COVID-19: Clinical Guidance for Primary Care Providers

Last Updated: April 13, 2022

No Results Found 0/0
This resource is revised often and new content is added regularly to guarantee that the latest evidence and regulatory recommendations are included. The CEP is committed to ensuring this information is accurate and up to date.

Use this resource to provide the best possible COVID-19 care for your patients, with evidence-based recommendations on assessment and testing, management, recovery, palliative care, long COVID and more.

Click on the sections below to get started:

Testing and isolation requirements

Jump to:

Most COVID-19 patients have mild to moderate symptoms and can be safely managed as outpatients in the community setting (PHAC, August 17, 2020; BCCDC, May 10, 2021).

Although current evidence suggests that new COVID-19 variants of concern are more easily transmissible, there is insufficient evidence to suggest changes to the management of patients infected with these variants. Established measures for social distancing and reducing the spread of COVID-19 should be maintained (PHE, December 20, 2020).

Testing in the Omicron context

Molecular Testing

The following people are eligible for molecular testing (PCR or rapid molecular testing) (MOH, April 11, 2022):

  • Symptomatic individuals who fall into one of the following groups:
    • People aged 70 and older
    • People aged 60 years and older who have less than three doses of COVID-19 vaccine
    • People who are immunocompromised
    • Adults aged 18 years and older who have had less than three doses of COVID19 vaccine and have risk conditions:
      • obesity (BMI ≥ 30kg/m2)
      • diabetes
      • heart disease, hypertension, congestive heart failure
      • chronic respiratory disease, including cystic fibrosis
      • cerebral palsy
      • intellectual disability
      • sickle cell disease
      • moderate or severe kidney disease (eGFR <60mL/min)
      • moderate or severe liver disease (e.g., Child Pugh Class B or C cirrhosis
    • Other people at higher risk of severe disease who may be eligible for COVID19 treatment if they tested positive
    • Patient-facing healthcare workers
    • Staff, volunteers, residents/inpatients, essential care providers, and visitors in highest risk settings
    • Highest risk settings include: hospitals (including complex continuing care facilities and paramedic services), and congregate living settings with medically and socially vulnerable individuals, including, but not limited to Long-Term Care, retirement homes, First Nation elder care lodges, group homes, shelters, hospices, correctional institutions, Provincial Demonstration Schools and hospital schools.
    • Home and community care workers
    • Household members of staff in highest risk settings and patient-facing health care workers
    • International Agriculture Workers in congregate living settings
    • Patients seeking emergency medical care, at the discretion of the treating clinician
    • Other outpatients for whom a diagnostic test is required for clinical management, at the discretion of the treating clinician
    • Pregnant people
    • People who are underhoused or experiencing homelessness
    • First responders, including fire, police and paramedics
    • Elementary and secondary students and education staff who have received a PCR self-collection kit through their school
    • Staff and students in Provincial and Demonstration Schools
  • Symptomatic/asymptomatic people:
    • Individuals who are from a First Nation, Inuit, Métis community, and/or who self-identify as First Nation, Inuit, and Métis and their household members
    • Individuals travelling into First Nation, Inuit, Métis communities for work.
    • On admission/transfer to or from hospital or congregate living setting
    • People in the context of confirmed or suspected outbreaks in highest risk settings as directed by the local public health unit
    • Individuals, and one accompanying caregiver, with written prior approval for out-of-country medical services from the General Manager, OHIP
    • Any patient with a scheduled surgical procedure requiring a general anaesthetic 24-48 hours prior to procedure date
    • Newborns born to people with confirmed COVID-19 at the time of birth within 24 hours of delivery, with a repeat test at 48 hours after birth if baseline test is negative, or if the parental test results are pending at the time of discharge
    • People 24-48 hours prior to treatment for cancer or prior to hemodialysis, at the discretion of the treating clinician
Rapid Antigen Testing

There are several uses for Rapid Antigen Testing (RATs). These include (MOH, March 9, 2022):

  • Routine Screen testing
    • Screen testing is frequent, systematic testing of people who are asymptomatic and without known exposure to a COVID-19 case with the goal of identifying infectious cases that are pre-symptomatic or asymptomatic.
    • Screen testing with rapid antigen tests involves routine testing multiple times per week.
    • An individual with confirmed COVID-19 based on a molecular or rapid antigen test may resume asymptomatic screen testing after 30 days from their COVID-19 infection (based on the date of their symptom onset or specimen collection, whichever is earlier). If there is uncertainty about the validity of the COVID-19 infection (e.g., asymptomatic infection with high cycle threshold value result), they may resume asymptomatic screen testing immediately.
  • For people with symptoms if a Rapid Antigen Test is available, it may be used to assess the likelihood that the symptoms are related to COVID-19. A positive Rapid Antigen Test is highly indicative that the individual has COVID-19. Two consecutive Rapid Antigen Tests (separated by 24-48 hours) that are both negative indicates that the individual is less likely to have COVID-19.
  • Test to work for symptomatic individuals in a highest risk setting.
  • One-off asymptomatic testing. Rapid Antigen Tests should be completed as close to the event as possible and have important limitations to understand. The tests have low sensitivity for COVID-19 in people who are asymptomatic and those infected with COVID-19 may test negative for several days before testing positive. After a negative Rapid Antigen Test, individuals should still follow public health measures.

At this time, a positive result from a self-administered or provider-administered positive rapid antigen test is sufficient evidence of COVID-19 infection to initiate outpatient therapies, if molecular testing is not available or would delay treatment initiation.

Isolation requirements

Note that at this time in Ontario, those who have received at least 2 doses of an approved COVID-19 vaccine are considered fully vaccinated in the context of the isolation requirements below. In other words:

  • 2 doses = fully vaccinated
  • 3 doses = boosted

For symptomatic individuals who test positive for COVID-19, day 0 of all isolation periods is whichever comes first between symptom onset, and the day a positive test was taken.

Guidelines for Close Contacts

A close contact is defined as an individual who has an exposure to a confirmed positive COVID-19 case, an individual with COVID-19 symptoms, or an individual with a positive rapid antigen test result (MOH, April 11, 2022).

  • Close contacts have been in contact with the case/symptomatic person within the 48 hours prior to the case’s symptom onset if symptomatic or 48 hours prior to the specimen collection date (whichever is earlier/applicable) and until they have completed their self-isolation period;
    AND
  • Were in close proximity (less than 2 meters) for at least 15 minutes or for multiple short periods of time without measures such as masking, distancing and/or use of personal protective equipment (see Page 17 of Guidance on Cases and Contacts, MOH, April 11, 2022 for examples)
  • Note: Outside of suspect and confirmed outbreaks managed by the PHU, it is the responsibility of the individual with COVID-19 symptoms or COVID-19 positive test to determine who their close contacts are and to notify them of their potential exposure.

Should be considered likely infected with COVID-19 if ineligible for PCR/rapid molecular testing and should take the isolation measures listed in the below table (MOH, April 11, 2022):

Isolation Requirements for Close Contacts Outside of Highest-Risk Settings

Population

Isolation Period and Requirements

Non-Household Close Contacts

For a total of 10 days after the last exposure to the COVID-19 positive case or individual with COVID-19 symptoms, the non-household member notified by a case should:

  • Self-monitor for symptoms and self-isolate if they develop any symptom of COVID-19;
  • Wear a well fitted mask in all public settings;
  • Not visit anyone who is immunocompromised or at higher risk of illness (e.g., seniors);
  • Avoid non-essential visits to highest risk settings such as hospitals and long-term care homes.
  • Employees working in highest risk settings should report their exposure and follow their workplace guidance.

Household Close Contacts

Household members of the COVID-19 positive case/individual with COVID-19 symptoms should self-isolate while the case is isolating, with the following exceptions:

  • Household members who are 18 years of age or older and have already received their booster dose
  • Household members who are under 18 year of age and are considered fully vaccinated
  • Household members who have previously tested positive for COVID-19 in the last 90 days (based on a positive PCR, molecular or rapid antigen test result) and have since completed their isolation period. These individuals may also attend highest risk settings, as long as they are currently asymptomatic.

If self-isolation is complete at less than 10 days, or if self-isolation is not required, for a total of 10 days after the last exposure to the COVID-19 case, ALL household members should:

  • Self-monitor for symptoms and self-isolate if they develop any symptom of COVID-19;
  • Wear a well fitted mask in all public settings;
  • Not visit anyone who is immunocompromised or at higher risk of illness (e.g., seniors);
  • Avoid non-essential visits to highest risk settings such as hospitals and long-term care homes.
  • Employees working in highest risk settings should report their exposure and follow their workplace guidance.

Individuals who develop symptoms should follow the isolation requirements below.

Individuals with COVID-19 symptoms

Anyone experiencing:

  • Fever/chills OR
  • Cough OR
  • Shortness of breath OR
  • Decrease/loss of smell and taste

Or two or more of the following symptoms:

  • Sore throat
  • Headache
  • Muscle aches/joint pain
  • GI symptoms (i.e. vomiting or diarrhea)
  • Extreme fatigue
  • Runny nose/nasal congestion

Should be considered likely infected with COVID-19 if ineligible for PCR/rapid molecular testing and should take the following isolation measures (MOH, March 9, 2022):

Population

Isolation period

 

Additional Precautions after Self-Isolation Period

Individuals with severe illness (requiring ICU level of care)

20 days (or at discretion of hospital IPAC) after the date of specimen collection or symptom onset (whichever is earlier/applicable)

N/A

  • Individuals 12+ who are not fully vaccinated
  • Individuals residing in a highest-risk setting
  • Individuals hospitalized for COVID-19 related illness (not requiring ICU level of care)
  • Immunocompromised individuals

10 days (or at discretion of hospital IPAC) after the date of specimen collection or symptom onset (whichever is earlier/applicable)

For a total of 20 days after the date of specimen collection or symptom onset (whichever is earlier/applicable), immunocompromised individuals should follow the additional precautions listed in the row below.

  • All other individuals not listed above, who have COVID-19 symptoms, or a positive COVID-19 test (PCR, rapid molecular or rapid antigen test)

5 days after the date of specimen collection or symptom onset date (whichever is earlier/applicable)

For a total of 10 days after the date of specimen collection or symptom onset (whichever is earlier/applicable), individuals should:

  • Continue to wear a well-fitted mask in all public settings (including schools and child care, unless under 2 years old) and avoid non-essential activities where mask removal is necessary (e.g., dining out, playing a wind instrument, high contact sports where masks cannot be safely worn).
  • Not visit anyone who is immunocompromised or at higher risk of illness (e.g., seniors)
  • Avoid non-essential visits to highest risk settings such as hospitals and long-term care homes.
  • Employees working in highest-risk settings should report their exposure and follow their workplace guidance on return to work

Other symptoms that may be associated with COVID-19 and should be monitored include:

  • Abdominal pain
    • Not related to other known causes or conditions (e.g., menstrual cramps, gastroesophageal reflux disease)
  • Conjunctivitis (pink eye)
    • Not related to other known causes or conditions (e.g., blepharitis, recurrent styes)
  • Decreased or lack of appetite
    • For young children and not related to other known causes or conditions (e.g., anxiety, constipation)

Outpatient management of patients with COVID-19

Jump to:
Who can be managed at home?
  • Have mild to moderate, uncomplicated COVID-19.
  • Have an O2 saturation > 93% (if pulse oximeter is available).
  • Have a respiratory rate < 30.
  • Show no signs of respiratory distress.
  • Show no signs of confusion.
  • Are able to stay well hydrated.
  • Have the appropriate resources and social supports to manage any comorbidities at home, self-isolate and carry out regular activities of daily living.
Who should be hospitalized?
  • Severe shortness of breath at rest.
  • Difficulty breathing.
  • Increasing significant fatigue (reported in some patients as a marker for hypoxemia without dyspnea).
  • Reduced level of consciousness or new confusion.
  • Cold, clammy or pale and mottled skin.
  • Blue lips or face.
  • Little to no urine output.
  • Pain or pressure in the chest.
  • Neck stiffness.
  • Non-blanching rash.
  • Syncope.
  • Coughing up blood.

Managing patients at home

  • Counsel all patients about self-monitoring for red flag symptoms of worsening disease (see Who should be hospitalized?) and provide them with an on-call (or your) number. Encourage them to seek an urgent follow-up assessment with a family physician (by calling the on-call/your number) or hospitalization if they experience any of these symptoms (PHAC, August 17, 2020).
  • Assess patients for pre-existing conditions that may put them at a higher risk of deterioration (older age, asthma, COPD, cardiovascular disease and immunocompromising conditions are particularly relevant). Monitor these patients closely (CEBM, April 20, 2020BCCDC, May, 2021NICE, October 13, 2020UpToDate, January 26, 2021). See Symptom management and comorbid considerations.
  • Provide treatment as necessary to patients with COVID-19. For information on recommended treatment and evidence see Therapeutic management of mild COVID-19 and COVID-19 therapy research.
  • Determine an appropriate follow-up frequency based on the patient’s risk for severe disease, severity of respiratory symptoms, and your comfort level with their ability to self-report worsening symptoms (UpToDate, January 26, 2021).
    • For most patients being managed at home, telehealth visits can be scheduled on days 4, 7, and 10 following the onset of clinical illness (or date of positive test result) (UpToDate, January 26, 2021).
    • For patients aged ≥65 years who have one or more additional risk factors for severe disease, those with moderate dyspnea at the time of initial evaluation, and/or those whose symptoms are worsening, consider scheduling telehealth visits within the first 24 hours, and every other day until symptom resolution (UpToDate, January 26, 2021).
    • More frequent phone/video calls (e.g., daily or twice/day) can be considered based on clinical judgement of the patient’s risk for severe illness, especially for patients who have significant comorbidities (WCH, 2020).
Putting it into practice

Consult the COVID@Home Monitoring for Primary Care toolkit (OH, March 17, 2021) to help you implement home monitoring for COVID-19 patients.

For additional information and support, join the Primary Care Vaccination Pilot CoP online:

  • Visit Quorum and click the “Sign Up” button to create your account.
  • Visit the COVID@Home Monitoring for Primary Care CoP and click on “Join Group”.

Patients who cannot be safely monitored at home by their primary care provider (but are not severe enough to be referred to their local Emergency Department) can be referred to a COVID-19 Clinical Assessment Centre (CAC). See COVID-19 Clinical Assessment Centres (CACs): Information for Primary Care Providers.

Therapeutic management of mild COVID-19

The following recommendations apply to adult patients in any setting (community, hospital, congregate care) who do not require new or additional supplemental oxygen from their baseline status.

Below is a general pathway for how primary care providers can access outpatient therapies for people at higher risk of severe disease, specifically remdesivir and Paxlovid. Local pathways may vary based on availability of services and pre-existing pathways.

Pathway to accessing outpatient therapies

Proactively inform potentially eligible patients that they should contact a health care professional if they develop symptoms of COVID-19. This can be done during appointments, via email or telephone, or by updating the practice’s website or online booking portal.  See I think I have COVID. When should I call my doctor? for a handout to give patients who are at higher risk of severe disease.

Individuals are higher risk of severe outcomes if they:

  • Over 70 years old, regardless of vaccination status
  • Over 60 years old with fewer than three vaccine doses
  • Over 18 years old and
    • Immunocompromised (have an immune system that is weakened by a health condition or medications)
      OR
    • Have fewer than three vaccine doses and at least one of the following risk conditions:
      • Obesity
      • Diabetes
      • Heart disease, hypertension, congestive heart failure
      • Chronic respiratory disease (including cystic fibrosis)
      • Cerebral palsy
      • Intellectual and developmental disabilities
      • Sickle cell disease
      • Moderate or severe kidney disease
      • Moderate or severe liver disease
      • Pregnant and unvaccinated (zero doses)
  • Indigenous people, Black people, and members of other racialized communities may be at increased risk of disease progression due to disparate rates of comorbidity, increased barriers to vaccination, and social determinants of health. They should be considered priority populations for access to COVID-19 drugs and therapeutics.

 

For more detailed information on determining a patient’s risk of disease progression, see Ontario COVID-19 Science Advisory Table’s Recommended Drugs and Biologics in Adult Patients with COVID-19.

Try to connect virtually or in-person with patients at higher risk of severe disease who have developed symptoms of COVID-19 within 24 hours of the patient seeking support.

If unable to connect with the patient within 24 hours, direct patient to a clinical assessment centre to receive an assessment, test, diagnosis, and disposition planning (including referral for treatment with Paxlovid or remdesivir, if appropriate). See COVID-19 Clinical Assessment Centres (CACs): Information for Primary Care Providers.

*If directing patients to a CAC, jump to step 5

Assess the patient and determine an appropriate treatment course, considering patient eligibility and contraindications and local availability of therapies. See Recommended drugs for patients with mild COVID-19.

  • Prescribe Paxlovid to eligible patients if they are within 5 days of symptom onset. See New guidance for the prescription of nirmatrelvir / ritonavir (PaxlovidTM) for information on prescribing Paxlovid.
  • If you are unable to prescribe Paxlovid (e.g., patient is not within 5 days of symptom onset, Paxlovid contraindicated, etc.), consider referring the patient to  a clinical assessment centre for treatment. See COVID-19 Clinical Assessment Centres (CACs): Information for Primary Care Providers for information on the testing and referral process

Follow-up provided after treatment will vary depending on local arrangements and may include handoff back to primary care for ongoing monitoring (e.g., via COVID@Home). See Assessment, monitoring and management of COVID-19: Monitoring and follow-up (tab 6) for information on monitoring and follow-up based on risk level.

Recommended drugs for patients with mild COVID-19

Role in therapy
Dosage, cost and administration
  • 500 mg IV x 1 dose over 30 minutes. Monitor for 60 minutes after infusion.
  • Approximate cost per dose = $2000. Administration costs must also be considered.
  • Outpatient infusion clinics are operating at the following hospitals (with limited supply):
    • Health Sciences North
    • Humber River Hospital
    • The Ottawa Hospital
    • Joseph’s Healthcare Hamilton (initial pilot site)
    • Scarborough Health Network
    • Thunder Bay Regional Hospital
    • Windsor Regional Hospital
  • Referral to one of the infusion sites can be made using this referral form.
Adverse effects
  • Allergic reaction including anaphylaxis (rare)
  • Infusion reaction (rare): Fever, chills, nausea, headache dyspnea, chest tightness, change in blood pressure, face swelling, throat irritation, hives, itching, myalgia, arrhythmia, hypoxia, sweating, dizziness, light-headedness
  • Infusion site reaction: Pain, bruising, swelling and redness at the infusion site
  • Other adverse events: Nausea, diarrhea, headache
Key drug interactions
  • No formal drug interaction studies have been conducted (sotrovimab is not renally excreted or metabolized by CYP450, so interactions through these mechanisms are unlikely)


Legend:
* Individuals at higher risk of severe outcomes = immunocompromised (have an immune system that is weakened by a health condition or medications); OR unvaccinated or partially vaccinated (have received only one or two doses of a vaccine); OR have one or more risk factors, such as a long-term medical condition (obesity [BMI ≥30 kg/m2], diabetes, heart disease, hypertension, congestive heart failure, chronic respiratory disease inclduing cystic fibrosis, cerebral palsy, intellectual disability, sickle cell disease, moderate or severe kidney disease [eGFR,60 mL/min], moderate or severe liver disease [e.g., Child Pugh Class B or C cirrhosis]) or being of older age (e.g., ≥ 70). Indigenous people, Black people, and members of other racialized communities may be at increased risk of disease progression due to disparate rates of comorbidity, increased barriers to vaccination, and social determinants of health. They should be considered priority populations for access to COVID-19 drugs and therapeutics.
For more detailed information on determining a patient’s risk of disease progression, see Ontario COVID-19 Science Advisory Table’s Recommended Drugs and Biologics in Adult Patients with COVID-19.

Role in therapy
  • Recommended for patients with mild COVID-19 at higher risk* of severe disease who present within 7 days of symptom onset.
  • Indicated (notice of compliance with conditions) for age 12+ with weight of at least 40 km.
Dosage, cost and administration
  • 200 mg IV x 1 day, then 100 mg IV daily x 2 days.
  • Price of drug in Canada currently not publicly available. Administration costs must also be considered.
Adverse effects
  • Allergic reaction or infusion reaction (rare): changes to blood pressure or heart rate, low blood oxygen levels, high temperature, shortness of breath or wheezing, swelling of face, lips, tongue or throat, rash, nausea, sweating, shivering.
  • Infusion site reaction: Pain, bruising swelling or redness at the infusion site.
  • Other adverse events: increased transaminases, nausea, headache, rash
Key drug interactions
  • Avoid use with:
    • Chloroquine and hydroxychloroquine (antagonize the effects of remdesivir)
    • Drugs which reduce renal function
    • Strong inducers of CYP450 (e.g., rifampinin)
  • The potential for drug interactions with inhibitors inducers of CYP2C8, 2D6 or 3A4 (remdesivir is a substrate of these enzymes) has not been studied.


Legend:

* Individuals at higher risk of severe outcomes = immunocompromised (have an immune system that is weakened by a health condition or medications); OR unvaccinated or partially vaccinated (have received only one or two doses of a vaccine); OR have one or more risk factors, such as a long-term medical condition (obesity [BMI ≥30 kg/m2], diabetes, heart disease, hypertension, congestive heart failure, chronic respiratory disease inclduing cystic fibrosis, cerebral palsy, intellectual disability, sickle cell disease, moderate or severe kidney disease [eGFR,60 mL/min], moderate or severe liver disease [e.g., Child Pugh Class B or C cirrhosis]) or being of older age (e.g., ≥ 70). Indigenous people, Black people, and members of other racialized communities may be at increased risk of disease progression due to disparate rates of comorbidity, increased barriers to vaccination, and social determinants of health. They should be considered priority populations for access to COVID-19 drugs and therapeutics.
For more detailed information on determining a patient’s risk of disease progression, see Ontario COVID-19 Science Advisory Table’s Recommended Drugs and Biologics in Adult Patients with COVID-19

Due to increased supply, Paxlovid is now available in community pharmacies. For information on how to prescribe Paxlovid, see New guidance for the prescription of nirmatrelvir / ritonavir (PaxlovidTM).

Role in therapy
  • Recommended for patients with mild COVID-19 at higher risk* of severe disease who present within 5 days of symptom onset.
    • May be considered in pregnant or lactating patients if the benefits of treatment outweigh the potential risks.
  • Indicated for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
  • For more information, see Nirmatrelvir/Ritonavir (Paxlovid): What Prescribers and Pharmacists Need to Know.
Dosage, cost and administration
  • Normal renal function: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three taken together orally twice daily for 5 days.
  • Mild-moderate renal impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), taken together orally twice daily for 5 days.
  • Not recommended for patients with severe renal impairment (eGFR <30 mL/min) or severe hepatic impairment.
  • Price of drug in Canada is currently not publicly available.
Adverse effects
  • Altered sense of taste, diarrhea, muscle pain, vomiting, high blood pressure, headache.
Key drug interactions
  • Contraindicated in patients taking drugs that are:
    • Highly metabolized by CYP3A4 where elevated concentrations can be life-threatening
    • Potent CYP3A4 inducers which may reduce the effectiveness of nirmatrelvir/ritonavir and contribute to the development of drug resistance.
  • Nirmatrelvir/ritonavir have many drug interactions. See Nirmatrelvir/Ritonavir (Paxlovid): What Prescribers and Pharmacists Need to Know.


Legend:

* Individuals at higher risk of severe outcomes include those who are:

  • Over 70 years old, regardless of vaccination status
  • Over 60 years old with fewer than three vaccine doses
  • Over 18 years old

    • Immunocompromised (have an immune system that is weakened by a health condition or medications)
      OR
    • Have fewer than three vaccine doses and at least one of the following risk conditions:
      • Obesity
      • Diabetes
      • Heart disease, hypertension, congestive heart failure
      • Chronic respiratory disease (including cystic fibrosis)
      • Cerebral palsy
      • Intellectual and developmental disabilities
      • Sickle cell disease
      • Moderate or severe kidney disease
      • Moderate or severe liver disease
      • Pregnant and unvaccinated (zero doses)
Role in therapy
  • May be considered for patients with mild COVID-19 who present within 7 days of symptom onset and:
    • are at higher risk* of severe disease (if Paxlovid, sotrovimab and remdesivir are unavailable or contraindicated)
    • are at standard risk* of severe disease
  • There is currently no evidence to support the use of other SSRIs for COVID-19 (fluvoxamine is more anti-inflammatory than other SSRIs, so its benefits are not a class effect).
  • For more information from the Ontario COVID-19 Science Advisory Table, see Fluvoxamine: What prescribers and pharmacists need to know.
Dosage, cost and administration
  • 50 mg PO at bedtime x 1 day, then 100 mg BID x 2 days if tolerated, then 100 mg TID through day 15 of treatment.
    • Note: This titration is based on the STOP-COVID trials. For tolerability reasons, a slower titration may be required. A final dose and duration of 100 mg BID x 10 days may be considered based on the TOGETHER trial.
  • Cost (covered by ODB):
    • Generic fluvoxamine 50 mg tab = $0.21
    • Generic fluvoxamine 100 mg tab = $0.38
Adverse effects
  • Common (generally mild): Sedation, headache, insomnia, dizziness, nervousness, weakness, nausea, diarrhea, dry mouth, anorexia.
    • Note: Preference for larger doses to be given at bedtime for tolerability if required.
  • Rare (but serious): Serotonin syndrome (especially if maximum dose is exceeded or when used with other serotonergic drugs), QT prolongation (baseline ECG not recommended in otherwise healthy patients with no risk factors; avoid in patients with congenital long QT syndrome or taking medication with significant QT prolongation potential).
Key drug interactions
  • Note: Below are selected key drug interactions (not a comprehensive list). Pharmacist consultation and close follow-us is needed to avoid any significant adverse drug interactions.
  • Contraindicated with:
    • Clopidogrel (reduces anti-platelet effect)
    • MAO (monoamine oxidase) inhibitors
    • Thioridazine and mesoridazine
    • Pimozide
    • Terfenadine, astemizole and cisapride
    • Tizanidine
  • Use with caution:
    • Caffeine (fluvoxamine raises serum concentrations of caffeine us to 5-fold; patients should avoid caffeine as much as possible)
    • Drugs affecting bleeding risk (ASA, warfarin and nonsteroidal anti-inflammatory drugs [NSAIDs])
    • Specific benzodiazepines (triazolam, midazolam, alprazolam and diazepam)
    • Drugs affecting seizure threshold (e.g., select antidepressants, mefloquine, tramadol)
    • CYP1A2 Substrates (e.g., amitriptyline, clomipramine, clozapine, quetiapine, olanzapine)
    • CYP2C19 Substrate (e.g., diazepam, phenytoin, warfarin, lansoprazole, omeprazole)
    • CYP2C9 Substrates (e.g., valproate)
    • CYP3A4 Substrate (e.g., alprazolam, diltiazem, carbamazepine, methadone, cyclosporine, sildenafil)
    • Others: propranolol and ropinirole
    • Other serotonergic drugs
    • Other QT-prolongating drugs


Legend:

* Individuals at higher risk of severe outcomes = immunocompromised (have an immune system that is weakened by a health condition or medications); OR unvaccinated or partially vaccinated (have received only one or two doses of a vaccine); OR have one or more risk factors, such as a long-term medical condition (obesity [BMI ≥30 kg/m2], diabetes, heart disease, hypertension, congestive heart failure, chronic respiratory disease inclduing cystic fibrosis, cerebral palsy, intellectual disability, sickle cell disease, moderate or severe kidney disease [eGFR,60 mL/min], moderate or severe liver disease [e.g., Child Pugh Class B or C cirrhosis]) or being of older age (e.g., ≥ 70). Indigenous people, Black people, and members of other racialized communities may be at increased risk of disease progression due to disparate rates of comorbidity, increased barriers to vaccination, and social determinants of health. They should be considered priority populations for access to COVID-19 drugs and therapeutics.
For more detailed information on determining a patient’s risk of disease progression, see Ontario COVID-19 Science Advisory Table’s Recommended Drugs and Biologics in Adult Patients with COVID-19.

Role in therapy
  • May be considered for patients with mild COVID-19 who present within 7 days of symptom onset and:
    • are at higher risk* of severe disease (if Paxlovid, sotrovimab and remdesivir are unavailable or contraindicated)
    • are at standard risk* of severe disease
Dosage, cost and administration
  • 800 mcg inhaled BID x 14 days
  • Cost (covered by ODB):
    • Pulmicort Turbuhaler 400mcg x 200 doses = $100.29
    • Pulmicort Turbuhaler 200mcg x 200 doses = $68.70
  • Note: The 100mcg strength does not provide enough doses for the full 14-day treatment course.
Adverse effects
  • Most common (2-4%): Cough, throat irritation and hoarseness
  • Less frequent: Bad taste, nausea, throat dryness, tiredness, thirst, diarrhea
  • Rare: anaphylaxis, skin reactions (hives, rash, dermatitis, angioedema, bruising)
Key drug interactions
  • Avoid use with (increase exposure to budesonide):
    • Ritonavir
    • Azole antifungals

Legend:
*Individuals at higher risk of severe outcomes = immunocompromised (have an immune system that is weakened by a health condition or medications); OR unvaccinated or partially vaccinated (have received only one or two doses of a vaccine); OR have one or more risk factors, such as a long-term medical condition (obesity [BMI ≥30 kg/m2], diabetes, heart disease, hypertension, congestive heart failure, chronic respiratory disease inclduing cystic fibrosis, cerebral palsy, intellectual disability, sickle cell disease, moderate or severe kidney disease [eGFR,60 mL/min], moderate or severe liver disease [e.g., Child Pugh Class B or C cirrhosis]) or being of older age (e.g., ≥ 70). Indigenous people, Black people, and members of other racialized communities may be at increased risk of disease progression due to disparate rates of comorbidity, increased barriers to vaccination, and social determinants of health. They should be considered priority populations for access to COVID-19 drugs and therapeutics.
For more detailed information on determining a patient’s risk of disease progression, see Ontario COVID-19 Science Advisory Table’s Recommended Drugs and Biologics in Adult Patients with COVID-19.

Potential management strategies (NICE, October 13, 2020)

Potential management strategies (NICE, October 13, 2020)

Potential management strategies (NICE, October 13, 2020)

Comorbid considerations

It is possible that COVID-19 infection can trigger asthma exacerbation (CTS, April 7, 2020; CPS, September 8, 2020).

The Canadian Thoracic Society (April 7, 2020) recommends that:

  • Patients with asthma restart or continue to use their prescribed inhaled maintenance therapy, regardless of COVID-19 status.
  • Prednisone can be used to treat severe asthma exacerbations, including those caused by COVID-19 infection.
  • Anti-IgE and anti-IL-5 monoclonal antibodies (biologics) be continued during the COVID-19 pandemic, regardless of COVID-19 status.
  • Patients who are already using nebulizers do so in a separate room from others and implement other infection control recommendations (CTS generally recommends that patients switch from nebulized therapy to metered dose inhalers with spacing devices or dry powder inhalers during the COVID-19 pandemic).

Patients with CVD are not more likely to acquire COVID-19, but they do appear to be at a greater risk for developing severe COVID-19 if infected (J Med Virol, May 22; Int J Public Health, May 25, 2020).

For patients with known heart failure, see the virtual assessment guide (CCS, April 1, 2020) to differentiate between COVID-19 and heart failure exacerbations.

The Canadian Cardiovascular Society (March 20, 2020) recommends that:

  • Patients with confirmed or suspected COVID-19 should not stop taking an ACEi/ARB/ARNi unless there is a compelling reason to do so, such as symptomatic hypotension or shock, acute kidney injury, or hyperkalemia.
  • Patients with confirmed or suspected COVID-19 should not stop low-dose acetylsalicylic acid.

Based on current evidence, COPD patients do not appear to be more likely to acquire COVID-19 infection, however they do appear to be at a significantly greater risk for developing severe COVID-19 if infected (CTS, April 8, 2020; Int J Public Health, May 25, 2020; PLoS One, May 11, 2020).

It is probable that COVID-19 infection can trigger COPD exacerbation (Canadian Thoracic Society, 2020).

The Canadian Thoracic Society (April 8, 2020) recommends that:

  • Patients who are diagnosed with COVID-19 infection continue their inhaled maintenance therapies.
  • Oral prednisone (or other forms of systemic steroids if clinically warranted) be used to treat acute exacerbations of COPD, including those caused by COVID-19 infection.
  • Patients who are currently on oxygen continue their oxygen use as prescribed, regardless of COVID-19 status, while routinely cleaning their equipment using manufacturer’s instructions. For a list of local respiratory services and equipment, including for home oxygen therapy, see Local Services > Oxygen and respiratory services.
  • Patients who are already using nebulizers do so in a separate room from others and implement other infection control recommendations (CTS generally recommends that patients switch from nebulized therapy to metered dose inhalers with spacing devices, dry powder inhalers, or soft mist inhalers during the COVID-19 pandemic).

Patients with diabetes appear to be at increased risk of having a more severe COVID-19 infection and more likely to suffer poor outcomes (Canadian Healthcare Network, May 9, 2020 [login required]; Aging and Disease, June, 2020).

  • Controlling blood glucose may possibly impact the severity of COVID-19. Previous studies have shown that patients with chronically higher blood glucose levels are more likely to acquire bacterial or some viral infections.
  • Data is not yet available differentiating the impact of Type 1 from Type 2 diabetes in relation to COVID-19.
  • During acute illness, patients may be susceptible to adverse drug events due to comorbidities or medicine use. The following medications (SADMANS) may be of concern in some patients (Can J Diabetes, 2018):
    • Sulfonylureas
    • ACE Inhibitors and angiotensin receptor blockers (ARBs)
    • Diuretics
    • Metformin
    • NSAIDs
    • SGLT2 Inhibitors

Holding diabetes medications

Specific populations

Most children with COVID-19 require only supportive care. If present, fever can be managed by administering either acetaminophen or ibuprofen (CPS, April 20, 2020)

Infants and young children considered to be at higher risk for severe illness from COVID-19 are those with (CPS, April 20, 2020):

  • medical complexity
  • genetic, neurologic, metabolic conditions
  • congenital heart disease
  • obesity
  • diabetes
  • asthma or chronic lung disease
  • sickle cell disease
  • immunosuppression

It is probable that a weakened immune system may reduce a patient’s ability to fight infectious diseases like COVID-19. Immunocompromised patients may be at risk of more severe illness and may remain infectious for longer than other COVID-19 patients (CDC, December 29, 2020).

It is recommended that:

  • Primary care providers consult the patient’s specialist (or a specialist in the same field if the patient’s usual specialist is unavailable) for direction related to the condition they are treating. If immunocompromised patients with COVID-19 are on immunosuppressant therapy, treatment may need to be modified or stopped. Systemic corticosteroids should not be stopped abruptly (NICE, April 3, 2020NICE, April 23, 2020NICE, April 9, 2020CEBM, March 30, 2020).
  • Inflammatory bowel disease (IBD) medications have been shown to be associated with significant increased risk of COVID-19 (BMJ, October 20, 2020).
  • Do not delay life-saving treatment or emergency care (CDC, December 29, 2020).
  • Apply more stringent requirements to criteria for discontinuation of self-isolation for immunocompromised patient with resolved COVID-19 (CDC, October 10, 2020).
  • An infectious diseases specialist (especially one who has expertise working with patients who are immunocompromised) may also need to be consulted for assistance with COVID-19 management.

See Top resources for condition-specific guidance.

New Evusheld
Evusheld is a single dose of long-acting antibodies (tixagevimab and cilgavimab) that provides protection for immunocompromised individuals from COVID-19 for six months. Evusheld is authorized for patients who:

  • are not positive for COVID-19 at the time of treatment
  • are 12 and older, weighing at least 40 kg
  • have certain health conditions that make them higher risk and need additional protection, including
    • solid organ transplant recipients
    • stem cell transplant recipients
    • CAR-T therapy recipients
    • other hematologic cancer patients undergoing treatment

Evusheld is accessible to eligible patients through select clinics, including cancer centres and transplant sites. Patients can discuss this option with their treating specialist. Distributing clinics may work with partners such as primary care providers or community clinics to support care delivery close to home for patients (Ontario Health, May 9, 2022).

For more information see Ontario Health’s Information about Evusheld.

Keep in mind: Older adults ≥ 80 have the highest mortality rate due to COVID-19 in Ontario (Public Health Ontario, August 10, 2021).

Atypical COVID-19 presentations in frail older adults

It’s important to monitor atypical symptoms because COVID-19 presents itself differently among older adults. For example, an older patient may not experience a fever or may experience unexplained or an increased number of falls (RGP, April 2, 2020MOH, September 21, 2020).

Refer to the Atypical COVID-19 Presentations in Frail Older Adults (RGP, April 2, 2020) for a summary of what to look for such as:

  • Milder symptoms
  • Delirium or acute functional decline
  • Little or no temperature elevation
  • Mild hypoxia (O2S <90%) without respiratory symptoms
  • Unexplained or increased number of falls

Discuss and establish goals-of-care (e.g. supportive care in the ED vs. palliative care in home). Involve caregivers and family members. See Navigate difficult conversations with patients, families and caregivers and identify the patient’s goals of care for more information (WCH, 2020; PHAC, August 17, 2020).

Adverse pregnancy outcomes

  • Most babies of mothers with COVID-19 are born healthy and at term (SOGC, February 15, 2021).
  • Evidence to date suggests that COVID-19 infection may increase the risk of preeclampsia, preterm birth and other adverse pregnancy outcomes, with even greater risk of these outcomes among severe COVID-19 cases (CMAJ, March 19, 2021).
  • Pregnancy complications such as diabetes, preeclampsia, advanced maternal age, obesity and postpartum hemorrhage increase the risk of severe COVID-19(SOGC, February 15, 2021).

Prenatal care, referral to hospital, and delivery

Mother-to-child transmission and infant testing

Breastfeeding

  • It is not known whether COVID-19 can be spread through breast milk, but the limited amount of evidence available suggests this is unlikely (CDC, February 26, 2021).
  • It is recommended that women with suspected or confirmed COVID-19 continue to breastfeed, while exercising caution (CPS, January 19, 2021; WHO, 2021).
  • Breastfeeding COVID-19 positive mothers should:
    • Wash hands while holding the baby, bottles, breast pump or other materials
    • Be masked while holding or feeding the baby
    • Cough or sneeze away from the baby when holding or feeding
    • Follow breast and skin cleansing hygiene before holding or feeding
    • Clean breast pumps and bottles and do not share these supplies with other mothers (MOH, November 10, 2020).
  • If a mother is too sick to breastfeed, she can pump milk (CPS, January 19, 2021).

Top resources

These supporting materials and resources are hosted by external organizations. The accuracy and accessibility of their links are not guaranteed. CEP will make every effort to keep these links up to date.

New guidance for the prescription of nirmatrelvir / ritonavir (PaxlovidTM)

Jump to:

To date, Paxlovid has only been available through designated Clinical Assessment Centres. Recently, the supply of Paxlovid has increased in Ontario, and as of April 11th, community pharmacies are now able to dispense Paxlovid. The following guidance is intended to support family physicians, nurse practitioners and specialist physicians as they prescribe Paxlovid to patients with mild COVID-19 disease who are not on supplemental oxygen.

How to determine which patients should be prescribed Paxlovid

Family physicians, nurse practitioners and specialist physicians can use their clinical judgment to prescribe Paxlovid. In order to determine eligibility for Paxlovid, providers must consider the following patient factors:

Symptom onset and positive test

Patients must be within 5 days of symptom onset and have tested positive for COVID-19 (by PCR, rapid molecular or rapid antigen test*) to be eligible for Paxlovid (MOH, 2022).

However, healthcare providers should strongly consider pre-assessing their patients to determine if they are at higher risk of severe outcomes and do not have contraindications for taking Paxlovid, in the event that they do test positive (MOH, 2022). See Pre-aseessing your patients.

Consider referring patients with suspected COVID-19 who have tested negative using a RAT at home to their local Clinical Assessment Centre for clinical assessment and testing. See COVID-19 Clinical Assessment Centres (CACs): Information for Primary Care Providers.

*At-home rapid antigen test with provider verification (in-person, virtual, picture or video) is acceptable

Risk for COVID-19 infection progression

Coming Soon – EMR searches are being developed by the eHealth Centre of Excellence to identify individuals at higher risk of severe COVID-19 infection.

The Ontario COVID-19 Science Advisory Table (SAT) has provided detailed guidance as to which patients would derive the greatest benefit from receiving Paxlovid, based on a 5% threshold for adverse outcomes (i.e., hospitalization). However, the SAT guidance should not be interpreted as absolute eligibility criteria, and it should not preclude patients outside of these criteria from being prescribed.

  • There may be individuals who do not strictly meet the SAT criteria, who still have a sufficiently high risk of hospitalization to warrant the prescription of Paxlovid.
  • Expanding beyond the SAT guidance will likely increase the number needed to treat (NNT), however it will also likely decrease the number of hospitalizations. Given the favourable supply of Paxlovid available in Ontario, increasing the NNT (which is approximately 20 according to SAT guidance) is appropriate as long as providers consider the individual benefits and risks to their higher risk patients.
  • Providers should use their clinical judgement and the guidance below to prescribe Paxlovid, including for those patients who do not strictly meet SAT criteria.

Patients belonging to the following groups may be at higher risk of COVID-19 infection progression and should be considered for Paxlovid (if they test positive and are within 5 days of symptom onset) (MOH, 2022):

  • Over 70 years old, regardless of vaccination status
  • Over 60 years old with fewer than three vaccine doses
  • Over 18 years old and
    • Immunocompromised (have an immune system that is weakened by a health condition or medications)
      OR
    • Have fewer than three vaccine doses and at least one of the following risk conditions:
      •  Obesity
      •  Diabetes
      • Heart disease, hypertension, congestive heart failure
      • Chronic respiratory disease (including cystic fibrosis)
      • Cerebral palsy
      • Intellectual and developmental disabilities
      • Sickle cell disease
      • Moderate or severe kidney disease
      • Moderate or severe liver disease
        OR
    • Pregnant and unvaccinated (zero doses)
      • There is a lack of data on nirmatrelvir/ritonavir use in pregnant patients; however, there is extensive experience with ritonavir use in pregnant patients living with HIV. If a pregnant patient fits the risk profile to potentially derive benefit from nirmatrelvir/ritonavir, the risks and benefits of initiating treatment should be discussed with the patient (SAT, February 23, 2022).

Paxlovid may be considered for patients who do not belong to one of the groups listed above, if they are still believed to be at higher risk of COVID-19 disease progression (as per a healthcare provider’s clinical judgement). Consider the following social and clinical risk factors when determining whether your patients may be at higher risk of disease progression.

  • Social risk factors
    • Indigenous individuals aged 40 and over who have not received a complete vaccine series (BCCDC, 2022)
    • Members of marginalized or racialized communities (MOH, 2022)
    • Living in congregate care or receiving homecare (GNB, 2022)
    • Other social determinants of health (MOH, 2022)
  • Additional clinical risk factors
    • Active or recent cancer
    • Neurological conditions (epilepsy, dementia, MS, neuropathy, stroke)
    • Arrhythmia
    • Schizophrenia, bipolar, mania
    • Substance use disorders
    • RA, psoriatic arthritis, lupus
    • Inflammatory bowel disease such as Ulcerative colitis, Crohn’s disease
    • Solid organ transplant recipient
    • Recent stem cell transplant
    • Smoking
    • Frailty
Updated Drug interactions and contraindications

Drug interactions leading to potentially serious and/or life-threatening reactions are possible due to the effects of ritonavir on the hepatic metabolism of certain drugss (OH, April, 2022).

Check for possible drug interactions and contraindications before prescribing Paxlovid for your patients. Note that some medications will be able to be paused during Paxlovid treatment, and others will not (therefore, Paxlovid cannot be prescribed, and referral to a Clinical Assessment Centre should be considered).

For a list of drug interactions and contraindications, as well as guidance on what to do for each of those interactions see Nirmatrelvir/Ritonavir (Paxlovid): What Prescribers and Pharmacists Need to Know

Considerations when prescribing Paxlovid

Updated Writing the prescription

Physicians and nurse practitioners should strongly consider sending an up-to-date medication list for the pharmacist to double check possible contraindications

  • When writing a prescription, clearly indicate the following:
    • Confirmed COVID-19 (PCR or RAT+)
    • Symptomatic for 5 days or less (symptom onset is considered day 0)
    • Increased risk for COVID-19 infection progression
    • eGFR (if known) or an indication that no kidney impairment exists
    • Confirmation that patients are not on supplemental oxygen
    • Which risks factors make Paxlovid appropriate for this patient
    • Whether the patient has severe hepatic impairment
  • For a sample prescription, see here
  • See available Paxlovid EMR prescription and referral supports. These resources were developed by Partnering for Quality and the eHealth Centre of Excellence and are available for PS Suite, Oscar and Accuro.
  • As this medication is new in the formulary, you may need to enter it as a custom drug in your electronic medical record.
  • Consider renal function and dose adjust accordingly for safety:
    • Normal renal function (eGFR > 60mL/min): 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three taken together orally twice daily for 5 days
    • Mild-moderate renal impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), taken together orally twice daily for 5 days.
    • For patients with eGFR < 30 mL/min, and those on dialysis, consult the Ontario Renal Network’s Supplemental Clinical Guidance #4, which provides information on the rationale for Paxlovid use in these populations, as well as dosing recommendations on Page 10
  • Inform patient or caregiver of
    • The pill burden (6 tablets daily) and emphasize the importance of adherence once initiated to minimize the development of drug resistance
    • Common side eff­ects, which are generally mild and can include dysgeusia (taste disturbance), diarrhea, hypertension, myalgia, vomiting and headache. See Product Monograph for details.
    • Filling a Paxlovid prescription may take up to 60-90 minutes as pharmacists will need to confirm the patient’s:
      • Test results
      • Vaccination history
      • Complete drugs list
      • Current kidney function test
    • Preparation for filling their prescription by bringing a complete list of medications and their vaccination history
Updated Participating pharmacies
  • Most pharmacies are eligible to dispense Paxlovid, however participation in this initiative is voluntary.
  • Patients should contact their local pharmacy to confirm availability of Paxlovid prior to bringing their prescription.
  • Pharmacies can obtain Paxlovid (at no cost) through participating pharmaceutical distributors.
  • There is no cost to eligible patients who receive Paxlovid.
  • See a list of participating pharmacies.

Pre-assessing your patients

Note, the below recommendations may not be feasible for many primary care providers due to resource and time constraints.

Pre-assess your patients to determine whether they would be eligible for Paxlovid (based on their Risk for COVID-19 infection progression and lack of drug interactions and contraindications) in the event that they do test positive.

Consider putting a prescription on file with such patients’ local pharmacies. Patients will then be allowed to bring in their positive COVID-19 test result and fill their prescription, without needing to contact their primary care provider.

  • Where appropriate, consider reviewing medication lists to ensure any unnecessary medications that might preclude future Paxlovid prescribing are stopped.

If you do pre-assess your patients, be sure to contact the appropriate pharmacy as soon as possible if there are any changes to the patient’s health or medications (e.g., changes in renal function or new medications) that may impact or contraindicate their Paxlovid prescription. Remove their Paxlovid prescription on file if appropriate.

New Additional Resources for Paxlovid

COVID-19 Clinical Assessment Centres (CACs): Information for Primary Care Providers

Jump to:

CACs are an optional resource intended for patients with known or suspected COVID-19 who:

  • Are at higher risk of severe disease and may be eligible for treatment with remdesivir or Paxlovid
    AND/OR
  • Cannot be safely monitored at home and for whom an in-person assessment by their primary care provider is not feasible or sufficient (e.g., if the patient cannot be seen within 24 hours, if the patient requires services such as testing that the provider cannot provide). See Outpatient management of patients with COVID-19 for information on managing patients at home.

Paxlovid is now being dispensed at community pharmacies, and remains available at a number of sites associated with clinical assessment centres.

COVID-19 Clinical Assessment Centres (CACs) in Ontario will offer standard elements of care, including assessment and appropriate testing, diagnosis, and disposition planning. Select CACs will also be able to distribute Paxlovid to eligible patients, or refer patients to other locations where Paxlovid is distributed. These CACs do not provide ongoing monitoring of patients. This approach builds on the COVID-19, cough and flu clinics and other influenza-like illness clinics already established (Ontario Health, January 4, 2022).

COVID-19 CACs are not intended to reduce or replace testing capacity. Rather, they augment the existing Assessment Centre (AC) model (Ontario Health, January 4, 2022).

Services available at Clinical Assessment Centres

Health professionals and specific services available may differ between CACs. See the List of Clinical Assessment Centres for information on your local CACs.

Not all CACs offer services for children. At this time, it is recommended that existing local pediatric care pathways continue to be used. See the List of Clinical Assessment Centres for information on your local CACs

Patients do not have to be covered by OHIP to be referred to or receive services at CACs.

The following services are typically available for referred patients at CACs (Ontario Health, January 4, 2022):

  • Assessment and testing
    • Assessment by an appropriate health professional, which may include oxygen saturation, vital signs, and identifying relevant risk factors/comorbidities. 
    • Testing may include using a rapid test, if appropriate and in keeping with the provincial guidance.
  • Diagnosis 
    • Diagnosis by an appropriate health professional
  • Disposition planning 
    • Depending on the patient’s condition and risk, disposition options may include:
      • Direct to patient’s Primary Care Provider
      • Home with self-monitoring (See Testing and isolation requirements)
      • Home with remote care monitoring as available in your region (e.g., COVID@Home Monitoring for Primary Care)
      • Direct to emergency department for further investigation
      • Direct to inpatient COVID-19 unit
      • Direct to outpatient therapeutics (e.g., remdesivir for eligible patients, based on limited supply)
      • Prescription of Paxlovid to eligible patients, based on limited supply (and only at select CACs)

Determining whether a patient should be referred to a Clinical Assessment Centre

CACs are not intended to replace in-person assessments by primary care providers. If you have determined that a patient should be seen in person, and you can safely offer the services that you think the patient needs (e.g., access to testing and/or medications, similar timing of appointment), consider seeing the patient in-person at your office/clinic.

Due to the limited availability of COVID-19 tests, many patients will not know whether they are COVID-positive. Lack of a positive test (i.e., PCR or RAT) should not preclude you from referring a patient to a CAC. If a test is required for disposition planning (e.g., for prescription of Paxlovid) a CAC will administer the test.

CACs are not extended emergency rooms. Primary care providers should continue to refer patients to the appropriate Emergency Department if they are experiencing one or more of the following symptoms (Ontario Health, January 4, 2022):

  • Severe difficulty breathing
  • Severe chest pain
  • Feeling confused
  • Losing consciousness

If the patient is part of one of the high-risk population groups below and their symptoms began within the last 6 days, referral to a CAC should be strongly considered as they may be eligible for remdesivir (if within 6 days of symptom onset) or Paxlovid (within 4 days). Therapeutic Management of Adult Patients with COVID-19 provides full details on which patients may be eligible for outpatient therapies.

  • Over 70 years old, regardless of vaccination status
  • Over 60 years old with fewer than three vaccine doses
  • Over 18 years old and
    • Immunocompromised (have an immune system that is weakened by a health condition or medications)
      OR
    • Have fewer than three vaccine doses and at least one of the following risk conditions:
      • Obesity
      • Diabetes
      • Heart disease, hypertension, congestive heart failure
      • Chronic respiratory disease (including cystic fibrosis)
      • Cerebral palsy
      • Intellectual and developmental disabilities
      • Sickle cell disease
      • Moderate or severe kidney disease
      • Moderate or severe liver disease
      • Pregnant and unvaccinated (zero doses)

If you are not referring a patient to a CAC based on the criteria outlined above (or if you are unsure of referring them based solely on those criteria), consider:

If after considering these factors you determine that a patient with known or suspected COVID-19 cannot be safely monitored at home, consider referring the patient to a CAC (See How to refer patients to Clinical Assessment Centres) or seeing the patient in person at your office/clinic.

Underlying illness or risk factors

Patients who are not able to access remdesivir or Paxlovid (e.g., ineligible, supply not available), may still have underlying illness or risk factors that should be assessed in-person to determine differential diagnoses and/or management of exacerbations of comorbidities due to COVID. Patients with underlying cardiopulmonary disease may need an assessment of their COVID-19 illness as well as their underlying illness because of concerning symptoms or vital signs, to determine next steps in management.

Symptoms or patterns of symptoms

Symptoms or patterns of symptoms that may suggest that they cannot be safely monitored at home and that may require in-person assessment at a CAC (HFAM, July 21, 2021):

  • New or worse trouble breathing (if severe, patient should go to Emergency Department)
  • Symptoms that have improved but then become worse
  • Severe dehydration, such as:
    • Having a very dry mouth
    • Passing only a little urine
    • Feeling very lightheaded
  • Other symptoms that are getting worse that you determine require in-person assessment that you are unable to provide
Your ability to monitor remotely

Your ability to monitor remotely and/or assess the patient remotely:

  • A one-off O2 saturation assessment may be indicated (e.g., to determine whether a patient is severe enough to seek ED admission) but not feasible without sending a patient to a Clinical Assessment Centre. Pulse oximeters for lending to patients for routine monitoring can be ordered by primary care providers for free using this link.
  • Assessment of other vital signs may be indicated that would require in-person assessment.
  • If a patient with suspected or confirmed COVID-19 needs to be examined in-person, and a provider is unable to safely see the person in their own clinic within 24 hours, referral to a Clinical Assessment Centre should be considered.

How to refer patients to Clinical Assessment Centres

If you are instructing a patient to go to the CAC for assessment, remind them to bring with them a list of their medication and a short list of any important medical conditions. Patients may incorrectly assume that CACs will have that information.

Patients may also be referred to a COVID-19 clinical assessment centre by (Ontario Health, January 4, 2022):​

  • Self-referral/walk-in​ 
  • Telehealth​
  • Emergency department​
  • Assessment centres that offer testing only (i.e., an Assessment Centre referring a patient to a Clinical Assessment Centre)

Referral processes and processes for communicating visit results back to primary care providers may vary by region and/or by specific CAC. For specific questions, primary care providers should reach out to their local CAC

List of Clinical Assessment Centres

The Ministry of Health’s COVID-19 testing locations and clinical assessment centres webpage contains contact information for all Assessment Centres (ACs) and Clinical Assessment Centres (CACs) in the province. To find CACs, check off the “Provides clinical assessments” box under Services Available on the left side of the page.

List of sites distributing Paxlovid

The following links provide lists of sites distributing Paxlovid, including contact information:

Long-term symptoms / Post-acute sequelae of COVID-19 (PASC)

Jump to:

What is “long COVID”?

Long COVID/PASC describes when patients experience symptoms that continue or develop after an acute COVID-19 infection, which cannot be explained by another diagnosis. This includes on-going symptomatic COVID-19 (4-12 weeks post-infection) and post-COVID-19 syndrome (12 or more weeks post-infection). Long COVID is estimated to affect approximately 10% of COVID-19 patients (Int J Environ Res Public Health, April 18, 2021).

  • Constitutional symptoms: fatigue, fever, chills and shivers, wheezing, fainting, swelling
  • Respiratory Symptoms: breathlessness, cough, coughing up sputum, chest pain
  • Cardiovascular symptoms: cardiovascular abnormalities, chest tightness, chest pain, palpitations
  • Neurological symptoms: cognitive impairment (brain fog, loss of concentration, memory issues), headache, sleep disturbance, peripheral neuropathy symptoms (pins and needles and numbness), dizziness, delirium (in older populations)
  • Gastrointestinal symptoms: abdominal pain, nausea, diarrhoea, anorexia and reduced appetite (in older populations)
  • Musculoskeletal symptoms: joint pain, muscle pain
  • Psychological/psychiatric symptoms: depression, anxiety
  • Ear, nose and throat symptoms: tinnitus, earache, sore throat, runny nose, nasal congestion, coughing up blood, dizziness, loss of taste and/or smell
  • Dermatological symptoms: skin rashes
  • Conjunctivitis
Supporting patients with long COVID/PASC
  • Assess and investigate
    • Use a holistic, person-centred approach to investigate symptoms, take a comprehensive history, and to understand the symptoms’ effects on the patient’s quality of life
    • Use tests and investigations to determine the exact cause of symptoms and eliminate other non-COVID diagnoses.
  • Refer to appropriate supports or specialists
    • Initiate an urgent referral to the appropriate services if a patient’s symptoms could be life-threatening
    • Considering referring to relevant supports or specialists, especially for psychiatric symptoms
  • Support patients in the symptom management and multidisciplinary rehabilitation
    • Assist patients to optimize function and quality of life
    • Explain to patients that the effects of over-the-counter vitamins and supplements on long COVID/PASC is unknown.
    • To assist in the short term, help patients create a self-management plan that will support their return to daily activities, including symptom management approaches (e.g. breathing exercises for dyspnea). Discuss possible patient self-monitoring at home as appropriate, and advise patients when to seek additional care.
    • To assist in the longer term, create a rehabilitation plan with patients, including their goals and interventions, and refer to the appropriate supports for interdisciplinary care.  This may include physical, psychological, and psychiatric aspects of rehabilitation.
  • Ensure continuity of care
    • Agree on a plan for follow-up care and monitoring with the patient, tailoring it to their needs and symptoms
    • Be alert to changes in symptoms and refer as necessary
    • When possible, make information, documents and records available to patients and multidisciplinary team members.

‘Long COVID’ Resources for Patients

Emerging evidence: COVID-19 variants, transmission, paediatric symptoms, and Rx research

Jump to:

There is primarily only low-quality evidence available on COVID-19, as it is an emerging virus. Many studies being released have not been peer-reviewed. Among those that have been peer-reviewed, many are small, retrospective observational studies and thus have serious limitations and risks of bias. While the findings of emerging COVID-19 studies can be useful in helping to broaden our understanding about how the virus might operate, the results of COVID-19 studies should not be considered validated.

COVID-19 variants

Why has this been in the news?

Variants of viruses are common and changes to the genetic material of the virus are expected over time. COVID-19 variants contain multiple mutations, including some in the receptor-binding domain (RBD) of the spike protein, which raises theoretical concerns over vaccine efficacy.

Variants and transmission

These COVID-19 variants are currently associated with an increased risk of transmission. Research is ongoing to understand the rate of spread for each variant (PHAC, November 28, 2021; CDC, November 27, 2021). Preliminary epidemiological data suggests that the Omicron variant is more transmissible than the Delta variant. Public Health Ontario estimates that each Omicron case is infecting 7.7 times more individuals than Delta in Ontario (PHO, December 14, 2021)

Variants and severity

COVID-19 variants may affect the severity of disease. Research is ongoing to understand the impact of these variants on disease severity (Health Canada, November 29, 2021; CDC, November 27, 2021). The severity of disease caused by the Omicron variant and its impact on populations like Ontario’s is still not well understood. Emerging evidence from South Africa is not directly comparable to Ontario because of differences in previous infection rates, vaccination status, and age distribution between the populations (PHO, December 14, 2021)

Variants and vaccines

Limited, emerging evidence suggests that some variants of COVID-19 may have an impact on the efficacy of approved COVID-19 vaccines. Additional research is required in this area (Health Canada, November 29, 2021). For additional information regarding COVID-19 vaccines and variants see CEP’s COVID-19: Vaccines resource.

COVID-19 vaccines

This resource guides family physicians and primary care nurse practitioners through the latest information about vaccines in Ontario. It covers:

  • Availability, rollout and prioritization in Ontario
  • Emerging evidence: specific populations and allergic reactions
  • Addressing patient questions about vaccines
  • Pfizer-BioNTech mRNA vaccine (side effects, contraindications and precautions, point-of-care guidance and ingredients)
  • Moderna mRNA vaccine (side effects, contraindications and precautions, point-of-care guidance and ingredients)

Mixed COVID-19 vaccines

NACI and the Ontario government now recommend that individuals who have received AstraZeneca for their first dose may receive AstraZeneca or an mRNA vaccine (Pfizer or Moderna) as their second dose, based on their preference (MOH, June 3, 2021; NACI, June 1, 2021). Second doses (regardless of vaccine type chosen) will be provided at the recommended 12-week interval (MOH, June 3, 2021).

For patients who received an mRNA vaccine (Pfizer or Moderna) as their first dose, NACI and the Ontario government now recommend that if supply of the first dose vaccine is limited, a second dose can be provided using the alternative mRNA vaccine (MOH, June 3, 2021; NACI, June 1, 2021). It is still recommended to administer both doses with the same mRNA vaccine product, if supply permits (MOH, June 3, 2021; NACI, June 1, 2021).

Booking second doses of AstraZeneca or mRNA vaccines

Individuals who received their first dose of the AstraZeneca vaccine 12 weeks ago and who would like their second dose of the AstraZeneca vaccine, can contact the pharmacy or primary care provider where they received their first dose to book an appointment (MOH, June 3, 2021). Those choosing to receive an mRNA vaccine have the option to schedule their second dose appointment at a participating pharmacy where the Pfizer or Moderna vaccines are available (MOH, June 3, 2021).

Beginning the week of June 7, 2021, individuals who received their first dose of the AstraZeneca vaccine and who choose to receive an mRNA vaccine for their second dose can register for a “second dose only” appointment at a 12-week interval through the provincial booking system (MOH, June 3, 2021). Eligible individuals will also be able to schedule these appointments directly through public health units that use their own booking systems (MOH, June 3, 2021).

What evidence is there that mixed dose vaccine schedules are safe and effective?

For other public health situations (flu, hepatitis A, etc.) mixed dose schedules have been used with similar vaccine products safely and effectively (NACI, June 1, 2021). In order to be extremely cautious, NACI and the Ontario government waited until information was available on doing this with COVID-19 vaccines, specifically.

Recent studies in Europe (i.e., Germany, Spain, and the U.K.) have demonstrated the safety and immune responses produced using mixed COVID-19 vaccine schedules, and therefore support vaccine interchangeability (NACI, June 1, 2021). More results from ongoing studies, including Canadian data, will be closely monitored by NACI to ensure the ongoing safety of this approach (NACI, June 1, 2021).

Transmission

The COVID-19 virus is transmitted primarily at short distances through respiratory particles that range in size from large droplets which fall quickly to the ground to smaller droplets, known as aerosols, which can remain suspended in the air (PHO, May 20, 2021). However, other transmission routes are possible (PHO, June 30, 2021) :

  • SARS-CoV-2 can survive on a variety of surfaces, potentially leading to transmission via fomites; however, epidemiological evidence supporting fomite transmission is limited.
  • Transmission through the ocular surface is a possible route of transmission of SARS-CoV-2 based on the detection of viral RNA in ocular samples and limited epidemiological evidence that eye protection decreases the risk of infection.
  • There is evidence for vertical intrauterine transmission of SARS-CoV-2 from mother to child; however, intrauterine transmission is uncommon.

Multisystem Inflammatory Syndrome in Children (MIS-C)

Also called paediatric inflammatory multisystem syndrome (PIMS), multisystem inflammatory vasculitis, hyperinflammatory syndrome, Kawasaki-like disease or toxic shock-like syndrome.

As reports of children experiencing multi-system inflammatory syndrome increase, the Canadian Paediatric Surveillance Program issued a Public Health Alert (CPSP, May 12, 2020) encouraging those providing paediatric care to familiarize themselves with the presentations of this emerging syndrome. It has now been included in the case definition and is reportable to public health.

While rare, clinicians should be aware of this potential syndrome and maintain a high index of suspicion to identify cases. Some patients have deteriorated quickly and have required intensive care unit admission for vasopressors and mechanical ventilation.

Clinical presentations include:
  • Persistent fever and features suggestive of Kawasaki disease (complete or incomplete).
  • Toxic shock-like syndrome.
  • Euvolemic shock states.
  • Severe gastrointestinal illness.
  • Severe myocardial dysfunction and multiple organ failure have also been reported.
If these symptoms present:
  • Take a comprehensive history to identify confirmed or potential COVID-19 contacts.
  • Order screening laboratory tests for hyperinflammation as outlined in the Canadian Paediatric Society’s guidance.  Laboratory features suggestive of MIS-C:
    • C-reactive protein (CRP) ≥50 mg/L and at least one of the following:
    • ferritin >500 mcg/L
    • platelets <150 x109/L
    • lymphopenia <1000/µL
    • hypoalbuminemia
    • neutrophilia
  • When laboratory evidence of significant hyperinflammation is present, consider additional work-up as available for an evolving picture of CSS/MAS (ferritin, LDH, fibrinogen, D-dimers, PTT, INR, triglycerides), and for cardiac involvement (troponin, NT-proBNP, and ECG).

Note: Serology may be positive or negative for SARS-CoV-2. While the WHO cites positive serology or possible contact as a criteria for the case definition, a recent study found that not all children with the syndrome had positive serology at time of testing (The Lancet, May 13, 2020).

  • Children and adolescents 0–19 years of age with fever > 3 days.
  • AND two of the following:
    • Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet)
    • Hypotension or shock
    • Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP)
    • Evidence of coagulopathy (by PT, PTT, elevated d-Dimers)
    • Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain)
  • AND elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin.
  • AND no other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.
  • AND evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19 (Note: not all children with the syndrome will have positive serology).
Current evidence
  • A systematic review of 27 studies has found that the common manifestations of MIS-C were gastrointestinal symptoms (87.3%; 95% CI, 82.9-91.6) and cardiovascular involvement such as myocardial dysfunction (55.3%; 95% CI, 42.4-68.2), coronary artery aneurysms (21.7%; 95% CI, 12.8-30.1) and shock (65.8%; 95% CI, 51.1-80.4), with marked elevated inflammatory and cardiac markers (Pediatr Pulmonol, January 11, 2021).
  • A systematic review of 39 observational studies in 662 patients found that 90% of children with MIS-C had cardiac involvement, 71% were admitted to ICU, 60% presented with shock, and 1.7% died. Half of patients with MIS-C had an underlying medical condition. Children generally developed MIS-C 3-4 weeks after COVID infection, and 4 studies reported that some children developed MIS-C after an asymptomatic COVID infection (Lancet, September 4, 2020).
  • A systematic review and meta‐analysis of 21 studies has found that inflammatory markers were different while comparing MIS-C vs. severe/non-severe COVID-19, severe MIS-C vs. non-severe MIS-C and age groups of MIS-C. The measurement of these inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders (J Med Virol, March 19, 2021).
  • A recent systematic review and meta‐analysis of 18 studies analyzed the demographic profile, clinical spectrum, management strategies, prognosis, and pathophysiology of MIS-C among children with SARS-CoV-2 infection. The study identified the stark differences of MIS-C from Kawasaki disease with respect to demographics and also addressed the clinical spectrum. The study found that over-reliance on RT-PCR for diagnosis can miss the diagnosis of MIS-C (Pediatr Res, May 18, 2021).

Multisystem Inflammatory Syndrome in Adults (MIS-A)

Case series report a small number of adults developing a condition similar to MIS-C, referred to as MIS-A (Multisystem Inflammatory Syndrome in Adults). Further research is needed to better characterize this new condition, including whether it is associated with acute COVID-19 or if it is “an entirely post-acute phenomenon” (Johns Hopkins Center for Health Security, October 2, 2020). See the CDC’s case definition for MIS-A (CDC, May 11, 2021).

MIS-A is a condition where problems can occur in different parts of the body like the heart, gastrointestinal tract, skin, or brain. Adults with MIS-A may present with the following signs and symptoms:

  • Fever
  • Low blood pressure
  • Abdominal (gut) pain
  • Vomiting
  • Diarrhea
  • Neck pain
  • Rash
  • Chest tightness/pain
  • Feeling very tired
Emerging evidence for MIS-A
  • A CDC case series analyzed 27 adult patients identified as having MIS-A: 9 patients reported to CDC, 7 from published case reports, and 11 patients described in three case series in peer-reviewed journals. The patients exhibited cardiovascular, gastrointestinal, dermatologic and neurological symptoms without severe respiratory presentation, similar to what has been observed in children experiencing MIS-C (CDC, October 2, 2020; Johns Hopkins Center for Health Security, October 2, 2020).
  • A recent retrospective cohort study of 698 patients has found that MIS-A has a more heterogeneous clinical presentation than previously appreciated and is commonly underdiagnosed (JAMA Netw Open, May 3, 2021).

COVID-19 Therapy research

Medications

Paxlovid (Pfizer), Remdesivir, Dexamethasone, Bamlanivimab, Sotrovimab, and Casirivimab / Imdevimab, are currently authorized by Health Canada for the prophylaxis or treatment of COVID-19 (Health Canada, January 17, 2022).

The Ontario COVID-19 Science Advisory Table has issued a series of recommendations for possible medications to treat mild, moderate and severe COVID-19. Supporting evidence for each of these medications can be found below. Additional information on approved medications, including practical considerations, can be found in CEP’s Outpatient Management section.

Current Evidence

Budesonide may be considered in some patients with mild COVID-19 (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting evidence

  • A UK open-label, parallel-group, randomised controlled trial (STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms found that early administration of the treatment reduced the likelihood of urgent medical care and helped reduce time to recovery. The group treated with budesonide experienced 1 day faster clinical recovery and fewer days with fever. Fewer participants in the budesonide group experienced fever and had persistent symptoms at days 14 and 28 compared to the group treated with usual care (Lancet Respiratory Medicine, July 1, 2021).
  • The PRINCIPLE study is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done in the UK. The participants were 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. 4700 participants were randomized to three groups – usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions – and followed up for 28 days. The group treated with budesonide experienced a shorter time to self reported recovery. The researchers also outlined a possible reduction in hospital admissions and deaths among this group, though the results did not meet their superiority threshold (Lancet, September 4, 2021).

Dexamethasone is recommended for COVID-19 patients with moderate or critical illness (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting evidence

  • The RECOVERY Trial, a controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation and among those receiving oxygen without invasive mechanical ventilation but not among those who were receiving no respiratory support at randomization (NEJM, February 25, 2021).
  • A systematic review and meta-analysis of corticosteroid treatment in severe COVID-19 patients showed that the treatment was associated with a decreased all-cause mortality. However, this association was absent if the RECOVERY trial was excluded. Corticosteroids were found to decrease the occurrence of composite disease progression, but not increase the incidence of serious adverse events (Signal Transduct Target Ther, February 21, 2021).

For mildly ill patients presenting within 7 days of symptom onset, the Science Table indicates that 50 mg PO daily titrated up to 100 mg PO TID for 15 days may be considered as treatment and advises pharmacist consultation and patient follow-up to avoid any significant adverse drug interactions with Fluvoxamine (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting evidence

  • One placebo-controlled, randomized clinical trial (RCT) found that Fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation (Lancet Global Health, January 10, 2022).
  • Another RCT concluded that Fluvoxamine reduced the likelihood of clinical deterioration in adult outpatients with symptomatic COVID-19 over 15 days (JAMA, December 8, 2020).
  • A retrospective cohort study found that the SSRIs Fluoxetine and Fluvoxamine may be associated with reduced severity and relative-risk of mortality of COVID-19 (JAMA, November 15, 2021).
  • An open-label prospective cohort study investigated fluvoxamine for early treatment of COVID-19. The study found that at day 14, ongoing symptoms were present in 0% of patients who received fluvoxamine compared with 60% of patients with observation alone (Open Forum Infectious Diseases, February 2, 2021)
  • Another open-label prospective cohort study found that overall mortality was lower in the group of hospitalized patients treated with fluvoxamine than among the group that was not (Br J Clin Pharmacol, November 1, 2022).

Prophylactic dose low molecular weight or unfractionated heparin are recommended in critically ill patients hospitalized with COVID-19. These patients should not receive therapeutic dose anticoagulation unless they have a separate indication for this treatment (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting evidence

  • In an open-label, adaptive, multiplatform, randomized clinical trial,of critically ill COVID-19 patients, the use of heparin for anticoagulation was compared with pharmacologic thromboprophylaxis in accordance with local usual care.
  • The RAPID trial, a randomized controlled, adaptive, open label clinical trial, examined the use of heparin in moderately ill hospitalized COVID-19 patients with increased D-dimer levels. The trial found that therapeutic heparin was not significantly associated with a reduction in the primary outcome, a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, but that the odds of death at 28 days was decreased (BMJ, October 14, 2021).
  • A meta-analysis of RAPID and the multiplatform studies was performed, to evaluate safety and efficacy outcomes for moderately ill patients. There was no significant reduction in all-cause death with therapeutic heparin. There were significant reductions in the composite of death or invasive mechanical ventilation, death or organ support,death or major thrombotic event, and major thrombotic events. There were significant decreases in ventilator-free days alive and organ support-free days alive with therapeutic heparin. There was a non-significant increase in major bleeding (Ontario COVID-19 Science Advisory Table, September 3, 2021).
  • A systematic review of observational cohort studies and RCTs demonstrated both prophylactic and full dose heparin reduced mortality in participants. However, full dose heparin was associated with a higher risk of major bleeding (Pharmacol, September 2, 2021).

Paxlovid is recommended for patients with mild COVID-19 and high risk of hospitalization or who are immunocompromised (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting Evidence

  • A meta-analysis of eight studies examined the use of three oral antiviral treatments (molnupiravir, fluvoxamine and Paxlovid) for the treatment of COVID-19. The meta-analysis compared the outcomes of COVID-19 patients treated with any of these oral antiviral drugs. The study concluded that the drugs reduced mortality or hospitalization by approximately 67% among the participants (Annals of Medicine, February 4, 2022).
  • A double-blind, randomized, controlled trial studied symptomatic, unvaccinated, non hospitalized adults at high risk for progression to severe COVID-19. Participants were assigned to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir or placebo every 12 hours for 5 days. Those who received the treatment had a risk of disease progression that was 89% lower than those in the placebo group (NEJM, February 16, 2022).

Remdesivir is recommended in mildly ill COVID-19 patients with a high risk of severe disease progression if administered within 7 days of symptom onset. It is also recommended in moderately ill patients (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting Evidence

  • In the ACTT-1 trial, remdesivir shortened time to recovery but failed to show a mortality benefit (hazard ratio for death was 0.70, 95% CI 0.47 to 1.04) (NEJM, May 22, 2020). In another study, there was a 31% faster time to recovery (median time to recovery was 11 days with remdesivir and 15 days with placebo, p<0.001) and a numerically shorter duration of mechanical ventilation (7 days vs. 15.5 days; not statistically significant) (NIH, April 29, 2020; NEJM, April 10, 2020). Adverse events leading to medication discontinuation were 12% with remdesivir vs. 5% in placebo; number needed to harm = 15 (Lancet, April 29, 2020).
  • In an open-label randomized trial comparing remdesivir to standard care in 596 patients with moderate COVID-19 pneumonia, patients randomized to 10 days of remdesivir treatment did not have a statistically significant difference in change of clinical status (based on a 7-point scale ranging from death to discharge) 11 days after treatment initiation, while patients randomized to 5 days of remdesivir did show a statistically significant difference, but this difference was of uncertain clinical importance (JAMA, August 21, 2020).
  • A meta-analysis of 2,276 patients treated with Remdesivir, with patients randomized to 10-day or 5-day treatment with Remdesivir, or a control group, suggests that Remdesivir may be successful in increasing the recovery rate among moderate and severe hospitalized Covid‐19 patients. Limitations in this publication include heterogeneity of data and the small number of studies pooled for data (Reviews in Medical Virology, October 31, 2020).
  • A systematic review and meta-analysis indicated that remdesivir may be associated with improvement in the 28-day recovery, low flow oxygen support through days one to 14, and invasive mechanical ventilation or extracorporeal membrane oxygenation requirement through days 14 to 28 of the follow-up time. The study also found that the risk of experiencing serious adverse drug reactions was lower in the remdesivir group than the comparison/control group (Eur J Pharmacol, February 4, 2021).
  • A randomized, double-blind, placebo-controlled trial was conducted among nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The trial found that a 3-day course of remdesivir resulted in an 87% lower risk of hospitalization or death than placebo (NEJM, January 27, 2022).

Sotrovimab is recommended for patients with mild COVID-19 and high risk of hospitalization or who are immunocompromised (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting Evidence

  • A multi-center, randomized, double-blind, placebo-controlled trial of non-hospitalized, unvaccinated patients found that sotrovimab greatly reduced the risk of COVID-19 Patients with at least one risk factor for disease progression were randomized to an IV infusion of sotrovimab 500 mg or placebo.The study found an 85% relative risk reduction in the sotrovimab arm (NEJM, November 18, 2021).

Tocilizumab is recommended for patients who are  on recommended doses of dexamethasone therapy (or a dose-equivalent corticosteroid) and are within 14 days of hospital admission. It is also recommended for patients who have  evidence of systemic inflammation, have evidence of disease progression despite 24-48 hours of recommended doses of dexamethasone therapy, and are within 14 days of hospital admission (Ontario COVID-19 Science Advisory Table, February 23, 2022).

Supporting Evidence

  • A systematic review of retrospective studies indicated Tocilizumab may have potential to treat Covid-19. Due to limitations of this evidence, further large-scale studies are needed in this area (European Journal of Clinical Pharmacology, October 31, 2020).
  • A retrospective multicenter study of adults requiring mechanical ventilation for COVID-19 found that while tocilizumab was not associated with decreased mortality it was associated with an increased rate of extubation (Expert Review of Anti-infective Therapy, February 24, 2022)
  • A systematic review examined combined data from 20,616 hospitalized patients with COVID-19. 7668 patients received Tocilizumab in addition to usual care (including 1915 patients admitted to intensive care units (ICU) with reported mortality) and 12,948 patients only receiving usual care. Tocilizumab was found to reduce mortality among admitted patients, but was found to have greater benefit when administered with concomitant corticosteroids within the first 10 days of symptom onset (Pharmacotherapy, September 24, 2021).
  • A bayesian reanalysis of a previous meta-analysis of hospitalized patients with COVID-19 treated with tocilizumab and corticosteroids, found that the use of simple oxygen and noninvasive ventilation was associated with a probability of a clinically meaningful mortality benefit from tocilizumab (JAMA, February 28, 2022).

Evidence summaries and guidelines

Palliative care and COVID-19

Jump to:

The role of primary care

Navigate difficult conversations with patients, families and caregivers and identify the patient’s goals of care

Due to COVID-19’s increased strain on the healthcare system, primary care providers will need to engage in difficult conversations regarding restricted treatment options, rapid deterioration and end-of-life planning. Importantly, the provider will need to ensure the patient understands the nature and severity of their illness, and explore their goals of care to support decision-making and enable person-centred care.

Putting it into practice

  • Prepare yourself and explain the purpose of the meeting to the patient – or their family, power of attorney (POA), and/or substitute decision maker (SDM). Gather the information you need to know in order to have an informed goals of care discussion.
  • Explore your patient’s understanding of COVID-19 to determine what information your patient has and needs.
  • Discuss goals of care that are most aligned with the patient’s values and what is clinically appropriate/available.
  • Recommend and document a plan that summarizes the patient’s values and discuss what you will do first to help the patient before discussing treatments that will be stopped or not offered.
  • Reaffirm and support the patient.

Document decisions regarding do not resuscitate (DNR)

Putting it into practice

Prognostic considerations regarding DNR in the event of COVID-19:
Prognostic factors for complications and worse outcomes
  • In those over age 80, mortality increases to 15-20%.
  • Between five to 10 days after exposure, patients tend to stabilize or decompensate rapidly – e.g. Acute respiratory distress syndrome (ARDS).
  • Age > 65, diabetes, hypertension are all associated with ARDS.
  • Of those who develop ARDS, 52% may go on to a fatal outcome.
  • Anecdotal experience suggests that those who develop ARDS will likely die within eight to 12 hours if not intubated.
Lab markers associated with worse outcomes
  • Worsening lymphopenia
  • Elevated LDH
  • Elevated CRP, ferritin, IL-6
  • Elevated troponin
  • Other factors associated with outcome include their premorbid state and duration of illness

Manage symptoms, and address other palliative care needs for patients with COVID-19

Access to palliative care and hospice services for COVID-19 patients may become limited or unavailable. Family physicians and community palliative care nurse practitioners need to be prepared to address the palliative care needs of their COVID-19 patients.

Provide end-of-life care for COVID-19 patients

When patients with COVID-19 are in their final weeks and days of life, family physicians and community palliative care nurse practitioners need to be prepared to support and provide end-of-life care.

  • It is important to ensure rapid access to palliative medications that are often at higher doses than seen in standard practice (RCGP).
  • Dose ranges should be considered to allow for urgent decision-making regarding escalation of dose for distressing symptoms.
  • The most common terminal symptoms (fever, rigors, severe dyspnea, cough, delirium and agitation) can develop rapidly and be distressing.
  • Where possible, avoid use of the following as they may generate aerosolized COVID-19 virus particles and increase the risk of infecting healthcare providers, and family members:
    • Oscillatory devices (fans)
    • Oxygen Flow greater than 6L/min
    • High-flow nasal cannula oxygen
    • Continuous positive airway pressure (CPAP) or bilevelpositive airway pressure (BiPAP)
    • All nebulized treatments (bronchodilators, epinephrine, saline solutions, etc.)
    • Oral or airway suctioning (especially deep suctioning)
    • Bronchscopyand tracheostomy

Putting it into practice

Scroll (left-right) for details
  • Pain or dyspnea

    Hydromorphone

    • Dose: 0.25-0.5 mg; may start at lower dose (0.25 mg) if patient is opioid naive, frail or an older adult 
    • Route: Subcut
    • Frequency: q30min PRN; but low threshold to change to scheduled q4h dosing

    Morphine

    • Dose: 1-2.5 mg; may start at lower dose (0.25 mg) if patient is opioid naive, frail or an older adult
    • Route: Subcut
    • Frequency: q30min PRN; but low threshold to change to scheduled q4h dosing
    Click for treatment tips
  • Respiratory secretions / congestion

    Scopolamine (hyoscine HYDRObromide)

    • Dose: 0.4-0.6 mg
    • Route: Subcut
    • Frequency: q4h PRN

    Glycopyrrolate

    • Dose: 0.4 mg
    • Route: Subcut
    • Frequency: q2h-q4h PRN

    Atropine 1% ophthalmic drops

    • Dose: 3-6 drops
    • Route: SL
    • Frequency: q4h PRN

    Furosemide (if fluid overload)

    • Dose: 20 mg
    • Route: Subcut
    • Frequency: q2h PRN and monitor
    Click for treatment tips
  • Nausea or delirium

    Haloperidol

    • Dose: 0.5-1 mg (if patient is frail elderly, may start with 0.25 mg)
    • Route: Subcut
    • Frequency: q6h-q12h PRN
    Click for treatment tips
  • Sedation

    Midazolam

    • Dose: 1-2 mg (higher doses can be used for refractory dyspnea)
    • Route: Subcut
    • Frequency: q30 min PRN
    • Note: Higher doses can be used for refractory dyspnea

    Lorazepam

    • Dose: 0.5 mg (1-2 mg, if severe respiratory distress)
    • Route: SL (subcut, if more suitable for the patient)
    • Frequency: q1h PRN (q4h-q8h, if severe respiratory distress)
    Click for treatment tips
  • Fever and chills

    Acetaminophen 650 mg Suppositories

    • Dose: 650 mg
    • Route: PR
    • Frequency: q6h PRN
  • Agitation/restlessness

    Methotrimeprazine (if more sedation is desirable)

    • Dose: 2.5-12.5 mg
    • Route: PO / Subcut
    • Frequency: q2h PRN (up to three doses in 24 hours)*

    Haloperidol (if less sedation desirable)

    • Dose: 0.5 mg
    • Route: Subcut
    • Frequency: q1h PRN


    * If > 3 PRN in 24h, provider to review and consider scheduled q4h and q2h PRN dosing

    Click for treatment tips
  • Urinary retention

    Foley catheter 16 French

    • Insert catheter PRN
  • Dry mouth

    Mouth swabs

    • Mouth care q.i.d and PRN

Plan for an expected death in the home

In the final weeks and days of life, the focus of care moves towards managing the active dying process, which includes identifying that the patient is near death and ensuring that the patient, their substitute decision maker(s), their family and caregivers understand what to expect as death approaches. For many patients, the preference is to die at home. The processes for planning and managing expected deaths in the home are generally developed at the local or regional level.

Provide grief and bereavement support

For many people, the time following the death of a loved one can be filled with a range of emotions and physical reactions. It is important in the grief journey that people are able to openly talk about these experiences, reactions and feelings. Providers can recommend the following resources for those who have lost a loved one:

Grief and bereavement support for health care providers

New fee codes

Top resources