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Find information on the use of therapies in the management of adult patients with confirmed COVID-19 across all disease severities (mild-moderate, severe, and critically ill).

Last updated: November 14, 2023

These therapy recommendations apply to adult patients with confirmed COVID-19 across all disease severities (mild-moderate, severe, and critically ill).

Clinical practice guide and tools
Various novel agents have become available in B.C. for the treatment of COVID-19 in mild-moderately ill patients. These therapies include a direct-acting oral combination antiviral nirmatrelvir/ritonavir (Paxlovid) and an IV direct acting antiviral remdesivir (Veklury). 

A monoclonal antibody, sotrovimab (Xevudy) is no longer in routinely use due to potential loss of activity against current variants of concern. It likely retains some activity but it is reserved as a last-line agent. Tixagevimab/cilgavimab (Evusheld) is no longer used due to complete loss of activity.

Clinical Practice Guide and tools for managaing mild to moderate illness

 

Clinical Practice Guide: Recommendations and Evidence -updated November 14, 2023


  • This document provides general guidance on the use of four therapeutic agents for clinicians and supporting evidence. It includes information on:
    • nirmatrelvir/ritonavir (Paxlovid). 
    • remdesivir (Veklury)

    • sotrovimab (Xevudy)

    • molnupiravir (Lagevrio)

 

Pathway for treatment of mild‐moderate COVID‐19 treatment

- updated November 4, 2022

  • This document provides a succinct, hyperlinked flowchart that guides clinicians in assessment and treatment of patients with mild-moderate COVID-19. 

 

Practice Tool #1: Step-by-Step Assessment for Clinicians - Updated November14, 2023


  • This guide is a step-by-step clinical assessment tool for clinicians such as nurses or physicians who are directly involved in assessment and management of patients with mild-moderate COVID-19.
 

 

Practice Tool #2: Definitions of Clinically Extremely Vulnerable (CEV) - updated July 26, 2022


  • Clinically Extremely Vulnerable (CEV) criteria were developed by a group of provincial experts caring for patients with conditions such as cancer, cystic fibrosis, organ transplant and renal disease. There are three CEV Groups: 1, 2 and 3.
 

 

Practice Tool #3: Drug-Drug Interactions and Contraindications - updated  September 6, 2022


  • This document was developed to identify drug-drug interactions and contraindications with nirmatrelvir/ritonavir (Paxlovid), as well as their potential management strategies.

 

Practice Tool #4: Pharmacist Counselling Checklist - updated June 21, 2022


  • This checklist is intended for use by pharmacists as a quick reference guide and should not be regarded as a substitute for clinical judgement and patient-specific counselling.

 

Practice Brief: Crushing Nirmatrelvir/ritonavir (Paxlovid) - new July 4, 2022


  • Both ritonavir and nirmatrelvir can be split or crushed and mixed with apple sauce, pudding or any common food or liquid including dairy-containing products based on Phase I studies demonstrating that suspensions achieve similar pharmacokinetics to whole tablets.
  • Both ritonavir and nirmatrelvir can be crushed and mixed with water to the desired consistency and considered for administration via feeding tubes; the tube should be flushed with water after administration. There are currently no precise recipes available; standard practices for administering regular powered tablets via feeding tubes should be applied. It may not be appropriate to administer crushed medications through smaller bore feeding tubes where obstruction is a concern (e.g., jejunal or naso-jejunal); consultation with an expert dietician or nursing staff may be required.
  • Due to lack of information pertaining to stability and storage of nirmatrelvir suspension, it is recommended that any suspension made with crushed nirmatrelvir and ritonavir be extemporaneously compounded as single-dose preparation and not as multi-dose liquid.

 

COVID-19 Action Plan - Updated November 4, 2022

  • This Action Plan can be used with high-risk patients who are candidates for COVID-19 therapy before they get sick.
  • Patients can follow testing, treatment and public health recommendations contained in the Green, Yellow and Red zones.

 

Health Care Provider Information on Paxlovid, remdesivir and sotrovimab  - May 2023

  • Overview for health care providers onC OVID-19 Therapies: nirmatrelvir/ritonavir (Paxlovid), remdesivir (Veklury) and sotrovimab (Xevudy)
 

Clinical Practice Guide for Tixagevimab/Cilgavimab (Evusheld) for Prophylaxis

Health Canada approved a monoclonal antibody cocktail tixagevimab/cilgavimab (Evusheld) for the prevention of COVID-19 in those who are severely immune compromised and unlikely to mount an adequate immune response to COVID‐19 vaccination or for whom COVID-19 vaccination is not recommended. 

Most variants of concern circulating in BC, including BQ.1, BQ. 1.1 and XBB 1.5, are resistant to tixagevimab/cilgavimab (Evusheld) and Health Canada has issued a warning regarding the high risk of failure if used against these variants. Tixagevimab/cilgavimab is therefore not recommended for any indication in any patient population. 

Therapies for mild to moderate illness

Mild to moderate disease refers to patients with COVID-19 symptoms such as cough, nasal congestion, headache, sore throat, taste disturbance, muscle aches, fever and/or malaise who do not require supplemental oxygen support (i.e., have oxygen saturations of ≥ 94% on room air) for COVID-19 illness. 

Patients are usually ambulatory and recovering at home; however, patients with mild-moderate COVID-19 may also reside in Long-Term-Care or Assisted Living or be hospitalized for reasons other than to receive respiratory/organ support for COVID-19.

For more detailed information, refer to the Clinical Practice Guide 

 
Nirmatrelvir/ritonavir 300/100mg PO BID x 5 days (or 150/100mg PO BID x 5 days for eGFR 30-60 ml/min) is recommended within 5 days of symptom onset* for patients without contraindications** with a non-reassuring symptom presentation and trajectory who are at increased risk# for hospitalization or progression to severe COVID-19 

*It is appropriate to allow the addition of adequate time for delivery of medication for those living in remote and rural communities.

**Contraindications include eGFR <30 ml/min, end-stage liver disease (Child Pugh C or cirrhosis), hypersensitivity to protease inhibitors, or serious drug-drug interactions that cannot be managed (see Practice Tool #3: Drug-Drug Interactions and Contraindications for a complete list)

#Patients at high-risk for disease progression and hospitalization from COVID-19 are those who are:

  • Immunocompromised individuals and those with high-risk conditions identified as Clinically Extremely Vulnerable Group 1, Group 2, and Group 3 (CEV 1, CEV 2 and CEV 3),regardless of vaccine status or previous infection (See also Practice Tool 2 CEV Definitions).  

  • Individuals with TWO of the three following risk factors:
    • ≥70 years (≥ 60 years if Indigenous), AND/OR
    • unvaccinated or under-vaccinated as per Strong Recommendations by NACI^, AND/OR
    • have a serious chronic medical condition*

  • ^ National Advisory Committee on Immunization: i.e., lack of a primary two-dose series PLUS a “Fall Booster” (or a booster in the last year), which may be delayed up to 6 months post COVID-19 infection
*Serious chronic medical conditions may include stroke, heart failure, heart disease, diabetes, kidney or liver disease, chronic lung disease like COPD or interstitial lung disease, neurological conditions. Some discretion can be used


 
Remdesivir 200mg IV on day 1, followed by 100mg IV on days 2 and 3 (200mg IV on day 1, followed by 100mg IV 48-72 hours later in eGFR <30ml/min) is recommended within 7 days of symptom onset as an alternative to nirmatrelvir/ritonavir. Outpatients at the highest risk of progression to severe disease are currently being prioritized for treatment with remdesivir, which includes those who are:  
  • Severely immunocompromised individuals identified as Clinically Extremely Vulnerable Group 1 (CEV 1), regardless of vaccine status or previous infection (See also Practice Tool 2 CEV Definitions).

  • Moderately immunocompromised individuals and those with high-risk conditions identified as Clinically Extremely Vulnerable Group 2 and 3 (CEV 2 and CEV 3) (See also Practice Tool 2 CEV Definitions), who are either ≥ 60 regardless of vaccine status or previous infection 

  • Under extenuating circumstances, (clinical judgment required), patients who have NOT had a COVID-19 vaccine or COVID-19 infection in the last year who are: 
    • CEV 2 and CEV 3 less than 60 years, or 
    • Elderly 70 years or older with 3 or more chronic conditions 

Outpatients with the highest risk of hospitalization are currently being prioritized and offered treatment with remdesivir due to operational constraints and unclear benefit in lower risk individuals. 


Inpatients with mild-moderate COVID-19 are at higher risk of progression to severe disease than outpatients, and they may be offered remdesivir in accordance with the nirmatrelvir/ritonavir eligibility criteria if drug-drug interactions or contraindications are present. 

 

Sotrovimab 500mg IV X 1 dose has reduced efficacy against recombinant Omicron variants such as XBB, although it may retain some activity. Real-world evidence shows limited efficacy against the BA 1. and BA. 2 variants of concern (VoCs) in immunocompromised or non-immune individuals, which may predict its performance against most XBB VoCs. 


If sotrovimab is used in cases where remdesivir or nirmatrelvir/ritonavir cannot be used, patient disclosure to risks and benefits in consideration of individual circumstances (clinical and immune status, patient values, logistics) is necessary. The convenience of single dose sotrovimab should not be the primary indication for use.

 

 

Tixagevimab/cilgavimab 600mg IM x 1 dose has demonstrated a 50.5% relative risk reduction (RRR) in COVID-19 hospitalization and death in unvaccinated, non-hospitalized adults with mild- moderate COVID-19 (TACKLE), which is lower than the RRR seen with other COVID-19treatments in similar trials. Tixagevimab/cilgavimab is likely ineffective against many currently circulating VoCs including BA. 4.6, BF. 7, BA. 2.75.2, BQ 1, BQ 1.1 and XBB where 300-1000-fold reductions in binding are seen. 


If tixagevimab/cilgavimab is used as a last line treatment in cases where nirmatrelvir/ritonavir, IV remdesivir or sotrovimab cannot be used, disclosure to patients of risks, including cardiovascular serious adverse events (SAEs), and benefits and consideration of individual circumstances (clinical and immune status, patient values, logistics) is necessary. The convenience of the IM route of administration of tixagevimab/cilgavimab should not be the primary indication for use.

 
Colchicine was evaluated at 0.6 mg PO BID x 3 days, then 0.6 mg daily x 27 days in a large Canadian RCT (COLCORONA) and demonstrated a reduction in progression of COVID-19 and hospitalization in a sub-group of patients with PCR confirmed COVID-19. The trial’s primary endpoint was not statistically significant and impact of colchicine against hospitalizations from Omicron is unclear. 

The trial was stopped early; due to decreased power leading to the low certainty of its results, as well as a higher risk of adverse events (diarrhea and blood clots) guidelines (WHO, NIH) do not recommend colchicine. 

If colchicine is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values are necessary.

 
Fluvoxamine was evaluated at 100 mg PO BID x 14 days in a Brazilian RCT (TOGETHER) and shown to reduce emergency room visits lasting > 6 hours, a surrogate endpoint for hospitalizations. It did not demonstrate reductions in actual hospitalizations from COVID-19, length of stay or mortality. For every 12 trial participants, one additional patient stopped fluvoxamine prematurely. 

Due to low generalizability from a very high event rate during the Delta wave, as well as lack of robust safety data considering that the maximum daily dose was used in the trial, guidelines (e.g., IDSA, NIH) do not recommend the use of fluvoxamine. A Canadian fluvoxamine study (STOP COVID 2) stopped enrollment due to futility. 

If fluvoxamine is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values are necessary.

 
Inhaled corticosteroids budesonide 800 µg twice daily OR ciclesonide 320 µg twice daily for 14 days may be considered within 14 days of symptom onset in adults with mild-moderate lower respiratory track symptoms of COVID-19 (e.g., cough, increased work of breathing or pneumonia) aged ≥65 OR aged ≥50 with underlying health conditions (e.g., heart disease, chronic lung disease, diabetes, stroke or other neurological conditions) who are not candidates for nirmatrelvir/ritonavir, sotrovimab or remdesivir. 

Patients should be informed of uncertainty in the benefit of treatment in decreasing symptom severity or progression, and the risks and potential adverse effects. 
 

 
Based on the current scientific evidence and best practice guidelines, inclusive of considering retracted publications, the College of Physicians and Surgeons of BC, the College of Pharmacists of BC, the BC College of Nurses and Midwives and the CTC do not approve of the use of ivermectin for either treatment or prophylaxis for COVID-19 and BC registrants must not prescribe it for this purpose. Ivermectin should not be used outside of approved clinical trials.

 
Various therapies have been evaluated to be ineffective and/or unsafe in treatment of mild-moderate COVID-19 and are not recommended outside of clinical trials. These include:
  • Lopinavir/ritonavir (Kaletra)
  • Oseltamivir (Tamiflu)
  • Chloroquine or hydroxychloroquine
  • Ribavirin and interferon
  • Antivirals used for Hepatitis C (e.g., sofosbuvir/ledipasvir)
  • Oral corticosteroids (e.g., dexamethasone)
  • Intravenous Immunoglobulin G (IVIg)
  • Convalescent Plasma
  • Vitamins D and C
  • Acetylsalicylic Acid (ASA, Aspirin)



Therapies for severe to critcally ill

Severe disease

Severe disease refers to patients with COVID-19 symptoms who require supplemental low-flow oxygen support (i.e., have oxygen saturations of <94% on room air) for COVID-19 illness.

Patients are usually hospitalized but not in the Intensive Care Unit; however, patients with severe COVID-19 may also reside in Long-Term-Care or Assisted Living, present to the emergency department, or receive oxygen therapy for COVID-19 at home.

 
Dexamethasone 6 mg IV/SC/PO q24h for up to 10 days is strongly recommended (RECOVERY trial), unless higher doses are clinically indicated*. Hydrocortisone 50 mg IV q6h is recommended as an alternative (REMAP-CAP trial). If dexamethasone and hydrocortisone are not available, methylprednisolone 32 mg IV q24h or prednisone 40 mg PO daily are recommended.

* e.g., asthma exacerbation, refractory septic shock, history of chronic steroid use, obstetric use for fetal lung maturation

 
Baricitinib 4 mg PO daily (for GFR ≥60 mL/min), or 2 mg PO daily (for GFR 30-59 mL/min), or 2 mg PO every 2nd day (for GFR 15-29 mL/ min) up to 14 days**, or until hospital discharge (whichever occurs first) is recommended (COV-BARRIER, RECOVERY) for patients hospitalized from COVID-19 requiring supplemental oxygen who show signs of systemic inflammation/cytokine storm (e.g., elevated C-reactive protein ≥ 50 mg/L, ferritin ≥ 1000 µg/L). Baricitinib should only be initiated when oxygen support is required due to COVID-19 pneumonia (not from other causes such as heart failure, pulmonary embolism, etc.).  Baricitinib should not be administered to patients with neutrophils <1.0 x 109/L, lymphocytes <0.2 x 109/L, ALT or AST >5 x ULN, GFR<15 mL/min/1.73 m2. Patients who received immunosuppressants (high-dose corticosteroids, biologics, or JAK inhibitors) were generally excluded from RCTs of baricitinib; if baricitinib is being considered in these patients, benefits vs. risks of over-immunosuppression should be assessed on a case-by-case basis.

**Early baricitinib discontinuation should be considered in patients who have clinically improved and no longer require supplemental oxygen

*Limited data exist on baricitinib in pregnancy. Risks and benefits should be discussed on a case-by-case basis with pregnant patients with severe COVID-19

 
Tocilizumab is not recommended for patients receiving low-flow oxygen support. The RECOVERY trial found a survival benefit of 4% (28-day mortality: tocilizumab 29% vs. usual care 33%) in patients who had CRP >75 mg/L and on low-flow oxygen, non-invasive respiratory support, or invasive mechanical ventilation. However, considering the scarcity of IL-6 blockers in Canada, CTC and CTRAWG recommend prioritizing tocilizumab use only for critically ill patients at this time, which is the population shown to benefit most in both the REMAP and RECOVERY trials.

 
Therapeutic anticoagulation (LMWH preferred) can be considered in patients without high-risk features for serious bleeding*. It should start within 72 hours of admission and continue for 14 days or until hospital discharge. Patients who decompensate and require organ support while on therapeutic anticoagulation should continue on therapeutic anticoagulation, if the risk of bleeding remains low.

Pooled data from RCTs showed that therapeutic anticoagulation with LMWH/UFH significantly reduces major thrombotic events (OR 0.47; 95% CI 0.24-0.90) but may increase major bleeding (OR 1.45; 95% CI 0.77-2.70) compared with lower doses. Organ support-free days alive were significantly increased with therapeutic heparin (OR 1.29; 95% CI 1.07-1.57). Benefit is more likely in those with elevated D-dimer level or additional risk factors for thrombosis. No differences were observed in the need for invasive mechanical ventilation, intracranial hemorrhage or all-cause mortality.

*High risk features for bleeding include age ≥75, eGFR less than 30 mL/min, any coagulopathy, platelet count less than 50, use of dual antiplatelet therapy, recent history of serious GI bleed or recent intracranial condition (stroke, neurosurgery, aneurysm, cancer), epidural or spinal catheter.
 

 
Remdesivir 200mg IV on day 1 followed by 100mg IV on days 2-5 can be considered in patients who are not receiving baricitinib for COVID-19-related inflammation/cytokine storm. Remdesivir has demonstrated a small survival (14.6% vs. 16.3%, p=0.03) in the final analysis of SOLIDARITY and need for requiring mechanical ventilation (8% vs. 15%) as a secondary endpoint of CATCO. As data supporting the use of baricitinib is stronger, baricitinib should be initiated first in those meeting criteria. Remdesivir may be added in patients who are deteriorating (but not requiring organ support), or not improving despite baricitinib as the combination has been shown to reduced recovery time and improved clinical status for patients with severe COVID-19 (ACTT-2). If remdesivir is used for this indication, a 5-day course is recommended as a 10-day course was shown to be equivalent but increased the length of hospital stay.

 
Monoclonal antibody combination REGEN-COV 2.4g (casirivimab 1.2g + imdevimab 1.2g) is NO LONGER recommended due to its lack of neutralization activity against Omicron. Other antibodies are currently being evaluated for treatment of seronegative patients with severe COVID-19.  Sotrovimab should not be used as a substitute until there is evidence to support its use and recommendations are issued.
 

 
Based on the current scientific evidence and best practice guidelines, including in consideration of retracted publications, the College of Physicians and Surgeons of BC, the College of Pharmacists of BC, the BC College of Nurses and Midwives and the CTC do not approve of the use of ivermectin for either treatment or prophylaxis for COVID-19 and BC registrants must not prescribe it for this purpose. Ivermectin should not be used outside of approved clinical trials.

 
Various therapies have been evaluated to be ineffective and/or unsafe in treatment of mild-moderate COVID-19 and are not recommended outside of clinical trials. These include:
  • Lopinavir/ritonavir (Kaletra)
  • Oseltamivir (Tamiflu)
  • Chloroquine or hydroxychloroquine
  • Ribavirin and interferon
  • Intravenous Immunoglobulin G (IVIg)
  • Convalescent Plasma
  • Vitamins D and C
  • Acetylsalicylic Acid (ASA, Aspirin)

Critically ill

Critical disease refers to patients with COVID-19 symptoms who require respiratory support beyond low-flow oxygen such as high-flow oxygen, non-invasive ventilation, mechanical ventilation, and/or vasopressor/inotropic support for COVID-19 illness. Patients are usually hospitalized in the Intensive Care Unit.

 
Dexamethasone 6 mg IV/SC/PO q24h for up to 10 days is strongly recommended (RECOVERY trial), unless higher doses are clinically indicated*. Hydrocortisone 50 mg IV q6h is recommended as an alternative (REMAP-CAP trial). If dexamethasone and hydrocortisone are not available, methylprednisolone 32 mg IV q24h or prednisone 40 mg PO daily are recommended.

* e.g., asthma exacerbation, refractory septic shock, history of chronic steroid use, obstetric use for fetal lung maturation

 
Tocilizumab AND/OR Baricitinib (see baricitinib) are recommended for patients requiring life support due to confirmed COVID-19. This includes high flow oxygen support (e.g., Optiflow) if flow rate > 30 L/min and FiO2 > 0.4 OR invasive or non-invasive ventilation OR vasopressor or inotropic support. While head-to-head comparative data are lacking, the magnitude of benefit of each agent appears equivalent. However, more robust data exist to support the use of tocilizumab. Baricitinib also carries the additional challenges related to gastric access and cytotoxic precautions. The ultimate choice of agent depends on patient characteristics and practical considerations. Patients receiving baricitinib prior to becoming critically ill may stop baricitinib and be switched to a one-time dose of tocilizumab or continue baricitinib. In patients who continue to deteriorate on immunomodulator monotherapy due to COVID-19-related inflammation/cytokine storm, the combination of tocilizumab and baricitinib can be considered as the addition of baricitinib to tocilizumab has been shown to provide an incremental survival benefit of 2.4% (OR 0.79, CI 0.63-0.97; RECOVERY). 

Tocilizumab 400 mg IV (single dose) is recommended (REMAP-CAP, RECOVERY). Dose-capping continues to be recommended over 8mg/kg due to a lack of robust drug supply and similar benefits between the two doses seen in observational studies. Tocilizumab should only be initiated when life support is required because of COVID-19 rather than other causes (such as bacterial infection, pulmonary embolism, etc.).


 
Baricitinib 4 mg po daily (for GFR ≥ 60 mL/min) or 2 mg po daily (for GFR 30-59 mL/min) or 2 mg po every 2nd day (for GFR 15-29 mL/min) up to 14 days, or until discharge from hospital (whichever occurs first) is recommended (COV-BARRIER, RECOVERY). Baricitinib should only be initiated when life support is required because of COVID rather than other causes (such as bacterial infection, pulmonary embolism, etc.). Baricitinib should not be administered to patients with neutrophils < 1.0 x 109/L, , lymphocytes < 0.2 x 109/L, , ALT or AST > 5 x ULN, or eGFR < 15 mL/min (or receiving renal replacement therapy).

*Limited data exist on baricitinib in pregnancy. Risks and benefits of baricitinib should be discussed on a case-by-case basis with pregnant patients with critical COVID-19


 
Prophylactic-intensity dosing of low molecular weight heparin (LMWH) is recommended for VTE prophylaxis in patients who do not have suspected or confirmed VTE (or other indications for therapeutic anticoagulation). 

There is a high probability of harm when therapeutic anticoagulation is initiated in patients who have received organ support for greater than 48 hours (n=1074; NIH mpRCT). Patients receiving therapeutic anticoagulation for COVID-19 prior to organ support should REMAIN on therapeutic anticoagulation and continue for up to 14 days or until hospital discharge.


 
Monoclonal antibodies (mAbs; Bamlanivimab/etesevimab, REGEN-COV, Sotrovimab, Regdanvimab) are not recommended. An RCT of REGEN-COV in this population was halted due to signals of harm. Regdanvimab and REGEN-COV conditions for use state that it may be associated with worse outcomes in the critically ill.

RECOVERY showed no benefit in the subgroup that required organ support. Various guidelines (IDSA, NIH, INESSS) recommend against mAbs in this setting. 


 

Remdesivir is not recommended in patients with critical COVID-19 as it has not demonstrated to improve survival or time to clinical recovery.

 

 
Antibiotic therapy is not routinely recommended for the
treatment of COVID-19 pneumonia. If bacterial co-infection is suspected, follow local practice guidelines for CAP, HAP and VAP.

 

Based on the current scientific evidence and best practice guidelines, including in consideration of retracted publications, the College of Physicians and Surgeons of BC, the College of Pharmacists of BC, the BC College of Nurses and Midwives and the CTC do not approve of the use of ivermectin for either treatment or prophylaxis for COVID-19 and BC registrants must not prescribe it for this purpose. Ivermectin should not be used outside of approved clinical trials.

 

 
Various therapies have been evaluated to be ineffective and/or unsafe in treatment of mild-moderate COVID-19 and are not recommended outside of clinical trials. These include:
  • Lopinavir/ritonavir (Kaletra)
  • Oseltamivir (Tamiflu)
  • Chloroquine or hydroxychloroquine
  • Ribavirin and interferon
  • Intravenous Immunoglobulin G (IVIg)
  • Convalescent Plasma
  • Vitamins D and C
  • Acetylsalicylic Acid (ASA, Aspirin)

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