COVID-19: Clinical Guidance for Primary Care Providers

Last Updated: March 8, 2023

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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:

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Testing and isolation requirements

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Most COVID-19 patients have mild to moderate symptoms and can be safely managed as outpatients in the community setting (BCCDC, July 16, 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 (MOH, August 31, 2022; Public Health Ontario, October 11, 2022).

Testing in the Omicron context

Does increased immunity (through vaccines or previous infection) impact the ability of rapid antigen tests to detect COVID-19?

An individual’s vaccination status will not affect the results of their viral test for SAR-CoV-2 (this includes rapid antigen tests) (CDC, June 15, 2022). None of the current authorized and recommended COVID-19 vaccines can cause a positive viral test result as these tests are used to indicate if an individual has a current infection, and these mRNA vaccines do not contain the live virus (CDC, July 20, 2022).

Moderna and Pfizer/BioNTech vaccines are composed of non-replicating mRNA (John Hopkins, Feb 2, 2021). After receiving an mRNA vaccine, spike proteins are formed to confer an immune response. Instead of detecting the mRNA or other proteins associated with vaccination, COVID-19 antigen tests detect other proteins (most commonly the nucleocapsid protein also known as N-proteins) ensuring that a SARS-CoV-2 vaccination will not affect the result of an antigen test (Federal Institute for Vaccines and Biomedicine, 2022; National Collaborating Centre for Infectious Diseases, 2021).

Individuals who have recovered from COVID-19 may continue to test positive for the SAR-CoV-2 virus. However, 10 days after developing symptoms or the initial positive test (20 days for immunocompromised individuals), few people continue to have any viable virus; this indicates that they are no longer contagious (Ottawa Public Health, July 5, 2022). 

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
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, August 31, 2022):

Isolation requirements by populations

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) and until symptoms have been improving for 24 hours (or 48 hours if gastrointestinal symptoms) and no fever present

 

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) and until symptoms have been improving for 24 hours (or 48 hours if gastrointestinal symptoms) and no fever present

Additional Precautions after Self-Isolation Period

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)
  • Until symptoms have been improving for 24 hours (or 48 hours of gastrointestinal symptoms) and no fever present
  • Asymptomatic individuals with a positive test do not need to self-isolate unless symptoms develop. If symptoms develop, they should self-isolate immediately

 

Additional Precautions after Self-Isolation Period

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

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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?

Patients should be instructed to seek an urgent follow-up assessment with their family physician or hospitalization if they experience any of the following red flag symptoms (BMJ, October 11, 2022; WCH, 2020):

  • 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

For patients with symptoms compatible with COVID-19 and those who have tested positive for COVID-19 (BMJ, October 11, 2022):

  • 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.
  • 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 (BCCDC, July 16, 2021; UpToDate, August 8, 2022). 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, August 8, 2022).
    • 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, August 8, 2022).
    • 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, August 8, 2022).
    • 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.

Symptom management (Common symptoms (MOH, August 31, 2022))

Potential management strategies (NICE, July 14, 2022)

Potential management strategies (NICE, July 14, 2022)

  • Avoid lying on back (makes coughing ineffective).
  • A teaspoon of honey.
  • Only if cough is distressing, short-term, limited supply prescription for codeine linctus, codeine phosphate tablets or morphine sulfate oral solution may be considered. See the COVID-19 rapid guideline: managing COVID-19 (NICE, July 14, 2022) for dosing.

Potential management strategies (NICE, July 14, 2022)

  • Keep the room cool.
  • Encourage relaxation and breathing techniques (positioning, pursed-lip breathing, breathing exercises and coordinated breathing training). See the COVID-19 rapid guideline: managing COVID-19 (NICE, July 14, 2022) for more information on these techniques.
  • Improve air circulation by opening a window or door (avoid using a fan because this can spread infection).

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 have a mild illness and can be cared for safely at home. If a fever is present, it can be treated with over-the-counter medicine. Acetaminophen (Tylenol/Tempra) is the best choice if the child can take it. Treat nasal congestion with saline drops or sprays or suggest using steam from a shower. Coughs can also be treated with steam from a shower or a humidifier. If the cough sounds like a bark, cold outside air may help. For children at least 1 yrs old, 1-2 teaspoons of honey in the evening can also lessen a cough (OCFP, Oct 27, 2022).

Infants and young children considered to be at higher risk for severe illness from COVID-19 are those with (CPS, May 3, 2021):

  • 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, 2020; NICE, April 23, 2020; NICE, April 9, 2020; CEBM, 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.

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, 2020; MOH, 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

General resources

Condition-specific guidance

Local Services (CEP, 2020)

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.

Guidance for the prescription of PaxlovidTM (nirmatrelvir / ritonavir)

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While evidence is still emerging, prescribers should feel confident that Paxlovid is effective for patients at high risk of severe COVID-19 when initiated within the first 5 days of symptom onset.  

Evidence in brief 

Paxlovid is intended for patients with mild COVID-19 who are not on supplemental oxygen but are at risk of progressing to severe COVID-19 infection. Primary care clinicians should engage in shared decision-making with every confirmed COVID-positive patient eligible for Paxlovid.  

To be eligible for Paxlovid, patients must: 

  • have tested positive for COVID-19 by PCR, rapid molecular or rapid antigen test. At-home rapid antigen test with provider verification is acceptable (in-person, virtual, picture or video) AND 
  • be within 5 days of symptom onset (symptom onset is considered day 0) 

Paxlovid should be strongly considered for individuals in these categories: 

  • 60 years or older 
  • Living with comorbidities: See Health Canada’s list of underlying medical conditions associated with more severe COVID-19 disease  
  • Those with lowered Immune status: Either unvaccinated or with an incomplete primary series, or completed primary series with last COVID-19 vaccine dose more than 6 months ago AND last COVID-19 infection more than 6 months ago 
  • Groups with poorer COVID-19 outcomes including Indigenous people, Black people and other members of racialized communities, Individuals with intellectual, developmental, or cognitive disability, people who use substances regularly, who live with mental health conditions, and who are underhoused. 
  • Dosage information, including special dosing considerations for dialysis patients 
  • Side effects 
  • Extensive list of prescribing guidance to avoid drug indications, including drug-specific recommendations on coadministration, contraindications, and context for clinical relevance for potential interactions 

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

Adapted from: Ontario Health Recommendation on the Use of Nirmatrelvir/Ritonavir (Paxlovid) (Dec 8, 2022)

Patient resources

New guidance for the prescription of tixagevimab / cilgavimab (Evusheld™)

Ontario Health no longer recommends use of Evusheld for pre-exposure prophylaxis or treatment of COVID-19 due to the lack of effectiveness against currently circulating variants in Ontario and the availability of more effective treatments (e.g., Paxlovid) (Ontario Health, December 12th, 2022). 

Pre-exposure prophylaxis 

Ontario Health does not recommend routine use of Evusheld for pre-exposure prophylaxis for any patient group, including immunocompromised patients. By December 2022, 55% of variants are resistant to Evusheld and that number is expected to rise.  

Exceptional circumstances: Considering regional prevalence of resistant subvariants and individual patient risk factors, healthcare providers and patients together may determine that potential benefits outweigh risks. Evusheld will remain available through pharmacies for this purpose; however, any healthcare provider administering Evusheld due to exceptional circumstances should refer to the product monograph for details on Evusheld to review information on dosing/repeat dosing.  

For information on variant prevalence, refer to Public Health Ontario’s weekly summary (Genome Surveillance Report) that breaks data down by health unit and region. 

Communicating with patients who have received Evusheld for post-exposure prophylaxis 

  • The potential lack of effectiveness against certain circulating variants 
  • The importance of immunization as the best method to remain protected against COVID-19 
  • The value of continuing to adhere to public health measures such as masking and limiting contacts 
  • To immediately seek medical advice if signs or symptoms of COVID-19 occur 

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

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CACs are an optional resource intended for adult and pediatric individuals who:

  • Have a known or suspected case of COVID-19, are experiencing cold-like or flu-like symptoms, or have a known or suspected respiratory illness or influenza-like illness (ILI).
    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.
    AND/OR
  • Have milder symptoms but are at a higher risk of severe infection who may require access to testing and/or therapeutics that are not otherwise available through existing care pathways

CACs are also an avenue of care for patients with ILI who do not have a regular primary care clinician. 

The CACs are not intended:  

  • To replace the health care provided through existing primary and community care options, including the patient’s primary care clinician, walk-in clinics, and Health Connect Ontario.
  • For patients with mild COVID-19 and/or expanded ILI symptoms who are self-isolating and self-monitoring at home and/or who can be monitored safely in the community with support by their primary care clinician.
  • For patients with severe COVID-19 and/or expanded ILI symptoms, who must be directed to call 911 or go directly to the emergency department. 

Clinical Assessment Centres (CACs) in Ontario will offer standard elements of care, including assessment and appropriate testing, diagnosis, and disposition planning. Coverage includes assessment for COVID-19, cold, influenza and other respiratory illnesses (Ontario Health, November 28, 2022). 

Services available at Clinical Assessment Centres

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 patients at CACs (Ontario Health, November 28, 2022): 

Assessment and appropriate testing
  • Assessment by an appropriate health professional, which may include oxygen saturation, vital signs, and identifying relevant risk factors/comorbidities.
  • Depending on symptoms, testing may include using a rapid test, if appropriate and in keeping with the provincial guidance.
  • Testing for influenza using multiplex respiratory virus PCR (MRVP). Eligible populations include:
    • Symptomatic children (<18 years) in Emergency Department; 
    • Symptomatic hospitalised patients (ward in ICU/CCU); 
    • Symptomatic healthcare workers in institutionalised settings (non-outbreak); 
    • Specimens from first four symptomatic individuals in an outbreak respiratory virus testing including healthcare workers/staff.
  • Additional testing may be considered including rapid strep testing and/or direction for patients to obtain blood tests or chest x-rays.
  • CAC should use existing laboratory pathways in affiliated hospitals or the community. 
Diagnosis
  • Diagnosis by an appropriate health professional
Disposition planning and appropriate testing
  • Planning and treatment will require clinical expertise and judgement of CAC health professionals.
  • CAC is responsible for handover of patients and/or a follow-up plan created for patients at higher risk with their primary care physician or back to the CAC.
  • Depending on the patient’s condition and risk, disposition options may include:
List of Clinical Assessment Centres
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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. Individuals can book appointments for Clinical Assessment Centres through the Care-Clinics booking portal.

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

Patients can either self-refer or be referred by a health care professional (i.e., primary care clinician, pharmacist, public health staff, Health Connect Ontario nurse).  

Target patient population for CACs (Ontario Health, November 28, 2022)
Patient Symptoms
Refer to

Mild symptoms of COVID-19 and/or expanded ILI* 

  • Fever and/or chills lasting < 5 days (in adults and infants > 3 months)**  
  • Cough (not related to other causes)  
  • Mild shortness of breath  
  • Decrease or loss of taste or smell  
  • Muscle aches/joint pain  
  • Extreme tiredness  
  • Sore throat 
  • Runny or stuffy/congested nose 
  • Headache  
  • Nausea, vomiting and/or diarrhea  
  • Abdominal pain (not related to other causes)  
  • Pink eye (not related to other causes)  
  • Decreased appetite (young children only) 

Patients can self-isolate and self-monitor at home

Moderate or worsening symptoms or as advised by a health care professional  

AND/OR

Patient at higher risk of severe outcomes who requires access to outpatient assessment or therapeutics that are not otherwise available through their primary care clinician 

DIRECT PATIENT TO CAC 

Severe symptoms* 

In adults:  

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

In children:

  • Severe chest wall indrawing  
  • Grunting, nostril flaring  
  • Central cyanosis  
  • Presence of any other danger signs (e.g., inability to breastfeed or drink, lethargy, reduced level of consciousness)  
  • Reduced urinary output, fewer than 5 wet diapers per day  
  • Concerning vitals (including oxygen saturation <95%)  
  • Fever with rash  
  • Seizure or convulsions  
  • Increasing parent concern  
  • Fever in an infant < 3 month**  
  • Signs and symptoms of multisystem inflammatory syndrome in children (MIS-C)

Direct patient to call 911 or go directly to nearest emergency department 

*The lists of mild and severe symptoms and direction for patients are consistent with Ontario’s COVID-19 self-assessment tool (updated October 2022)  

**Fevers in children:  

  • Infants < 1 month with a fever need to be assessed in the emergency department; those 1-3 months require an urgent clinical assessment.  
  • A fever lasting up to 5 days in an otherwise well child is being observed in the current environment and is not itself a cause for concern.  
  • A biphasic fever, where a fever returns after being gone more than 24 hours, requires clinical assessment as it may be an indication of worsening or new infection. 

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

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What is “long COVID”?

The WHO defines Long COVID as a condition that occurs in individuals with a probable or confirmed history of COVID-19 infection. Usually occurring 3 months from the onset of COVID-19 symptoms, with symptoms persisting for at least 2 months without an explanation from alternative diagnosis. These symptoms may be new following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time. It is important to note that symptoms may emerge beyond the usual 3 months and may be linked to a previous COVID-19 infection. While more than 100 symptoms have been reported in patients with Long COVID, common symptoms include fatigue, shortness of breath and cognitive dysfunction that generally impact everyday functioning. There are still many uncertainties in the understanding of Long COVID including in definition, prevalence, causes, risk factors, prevention and prognosis as well as its impact on quality of life, function, and ability to work (World Health Organization, October 6 2021; Science Table COVID-19 Advisory for Ontario, Sept 07 2022). 

Symptoms

Note: This chart includes the most reported symptoms amongst patients experiencing Long COVID. There have been over 100 symptoms reported that are linked to the post-COVID condition. 

Common Symptoms (15% – >30% prevalence) 
Less Common Symptoms (5%-15% prevalence)
Unlikely Symptoms ** but still possible 
  • Fatigue/Malaise 
  • Sleep disorder 
  • Anxiety 
  • Depression
  • Shortness of breath
  • New HTN
  • Difficulty Concentrating
  • Memory Deficits
  • Dizziness
  • Headache
  • Visual Impairment
  • Smell Disorder
  • Taste Disorder
  • Tinnitus
  • Hair Loss
  • Cough
  • O2 Use
  • Palpitations
  • Chest Pain
  • Lack of Appetite
  • Diarrhea
  • Abdominal Pain
  • Decreased Mobility
  • Joint Pains
  • Muscle Pains
  • Voice change
  • Nausea/Vomitting

Patient evaluation for suspected Long COVID

Long COVID is a diagnosis of exclusion and is primarily diagnosed based on two factors: having been infected with COVID-19 in the past and presenting with post-COVID-19 symptoms. It is not necessary for patients to have had a positive COVID-19 test, rather a suspected previous case of COVID-19 is an adequate reason to suspect Long COVID. It is important to note that diagnostic criteria for Long COVID may be updated to reflect the evidence as it emerges, and that Long COVID may present differently in children. 

When Long COVID is suspected, an initial full review of symptoms is suggested, to determine the various organ systems involved and any symptom patterns and clustering, as recommended by the Science Table. This will allow for targeted outpatient treatment specific to their experienced symptoms (CADTH, September 2021). 

Reminder for providers to convey empathy, listen and validate 

It is important to approach patients possibly dealing with Long COVID with empathy, listen to what symptoms they are experiencing, and validate what they are going through (NICE, March 1 2022). Many patients report feeling like their symptoms are not taken seriously or they do not realize that what they are experiencing is connected to COVID-19, making a holistic approach to assessment highly important (NICE, March 1 2022). 

Symptom Management 

SMART goals

It is important for patients to set goals for self-management of their ongoing symptoms. The SMART acronym (Specific, Measurable, Achievable, Realistic, and Time-limited) can help guide the development of their goals for managing their presenting symptoms. Symptoms that can be managed with this framework include (Public Health Services Authority, 2022):  

Breathlessness
  • Breathlessness is a very common symptom of Long COVID. There are several techniques to manage breathlessness including changing resting positions, pursed lip breathing, rectangle breathing and tummy breathing. 
Hair loss
  • It is commonly reported by COVID-19 survivors that they experience hair loss post-infection. Patients can experience clumps of hair falling out when brushing or showering. While there is no treatment for this greater than normal hair loss, most patients report that their hair returns to normal fullness within six to nine months. 
Headaches
  • There are a few different types of headaches that can occur in patients struggling with Long COVID symptoms; they are primarily categorized based on location and severity (tension headache vs migraine, etc). They can be triggered by various things including dehydration, stress, sleep deprivation, neck pain, and/or overstimulation. Depending on what type of headache is being experienced, there are both medication and non-medication options that can help relieve headache symptoms including applying a hot or cold compress to the head, mindfulness exercises, breathing exercises, rest, self-massage to shoulder and neck area, and drinking water. 
  • Medications can also be prescribed to relieve migraine symptoms, falling into two categories: rescue medications (once the headache has started) and preventative medications (to prevent headaches). 
  • Headaches following COVID-19 infection usually improve over time. 
Mental health
  • Many patients report changes in their mental wellbeing when dealing with long COVID symptoms. There are many self-management techniques that can help improve patient mental health including meditation/relaxation techniques, social support groups, healthy eating, physical activity, and online resources to help manage depression and anxiety post-COVID infection. 
Ringing in ears (tinnitus)
  • Tinnitus can be a bothersome symptom when dealing with Long COVID and is often described as a whistling, hissing, or ringing in the ears. Most of the time, tinnitus symptoms improve as time goes on without any specific treatment. 
Changes in taste and smell
  • It is reported that just over 50% of COVID-19 patients will lose their sense of taste and smell. It can last anywhere from two to three weeks to many months post-infection. While there is no treatment for this, studies have indicated that ‘smell training kits’ can help individuals recover faster. Adding spices to foods can also possibly help improve taste. 
Post-Exertional Malaise and Activity Tolerance 
  • Patients recovering from Long COVID can often experience times of exhaustion, difficulty thinking, and other symptoms after periods of minimal activity which is called Post-Exertional Malaise (PEM). PEM is often associated with a cycle of “push and crash” where individuals get caught in a loop of alleviated symptoms leading to a “push” in activity which then leads the body into a state of overexertion resulting in forced periods of rest (“crashes”). Self-management of PEM consists of a technique called ‘pacing,’ meaning that patients should divide their activities up into little bits at a time to stay within what is known as their “energy envelope.” Over time, with pacing, the energy envelope may expand. 
  • If PEM “crashes” are lasting a day or longer, evaluation for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be undertaken. 
  • Post-COVID condition patients who describe fatigue symptoms, but do not meet criteria for PEM, can also benefit from pacing and staying within their ‘energy envelope.’ 
Brain Fog
  • Symptoms of cognitive difficulties are also reported amongst patients experiencing Long COVID. They typically experience issues with focus and concentration, problem-solving, remembering things, etc. Techniques for managing these symptoms include pacing, mindfulness activities to cope with stress, avoiding drugs and alcohol, and regular physical activity as tolerated (i.e. If a patient has PEM, they need to prioritize pacing).
Orthostatic Intolerance 
  • If patient feels unwell when standing, for example, with lightheadedness, fatigue, malaise, nausea or tachycardia/palpitations, they should be screened for POTS and delayed/prolonged orthostatic hypotension (NMH) using the NASA Lean test. Managing their symptoms can include lifestyle and pharmacological interventions, with consideration of referral to a cardiac or dysautonomia clinic. 

Guidance for how to help patients recover

The primary recommendation for managing patient recovery is self-management and supported self-management through several techniques. It is important to note that care plans are recommended to be developed using a shared decision making approach, ensuring that the patient’s preferences, support network, and goals are taken into account to create a management plan that works best for them (NICE, March 01 2022). 

  • Encouraging patients to keep diaries or calendars that document their symptom severity and any changes to health conditions. This can help identify any possible triggers such as physical exertion, medical treatments, medications, or menstruation. Examples include mood diaries which can aid in the screening and diagnosis of related or comorbid mental health conditions. 
  • Develop a comprehensive plan based on patient symptoms that incorporates their treatment goals. 
  • Consider providing referrals to other support services such as home care, mental health support, employment, housing, or financial support depending on patient needs. Patients can also be directed to call 211 to be referred to relevant social service supports. 
  • Provide education and support materials for at-home self-care including nutrition, physical activity, sleep, stress, and chronic disease management. See “Self-management techniques for symptoms” tips below. 
  • If initial symptoms are moderate to severe, or continue worsening in severity, consider a referral to an interdisciplinary rehabilitation program or a relevant specialist. Note that COVID-19 and Post-COVID Condition advice is available through eConsult. 
  • Consider providing resources to support caregivers. 
  • Consider supporting an application for short or long term disability income support if unable to work or if work hours are reduced. 

For further guidance, BC ECHO for COVID-19 Recovery has a collection of videos and resources for practitioners addressing management of patient recovery from various clinical perspectives. The Ontario College of Family Physicians also has resources available for both clinicians and patients including tools and videos that cover the Post-COVID condition. 

Self-management techniques for symptoms: 

There are many health promotion education resources available to share with patients when developing their self-management care plan. Consider the following resources and guidance: 

General information regarding patient self-management of long COVID symptoms

What to do if patients aren’t getting better

In the case that patients are not getting better through self-management recovery, it may be beneficial to suggest participation in a rehabilitation program available in their area. A list of post-COVID-19 rehabilitation clinics in Ontario is available through the Rehabilitative Care Alliance. 

Research Trials

How to support patients completing disability applications

1. Identify the relevant disability support programs.  The Prosper Benefits Wayfinder produces an individualized list of income supports. Steps to Justice provides guides to income assistance.  Key programs include: 

2. Conduct a thorough assessment of symptoms and functional impairments:  disability support programs generally look toward impact on day to day life and function as opposed to medical proof of diagnosis.

3. Engage other supports for complicated cases or where a patient has been denied disability or other income support benefits:  

Reminder, presentation of Long COVID symptoms can look different from patient to patient and can present on different timelines. It is important to keep this in mind when assessing for Long COVID and providing corresponding documentation for disability claims. 

Peer support options

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

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COVID-19 variants

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 may raise concerns over vaccine efficacy. Over 70 sub-lineages of the Omicron variant have been identified globally, with some circulating in Ontario (PHO, April 2022). As of May 2022, sub-lineages of the Omicron variant have been the most prevalent variant in Ontario, especially BA.2 (PHO, May 20, 2022). Public Health Ontario is currently monitoring the increasing prevalence of Omicron sub-variants BA.4 and BA.5 in the province. Their projections indicate that BA.5 has experienced a weekly growth rate of 3.11 x that of BA.2 and BA.4 has experienced a weekly growth rate of 2.48 x BA.2 (PHO, July 8, 2022).

Variants and transmission

COVID-19 variants are currently associated with an increased risk of transmission. As of May 2022, sub-lineages of the Omicron variant have been the most prevalent variant in Ontario, especially BA.2 (PHO, May 20, 2022). Evidence continues to show that BA.4 and BA.5 are highly transmissible, due to reduced neutralizing antibody titers against BA.4 and BA.5,compared to other variants. Public Health Ontario has assessed the risk of transmissibility to be high with a low degree of uncertainty (PHO, July 8, 2022).

Variants and severity

COVID-19 variants may affect the severity of disease. Evidence is still emerging on the impact of different Omicron sub-variants on the severity of disease. As of July 8, 2022 Public Health Ontario has assessed the risk of severe disease to be low with a high degree of uncertainty and the risk of reinfection to be high with a low degree of uncertainty (PHO, July 8, 2022). The risks of lowered VE and breakthrough infection are high with a moderate degree of uncertainty.

Variants and vaccines

Emerging evidence suggests that variants of COVID-19 may have an impact on the efficacy of approved COVID-19 vaccines. As of July 8, 2022, Public Health Ontario has assessed the risk of impacted vaccine efficacy and breakthrough infection to be high with a moderate degree of uncertainty. However, vaccines remain an essential part of protection against COVID-19 (PHO, July 8, 2022). 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).

What is the nitric oxide nasal spray for COVID-19? Can it be used in Ontario and how/is it recommended?

Nitric oxide (NO) is a free radical gas molecule associated with innate immunity, wound healing, vasodilation, neurotransmission, and angiogenesis (J. Infect., May 13, 2021). NO has been used for antimicrobial purposes as part of a therapeutic regimen, and most recently, has been incorporated as a nasal spray (J. Infect., May 13, 2021). It is important to note minimal evidence is available on the use of nitric oxide nasal spray (NONS) as a therapeutic intervention for COVID-19 (Lancet Reg Health Southeast Asia, July 12, 2022). Clinical studies investigating NO as an intranasal treatment for COVID-19 infections include a randomized, double-blind, placebo-controlled phase II (in the United Kingdom) and III (in India) clinical trial (Lancet Reg Health Southeast Asia, July 12, 2022; J. Infect., May 13, 2021).

NONS has been associated with clearing nasal SARS-CoV-2 RNA (Lancet Reg Health Southeast Asia, July 12, 2022). NONS interacts with the virus in the nasal cavity, prior to nasal host cell entry and post-replication release (Lancet Reg Health Southeast Asia, July 12, 2022). NO essentially changes the structural integrity of the virus’ proteins and affects various variants of SARS-CoV-2 (Lancet Reg Health Southeast Asia, July 12, 2022). NONS has specifically been identified as an effective and safe treatment to lower the viral load in patients presenting with mild and symptomatic COVID-19 (J. Infect., May 13, 2021). Lower viral loads with patients using NONS may further be linked to reduced transmission, suggesting benefit to rapid use of NONS for patients with mild COVID-19 infection (J. Infect., May 13, 2021). It is also suggested that accelerated clearance of SARS-CoV-2 using NONS can aid in reducing/lowering symptom duration, infectivity period, hospital admissions, and disease severity (J. Infect., May 13, 2021). Currently, NONS is not approved in Canada or the United States; however, other iterations or brands of NONS have been approved in other countries.

Evidence summaries and guidelines

Palliative care and COVID-19

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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.

Additional resources:

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
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    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
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    Treatment tips

    • Advise family and/or caregiver that related sounds are not usually indicative of discomfort.
    • Symptoms of secondary bacterial infection (fever, cough, shortness of breath, delirium) (RCGP, March 2020): antibiotic treatment may improve symptoms.
    • Symptoms of comorbidities such as COPD and heart failure (cough and shortness of breath) (RCGP, March 2020): optimizing comorbidity management may improve symptoms.

    Other medication to consider for respiratory secretions:

    Scopolamine (hyoscine BUTYLbromide)

    • Dose: 10 mg
    • Route: Subcut
    • Frequency: q4h PRN
  • 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
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    Treatment tips

    • Relative contraindication in Parkinson disease.

    Other medication to consider for delirium:

    Olanzapine

    • Dose: 2.5–10 mg
    • Route: SL or subcut
    • Frequency: q12h

    Quetiapine

    • Dose: 25–50 mg
    • Route: PO
    • Frequency: q8h PRN

    Risperidone

    • Dose: 0.5–1 mg
    • Route: PO
    • Frequency: q12h PRN
  • 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)
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    Treatment tips

    Other medications to consider:

    Loxapine

  • 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

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    Treatment tips

    Other medication to consider:

    Olanzapine

    • Dose: 2.5–10 mg
    • Route: SL or subcut
    • Frequency: q12h

    Quetiapine

    • Dose: 25–50 mg
    • Route: PO
    • Frequency: q8h PRN

    Risperidone

    • Dose: 0.5–1 mg
    • Route: PO
    • Frequency: q12h PRN

     

    Note

    There will be some overlap between methotrimeprazine and benzodiazepines for symptom management in palliative patients. When choosing, consider the following: patients factors (e.g. contraindication to an antipsychotic due to EPS),  side effects (methotrimeprazine is more sedating at usual effective doses), route of delivery options and availability.

    Also, the Ontario Palliative Care Network resource (April 9, 2020) distinguishes anxiety from agitation/restlessness, suggesting the use of lorazepam for anxiety, and methotrimeprazine for agitation restlessness.

  • Urinary retention

    Foley catheter 16 French

    • Insert catheter PRN
  • Dry mouth

    Mouth swabs

    • Mouth care q.i.d and PRN

Legend
Route: Subcut = subcutaneous; SL = sublingual (under the tongue); PR = per rectum; PO = by mouth
Frequency: q15min = every 15 minutes; q30min = every 30 minutes; q1h = every 1 hour; q2h = every 2 hours; q4h = every 4 hours; q6h = every 6 hours; q8h = every 8 hours; q12h = every 12 hours; q.i.d. = 4 times per day; PRN = as needed

Adapted from:
Pandemic palliative care: beyond ventilators and saving lives (CMAJ, March 31, 2020).
Continuous palliative sedation therapy (CPST) protocol for COVID-19 pandemic (Division of Palliative Care at McMaster University, March 31, 2020).
Symptom management for adult patients with COVID-19 receiving end-of-life supportive care outside of the ICU (Ontario Palliative Care Network, April 9, 2020).
EOL Symptom Management for COVID-19 (Ontario Palliative Care Network, April 16, 2020).
Palliative Sedation Therapy during COVID-19 (Ontario Palliative Care Network, April 16, 2020).
Care of the Elderly – COVID19 (ECHO, 30-minute video, April 16, 2020).
Part 2: Pain and Symptom Management Nausea and Vomiting (BC Guidelines, 2017).

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

For regular palliative care codes, K081 and K082 could be used depending on the depth of the visit (Ontario MD). Focus practice physicians can bill as specialists using K083 (Ontario MD).

Top resources

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