COVID-19: Clinical Guidance for Primary Care Providers

Last Updated: September 21, 2021

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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.

What’s new!

This resource guides family physicians and primary care nurse practitioners through the latest information about vaccines in Ontario. It covers prioritization, availability and rollout, details about the approved vaccines, point of care guidance, addressing patient questions about vaccines and more.

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:

Primary care assessment and testing for COVID-19

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Screening

If a patient thinks they have symptoms, or is worried they have been exposed to COVID-19, they should complete the provincial COVID-19 Self-Assessment which gives guidance tailored to self-reported symptoms and exposure. If responses indicate possible COVID-19, patients will be directed to contact you as their family physician/primary care nurse practitioner, or Telehealth Ontario.

Putting it into practice

Patients with possible COVID-19 should be screened by video or phone, not in person. If an in-person visit is necessary and feasible, patients should be advised to wear their own mask (cloth or other) to the office/clinic, if available, and the primary care setting should undertake the following active and passive screening.

Passive screening
  • Post information on clinic website or send an email to all patients on screening requirements and advise them to call prior to coming to the office/clinic. Consider mailing by post for those patients without email and/or internet.
  • Where possible, post signage outside the office/clinic asking patients to call before entry for appropriate screening and direction.
  • Post signage at the office/clinic entrance and at reception reminding patients that, regardless of symptoms, they are expected to wear a mask for the entirety of their visit and perform hand hygiene before reporting to reception. If office/clinic is in a shared building, post signage at building entrance.
Active screening
If a patient presents with symptoms and/or exposure to COVID-19:

Patients with severe symptoms should be directed to the emergency department. Otherwise, patients should be instructed to self-isolate until further discussion with their primary care provider.

Patients should be offered an assessment by video or phone, ideally on the same day. This discussion should include a thorough history-taking and assessment of symptoms and managing them, even if COVID-19 testing is being considered as part of the diagnostic plan.

Patients should be provided with a surgical/procedure mask and be advised to perform hand hygiene. Ensure patients do not leave their masks in waiting areas.

Patients should be immediately placed in an exam room alone with the door closed to avoid contact with other patients the office/clinic. If the is not possible, instruct patients to return outside (e.g. vehicle or parking lot, if available and appropriate) and inform them they will be texted or called when a room becomes available.

Patients should be provided with hand sanitizer (if available), access to tissue and a hands-free waste receptacle for their used tissues and used masks.

Instruct patients to cover their nose and mouth with a tissue when coughing and sneezing, dispose of the tissue in the receptacle and to use the hand sanitizer right afterwards. Patients may also be instructed to take their surgical/procedure mask home with them with instructions for doffing masks.

Assessment

Patients with possible COVID-19 should be assessed by video or phone, not in person. If patients screen positive in-person, you may offer clinical assessment and examination only if you can follow Droplet and Contact precautions and know how to properly don and doff PPE, including gloves, gown, a surgical/procedure mask, and eye protection (goggles, face shield). See Primary Care Operations in the COVID-19 Context > Personal protective equipment (PPE) for details.

Any persons experiencing one of the following should be told to self-isolate and tested as soon as possible. When assessing for the symptoms below, focus on evaluating if they are new, worsening, or different from an individual’s baseline health status. Symptoms should not be chronic or related to other known causes or conditions:

  • Fever (temperature of 37.8°C or greater)
  • Cough, including croup (barking cough, making a whistling noise when breathing)
  • Shortness of breath (dyspnea, out of breath, unable to breathe deeply, wheeze)
  • Sore throat (painful or difficulty swallowing)
  • Rhinorrhea (runny nose)
  • Nasal congestion (stuffy nose)
  • New olfactory or taste disorder (decrease or loss of smell or taste)
  • Nausea and/or vomiting, diarrhea, persistent/ongoing abdominal pain
  • Chills
  • Headaches (new and persistent, unusual, unexplained, or long-lasting)
  • Conjunctivitis (pink eye)
  • Fatigue, lethargy, or malaise (general feeling of being unwell, lack of energy, extreme tiredness)
  • Myalgias (muscle aches and pain)
  • Decreased or lack of appetite (for young children); difficulty feeding in infants
  • New or unusual exacerbation of chronic conditions
  • Tachycardia (fast heart rate; including age specific tachycardia for children)
  • Low blood pressure for age
  • Hypoxia (i.e. oxygen saturation less than 92%)
  • Delirium (acutely altered mental status and inattention)
  • Increased number of falls in older persons
  • Acute functional decline
  • Contact with a confirmed case in the last 14 days without proper PPE

See COVID-19 Reference Document for Symptoms (MOH, September 21, 2020) for a full list of signs and symptoms and examples of when symptoms may be related to other causes or conditions.

Keep in mind

A systematic review of 131 studies found that fever and cough were the most common symptoms, followed by nasal congestion, fatigue and sore throat, while approximately 19% of children were asymptomatic (EClinicalMedicine, June 26, 2020).

In addition to the symptoms most commonly associated with COVID-19, other atypical symptoms/signs should be considered in children (MOH, September 21, 2020). These symptoms/signs include:

For suggested criteria for assessing the severity of COVID-19 disease in children, see The acute management of paediatric coronavirus disease 2019 (CPS, April 20, 2020).

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

When assessing patients by telephone or video, use the COVID-19 remote consultations infographic (BMJ, March 25, 2020) for guidance on setting up, connecting, taking a history and examination.

Although there are no evidence-based methods for assessing shortness of breath (dyspnea) by telephone or video, experts have recommended asking patients 7 key questions (Centre for Evidence-Based Medicine, March 23, 2020).

For information on differentiating between COVID-19 and heart failure exacerbation symptoms in patients with known heart failure, see Is it COVID-19 or Is It Heart Failure? (Canadian Cardiovascular Society, April 1, 2020).

Next steps based on symptoms and exposure:
  • Send patient to emergency department. Phone ahead and arrange safe transfer of patient to minimize contact/spread.
  • Tell patient to self-isolate immediately.

Testing

Frequently asked questions (FAQs)

Testing is available for the following populations:

  1. All people with at least one symptom of COVID-19.
  2. Asymptomatic people who have received a positive antigen point-of-care test result.
  3. Asymptomatic people who have been exposed to COVID-19, including people who are contacts of or may have been exposed to a confirmed case.
  4. Asymptomatic people who are at risk of exposure to COVID-19, including workers, residents and visitors of high-risk settings (e.g., long-term care homes, homeless shelters and other congregate settings). This includes residents and workers at specific outbreak sites.
  5. Asymptomatic people from certain populations but without known high-risk exposure may be considered for testing. This includes any individual identifies as part of a targeted testing campaign. For a list of groups, see COVID-19 Provincial Testing Guidance Update (May 26, 2021).

 

Adapted from COVID-19 Provincial Testing Guidance Update (MOH, May 26, 2021) and Additional Direction on Testing Strategy (MOH, May 24, 2020).

Testing in the primary care office/clinic can only be performed if the primary care provider is able to:

  • follow Droplet and Contact precautions outlined by the Ministry of Health (November 9, 2020);
  • has the appropriate tools and knowledge of how to test; and
  • can ensure coordination of sample delivery to the Public Health Ontario Laboratory or an alternative laboratory providing COVID-19 testing.

A single upper respiratory tract specimen will be accepted for COVID-19 testing, including nasopharyngeal swab (NPS), deep nasal swab, anterior nasal swab or viral throat swab. NPS is the preferred specimen when swabs are available, followed by deep nasal swab. Due to global shortages, Public Health Ontario (April 30, 2021) has provided information on alternative collection kits that are acceptable for COVID-19 testing (see Specimen Collection and Handling).

Nasopharyngeal swab collection is not considered an aerosol generating procedure and can be performed in the office/clinic with appropriate contact/droplet precautions of gloves, gown, surgical/procedure mask, and eye protection (e.g., goggles, face shield). This is important as many people will cough or sneeze when the nasal swab is done. Links to resources on properly conducting NP swabs are available under ‘COVID-19 Care’ on OCFP’s Clinical Care- Office Readiness page.

If testing is conducted in the office/clinic, it is important to conduct the nasopharyngeal swab properly to minimize the risk of a false negative sample:

  • Pre-label the swab so, once obtained, it can be placed in the bag without further handling.
  • Place the specimen in the bag, and place the completed requisition in the attached pouch.

Diagnosing COVID-19 is done by laboratory testing (NAAT result by PCR or nucleic acid sequencing) on at least one specific genome target.

Symptomatic patients

  • A single positive result is sufficient to confirm COVID-19.
  • A single negative result is sufficient to exclude COVID-19.

Asymptomatic patients

  • A positive result might represent one of the following scenarios:
    • current COVID-19 infection that is asymptomatic or pre-symptomatic, OR
    • prior COVID-19 infection (+/- symptoms) as testing can remain positive for several weeks after infection, OR
    • false positive result.
  • If a patient has a medium/high pre-test probability of infection, a single positive result is sufficient to confirm current or prior infection.
  • If a patient has a low pre-test probability of infection, a positive result should be immediately retested and may be cleared with a single negative retest (MOH, May 6, 2021). The patient must be managed as if they have current COVID-19 infection (i.e., immediate self-isolation) until cleared.
  • A single negative result is sufficient to exclude COVID-19.

In a patient who tested positive for COVID-19 AND was cleared, retesting should generally not be done due to persistent shedding (viral detection has been identified in some cases well beyond 4 weeks (>70 days) in some cases).

If the patient is within their 14-day self-isolation due to known exposure, the patient should remain in self-isolation for the rest of the 14-day period, regardless of the negative result.

See COVID-19 Quick Reference Public Health Guidance on Testing and Clearance (MOH, May 21, 2021) for more detailed information.

A recent study retroactively compared the results from 353 patients who received both OP and NP simultaneously, and found that 73.1% of NP-positive cases were negative in OP swab. The authors concluded that while use of both swabs slightly increased the positive rate over using NP swab only, NP swabs “may be more suitable” than oropharyngeal swab (Int. J. Infect. Dis., April 22, 2020).

Testing for COVID-19 involves sending a respiratory tract specimen – nasopharyngeal swab (NPS) or viral throat swab; NPS is preferred– to a PHO laboratory or other suitable laboratory with capacity for RT-PCR testing. RT-PCR is a type of nucleic acid amplification testing (NAAT), the gold standard used in Canada and abroad for the diagnosis of active COVID-19 infection, that tests for the presence of viral RNA during active infection (Health Canada, May 26, 2021). At this time, serology testing and antigen testing should not be used for diagnosis of acute COVID-19 infection (MOH, May 26, 2021).

Click here for a list of testing devices authorized by Health Canada.

The turnaround time for COVID-19 testing at a PHO Laboratory is for 60% of results to be completed within 24 hours and 80% to be completed within 48, but will vary depending on what laboratory performs the testing (PHO, April 30, 2021).

As of September 10, 2020, PHO Laboratory implemented a validated pooling approach to testing, which will allow an increase in testing throughput without greatly compromising sensitivity (PHO, March 30, 2021) . For pooled testing, a portion of three individual specimens are combined into a single pool and run on the SARS-CoV-2 PCR assay as a single test.

  • If the pool result is NOT DETECTED, all three specimens are individually reported as NOT DETECTED.
  • If the pool result is DETECTED, INDETERMINATE or INVALD, each individual specimen is tested individually and reported based on individual result obtained. ­­­­

Health Canada is prioritizing the review of point-of-care tests intended to diagnose COVID-19, including both nucleic acid-based tests and antigen-based tests, and have authorized several tests (Health Canada, May 26, 2021).

Click here for a list of testing devices authorized by Health Canada.

At this time, a positive result on a rapid test is considered a preliminary positive and should have a parallel sample taken for a confirmatory laboratory-PCR test (MOH, May 26, 2021).

Serology testing is only available for clinical use under specific clinical indications listed below. Serology testing should not be used for screening and diagnosis of acute COVID-19 infection, and a positive serology test does not mean a patient is immune to COVID-19 (MOH, May 26, 2021).

Clinical indications:

  • Patients presenting with symptoms compatible with Multisystem Inflammatory Syndrome in Children (MIS-C) who do not have laboratory confirmation of COVID-19 by PCR.
  • Patients with severe illness who have tested negative for COVID-19 by PCR and where serology testing would help inform clinical management and/or public health action. Serology testing for these patients requires consultation and approval by the testing laboratory.
  • A study retrospectively analyzed the results of tests administered to more than 15,000 individuals in order to identify the prevalence of false negative results. Of those results studied, 2,699 individuals who tested negative initially were subsequently tested again, and 60 (2.2%) of these individuals were determined to have false negative results in their initial test. The study led the researchers to recommend repeat testing for suspected COVID-19 patients, particularly those with symptoms and other clinical factors consistent with COVID-19 and during periods of high COVID-19 incidence (Open Forum Infect Dis, Nov 24, 2020; Johns Hopkins Center for Health Security, December 4, 2020).
  • The findings in a recently published systematic review (PLoS One, December 10, 2020) further reinforces the need for repeated testing in patients with suspicion of COVID-19 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR. This is based on very low certainty of evidence.
  • A cohort study has found that even rigorous RT-PCR testing protocols might miss a substantial proportion of SARS-CoV-2 infections, perhaps in part due to difficulties in determining the timing of testing in asymptomatic individuals for optimal sensitivity (Lancet, January 19, 2021).
  • A recent study has determined that most false negative results were found to be due to low amounts of SARS-CoV-2 virus concentrations in patients with multiple specimens collected during different stages of infection. Post-test clinical evaluation of each patient is advised to ensure that rtRT-PCR results are not the only factor in excluding COVID-19 (Virol J, January 9, 2021).
  • A recent retrospective observational cohort study identified clinical characteristics associated with false negative SARS-CoV-2 testing. The study found that negative test results were associated with anosmia/ageusia, having a COVID-19 positive contact, and having an elevated lactate dehydrogenase level. Demographics, symptom duration, other laboratory values, and abnormal chest imaging were not significantly associated with false negative test results in multivariable analysis (Infect Control Hosp Epidemiol, April 19, 2021).

For patients experiencing respiratory tract infection (RTI) symptoms who have tested negative for COVID-19, a viral RTI is the most likely diagnosis. These patients can usually be treated virtually with supportive management. For information on when an in-person visit might be indicated, see The Cold Standard 2nd Edition (Choosing Wisely Canada, October 15, 2020).

The following are being implemented as part on Ontario’s six-point variant action plan (Government of Ontario, January 29, 2021):

  • Mandatory testing of travelers: On-arrival testing for international travellers at Toronto Pearson International Airport will be mandated starting February 1. Additional testing measures at Pearson International Airport and land border crossings will be explored in the coming weeks.
  • Enhanced screening and sequencing: Led by Public Health Ontario (PHO), the provincial diagnostic lab network will screen all positive COVID-19 tests in Ontario for known variants within 2 to 3 days of initial processing starting February 3. By February 17, PHO will be sequencing up to 10% of all positive tests in an effort to identify new and emerging variants.

For more information on the COVID-19 variants, see COVID-19 Variants and vaccines

Top resources

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

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

COVID-19 variants

Why has this been in the news?

Through increased global monitoring, COVID-19 variants have been identified. Variants of viruses are common and changes to the genetic material of the virus are expected over time.

The COVID-19 Variants of Concern (VOCs) currently identified in Ontario include:

  • Alpha (B.1.1.7)
  • Beta (B.1.351)
  • Gamma (P.1)
  • Delta/Kappa (B.1.617.1/2)

These variants contain multiple mutations, including some in the receptor-binding domain (RBD) of the spike protein, which raises theoretical concerns over vaccine efficacy. RBD mutations include:

Variants and transmission
Variants and severity
Variants and vaccines

Limited, emerging evidence suggests that some variants of COVID-19 may have an impact on the efficacy of approved COVID-19 vaccines. Additional research is required in this area (Health Canada, February 1, 2021). For additional information regarding COVID-19 vaccines and variants see CEP’s COVID-19: Vaccines resource.

COVID-19 vaccines

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

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

Mixed COVID-19 Vaccines

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

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

Booking second doses of AstraZeneca or mRNA vaccines

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

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

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

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

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

Asymptomatic shedding

Due to community spread of COVID-19 within Ontario, and evidence for asymptomatic and pre-symptomatic transmission, it is recommended that (MOH, May 22, 2020):

  • Surgical/procedural masks be worn for the full duration of shifts for HCWs who are providing direct patient care.
  • Eye protection (e.g., goggles, facemasks) be considered for the full duration of shifts for HCWs who are providing direct patient care.
  • For the purpose of source control, surgical/procedural masks be worn for the full duration of shifts by HCWs who are working outside of direct patient care areas, if physical distancing from other HCWs cannot be maintained.

Asymptomatic shedding FAQs

The time between virus exposure and symptoms (incubation period) is 5-6 days on average, and may be up to 14 days (WHO, April 2, 2020). Viral shedding may occur before symptoms occur, with SARS-CoV-2 RNA detected 1-3 days before symptom onset and the highest viral loads around the day of symptom onset (WHO, July 9, 2020). One study of 39 asymptomatic carriers found that viable viruses were isolated predominately within 7 days of the positive PCR test (ASM, May 19, 2021).

There is epidemiologic, virologic and modeling evidence that asymptomatic and presymptomatic transmission can occur (Emerg Inf Dis., May 4, 2020). According to the CDC (September 10, 2020), there have been a number of reports of presumed asymptomatic transmission and viable virus has been cultured in patients with asymptomatic infection. The exact amount of viral shedding required for transmission is not yet clear.

Estimates vary widely:

  • A systematic review of 63 studies found that for studies with a large sample size (>1000 patients), 1.2-12.9% of patients with COVID-19 were asymptomatic, while studies with a small sample size indicated up to 87.9% of infected individuals could be asymptomatic (Int J Infect Dis, June 29, 2020).
  • When testing all individuals in closed environments (e.g. cruise ship, long-term care home), approximately 50% of patients testing positive were asymptomatic at the time of testing (ACFP, April 14, 2020).
  • The CDC (September 10, 2020) estimated that 40% of infections are asymptomatic.
  • A retrospective evaluation found that 36% of patients who tested positive for COVID-19 while under isolation in a Korean community treatment center were asymptomatic; 19.1% of the asymptomatic patients subsequently developed symptoms while in isolation within a median of 15 days (JAMA Intern Med, August 6, 2020).

Contact tracing reports suggest that asymptomatic individuals are much less likely to transmit the virus (WHO, June 5, 2020).

In an analysis of close contacts, symptomatic cases were more likely to transmit COVID-19, with a risk ratio (RR) of infectivity of 3.9 for symptomatic vs. asymptomatic patients (Int J Infect Dis, April 18, 2020).

In a case-control study, asymptomatic patients shed the virus for a median of 8 days compared to 19 days in symptomatic patients (virus shedding was measured with NP swab). However, it is unknown if the difference in length of shedding translates into any difference in infectivity (JAMA Netw Open, May 27, 2020).

A retrospective cross-sectional study of 90 SARS-CoV-2 positive samples found that samples were only infective in the first 8 days after symptom onset, suggesting infectivity may be highest in the first 8 days after symptom onset and low afterwards (Clin Infect Dis, May 22, 2020).

However, patients with mild to moderate COVID-19 may shed replication-competent virus for up to 10 days following symptom onset, and a small fraction of people with severe COVID-19, including immunocompromised patients, may shed replication-competent virus for up to 20 days (CDC, August 4, 2020).

For current guidance on when to consider a patient recovering from COVID-19 non-infectious, see Managing COVID-19: Outpatient management and resolution.

While we do not yet understand the immune response to SARS-CoV-2 infection, including duration of immunity, patients infected with other betacoronaviruses such as MERS-CoV are unlikely to be reinfected shortly (e.g., 3 months or more) after they recover (CDC, August 4, 2020). Available evidence supports that reinfection is unlikely in the short term and the duration of likely immunity is unclear (Alberta Health Services, May 12, 2020). A 4-month study of 1797 Icelandic COVID patients found that antibody levels reached a peak at 2 months after diagnosis and did not decline within 4 months after diagnosis (NEJM, Sept 1 2020).

An analysis of COVID-19 patients testing positive after recovery found that the positive test results were related to detection of non-viable virus rather than reinfection or reactivation (Korean CDC, May 19, 2020). However, re-infection has been reported; a 33 year old man who recovered from COVID-19 in April tested positive again 4 months later with a strain of SARS-CoV-2 that was genetically distinct from the one causing the initial infection (Clin Inf Dis, Aug 25, 2020).

A study comparing immune response of COVID-19 patients found that asymptomatic patients have a weaker antibody response with a shorter duration compared to patients with severe symptoms. After 8 weeks, 40% of asymptomatic patients were seronegative versus 12.9% of those who had severe symptoms (Nat Med, June 18, 2020).

A retrospective analysis of a COVID-19 outbreak on a fishing vessel with an attack rate of 85.2% (104/122 individuals on board) found that the presence of neutralizing antibodies from prior infection was significantly associated with protection against re-infection (J Clin Microbiol, August 21, 2020).

A systematic review of 504 patients with an asymptomatic course of COVID-19 found that 62.2% of cases had CT abnormalities, with ground glass opacities being the most frequent abnormality (43.09%). Most studies (61.74%) reported normal laboratory findings (Int J Infect Dis, June 13, 2020).

Transmission

COVID-19 transmission occurs through respiratory droplets and aerosols when an infected person coughs, sneezes, sings, shouts, or talks (PHAC, June 29, 2021).

The virus may also spread when a person touches another person (i.e. a handshake) or a surface or an object (also referred to as a fomite) that has the virus on it, and then touches their mouth, nose or eyes with unwashed hands (PHAC, June 29, 2021).

Key takeaways for primary care
  • Guidance from PHAC (June 29, 2021) and CDC (July 14, 2021) regarding airborne transmission do not represent a change for healthcare settings. Providing sufficient ventilation and avoiding overcrowding are already part of operational requirements for primary care, and ventilation infection control measures are required by the Canadian Standards Association for HVAC systems in health care.
  • In healthcare settings caring for symptomatic COVID patients but not performing aerosol-generating medical procedures, there was no transmission to healthcare workers when they followed droplet and contact precautions (including medical masks as part of PPE) (WHO, July 9, 2020).
Emerging evidence for airborne transmission

As the evidence surrounding airborne transmission develops, recent studies have been shedding light on this route of transmission:

  • A recent systematic review of 14 studies and a review of 126 studies has found that airborne transmission of COVID-19 in indoor air environments is quite possible but dependent on specific environmental conditions (Environ Res, December 15, 2020; Int J Environ Res Public Health, January 6, 2021).
  • More recently, commentary from a few researchers supports the theory that the primary mode of COVID-19 transmission is through airborne infectious aerosols. These commentaries appeal to the public health community to take action to help improve indoor air quality, ventilation, and filtration, through policy and structural changes, particularly in healthcare, work, and educational settings (Johns Hopkins Center for Health Security, April 20, 2021).
Emerging evidence for contact transmission

While the efficiency of surface transmission was feared in the early days of the pandemic, this has been undermined by subsequent research. PHAC’s current guidance states that the possibility of infection with COVID-19 from contact with surfaces or objects is unclear.

A recent study (Clin. Infect. Dis, Oct 20, 2020) provides a good overview of the body of literature on contact transmission, and outlines the following “key takeaways”:

  • Using PCR, variable degrees of SARS-CoV-2 contamination of surfaces in healthcare settings for periods ranging from hours to days have been demonstrated, depending on temperature, humidity, and type of surface. However, the use of PCR techniques in this context is problematic, as PCR does not distinguish between live and dead virus.
  • While successful culture of SARS-CoV-2 specimens from environmental surfaces has occurred under experimental conditions, attempts to culture live virus from surfaces in clinical settings have been largely unsuccessful, aside from two recently reported studies involving ICU patients.
  • No studies to date have definitively demonstrated healthcare-associated transmission via environmental surfaces or healthcare workers’ hands.
  • Distinguishing between respiratory and contact transmission is difficult, due to shared air space between cases and contacts.

An additional study examined contact transmission, indicating that while person-to-person encounters are the most common route of transmission, surface contact transmission is still a possibility. This research focused predominately on hospital settings and suggest that shedding from both symptomatic and asymptomatic patients can contaminate surfaces, upon which SARS-CoV-2 can survive for extended periods. The authors emphasized the decontamination of surfaces as part of infection prevention and control (Environ. Chem. Lett. February 11, 2021).

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).

Medication cautions

Current evidence

The World Health Organization issued a scientific brief (April 19, 2020) stating that there is currently no evidence of severe adverse events, acute health care utilization, long-term survival, or quality of life in patients with COVID-19, as a result of the use of NSAIDs.

The NICE rapid guidelines (April 3, 2020) have advised patients to take paracetamol or ibuprofen if they have fever and other symptoms that antipyretics would help treat, and to continue only while the symptoms of fever and the other symptoms are present. If using an NSAID they should take the lowest effective dose for the shortest period needed to control symptoms.

Caution should be taken when using NSAIDs in the context of acute respiratory infections (ARI) and patients with the following conditions:

  • Acute myocardial infarction (MI)
    • NSAIDs increase the risk of acute MI, even with short term-use (odds ratio = 1.5) (BMJ, 2017).
    • Dose-response with increasing risk for acute MI with increasing dose.
    • The risk of acute MI is increased in ARI and influenza (odds ratio = 2.7), and NSAIDs increase the risk of acute MI in ARI further (odds ratio = 3.4) (J. Infect. Dis, 2017Pharmacoepidemiol Drug Saf, 2017).
  • Stroke
  • Bacterial infection complication
    • NSAIDs may worsen the course of a bacterial community-acquired pneumonia (pleuropulmonary complications odds ratio = 5.7 – 8.1; pleuroparenchymal complications odds ratio = 2.57). However, this may be due to symptom masking as studies show patients taking NSAIDs have a longer time to antibiotic initiation (Lung, 2017Chest, 2011Respir Med, 2017J Crit Care, 2014).
  • Hypertension
  • Heart failure

Fever: A recent literature review found that while health professionals viewed fever as deleterious, outcomes with use of antipyretics were mixed and included several studies finding increased mortality risk associated with their use. In administering antipyretics, physicians should consider individual patients’ comorbidities and symptoms of their underlying illness (Br J Nurs, 2019). The NICE rapid guidelines (April 3, 2020) recommend not using antipyretics with the sole aim of reducing body temperature.

Total symptoms and duration: NSAIDs do not significantly reduce total symptoms or duration of respiratory infections (BMJ, 2013).

Acetaminophen: Primary care studies show acetaminophen is just as effective for symptom relief in viral illness (BMJ, 2013).

Antibiotics

Antibiotics are not recommended to treat cases of COVID-19 without clinical suspicion of bacterial co-infection. When there is evidence of a secondary infection, appropriate antibiotics should be administered pre-emptively without waiting for confirmatory test results (CPS, April 20, 2020).

Antivirals

According to the NIH COVID-19 Treatment Guidelines (April 21, 2021) there are insufficient data to recommend for or against the use of specific antivirals or immunomodulatory agents besides remdisivir for the treatment of COVID-19 in paediatric patients. In July 2020, Health Canada approved Remdisivir for the treatment of severe COVID-19 in adults and youth (aged ≥12 years and weighing ≥40 kg) with pneumonia requiring supplemental oxygen.

Anti-SARS-CoV-2 monoclonal antibody products

According to the NIH COVID-19 Treatment Guidelines (April 21, 2021) there are insufficient pediatric data to recommend for or against the use of anti-SARS-CoV-2 monoclonal antibody products for children with COVID-19 who are not hospitalized but who have risk factors for severe disease. In November 2020, Health Canada approved Bamlanivimab for the treatment of mild-to-moderate COVID-19 in adults and youth (aged ≥12 years and weighing ≥40 kg) who are at high risk of progressing to severe COVID-19 illness and/or hospitalization.

Medication misconceptions

Current evidence

There has been speculation that patients receiving these medications may be more susceptible to COVID-19 and are at increased risk for adverse outcomes.

There is currently no clinical evidence to support that taking an ACE inhibitor or ARB will make a patient more susceptible to COVID-19 or worsen outcomes (UpToDate, May 16, 2020; Therapeutic Research Centre, April 2020; NEJM, May 1, 2020; Drug Saf, August 27, 2020).

An observational study has found that patients admitted to hospital with COVID-19 who had a history of hypertension but were not receiving blood pressure medications had a significantly higher risk of mortality compared to patients receiving hypertension treatment. No harm was detected in patients with COVID-19 taking Renin-Angiotensin-Aldosterone System Inhibitors (RAAS) (Eur Heart J, June 4, 2020).

Systematic reviews and meta analyses also support these findings. Recent studies have found that ACEI/ARB use does not increase the risk of all-cause mortality of patients with COVID-19 (Thorax, January 27, 2021; Cureus, February 4, 2021; Ther Adv Drug Saf, May 14, 2021; J Clin Hypertens, July 28, 2021). A more recent systematic review even suggests that there is an added benefit and a protective effect of RAAS inhibitors in patients (J Clin Pharmacol, February 26, 2021; JAMA, March 31, 2021;).

See the HFAM resource COVID and ACEi’s ARBs: Helpful or Harmful? (March 31, 2020) for more information.

COVID-19 Therapy research

Medications

  • Aside from remdesivir, dexamethasone, and bamlanivimab there are currently no other medications recommended in the prophylaxis or treatment of COVID-19 (CMAJ, April 29, 2020; Health Canada, November 20, 2020).
  • As with any medication, these drugs are also associated with potentially serious harms.
  • Off-label prescriptions and the stockpiling of these drugs based on limited evidence to treat COVID-19 has led to drug shortages and compromised care for patients who need these medications for their intended use.

Current evidence

Why has this been in the news?

During the 2009 influenza pandemic, co-infection with bacteria led to the recommendation of empirical antibiotic therapy for patients with suspected influenza pneumonia (Infect Control Hosp Epidemiol, July 30, 2020). This knowledge served as a foundation for initial WHO recommendations to use empirical antibiotics in cases of COVID-19 pneumonia. However, subsequent concerns about inappropriate use of antibiotics has led the WHO to discourage empirical antibiotics in low to moderate suspected or confirmed COVID-19 (WHO, May 27, 2020).

How does this apply to my practice?

Do not prescribe antibiotics to suspected or confirmed COVID-19 patients with low suspicion of a bacterial infection (WHO, May 27, 2020). If co-infection with a bacterial pathogen is suspected, antibiotics should be initiated based on institutional antibiograms and sensitivities (BC Centre for Disease Control, July 6, 2021). See the BMJ’s using antibiotics wisely for respiratory tract infection in the era of COVID-19 for practice tips (November 13, 2020) and the Sinai Health System – University Health Network Antimicrobial Stewardship Program’s Ontario Clinical Practice Guidelines on Antimicrobial and Immunomodulatory Therapy in Adult Patients with COVID-19 for recommended antibiotic regimens.

The routine use of antibiotics is not supported in the management of confirmed COVID-19 infection as only a low proportion of patients have been found to have a bacterial co-infection (J Infect, May 27, 2020). This includes azithromycin because there is insufficient evidence that it will prevent COVID-19 (CEBM, April 14, 2020). As with any viral pneumonia, COVID-19 itself is not an indication for antibiotics. Widespread use of antibiotics should be discouraged, as their use may lead to higher bacterial resistance rates.

Supporting Evidence

The RECOVERY trial concluded that there is no benefit from azithromycin in patients hospitalized with COVID-19. A total of 2582 patients were randomized to azithromycin and compared with 5182 patients randomized to usual care alone. A preliminary analysis shows no significant difference in the primary endpoint of 28-day mortality (19% azithromycin vs. 19% usual care; relative risk 1.00 [95% confidence interval 0.90-1.12]; p=0.99). There was also no evidence of beneficial effects on the risk of progression to mechanical ventilation or length of hospital stay. The results were consistent in different subgroups of patients. This data convincingly rules out any meaningful clinical benefit of azithromycin in the hospitalized COVID-19 patients that have been studied (RECOVERY Trial, 2020).

Similarly, the PRINCIPLE trial has recently concluded that there is no beneficial effect in patients aged over 50 who are treated with the antibiotics azithromycin and doxycycline at home in the early stages of COVID-19 (Oxford University, January 25, 2021).

Systematic reviews and meta-analyses also support these findings. A systematic review (154 studies with antibiotic data from 30,623 patients) that estimated the prevalence and associated factors of antibiotic use in patients with confirmed COVID-19, has found that three-quarters of these patients have received antibiotics and prescribing is significantly higher than the estimated prevalence of bacterial co-infection. The study concludes that unnecessary antibiotic use is likely high in this patient population (Clin Microbiol Infect, January 5, 2021). More recently, a systematic review and meta-analysis has found that using azithromycin as routine therapy in COVID-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit (Rev Med Virol, June 2, 2021).

Why has this been in the news?

Some researchers have suggested that antiviral drugs researched for SARS and MERS, such as hydroxychloroquine, could be applied in the context of COVID-19 treatment (J Med Virol, February 27, 2020). However, current research has indicated that hydroxychloroquine is not effective in reducing deaths or moderate disease in COVID-19 patients (WHO, July 31, 2020). Research has also shown that these medications may also cause harm, and a recent meta-analysis found that evidence is weak and conflicting (Ann Intern Med, August 18, 2020). In the United States, Remdesivir has received full regulatory approval by the US Food and Drug Administration for hospitalized Covid-19 patients aged 12 and older, weighing at least 40 kg (Johns Hopkins Center for Health Security, October 23, 2020)

How does this apply to my practice?

  • The only antiviral drug approved for treatment of COVID-19 in Canada is remdesivir, which has been approved for treatment of adults and adolescents with severe symptoms of COVID-19 and pneumonia who require additional oxygen (Health Canada, July 28, 2020). However, the BC Centre for Disease Control strongly encourages further evaluation in approved clinical trials and recommends that, if used outside clinical trials, Remdesivir should be restricted to hospitalized patients requiring supplemental oxygen but not requiring non-invasive or invasive mechanical ventilation (January 29, 2021).
  • The World Health Organization (WHO) has issued a conditional recommendation against the use of Remdesivir in hospitalized COVID-19 patients. Further evaluation in approved clinical trials is strongly encouraged. If Remdesivir is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values and preferences are necessary, as it is not considered standard of care (BCCDC, December 1, 2020).
  • The likelihood of death from COVID-19 in patients with mild to moderate disease is extremely low; therefore, antiviral drugs will have little or no effect on mortality in such patients (CMAJ, April 29, 2020).
  • Other antiviral drugs, such as hydroxychloroquine or chloroquine, are currently not recommended for treatment of COVID-19 or prophylaxis due to insufficient quality evidence to support their use and the risk of adverse effects for patients (BC Centre for Disease Control, July 6, 2021).

Supporting evidence

Remdesivir

  • Remdesivir is authorized for use in adults and adolescents (aged 12 years and older with a body weight of at least 40 kg). Gilead Sciences Canada, Inc. did not seek authorization for an indication for use of remdesivir to treat children or pregnant women.
  • 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).

Chloroquine and hydroxychloroquine

  • A meta-analysis of randomized controlled trials suggests that there is no benefit to the addition of Hydroxychloroquine to the standard of care. Additionally, Hydroxychloroquine was found to be associated with increased adverse events (Sci Rep, June 7, 2021)
  • The BC Centre for Disease Control states that hydroxychloroquine or chloroquine are not recommended for treatment or prophylaxis of COVID-19 (October 16, 2020).
  • A multicenter randomized open-label trial in 504 patients with mild to moderate COVID-19 found no improvement in clinical status with hydroxychloroquine, with or without azithromycin, compared to standard care. Patients taking hydroxychloroquine were more likely to have QT prolongation and elevated liver enzyme levels (N Engl J Med, July 23, 2020).
  • Randomized controlled trials that studied hydroxychloroquine as a prophylactic treatment for Covid-19 suggest that this is not an effective preventative measure against Covid-19 transmission (JAMA Internal Medicine, September 30, 2020; New England Journal of Medicine, August 6, 2020).

For more information on adverse effects see Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline (CMAJ, April 29, 2020).

Other antivirals

Favipiravir: The BC Centre for Disease Control does not recommend favipiravir due to lack of data (October 2, 2020). Initial low-quality evidence suggests favipiravir may have a higher incidence of recovery and viral clearance compared with umifenovir and lopinavir-ritonavir (respectively) (CMAJ, April 29, 2020).

Lopinavir-ritonavir and umifenovir: Limited low-quality evidence suggests that umifenovir and lopinavir-ritonavir may reduce cough, fever and progression to severe disease in patients with mild to moderate COVID-19, and that Lopinavir-ritonavir may increase diarrhea, nausea and vomiting. (CMAJ, April 29, 2020). Lopinavir/ritonavir is not recommended for treatment of COVID-19 and is not recommended for prophylaxis of COVID-19 outside of approved randomized-controlled trials (BC Centre for Disease Control, July 6, 2021).

Oseltamivir: Not recommended for COVID-19 as neuraminidase inhibitors do not appear to have activity against the virus. Initial empiric therapy with oseltamivir might be reasonable during influenza season in critically ill patients if the patient is suspected to have influenza pneumonia; patients can have confirmatory NP swabs for influenza (BC Centre for Disease Control, July 6, 2021).

Ribavirin: The BC Centre for Disease Control does not recommend ribavirin outside of approved randomized controlled trials (October 16, 2020). Ribavirin may increase anemia and bradycardia but the evidence is low-quality (CMAJ, April 29, 2020).

Why has this been in the news?

Currently there are only preliminary studies that have illustrated the safety and efficacy of MSCs and exosomes in mitigating symptoms associated with COVID-19, and studies have shown that they can be used on compassionate basis, owing to their ability to repair and decrease the inflammatory reactions involved in the morbidity and mortality of COVID-19. A systematic review of cell therapy with mesenchymal stromal cells (MSCs) for COVID-19 acute respiratory distress syndrome (ARDS) found a favourable but not statistically significant trend towards reduced mortality, improved radiographic findings, pulmonary function and inflammatory biomarker levels with no related serious adverse events (Stem Cells Transl Med, 2020). Another systematic review was recently published that also illustrates how MSCs could be considered as a potential and immediate antiviral therapy for COVID-19 patients, on the basis of their anti-inflammatory, and immune-suppressive activity, contrasting directly the cytokine storms causing pneumonia and other organs disease (Aging Dis, October 1, 2020)

How does this apply to my practice?

More preclinical and clinical studies are required to understand the mechanism of action and establish the safety and efficacy of cell-based therapy before it can be used in practice (Hum Cell, August 11, 2020).

Why has this been in the news?

Colchicine has been examined by researchers for its properties as an anti-inflammatory drug and for its potential impact on cardiac biomarkers (JAMA, June 24, 2020). Researchers have suggested that it may be an inexpensive oral treatment as an anti-inflammatory and to treat myocardial injury caused by COVID-19 (Eur Heart J Cardiovasc Pharmacother, April 27, 2020).

How does this apply to my practice?

Colchicine is not recommended for treatment or prophylaxis outside of a randomized controlled trial. Some clinical trials are ongoing to investigate the use of Colchicine as a treatment for COVID-19 because of its anti-inflammatory properties (BC Centre for Disease Control, July 6, 2021).

Supporting Evidence

  • A double blind randomized controlled trial found that Colchicine reduced the length of supplemental oxygen therapy and hospitalisation among patients with moderate to severe COVID-19 (RMD Open, February 4, 2021)
  • A systematic review and meta-analysis of colchicine treatment in COVID-19 patients indicate that the drug improved the outcomes of COVID-19 patients by reducing the severity and mortality of the disease. Further clinical trials are needed in this area (Clin Exp Pharmacol Physiol, March 14, 2021).

Why has this been in the news?

On March 25, 2020 the U.S. Food and Drug Administration (FDA) approved the use of convalescent plasma as treatment for COVID-19 as an emergency investigational new drug (eIND) (CADTH, August 26, 2020). On August 23, 2020, the FDA issued an emergency use authorization (EUA) for COVID-19 convalescent plasma for the treatment of hospitalized patients with COVID-19 (FDA, September 2, 2020).

How does this apply to my practice?

Convalescent plasma is currently not recommended for treatment of COVID-19 outside of a randomized controlled trial, because there is insufficient evidence that it will inhibit COVID-19 (BC Centre for Disease Control, July 6, 2021; CMAJ, April 29, 2020; CMAJ, July 6, 2020).

In Canada, convalescent plasma therapy for COVID-19 is currently available only as an investigational drug treatment for participants in the CONCOR-1 clinical trial (CADTH, July 23, 2020).

Supporting evidence

Recent randomized trials have found no significant difference observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo (PLoS Med, March 3, 2021; Intern Emerg Med, April 10, 2021; Crit Care Med, April 16, 2021; Lancet, May 14, 2021). Systematic reviews and meta-analyses also support this by finding that convalescent plasma for the treatment of individuals with COVID-19 does not reduce mortality and has little to no impact on measures of clinical improvement (JAMA, February 26, 2021; Cochrane Database Syst Rev, May 20, 2021; Ther Adv Respir Dis, June 30, 2021).

However, a few studies are emerging to show a different picture. A retrospective study of 3082 patients has found that among patients hospitalized with COVID-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti–SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels (NEJM, January 13, 2021). Its potential as a therapy is also explored in systematic reviews and meta-analyses, which establish its use as a safe and potentially effective therapy for COVID-19, with studies focusing on its ability to reduce mortality rates and accelerate the decrease of viral titres (Rev Med Virol, February 23, 2021; Front Med (Lausanne), April 6, 2021; Front Med (Lausanne), April 9, 2021; Mayo Clin Proc, May, 2021; Eur Rev Med Pharmacol Sci, July 2021). However, more randomized controlled trials and studies are required in order to further evaluate the efficacy of convalescent plasma in COVID-19 patients.

Why has this been in the news?

Corticosteroids have received worldwide attention as a potentially effective treatment for COVID-19 (WHO, September 2, 2020). This recent attention can be attributed to a preliminary report featuring the results of the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial that was published on June 22, 2020 (it has since been followed by a peer-reviewed manuscript published one month later in the New England Journal of Medicine). The publication reported the effects of dexamethasone on the outcomes of hospitalized patients with COVID-19. The dexamethasone arm of RECOVERY represents the largest trial to-date to not only produce a statistically and clinically significant result, but one that also impacts survival, all by using a well-known, inexpensive treatment. The methodology and results of the dexamethasone arm of RECOVERY have quickly become a topic of debate and critique (BC Centre for Disease Control, July 6 2021).

How does this apply to my practice?

The BC Centre for Disease Control (January 29, 2021) strongly recommends dexamethasone as a treatment for hospitalized COVID-19 patients. The research from the RECOVERY trial provided patients a dosage of 6 mg IV/PO q24h for up to 10 days, unless higher doses are clinically indicated, for patients requiring mechanical ventilation and for hospitalized patients requiring supplemental oxygen. The REMAP-CAP trial recommends hydrocortisone 50 mg IV q6h as an alternative. The BCCDC recommends methylprednisolone 30 mg IV q24h or prednisone 40 mg PO q24h daily as the preferred alternatives if dexamethasone or hydrocortisone are not available. If dexamethasone supplies are limited, they should be reserved for critically ill patients.

Supporting evidence

  • 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. More trials are still required to confirm the results. 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).
  • Preliminary results from the RECOVERY Trial (June 16, 2020), where patients receiving 6 mg dexamethasone once daily (orally or by intravenous injection) were compared to patients receiving usual care, showed a reduction of deaths by one third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). No mortality benefits were seen in patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14). Trial results are pending publication.
  • Currently there are systematic reviews and meta-analysis emerging based off of low-quality evidence and more randomized control trials are needed to make effective conclusions. In a prospective meta-analysis of clinical trials (7 randomized trials that included 1703 patients of whom 647 died) of critically ill patients with COVID-19, the study found that the administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality (JAMA, September 2, 2020). However, a recent systematic review and meta-analysis of observational studies and one RCT suggests that systemic corticosteroid therapy was not associated with reduction in short-term mortality but possibly with delayed viral clearance in patients hospitalized with COVID-19 of different severities (Journal of Infection and Public Health, September 29, 2020). Both studies are based off of RCTs and studies with limitations and low evidence.
  • Outside of patients requiring mechanical ventilation or supplemental oxygen, steroids may also be used if the patient has another compelling indication, such as an asthma exacerbation, refractory septic shock, or for fetal lung maturation in obstetric patients (BC Centre for Disease Control, July 6, 2021).

Why has this been in the news?

Multiple recent clinical studies have evaluated different biological agents (“biologics”) that target specific cytokines. Currently, there is promising data developing around the inhibition of cytokine production by biologics, but these therapeutics come with multiple drawbacks for their use in treating COVID-19. Small molecule therapeutics (such as furosemide) are gaining attention as being a potentially “repurpose-able” known drug that is safe, available in reasonable quantities worldwide, easily synthesized at low cost, and easy to handle and store (Am J Med Sci, July 6, 2020). Since inhaled furosemide has broad-spectrum anti-inflammatory properties, targeting IL-6, IL-8 and TNF-α , it has been proposed as a possible therapeutic agent for COVID-19. (Am J Med Sci, July 6, 2020)

How does this apply to my practice?

As clinical trials have not yet begun, it is currently not recommended to use inhaled furosemide in practice.

Why has this been in the news?

Researchers have questioned whether repurposing already approved drugs offers any effective treatments of COVID-19. One class of drugs that may improve the body’s immune response to illness is immune modulators (Lancet, May 20, 2020). Coronaviruses may induce the production of cytokines that are present in many auto-inflammatory disorders. Some researchers have suggested that immune modulators might help to neutralize the hyperinflammatory state that is caused by COVID-19 and can be a cause of respiratory distress among patients (Lancet Rheumatology, May 29, 2020).

Monoclonal Antibodies have received media attention as pharmaceutical company Regeneron has applied for Emergency Use Authorization from the US Food and Drug Administration (Johns Hopkins Center for Health Security, October 9, 2020). Researchers are considering the effectiveness of monoclonal antibodies as a treatment for Covid-19 to block or neutralize Coronavirus in affected patients (Biomedicine and Pharmacotherapy, June 4, 2020). The U.S. Food and Drug Administration issued an Emergency Use Authorization for the investigational monoclonal antibody therapy Bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. Bamlanivimab is authorized for patients who are 12 years of age and older weighing at least 40 kilograms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (U.S. Food and Drug Administration, November 9, 2020).

How does this apply to my practice?

Bamlanivimab is the only monoclonal antibody treatment approved for treatment of COVID-19 by Health Canada. It has been approved for treatment of adults and pediatric patients 12 years of age or older with mild to moderate coronavirus disease 2019 (COVID-19), who weigh at least 40 kg and who are at high risk of progressing to severe COVID-19 illness and/or hospitalization. Bamlanivimab is formulated as a solution for infusion (35 mg/mL) and the recommended dose is a single infusion of 700 mg to be administered as soon as possible after a positive test for COVID-19 and to be administered within 10 days following the onset of clinical signs and symptoms of infection. For more information, refer to the Product Monograph for Bamlanivimab (Health Canada, November 20, 2020). Other Immune Modulators are not authorized in Canada for treatment or prophylaxis outside of a randomized controlled trial (Health Canada, December 22, 2020).

The BC Centre for Disease Control (January 29, 2021) recommends Tocilizumab for patients requiring life support due to confirmed COVID-19, including high-flow oxygen support (e.g., Optiflow) if flow rate > 30 L/min and FiO2 > 0.4 OR invasive or non-invasive ventilation OR vasopressor or inotropic support. The REMAP-CAP trial utilized a dosage of 8 mg/kg IV (single dose; up to maximum 800 mg) for this treatment. The BCCDC recommends that Tocilizumab must be administered within 24 hours of the initiation of life support measures. Tocilizumab is not recommended for patients admitted to hospital for more than 14 days with symptoms of COVID-19 or when life support is required for causes other an COVID-19 (BCCDC, January 29, 2021).

Supporting evidence 

Anakinra: Anakinra is currently not  recommended for treatment or prophylaxis for COVID-19 as there is insufficient data  (NIH, May 12, 2020). Clinical trials are ongoing. Two retrospective trials evaluated the efficacy of Anakinra in Covid-19 patients and found the drug may be effective in reducing mortality, although there are safety concerns related to its use and further research is needed in this area (Drugs, October 17, 2020)

Interferon-α: There is very low-quality evidence that the addition of interferon-α to umifenovir therapy may not affect time to viral clearance or length of hospital stay relative to umifenovir alone (CMAJ, April 29, 2020). There is no evidence available on the harms.

Interferon-β: There is no published evidence regarding benefit or harm of interferon-β in patients with mild to moderate COVID-19 (CMAJ, April 29, 2020). A randomized controlled trial in severe Covid-19 patients indicated that Interferon- β-1b may be effective in shortening the time to clinical improvement without serious adverse events. Further clinical trials with larger sample size are required in this area (International Immunopharmacology, August 24, 2020).

Interferon-λ: There is no published evidence on the benefits and harms in COVID-19. Clinical trials are ongoing.

Intravenous immunoglobulin (IVIG): The BC Centre for Disease Control states that intravenous immunoglobulin G is not recommended for treatment or prophylaxis outside of a randomized controlled trial (October 16, 2020).

Monoclonal antibodies: Bamlanivimab is the only monoclonal antibody treatment approved for treatment of COVID-19 by Health Canada. Approval of Bamlanivimab was based on Health Canada’s analysis of BLAZE-1 Phase 2, randomized, double-blind, placebo-controlled clinical trial studying bamlanivimab for the treatment of subjects with mild to moderate COVID-19. The study identified a potential reduction in the number of Covid-19-related hospitalizations among participants (Health Canada, November 20, 2020). Other Monoclonal Antibodies are not recommended for treatment or prophylaxis outside of a randomized controlled trial (BC Centre for Disease Control, July 6, 2021).

Sarilumab: Not recommended for treatment or prophylaxis outside of a randomized controlled trial (BC Centre for Disease Control,June 13, 2021).

Tocilizumab: In a retrospective observational cohort study, tocilizumab reduced the risk of a composite endpoint of invasive mechanical ventilation or death in adults with severe COVID-19 pneumonia (adjusted hazard ratio 0.61, 95% CI 0.40-0.92; Lancet, June 24, 2020). Another observational study of compassionate use of tocilizumab in patients with COVID-19 pneumonia found that tocilizumab reduced inflammation (measured by C-reactive protein), oxygen requirements, vasopressor support, and mortality. Adverse events and serious adverse events were minimal, but two deaths (7.4%) occurred that were felt unrelated to tocilizumab (Clin Inf Dis, June 23, 2020). 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 systematic review found that, based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19 (Int J Antimicrob Agents, July 23, 2020).

Why has this been in the news?

Ivermectin is primarily used for the internal and external treatment of parasites (FDA, May 1, 2020; HealthLinkBC, 2018). Despite diverse effects of this medication, many of its underlying mechanisms are not yet known (J Antibiot, September, 2020).

How does this apply to my practice?

Ivermectin is not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials (BC Centre for Disease Control, July 6, 2021; WHO, March 31, 2021).

Supporting Evidence

Evidence surrounding ivermectin as a possible COVID-19 treatment is still emerging. Well-designed systematic reviews and meta-analyses show that ivermectin does not appear to be effective for the treatment of COVID-19 (Clin Infect Dis, June 28, 2021; Cochrane Database Syst Rev, July 28, 2021). On the other hand, recent systematic reviews and meta-analyses are showcasing how it can reduce COVID-19 deaths, increase favourable clinical recovery and reduce hospitalization, yet these studies used many non-peer-reviewed trials with methodological variances, inadequate statistical significance, and a wide range of doses evaluated so no definitive conclusions can be drawn (Am J Ther, June 21, 2021; Open Forum Infect Dis, July 6, 2021; BC Centre for Disease Control, July 6, 2021; Diabetes Metab Syndr, June 27, 2021).

As evidence continues to emerge, more results from adequately powered, well-designed, and well-conducted clinical trials are still needed to provide specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19 and to understand its effects on other clinically relevant outcomes (NIH, February 11, 2021). Several clinical trials that are evaluating the use of ivermectin for the treatment of COVID-19 are currently underway or in development (NIH, February 11, 2021).

Why has this been in the news?

Researchers have proposed that the MMR vaccine could have a possible role in reducing COVID-19 complications related to lung inflammation and sepsis, which is strongly associated with COVID-related mortality (mBIO, Jun 19 2020). This is due to evidence that live attenuated vaccines can produce nonspecific protection against infections unrelated to the vaccine’s target pathogen by inducing a “trained” nonspecific innate immune response.

How does this apply to my practice?

There is insufficient evidence to support MMR vaccination as treatment or prophylaxis outside of clinical trials. Clinical trials are underway.

Why has this been in the news?

Current emerging studies are showing the potential benefit of statin use amidst patients with COVID-19. Two retrospective studies that investigated the association between the use of statins and in-hospital outcomes of patients with COVID-19 have found the use of statins was associated with better clinical outcomes (Front Med (Lausanne), November 17, 2020; Am J Med Sci, March 2, 2021). More recently, a meta-analysis of 7 studies with 2,398 patients (1,075 taking statins) has found that statins use was associated with nearly 40% lower odds of progressing toward severe illness or death and after excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified. However, the study concludes that randomized trials are necessary to confirm these preliminary findings (Semin Thromb Hemost, January 22, 2021). Likewise, recent systematic reviews and meta-analyses of patients with COVID-19 have found that statin use is associated with improved clinical outcomes and reduced risk of mortality (Postgrad Med J, February 4, 2021; Pharmacol Rep, February 20, 2021; J Clin Med, April 1, 2021; Postgrad Med, June 30, 2021; Atherosclerosis, June 25, 2021).

Yet, despite these findings, other meta-analyses and cohort studies paint a different picture. A meta-analysis (total of 9 studies with 3449 patients) has shown that statin use did not improve severity outcome nor mortality rate from in-hospital outcomes of patients with COVID-19 infection (Diabetes Metab Syndr, August 26, 2020). Similarly, a meta-analysis of retrospective observational studies (total of 13 studies with 10,829 statin users) and a cohort study (4842 patients with COVID-19) has shown no significant reductions in either in-hospital mortality or COVID-19 severity in this patient population (Diabetes Metab, December 23, 2020; BMJ Open, December 4, 2020).

How does this apply to my practice?

Current studies do not provide enough evidence to suggest using statins to lower mortality in COVID-19. There needs to be more high-quality evidence on statin use for COVID-19 before applying to practice. The aforementioned studies do offer some reassurance that patients already taking a statin for cardiovascular risk can continue, as this is unlikely to increase harms during COVID-19 infection, and may have some benefits.

Why has this been in the news?

Some researchers have hypothesized that supplements may be beneficial in preventing COVID-19 due to their potential to influence immune response (CCMJ, June 10, 2020). A systematic review of herbal medicine for COVID-19 examined 7 randomized controlled trials in a total of 855 patients (J Clin Med, May 23, 2020). When herbal medicine plus conventional medicine was compared with conventional medicine alone, the combined therapy significantly improved the total effective rate, cough disappearance rate, sputum production symptom disappearance rate and TCM (traditional Chinese medicine) syndrome score (which includes cough, fever, dry and sore throat, and fatigue).

How does this apply to my practice?

Supplements are currently not recommended as treatment or prophylaxis for COVID-19 outside of randomized controlled trials (BC Centre for Disease Control, July 6, 2021). Clinical trials are ongoing.

Supporting evidence 

Ascorbic Acid (Vitamin C): Ascorbic acid is not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials. (BC Centre for Disease Control, July 6, 2021). Some researchers suggest that ascorbic acid has antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions that are relevant to the treatment of Covid-19. Randomized controlled trials are underway (Nutrients, October 27, 2020).

Niacin (Vitamin B3): There is currently insufficient evidence to support the use of Niacin as treatment or prophylaxis for COVID-19 outside of randomized controlled trials (BC Centre for Disease Control, July 6, 2021).

Zinc: There is currently insufficient evidence to support the use of Zinc as treatment or prophylaxis for COVID-19 outside of randomized controlled trials. Some researchers have suggested that Zinc, as an anti-inflammatory and antioxidant micronutrient found in food, has a well-established role in immune function and could be an effective treatment or prophylaxis for Covid-19. Zinc is currently being used in some clinical trials against COVID-19 (Biological Trace Element Research, October 22, 2020).

Vitamin D: There is currently insufficient evidence to support the use of Vitamin D as treatment or prophylaxis for COVID-19 outside of randomized controlled trials. A number of randomized trials have examined the effect of vitamin D on the prevention of acute respiratory infections and, in a meta-analysis, vitamin D supplementation was found to decrease its incidence. Although some researchers suggest that vitamin D may provide these preventative effects, it has not been evaluated for the prevention or treatment of Covid-19 specifically (Cleveland Clinic Journal of Medicine, June 2, 2020).

Evidence summaries and guidelines

Blood type and risk of COVID-19

Studies are currently emerging on how blood type (or blood group) corelates to lower risk of COVID-19 infection and severe illness. At this time evidence is still evolving and should not be used to estimate a patient’s trajectory.

Current evidence

  • A population-based cohort study in Ontario suggests that there may be slightly lower risk for Covid-19 infection and severe illness associated with the O and Rh− blood groups (Annals of Internal Medicine, November 24, 2020).
  • A study of observational healthcare data of 14,112 individuals tested for SARS-CoV-2 with known blood type indicated that there may be an association between ABO and Rh blood types and infection and outcomes. The researchers found increased infection prevalence among non-O types. The study suggests that risk of intubation may be decreased among A and increased among AB and B types, compared with type O, while risk of death may be increased for type AB and decreased for types A and B (Nature Communications, November 13, 2020).
  • A Canadian multicenter retrospective analysis and nested prospective observational sub-study of 95 critically ill patients with COVID-19, identified patients with blood group A or AB were at an increased risk for requiring mechanical ventilation, continuous renal replacement therapy (CRRT), and prolonged ICU admission compared with patients with blood group O or B. They have stated that further work is needed to understand the underlying mechanisms (Blood Advances, October 14, 2020).
  • A Danish retrospective cohort analysis of (7,422 COVID-19 patients) found that blood group O is associated with a decreased risk for contracting COVID-19 infection (Blood Advances, October 14, 2020).
  • A cross-sectional study of 1935 confirnmed COVID-19 cases in Pakistan found an association between blood types B & AB and susceptibility to COVID-19 and that Rh- D positive blood types may be less susceptible to COVID-19. It did not find an association between blood types A and O with COVID-19 (Pak J Med Sci, December 8, 2020).
  • A study of data from WHO and Johns Hopkins University found that rates of COVID-19 infection and death positively correlated with the proportion of the population with blood type A and negatively correlated with the proportion of the population with blood type B (Epidemiol Infect, January 7, 2021).

Managing COVID-19: Outpatient management, resolution, and long-term sequelae

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

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

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?

There is no reliable scoring system currently available for deciding which COVID-19 patients should be hospitalized (CEBM, April 20, 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

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

Putting it into practice

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

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

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

Symptom management

Common symptoms (MOH, May 21, 2020)

Fever (≥37.8 °C)

Potential management strategies (NICE, October 13, 2020)

New or worsening cough

Potential management strategies (NICE, October 13, 2020)

Shortness of breath (dyspnea)

Potential management strategies (NICE, October 13, 2020)

Be aware of and counsel patients on the other symptoms of COVID-19, which can include (MOH, September 21, 2020):

  • Sore throat
  • Difficulty swallowing
  • New olfactory or taste disorder(s)
  • Nausea/vomiting, diarrhea, abdominal pain
  • Runny nose, or nasal congestion (in absence of underlying reason for these symptoms such as seasonal allergies, post nasal drip, etc.)
  • Unexplained fatigue/malaise/myalgias
  • Delirium (acutely altered mental status and inattention)
  • Unexplained or increased number of falls
  • Acute functional decline
  • Exacerbation of chronic conditions
  • Chills
  • Headaches
  • Croup
  • Conjunctivitis
  • Multisystem inflammatory vasculitis in children

Comorbid considerations

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

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

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

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

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

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

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

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

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

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

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

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

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

Holding diabetes medications

Specific populations

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

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

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

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

It is recommended that:

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

See Top resources for condition-specific guidance.

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

Atypical COVID-19 presentations in frail older adults

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

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

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

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

Adverse pregnancy outcomes

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

Prenatal care, referral to hospital, and delivery

Mother-to-child transmission and infant testing

Breastfeeding

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

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

What is “long COVID”?

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

Symptoms of long COVID/PASC include:

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

Resolution

Patients with mild to moderate COVID-19 who are not severely immunocompromised* can be advised to discontinue isolation (MOH, May 21, 2021):

  • 10 days from symptom onset (or 10 days from positive test collection date if never symptomatic), provided they are afebrile (without fever-reducing medications) and symptoms are improving for at least 24 hours (MOH, May 21, 2021).

Patients with severe COVID-19 who required ICU level care, and/or those who are severely immunocompromised*, can be advised to discontinue isolation (MOH, May 21, 2021):

  • 20 days from symptom onset (or 20 days from positive test collection date if never symptomatic and severely immunocompromised*), provided they are afebrile (without fever-reducing medications) and symptoms are improving for at least 24 hours (MOH, May 21, 2021).

OR

  • After two consecutive negative specimens are collected (at least 24 hours apart) AND the patient has become afebrile and symptoms are improving for at least 24 hours. If swab remains positive, test again in approximately 3-4 days (once negative, conduct swab at least 24 hours later) (MOH, May 21, 2021).

* Examples of patients who are severely immunocompromised include patients undergoing cancer chemotherapy, patients with untreated HIV infection with CD4 T lymphocyte count <200, patients with combined primary immunodeficiency disorder, patients taking prednisone >20 mg/day for more than 14 days and taking other immune suppressive medications. Advanced age, diabetes, and end-stage renal disease alone generally should not impact non-test-based clearance (MOH, May 21, 2021).

Please note that the absence of cough is not required for symptom resolution for those known to have chronic cough or who are experiencing reactive airways post-infection (MOH, May 21, 2021).

Top resources

Managing COVID-19: Long-term care homes

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Universal masking in long-term care homes

Universal masking measures have been put in place for all staff and essential visitors of long-term care homes (LTCHs) regardless of whether the home is in outbreak or not (MOH, April 7, 2021).

Surgical masks or procedural masks (“masks” in this section) can function either as source control (worn to protect others) or part of personal protective equipment (to protect the wearer) (PHO, February 1, 2021).

With every patient/resident:

Infection control: healthcare worker and resident cohorting

Long-term care homes must use staff and resident cohorting to prevent the spread of COVID-19 (MOH, April 7, 2021).

In smaller long-term care homes, or homes where it’s not possible to maintain physical distancing of staff or residents, all residents and staff should be managed as if they are potentially infected, and staff should use droplet and contact precautions when in an area affected by COVID-19.

Putting it into practice

Healthcare worker cohorting can include:
  • Designating providers to care for either ill residents or well residents.
  • Limit the number of healthcare facilities and locations each healthcare worker accesses.
Resident cohorting can include:
  • Alternative accommodation in the home to maintain physical distancing.
  • Cohorting of the well and unwell.
  • Utilizing respite, palliative care, and other beds and rooms, as appropriate.

Navigating difficult conversations

When implementing resident cohorting strategies, recognize the emotional impact of moving and/or isolating residents. Use the talking tips below to help address resident stress and anxiety.

  • “This is your home and we will make every effort to make you comfortable in your new room with all of your belongings.”
  • “In-room dining is important for you and other residents so that we can protect everyone, including yourself.”

For more help managing difficult patient conversations in the context of COVID-19, see:

Screening for COVID-19

Putting it into practice

Passive screening
  • Signage should remind all persons in the LTCH to perform hand hygiene (PHO, March 16, 2020) and follow respiratory etiquette.
  • Signage should also indicate signs and symptoms of COVID-19 and steps (MOH, April 15, 2020) that must be taken if COVID-19 is suspected or confirmed in a staff member or a resident.
Active screening for all staff and visitors
  • LTCHs must implement active screening of all staff, visitors and anyone else entering the LTCH for COVID-19 with the exception of first responders, who should, in emergency situations, be permitted entry without screening.
Active screening for all residents
  • LTCHs must conduct active screening and assessment of all residents, including temperature checks, at least twice daily (at the beginning and end of the day) to identify if any resident has fever, cough or other symptoms of COVID-19 (MOH, June 4, 2021).

For a LTCH specific screening tool, see COVID-19 Screening Tool for Long-Term Care Homes and Retirement Homes (MOH, May 6, 2020).

Testing for COVID-19

Putting it into practice

LTCH not under outbreak
LTCH under outbreak
  • In the event an outbreak of COVID-19 is declared in the home, all staff in the entire home AND all residents in the home should be tested including on symptomatic and asymptomatic residents and staff members who have been in contact with cases.
  • Asymptomatic contacts of a confirmed case include:
    • All residents living in adjacent room.
    • All staff working on the unit/carehub.
    • All essential visitors that attended at the unit/carehub.
    • Any other contacts deemed appropriate for testing based on a risk assessment by local public health unit.
Keep in mind

Outbreak management

A suspect outbreak in a home is defined as one lab-confirmed COVID-19 case in a resident.

A confirmed outbreak in a home is defined as two or more lab-confirmed COVID-19 cases in residents and/or staff (or other visitors) in a home with an epidemiological link, within a 14-day period, where at least one case could have reasonably acquired their infection in the home. Examples of reasonably having acquired infection in a home include:

  • No obvious source of infection outside of the LTCH setting; OR
  • Known exposure in the LTCH setting.
  • The local public health unit is responsible for managing the outbreak response. Local public health units have the authority and discretion as set out in the HPPA to coordinate outbreak investigation, declare an outbreak based on their investigation, and direct outbreak control measures (MOH, June 4, 2021).

For guidance on admissions and transfers of residents back to their LTCH, see Directive #3 “Admissions and Transfers” (MOH, June 4, 2021).

Types of absences in LTCHs

As per Directive #3 for Long-Term Care Homes under the Long-Term Care Homes Act, 2007 (MOH, June 4, 2021), short term absences are defined as leaving the LTCH’s property for social or other reasons that does not include an overnight stay.

  • A request must be submitted and approved by the LTCH.
  • Upon return to the LTCH, residents must be actively screened (refer to Active Screening of All Residents above) but are not required to be tested or self-isolate.
  • Residents must be provided with a medical mask to be worn when outside of the LTCH (if tolerated) and reminded about the importance of public health measures including maintaining a safe distance of at least 2 metres from others and hand hygiene.

As per Directive #3 for Long-Term Care Homes under the Long-Term Care Homes Act, 2007 (MOH, June 4, 2021), temporary absences are defined as leaving the LTCH’s property for social or other reasons that includes one or more nights.

  • A request must be submitted and approved by the LTC.
  • Upon return to the LTCH, residents must be actively screened (refer to Active Screening above) and self-isolate for 14 days.
  • Residents must be provided with a medical mask to be worn when outside of the LTCH (if tolerated) and reminded about the importance of public health measures including maintaining a safe distance of at least 2 metres from others and hand hygiene.

As per Directive #3 for Long-Term Care Homes under the Long-Term Care Homes Act, 2007 (MOH, June 4, 2021), medical absences defined as leaving the LTCH’s property for medical reasons (i.e., outpatient visits, single night emergency room visit).

  • LTCHs cannot deny a resident’s request to leave the LTCH for medical visits.
  • Upon return to the LTCH, residents must be actively screened (refer to Active Screening above) but are not required to be tested or self-isolate.
  • Emergency room visits that take place over a single night (e.g., assessment and discharge from the emergency department spans one overnight period) are considered equivalent to an outpatient medical visit.
  • Residents must be provided with a medical mask to be worn when outside of the LTCH (if tolerated) and reminded about the importance of public health measures including maintaining a safe distance of at least 2 metres from others and hand hygiene.

*The requirements in this Directive (MOH, December 7, 2020) related to absences are not meant to apply to retirement homes. The requirements related to resident absences for retirement homes should continue to be guided by applicable Retirement Home Regulatory Authority and Ministry for Seniors and Accessibility requirements and policies, as amended from time to time.

Family physicians/primary care nurse practitioners providing care in LTCHs

The information below provides clinical guidance and logistical support to redeployed or volunteer primary care providers to LTCHs when providing in-person individual health assessments and hands-on care. It is not limited to COVID-19 specific care.

Please note: All non-essential visits are to be conducted virtually. Primary care providers can use the VirtualCare App (ThinkResearch, 2020) to remotely connect with nursing staff and residents. Providers can also visit LTC+ Virtual Care Support for Long-term Care Homes in Ontario (WCH, 2020) for a virtual care program that connects providers working in LTCHs with 24/7 virtual consultations with medical specialists and services. See Primary Care Operations in the COVID-19 Context > Delivering patient care remotely for more general information on remote/virtual visits.

If you are able to and are interested in being matched to work at long-term care facilities, see the following matching tools for healthcare workers:

For questions about medical-legal protection while working in a different clinical setting, see:

  • CMPA Physician Advisors are available to provide support throughout the pandemic and can be reached at 1-800-267-6522 Monday to Friday from 8:30 a.m. to 4:30 p.m. ET or through the CMPA member portal.
  • CNPS beneficiaries with questions about nursing during a pandemic are encouraged to contact CNPS for advice at 1-800-267-3390.

Practical tips and clinical guidance to keep in mind when working in LTCHs

  • Introduce yourself to the administrator and participate in the screening process. If you fail the screening, immediately leave the site, proceed to self-isolate (PHO, April 10, 2020) and conduct virtual visits only.
  • Have a discussion with the care staff to establish understanding of specific protocols and procedures within the LTCH.
    • Ensure you know how to summon assistance for a fire, cardiac arrest, and other emergencies. The colour codes used are the same for all of Ontario. If you do not know the colour code when you hear one, please ask.
  • Determine which HCWs and staff are available to assist with any assessments or hands-on care, if necessary. Can communicate with staff or refer to a schedule, if available.
  • Perform hand hygiene (PHO, March 16, 2020) before and after every resident/patient interaction.
  • Conduct a personal risk assessment (AHS, 2018) and don appropriate PPE before engaging with patients/residents.
  • Review patient’s history and what medications they are currently on.
  • If the patient has dementia and/or other cognitive disorders that impair decision-making ask LTCH staff to engage with Substitute Decision-Maker (SDM) via virtual means or telephone.
  • Ensure the proper storage of the resident’s records according to the protocols of the facility.
  • If more than one site will be visited in a single day, repeat the self-assessment process prior to arrival at the next site.
  • Self-monitor (PHO, May 17, 2020) for 14 days following your last on-site visit.

Top resources

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

Managing COVID-19: Palliative care

Jump to:

The role of primary care

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

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

Putting it into practice

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

Document decisions regarding do not resuscitate (DNR)

Putting it into practice

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

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

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

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

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

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

Putting it into practice

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

    Hydromorphone

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

    Morphine

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

    Scopolamine (hyoscine HYDRObromide)

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

    Glycopyrrolate

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

    Atropine 1% ophthalmic drops

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

    Furosemide (if fluid overload)

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

    Haloperidol

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

    Midazolam

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

    Lorazepam

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

    Acetaminophen 650 mg Suppositories

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

    Methotrimeprazine (if more sedation is desirable)

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

    Haloperidol (if less sedation desirable)

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


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

    Click for treatment tips
  • Urinary retention

    Foley catheter 16 French

    • Insert catheter PRN
  • Dry mouth

    Mouth swabs

    • Mouth care q.i.d and PRN

Plan for an expected death in the home

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

Provide grief and bereavement support

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

Grief and bereavement support for health care providers

New fee codes

Top resources

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