Patients requiring respiratory support (high-flow oxygen, noninvasive ventilation, mechanical ventilation) and/or vasopressor/ inotropic support Remdesivir is not recommended in patients with critical COVID-19 outside of approved clinical trials as it has not demonstrated to improve survival or time to recovery. Based on the current scientific evidence and bestpractice guidelines, 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 treatment or prophylaxis of COVID-19 and BC registrants must not prescribe it for this purpose. Ivermectin should not be used outside of approved clinical trials. 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. Colchicine and other biologics (e.g., anakinra) are not recommended outside of approved clinical trials.# 
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.
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.

# ACE inhibitors and ARBs should not be discontinued solely on the basis of COVID-19
NSAIDs should not be discontinued solely on the basis of COVID-19

# Severely Ill Patients
Hospitalized, ward-based, longterm care

# Patients requiring low flow supplemental oxygen therapy
Based on the current scientific evidence and bestpractice guidelines, 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 treatment of COVID-19 and BC registrants must not prescribe it for this purpose. Ivermectin should not be used outside of approved clinical trials.
Tocilizumab is not recommended for patients receiving low-flow oxygen support. The RECOVERY trial found a survival benefit of 4% (28-day mortality for 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.
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 this indication. Other mAbs should not be used as a substitute.
Colchicine and biologics (e.g., anakinra) are not recommended outside of approved clinical trials.

# ACE inhibitors and ARBs should not be discontinued solely on the basis of COVID-19
NSAIDs should not be discontinued solely on the basis of COVID-19

# Mildly-Moderately Ill Patients
See the CTC Clinical Practice Guide and Practice Tool #1: Step-by-Step Assessment for treatment recommendation for ambulatory, LTC and in-patients with mild-moderate COVID-19 with nirmatrelvir/ritonavir, remdesivir and sotrovimab. Recommendations regarding tixagevimab/cilgavimab, colchicine, fluvoaxamine and inhaled corticosteroids are also included in within these resources. Bamlanivimab-etesevimab and REGEN-COV are not recommended due to resistance of Omicron to these agents. Due to lack of impact on hospitalization rates or mortality and low generalizability of clinical studies, administration of any mAbs s not recommended for postexposure prophylaxis. 

# NOT RECOMMENDED FOR ANY SEVERITY
Tocilizumab AND/OR 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 a tociluzumab or continue baricitinib. In patients who continue to deteriorate on immunomodulator monotherapy due to COVID-related inflammation/cytokine storm, the combination of tocilizumab plus 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 to 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). AND/OR 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  5 x ULN, or eGFR 5 x ULN, eGFR <15 mL/mmin/1.73 m2). 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, benefits vs risks of overimmunosuppression should be assessed 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  Tixagevimab/cilgavimab is not recommended, including in severely immunocompromised patients. Currently, there is a lack of high-quality evidence demonstrating a benefit of tixagevimab/ cilgavimab in preventing hospitalization from COVID-19, particularly from variants of concern (e.g., Omicron). Tixagevimab/cilgavimab was evaluated in unvaccinated non-immunocompromised individuals to prevent symptomatic infection with wild-type, Alpha and Delta virus; its role within the present vaccine and therapeutic landscape is unclear. Retrospective observational studies show it to be of minimal additive value. Tixagevimab/cilgavimab has reduced neutralization activity against BA 4/5 and nearly half of all VoCs in BC are completely resistant; according to real world data, this leads to lower serological and clinical activity that cannot be fully overcome by a dose increase. Further, any theoretical benefit may not outweigh by the potential risk of cardiac serious adverse events (SAEs).