COVID treatment
Therapeutic management for hospitalized patients with COVID infection
Note: For additional recommendations, please refer to the Ontario Science Table’s COVID-19 Clinical Practice Guideline
MILD DISEASE SEVERITY: Symptomatic hospitalized patients but do not require supplemental oxygen
Note: Asymptomatic individuals incidentally discovered to have positive COVID-19 diagnostic tests are not candidates for therapy in the mild illness category
Risk level |
Definition |
Recommended treatment approach |
Dosing |
Higher risk of severe disease |
Please refer to the latest Ontario Science Table COVID-19 Clinical Practice Guideline and Ontario Ministry of Health Guidance Document (nirmatrelvir/ritonavir). Note: Sotrovimab is no longer recommended based on data demonstrating reduced activity against the circulating strain. |
Nirmatrelvir/ritonavir (Paxlovid)† OR Remdesivir ψ Inhaled budesonide may be considered in select cases Ψ patients must be within 7 days of symptom onset † patients must be within 5 days of symptom onset |
Nirmatrelvir/ritonavir: Remdesivir: Budesonide inhalation: |
Standard risk |
Please refer to the latest Ontario Science Table COVID-19 Clinical Practice Guideline. |
Inhaled budesonide may be considered in select cases. |
Budesonide inhalation: 800 µg INH BID x 14 days |
Nirmatrelvir/ritonavir Dosing: eGFR 60 mL/min or greater: 300/100 mg twice daily; eGFR 30 to 59 mL/min: 150/100mg twice daily; eGFR less than 30 mL/min: not recommended by manufacturer; however, the following modified dosing schedule proposed by the Ontario Renal Network can be considered: 300/100 mg on day 1 then 150/100 mg once daily for 4 more days (to be dosed after dialysis if patient receiving dialysis). This medication is associated with significant drug interactions. For more information, please refer to: Nirmatrelvir/Ritonavir (Paxlovid): What Prescribers and Pharmacists Need to Know.
MODERATE SEVERITY & SEVERE / CRITICALLY ILL
Disease severity |
Definition |
Recommended treatment approach |
Dosing |
Moderate |
Hospitalized patients requiring low-flow supplemental oxygen |
Dexamethasone + Remdesivir (or dexamethasone monotherapy if remdesivir is contraindicated or not available) If clinical progression despite 24-48 hours of dexamethasone (with or without remdesivir) and CRP >75, use one* of the following: Tocilizumab (1st line) Sarilumab (2nd line) Baricitinib (3rd line) *contact ID for approval |
Dexamethasone (standard dose): Remdesivir: Tocilizumab: Sarilumab: Baricitinib: |
Severe/critically ill |
Hospitalized patients requiring oxygen by high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation |
Dexamethasone If clinical progression despite dexamethasone, use one* of the following: Tocilizumab (1st line) Sarilumab (2nd line) Baricitinib (3rd line) *contact ID for approval If IL-6 inhibitors (tocilizumab, sarilumab) and baricitinib are not available: Consider High dose dexamethasone |
Dexamethasone (standard dose): Tocilizumab: Sarilumab: Baricitinib: Dexamethasone: (high dose) 12 mg po/IV daily x 10 days (or until discharge, if sooner) |
Baricitinib dosing: eGFR 60 mL/min or greater: 4 mg PO/NG daily; eGFR 30 to 59 mL/min: 2 mg PO/NG daily; eGFR 15 to 29 mL/min: 2 mg PO/NG q48h; eGFR less than 15 mL/min: not recommended; renal replacement therapy: not recommended
IL-6 inhibitors (tocilizumab, sarilumab)
Criteria for use: Infectious diseases approval is required. Sarilumab will only be considered when tocilizumab is unavailable.
- Mildly ill (i.e. non-hospitalized patients, hospitalized patients who do not require supplemental oxygen): Tocilizumab is not recommended outside of clinical trials for patients who are mildly ill with suspected or confirmed COVID-19.
- Moderately ill (i.e. hospitalized patients requiring low-flow supplemental oxygen): Tocilizumab is recommended for patients who are moderately ill with suspected or confirmed COVID-19, who:
- have evidence of systemic inflammation, defined as a CRP 75 mg/L or higher; AND
- have evidence of disease progression (i.e., increasing oxygen or ventilatory requirements) despite 24-48 hours of optimal dexamethasone therapy;
- AND are within 14 days of hospital admission (or within 14 days of a new COVID-19 diagnosis if nosocomially acquired).
- Critically ill (i.e. hospitalized patients requiring oxygen by high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation): Tocilizumab is recommended for patients who are critically ill with suspected or confirmed COVID-19 who:
- are on optimal dexamethasone therapy; AND
- are within 14 days of hospital admission (or within 14 days of a new COVID-19 diagnosis if nosocomially acquired).
Exclusion criteria:
- Known hypersensitivity to tocilizumab and/or sarilumab
- ANC < 2 x109/L
- PLT < 50 x109/L
- AST/ALT > 5X ULN
Dose:
- Tocilizumab:
Body Weight |
Dose Amount |
40 kg or less |
8mg/kg Use actual body weight Prescriber to indicate total dose in mg in the order - for convenience of preparing the product, round to nearest 10 mg. |
41 kg to 65 kg |
400 mg |
66 kg to 90 kg |
600 mg |
Greater than 91 kg |
800 mg |
- Sarilumab: 400 mg IV x 1 dose
Adverse effects and monitoring:
Adverse effect |
Monitoring |
Notes |
Infusion reactions |
Monitor vitals periodically throughout and post-infusion |
See IV drug monographs for tocilizumab and sarilumab for monitoring parameters during infusion |
Elevated liver enzymes (ALT/AST) |
Measure baseline and throughout therapy |
Most common laboratory abnormality noted in clinical trials |
Leukopenia (neutropenia, lymphopenia) |
Measure baseline and throughout therapy |
Uncommon |
*Note: IL-6 inhibitors are associated with reactivation of tuberculosis, hepatitis B and Strongyloides. Consider screening for latent infection if applicable.
Baricitinib
Criteria for use: Infectious diseases approval is required. Baricitinib will only be considered when tocilizumab or sarilumab are unavailable.
- Mildly ill (i.e. non-hospitalized patients, hospitalized patients who do not require supplemental oxygen): Baricitinib is not recommended outside of clinical trials for patients who are mildly ill with suspected or confirmed COVID-19.
- Moderately ill (i.e. hospitalized patients requiring low-flow supplemental oxygen): Baricitinib is recommended for patients who are moderately ill with suspected or confirmed COVID-19, who:
- have evidence of systemic inflammation, defined as a CRP 75 mg/L or higher; AND
- have evidence of disease progression (i.e., increasing oxygen or ventilatory requirements) despite 24-48 hours of optimal dexamethasone therapy;
- AND are within 14 days of hospital admission (or within 14 days of a new COVID-19 diagnosis if nosocomially acquired).
- Critically ill (i.e. hospitalized patients requiring oxygen by high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation): Baricitinib is recommended for patients who are critically ill with suspected or confirmed COVID-19 who:
- are on optimal dexamethasone therapy; AND
- are within 14 days of hospital admission (or within 14 days of a new COVID-19 diagnosis if nosocomially acquired).
Patients meeting the following criteria will be excluded from receiving baricitinib:
- Receipt of an IL-6 inhibitor (Note: tocilizumab or sarilumab are preferred over baricitinib if supply is available)
- Known hypersensitivity to baricitinib
- ANC less than 0.5 x109/L
- Absolute lymphocyte count less than 0.2 x109/L
- AST/ALT greater than 5X ULN
- eGFR less than 15 mL/min
- Pregnancy
*Note: Baricitinib is associated with reactivation of tuberculosis, hepatitis B and Strongyloides. Consider screening patients at risk for latent infection.
Dose:
- eGFR 60 mL/min or greater: 4 mg PO/NG daily
- eGFR 30 to 59 mL/min: 2 mg PO/NG daily
- eGFR 15 to 29 mL/min: 2 mg PO/NG q48h
- eGFR less than 15 mL/min: not recommended
- Renal replacement therapy: not recommended
Duration of therapy:
- 14 days or until hospital discharge, whichever is shorter
Adverse effects & monitoring:
Adverse effect |
Monitoring |
Notes |
Transaminitis (ALT/AST) |
Measure baseline and monitor throughout therapy |
Discontinue therapy if AST or ALT is greater than 5X ULN |
Leukopenia (neutropenia, lymphopenia) |
Measure baseline and monitor throughout therapy |
Discontinue therapy if ANC is less than 0.5 x109/L or Absolute lymphocyte count is less than 0.2 x109/L |
Thrombosis |
Monitor clinically throughout therapy |
|
Accumulation in renal dysfunction |
Measure Baseline serum creatine and monitor throughout therapy |
Dose adjustments required for eGFR less than 60 mL/min. Not recommended if eGFR is less than 15 mL/min. |
Remdesivir CKD Dosing recommendation
The product monograph for remdesivir does not recommend use of remdesivir in patients with eGFR <30 ml/min, including those on renal replacement therapy. This is due to lack of data from randomized trials (which excluded patients with eGFR < 30 ml/min) in conjunction with theoretical concerns around nephrotoxic potential of the diluent (of sulfobutylether-β-cyclodextrin; SBECD) as well remdesivir’s active metabolite. These concerns have yet to be supported.
There is mounting experience and observational studies suggesting that full dose remdesivir is safe in patients with chronic kidney disease (CKD), including those on dialysis, particularly for the short durations commonly prescribed (3-5 days). Recognizing that patients with CKD are at high risk of poor outcomes secondary to COVID and the experience with using full doses without apparent toxicity, we are recommending full doses of remdesivir in patients with CKD (with the exception of outpatients receiving dialysis, where dosing post-dialysis may be used for ease of administration for presumed low severity of illness):
Kidney Function: |
Remdesivir Dosing recommendation |
eGFR < 30 ml/min not on dialysis |
Full dose (x3 days for mild, x5 days for moderate) |
CRRT / SLED |
Full dose (x3 days for mild, x5 days for moderate) |
IHD 3x/week |
Outpatients: 200 mg IV x1 dose at end of dialysis then 100 mg x 1 dose in 48-72 hours at end of dialysis (2 doses) Inpatients (more moderate illness): can consider full dosing |
IHD 5x/week – short daily |
Full dose (x3 days for mild, x5 days for moderate) |
PD |
Full dose (x3 days for mild, x5 days for moderate) |
It is noted that Gilead (manufacturer of remdesivir) is currently conducting a clinical trial (https://clinicaltrials.gov/ct2/show/NCT04745351) assessing full dose of remdesivir in patients with CKD. Once the results are available, dosing in this population will be re-evaluated.
References:
- Schieber TJ, Bennett N, Aragon L, Ploetz J, Boyd S. Real-world risk evaluation of remdesivir in patients with an estimated glomerular filtration rate of less than 30 mL/min. Am J Health Syst Pharm. 2021;78(23):2101-2102. doi:10.1093/ajhp/zxab245
- Thakare S, Gandhi C, Modi T, et al. Safety of Remdesivir in Patients With Acute Kidney Injury or CKD. Kidney Int Rep. 2021;6(1):206-210. doi:10.1016/j.ekir.2020.10.005
- Aiswarya D, Arumugam V, Dineshkumar T, et al. Use of Remdesivir in Patients With COVID-19 on Hemodialysis: A Study of Safety and Tolerance. Kidney Int Rep. 2021;6(3):586-593. doi:10.1016/j.ekir.2020.12.003
- Cheng M, Fowler R, Murthy S, Pinto R, Sheehan NL, Tseng A. Remdesivir in Patients With Severe Kidney Dysfunction: A Secondary Analysis of the CATCO Randomized Trial. JAMA Netw Open.2022;5(8):e2229236. doi:10.1001/jamanetworkopen.2022.29236