | The prospective, randomized, open-label WHO SOLIDARITY Trial compared remdesivir |
to standard of care in 8275 hospitalized patients with COVID-19 requiring supplemental or
| (1) | Patients were randomized 1:1 to remdesivir standard dosing for 10 days or standard of |
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care; 68% of patients received corticosteroids.
| (2) | In-hospital mortality: remdesivir 14.5% versus standard of care 15.6 (rate ratio 0.91; |
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95% CI, 0.82–1.02; p=0.12)
| (3) | Patients receiving oxygen: 14.6% versus 16.3% (rate ratio 0.87; 95% CI, 0.76–0.99; |
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p=0.03)
| (4) | Progression to mechanical ventilation: 14.1% versus 15.7% (rate ratio 0.88; 95% CI, |
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0.77–1.00; p=0.04)