Practice Update: Treating Patients Hospitalized With COVID-19

As more research is completed, COVID-19 treatment recommendations evolve. Guidance has been published by several institutions for treatment of patients hospitalized with COVID-19, and their basic recommendations are very similar. Although a standard of care has been offered, treatment of patients severely ill with COVID-19 is heavily dependent on a patient’s health condition and comorbidities. Clinical judgment should be used on a case-by-case basis.

Agents Recommended for Use

Corticosteroids, remdesivir, tocilizumab, and baricitinib are pharmaceutical agents commonly recommended for treatment of patients hospitalized with COVID-19.¹

Corticosteroids

Systemic corticosteroid use can reduce 28-day mortality in patients receiving respiratory support through oxygen supplementation and invasive or noninvasive mechanical ventilation, but not among those not receiving respiratory support.²

The immune response in patients with severe COVID-19 symptoms can cause lung injury and significant organ damage. Corticosteroids inhibit the inflammatory response, reducing cytokine release. This weakens the intensity of the immune response and lowers the severity of organ damage.¹

Common adverse effects (AEs) of steroid use include hyperglycemia, adrenal suppression, and myopathy, if given in high doses for long periods of time. Psychiatric disturbances may also occur, and steroids may also cause perforation risk in patients with gastrointestinal disease.²

Dexamethasone is the recommended corticosteroid. Other steroid equivalents can be substituted.²

Dosing regimen: Dexamethasone 6 mg intravenously (IV) or orally, once daily for up to 10 days or until hospital discharge.2

Remdesivir (Veklury)

As of press time, remdesivir (Veklury)—a nucleotide analogue RNA polymerase inhibitor³—is the only FDA-approved agent indicated for patients in this setting. It was approved in October 2020 for the treatment of adults and pediatric patients 12 years and older who weigh more than 40 kg and who require hospitalization for COVID-19. Remdesivir has an emergency use authorization (EUA) for hospitalized pediatric patients younger than 12 years, weighing between 3.5 kg and 40 kg with suspected or laboratory-confirmed COVID-19.³

Common AEs include nausea and increased liver enzymes.³

Dosing regimen: 200 mg IV once, then remdesivir 100 mg IV once daily for 5 days or until hospital discharge.³

Tocilizumab (Actemra)

Originally approved in 2010 for rheumatoid arthritis (RA), tocilizumab was issued an EUA for the treatment of COVID-19 in hospitalized adults and pediatric patients age 2 years and older who are receiving systemic corticosteroids and who require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).⁴

Tocilizumab, a monoclonal antibody to the IL-6 receptor, is administered by IV infusion. Tocilizumab may affect the expression of multiple cytochrome P450 enzymes. The precise effects are unknown, but they may last for several weeks after stopping therapy.⁴

Severe AEs include serious infections, gastrointestinal perforation, and hepatotoxicity. The most common AEs include upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased alanine transaminase level, and injection site reactions.⁴

Dosing regimen: Tocilizumab 8 mg/kg actual body weight (up to a maximum of 800 mg) is administered as a single IV dose. In clinical trials, one-third of participants received a second dose of tocilizumab 8 hours after the first if no clinical improvement was observed.¹

Baricitinib (Olumiant)

Another drug originally approved for RA, baricitinib has additional use in treating patients with COVID-19, and—at press time—is also under EUA in combination with remdesivir for those hospitalized with COVID-19.

Baricitinib is an oral Janus kinase inhibitor known to have anti-inflammatory effects. In the COV-BARRIER study (NCT04421027), baricitinib was found to have a safety profile similar to that of standard of care alone and was associated with reduced mortality in hospitalized adults with COVID-19. However, it did not show a significant reduction in the frequency of disease progression overall.⁵

Dose reductions should be considered when coadministered with strong OAT3 inhibitors (eg, probenecid).^6,7

Serious AEs include serious infections or worsening of active infections; increased risk of cancers; and increased risk of major cardiovascular events, blood clots, and tears in the stomach or intestines (especially with concomitant use of NSAIDs, corticosteroids, or methotrexate). The most common AEs include upper respiratory tract infections, nausea, cold sores, and shingles.⁶

Dosing regimen: Baricitinib dose is dependent on estimated glomerular filtration rate (eGFR). Duration of therapy is up to 14 days or until hospital discharge.¹

• eGFR at least 60 mL/min/1.73 m2: baricitinib 4 mg orally once daily
• eGFR 30 to less than 60 mL/min/1.73 m2: baricitinib 2 mg orally once daily
• eGFR 15 to less than 30 mL/min/1.73 m2: baricitinib 1 mg orally once daily
• eGFR less than 15 mL/min/1.73 m2: baricitinib is not recommended.¹
  

Treatment Recommendations

COVID-19 treatment is differentiated based on illness severity, determined by oxygen requirements. Prior to beginning therapy, patients severely ill with COVID-19 should be assessed for possible organ dysfunction and other comorbidities that could complicate potential therapy.¹

Drug Considerations

Tocilizumab may be preferred to baricitinib in patients who cannot take anything orally. However, baricitinib can also be administered via oral dispersion, gastrostomy tube, or nasogastric tube.^6,7

Fever Reduction

Acetaminophen is recommended for fever reduction for all patients with COVID-19, rather than NSAIDs. However, patients on chronic NSAIDs for other conditions should not discontinue use.¹

Patients Who Do Not Require Oxygen Supplementation

Patients who have an oxygen saturation greater than 95% on room air and who do not require oxygen supplementation above their baseline should receive supportive care and oxygen monitoring.² They should be closely monitored for disease progression.¹ In the case of high risk for disease progression, remdesivir may be appropriate.¹

The National Institutes of Health COVID-19 Treatment Panel recommends against the use of corticosteroids in these patients.1

For Patients Requiring Oxygen Supplementation

Therapy for patients who are severely ill with COVID-19 with oxygen requirements above their baseline depends on the level of oxygen.

For Patients Requiring Low-Flow Oxygen

For these patients, low-dose dexamethasone and remdesivir are recommended. Baricitinib or tocilizumab therapy is recommended as an adjuvant to be added based on different conditions, such as elevation of inflammatory marker C-reactive protein level (≥75 mg/L), increased oxygen requirements despite dexamethasone, and being within 96 hours of hospitalization.¹

For Patients Requiring High-Flow Oxygen

For patients requiring noninvasive high-flow oxygen, low-dose dexamethasone is recommended within 24 to 48 hours of patient admission to an ICU. Baricitinib or tocilizumab should be considered in addition to dexamethasone; the addition of remdesivir should be made if supplies are available. Remdesivir is prioritized for patients who are on low-flow oxygen supplementation at baseline.¹

Patients Requiring Mechanical Ventilation or ECMO

Low-dose dexamethasone is recommended within 24 to 48 hours of admission to an ICU and within 96 hours of hospitalization. Tocilizumab can be added to dexamethasone therapy. If tocilizumab is not available, baricitinib is a reasonable alternative.¹

Conclusions

Corticosteroids, remdesivir, tocilizumab, and baricitinib are not the only pharmaceutical agents available for treatment of hospitalized patients. Numerous other agents are under investigation, or are used on a case-by-case basis. Treating hospitalized patients with COVID-19 requires professional clinical judgment, as COVID-19 treatment guidelines are constantly evolving and can change based on evidence from studies and clinical trials.

Betsy Adegborioye is a PharmD candidate at South College School of Pharmacy, anticipated to graduate in spring 2022. Debra Lee, MBA, BA, is a PharmD candidate at Duquesne University School of Pharmacy, anticipated to graduate in spring 2022.

Jonathan Ogurchak, PharmD, CSP, is CEO and cofounder of STACK, a professional information management platform. He also serves as a preceptor at more than 15 schools of pharmacy for a virtual advanced pharmacy practice experiential rotation for specialty pharmacy, technology, and entrepreneurship.

References

1. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health. Updated January 14, 2022. Accessed January 17 2022. https://www.covid19treatmentguidelines.nih.gov/
2. YNHHS initial treatment algorithm for hospitalized adults with non-severe* COVID-19. Yale New Haven Health System. April 3, 2020. Accessed January 13, 2022. https://files-profile.medicine.yale.edu/documents/7801c631-3dcc-48fc-a438-3aa18f3b7130
3. Veklury (remdesivir). Veklury. Accessed January 13, 2022. https://www.vekluryhcp.com/
4. Emergency Use Authorization (EUA) for use of actemra for the treatment of COVID-19. Genentech. Accessed January 13, 2022. https://www.actemrahcp.com/covid-19.html
5. Marconi VC, Ramanan AV, de Bono S, et al; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomized, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021;9(12):1407-1418. doi:10.1016/S2213-2600(21)00331-3
6. Olumiant could be right for you. Olumiant. https://www.olumiant.com/. Accessed January 13, 2022.
7. Olumiant—baricitinib tablet, film coated. Boxed warning (prescribing information). Lilly; revised December 2021. Accessed January 13, 2022. https://uspl.lilly.com/olumiant/olumiant.html#s14