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The British Columbia COVID-19 Therapeutics Committee provides guidance on the most current research on the use of therapies in the management of COVID-19.

Last updated: September 8, 2022


Antimicrobial and immunomodulatory therapy in adult patients with COVID-19Table of COVID-19 therapy and treatments
The British Columbia COVID-19 Therapeutics Committee (CTC) reviews and critically appraises evidence on the use of therapies in the management of COVID-19.

The evidence that supports the recommendations of therapies for the treatment of COVID-19 is briefly summarized below. Within British Columbia, the use of unproven COVID-19 drug therapies outside of clinical trials is NOT recommended.

These recommendations apply to adult patients with confirmed COVID-19 across all disease severities (mild-moderate, severe, and critically ill). 
Management of COVID-19 in Pregnant Persons
Mild-Moderate

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.

Clinical Practice Guide for Tixagevimab/Cilgavimab (Evusheld)

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. 

However, due to the prevalence of the BA 4/5 Variants of Concern, the activity of tixagevimab/cilgavimab (Evusheld) is greatly reduced and the clinical evidence for its use has been non-reassuring. The updated Practice Guide includes a summary of this evidence and updated recommendations.


  • This document provides general guidance on tixagevimab/cilgavimab (Evusheld). It includes information on:
    • eligibility criteria
    • practical administration information
    • critical appraisal of the evidence
Clinical Practice Guide and Tools for Mild to Moderate COVID-19
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 the BA.2 variant of concern. It likely retains some activity but it is reserved as a last-line agent. 

Read: Health Care Provider Information on Paxlovid, remdesivir and sotrovimab  - updated April 12, 2022

Clinical Practice Guide: Recommendations and Evidence -updated June 10, 2022

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

Practice Tool #1: Step-by-Step Assessment for Clinicians - Updated July 20, 2022


  • 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.

Treatment recommendations

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** deemed at high risk# for disease progression/hospitalization from COVID-19 and who are appreciably symptomatic. (Conditional recommendation pending peer-reviewed publication)

*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 asidentified 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). 
  • Unvaccinated individuals without previous infection who are EITHER: 
    • ≥50 years OR 
    • have three or more chronic conditions/co-morbidities

  • Individuals ≥ 50 years with 1-2 vaccine doses or previous infection alone, with three or more chronic conditions/co-morbidities
  • Individuals aged ≥70 years with 1-2 vaccine doses or previous infection alone, with one or more chronic condition/co-morbidity

  • Individuals ≥ 70 years with three or more chronic conditions/co-morbidities, regardless of vaccine status or previous infection
  • Indigenous individuals (if not captured above) who are EITHER: 
    • unvaccinated without previous infection OR 
    • ≥ 50 years with 1-2 vaccine doses or with previous infection alone OR 
    • ≥ 70 years regardless of vaccine status or previous infection 
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. Patients at the highest risk# of progression to severe disease (≥ 5%) are currently being prioritized for treatment with remdesivir.  
 
#Patients at highest risk (≥ 5%) for disease progression and hospitalization from COVID-19 are 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:
    • ≥ 50 regardless of vaccine status or previous infection OR
    • < 50 with 0-2 doses of vaccine or previous infection alone

  • Individuals who have a combination of age, under-vaccination, and risk factors such as co-morbidities or Indigenous status who are shown to have a risk of ≥ 5%. (To assess risk, see the point system or thermal maps in the Clinical Practice Guide)

Sotrovimab has demonstrated reduced neutralization against the BA.2 variant although it may retain some activity. If sotrovimab is used as a last-line agent where potential of benefit outweighs the risk, disclosure to patients of risks and benefits in consideration of individual circumstances (clinical status, patient values, logistics) is necessary. Sotrovimab should not be chosen solely for convenience reasons.

 
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)


Severe

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) for hospitalized COVID-19 patients requiring supplemental oxygen. Baricitinib should be administered within 24 hours of initiation or change in baseline use of oxygen due to COVID-19 pneumonia (not from other causes such as heart failure, pulmonary embolism, etc.). 

Considerations for use include certainty of COVID-19 as cause of deterioration, clinical progression, evidence of inflammation (e.g., elevated C-reactive protein ≥ 50 mg/L, ferritin ≥ 1000 μg/L), and potential for adverse effects. Baricitinib should not be administered to patients with neutrophils <1.0 109/L, lymphocytes <0.2 109/L, ALT or AST >5 x ULN, GFR <15 mL/min/1.73 m2, or who have been admitted for more than 14 days with symptoms of COVID-19. Patients who received immunosuppressants (high-dose corticosteroids, biologics, or JAK inhibitors) before randomization were excluded from the COV-BARRIER trial; if baricitinib is being considered in these patients, risks and benefits should be discussed on a case-by-case basis.

*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

**Early baricitinib discontinuation should be considered in patients who have clinically improved and no longer require supplemental oxygen
Tocilizumab or sarilumab are not currently recommended for patients receiving low-flow oxygen support due to drug shortages. The RECOVERY trial found a survival benefit of 4% (tocilizumab 29% vs. usual care 33% 28-day mortality) in patients who had CRP >75 mg/L AND low-flow oxygen, non-invasive respiratory support, or invasive mechanical ventilation. However, considering the scarcity of IL-6 blockers in Canada, drug therapy should be prioritized to the persons with both the highest need and the greatest likelihood of benefiting from the therapy.

Combined with outstanding issues in the preliminary findings of the RECOVERY trial (e.g., 17% of patients randomized to tocilizumab not receiving the drug), the CTC recommends prioritizing tocilizumab use only for critically ill patients at this time, which is the population shown to benefit in both the REMAP and RECOVERY trials. 
Therapeutic anticoagulation (LMWH preferred) may be considered in patients without high-risk features for serious bleeding* and NOT requiring organ support. If used, anticoagulation for COVID-19 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. 

Therapeutic anticoagulation was superior to standard of care for composite 21-day organ support free survival in the ATTACC/ACTIV-4a/REMAP-CAP trials. Benefits
appear to be driven by reducing progression to high-flow oxygen, non-invasive ventilation, or vasopressors. There was insufficient certainty on whether therapeutic anticoagulation improves mortality or intubation. 

Therapeutic anticoagulation reduces thrombotic events
(1.4% vs 2.7%) but may increase major bleeding (1.9% vs 0.9%).

*High risk features for bleeding include: age 75 or greater, 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.
 
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.
 
Remdesivir has not demonstrated benefit in survival, progression to ventilation or length of hospital stay and remains uncertain with respect to shortening time to recovery by 5 days. The World Health Organization (WHO) has issued a conditional recommendation against the use of remdesivir in patients hospitalized from COVID-19. 

Further evaluation in approved clinical trials is strongly encouraged. If remdesivir is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values and preferences are necessary, as it is not considered standard of care. Furthermore, it should not be used in patients requiring non-invasive or invasive mechanical ventilation due to COVID-19.
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 400 mg IV (single dose) OR Sarilumab 400 mg IV (single dose) is recommended (REMAP-CAP, RECOVERY) 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. 

Tocilizumab/sarilumab must be administered within 24 hours of the initiation of life support measures. Patients admitted to hospital for more than 14 days with symptoms of COVID-19 should not receive tocilizumab/sarilumab for this indication.

Tocilizumab/sarilumab should only be initiated when life support is required because of COVID-19 rather than other causes (such as bacterial infection, pulmonary embolism, etc). Tocilizumab or sarilumab should not be combined with baricitinib.
If tocilizumab is not available due to drug shortages, baricitinib is recommended as an alternative.

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) 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 noninvasive ventilation OR vasopressor or inotropic support. Baricitinib should be administered within 24 hours of the initiation of life support measures. 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 giga/L, lymphocytes < 0.2 giga/L, ALT or AST > 5 x ULN, or eGFR < 15 mL/min (or receiving renal replacement therapy). Baricitinib should not be combined with tocilizumab or sarilumab.

*Limited data exist on baricitinib in pregnancy. Risks and benefits of baricitinib should be discussed on a case-by-case basis with pregnant women with severe 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 has not been shown beneficial in patients critically ill from COVID-19. Remdesivir is not recommended outside of approved clinical trials.

 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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