This Briefing Note was completed by the Research, Analysis, and Evaluation Branch (Ministry of Health) based on information provided by a member of the COVID-19 Evidence Synthesis Network. Please refer to the Methods section for further information.
This note summarizes the research evidence associated with ‘long COVID’, including definitions, risk factors, symptomatology, prognosis, therapeutics, and other emerging research findings.
*The full version of the Briefing Note including the Appendix can be accessed in the PDF file at the top of the page*
Commonly, long COVID is characterized as the persistence of any COVID signs and symptoms that continue or develop between four to 12 weeks after acute COVID-19, including both ongoing symptomatic COVID‑19 and post‑COVID‑19 syndrome.
- Emerging Research Findings: Research from systematic reviews, narrative reviews, and living reviews, and individual studies yielded the following details:
- Diagnosis: Long COVID is primarily diagnosed based on two factors: 1) having been infected with COVID-19 in the past; and 2) presenting with long COVID symptoms.
- Prevalence: Prevalence estimates vary widely; for example, 5% to 80% of people with confirmed COVID-19 may have symptoms past the acute phase of illness. Recent reports (September 2021) suggest that 150,000 Canadians currently have long COVID, though it is unclear if this is limited to people with confirmed COVID-19.
- Risk factors: The following factors may increase the risk for long COVID: a higher acuity of COVID-19 infection or presence of many acute COVID-19 symptoms, being female, being of older age, having a higher body mass index (e.g., obesity), pre-existing comorbidities (e.g., asthma, autoimmune disease), psychiatric disorders, and being a health care worker. Ethnicity and socioeconomic factors have been investigated but show mixed findings.
- Symptomatology: The most common symptoms include: chronic fatigue, dyspnea (e.g., shortness of breath), headache, pain (e.g., chest, joint, muscle), poor sleep quality, and reduced exercise capacity. In addition, persistent symptoms have also been described for the cognitive, musculoskeletal, respiratory, nervous, gastrointestinal, cardiac, and psychological systems (e.g., post-traumatic stress disorder, anxiety, depression).
- Management of Long COVID Patients: Research suggests that treating people with long COVID requires a multidisciplinary approach including evaluation, symptomatic treatment, treatment of underlying problems, physiotherapy, occupational therapy, and psychological support.
The evidence base currently precludes a precise definition of long COVID-19 symptoms and prevalence. In addition, no identified studies provided evidence regarding prognosis for individuals with long COVID. There is a clear need for robust, controlled, prospective cohort studies, including different at-risk populations and settings, incorporating appropriate investigations, collected, and recorded in a standardised way.
Analysis for Ontario
Since the time frame for assessing the risk factors and symptoms associated with long COVID has just been several months, there has been scant time to understand the longer-term implications of COVID-19 infection. The knowledge regarding long term effects and treatment options is still evolving.
This section below summarizes the emerging research evidence associated with ‘long COVID’, including definitions, risk factors, symptomatology, prognosis, and emerging trends or findings.
- ‘Long COVID’ Defined: A CADTH (September 2021) report on ‘post-COVID condition’ states that consensus on the terminology has yet to be reached in the research. The World Health Organization (WHO) uses the term post-COVID-19 condition but notes that multiple names are in use, such as: long COVID; chronic COVID syndrome; late sequelae of COVID-19; post-acute sequelae of SARS-CoV-2 infection (PASC); and long haul COVID. Different groups may use slightly different definitions for any of these terms; and formal definitions have also been proposed. For example:
- CADTH’s report (September 2021) uses the term post-COVID-19 condition, which refers to symptoms beyond the acute infection phase (i.e., four weeks after being infected).
- Symptomatology: Emerging evidence about the type of symptoms and long-term health effects of long COVID suggests that many adults can experience a heterogeneous range of symptoms after their initial COVID-19 infection. The most common symptoms reported in the literature were: chronic fatigue, dyspnea (e.g., shortness of breath), headache, pain (e.g., chest, joint, muscle), poor sleep quality, and reduced exercise capacity. In addition, persistent symptoms have also been described for the cognitive, musculoskeletal, respiratory, nervous, gastrointestinal, cardiac, and psychological systems (e.g., post-traumatic stress disorder, anxiety, depression).
- Long COVID and Other Coronaviruses: CADTH (September 2021) summarizes research that suggests there are similar long-term health consequences resulting from COVID-19, SARS, and MERS. For example:
- A systematic review (May 2020) on survivors of SARS and MERS reported that six months after hospital discharge patients had symptoms similar to those of long COVID, including lung abnormalities, reduced exercise capacity, and psychological impairment. An estimated 40% of people who had SARS had chronic fatigue 3.5 years after being diagnosed.
- Pediatric Population: Symptoms of long COVID among children range widely with the most frequent including: pain, breathing difficulties, fatigue, cough, and headache. Other symptoms include insomnia, rash, and neuropsychiatric symptoms, such as concentration difficulties. The CADTH report (September 2021) highlighted a study (preprint) of children with symptoms lasting for more than four weeks; the study reported that symptoms lasted, on average, for months and that 94% of study participants reported experiencing at least four symptoms.
- Subtypes in Children: Long COVID in children may include multiple subtypes or syndromes. Based on an analysis of 570 pediatric patients, the US Centers for Disease Control and Prevention (CDC) suggest that there may be three subtypes: multisystem inflammatory syndrome in children (MIS-C), atypical Kawasaki disease, and pediatric long COVID.
- Long COVID and Other Coronaviruses: CADTH (September 2021) summarizes research that suggests there are similar long-term health consequences resulting from COVID-19, SARS, and MERS. For example:
- Diagnosis: Currently, long COVID is primarily diagnosed based on two factors: 1) having been infected with COVID-19 in the past; and 2) presenting with above-noted long COVID symptoms.
- Prevalence: Estimates on prevalence vary widely across studies. For example:
- A systematic review (2021) reported estimates ranging from 5% to 80%.
- Two systematic reviews (March 2021; one preprint) estimated 63% to 84% of people with confirmed COVID-19 had symptoms four weeks after either diagnosis or hospitalization; and 46% to 56% experienced symptoms after 12 weeks.
- Three cohort studies (February 2021; July 2021; September 2021) reported that 33% to 39% of people may experience symptoms after six to nine months. Two cohort studies reported that 28% to 49% of people who had been hospitalized for COVID-19 experienced symptoms after 12 months.
- Studies of people who had been hospitalized during the acute phase tend to show a higher prevalence of long COVID compared to people who had milder acute illness and who did not require hospitalization.
- Prevalence When Including Suspected COVID-19: Emerging evidence indicates that people who were initially asymptomatic or had mild acute illness can develop long COVID. Studies that include suspected cases, together with confirmed COVID-19 cases, estimate that 21% to 23% of people who had COVID-19 develop ongoing or new symptoms after four weeks or 30 days, and approximately 14% experience symptoms after 12 weeks. Limited studies about long-term (beyond 12 weeks) prevalence rates among this subset of people was identified.
- Prevalence in Canada: A rapid systematic review (2021) estimated that 150,000 Canadians have long COVID, although the CADTH report (September 2021) states it is unclear if this is limited to confirmed COVID-19. A survey of 1,048 people in Canada with suspected or confirmed long COVID conducted by the COVID Long-Haulers Support Group Canada found that 80% of respondents had symptoms for more than three months and almost 50% had symptoms for more than 11 months.
- Risk Factors: The following factors may increase the risk for long COVID: a higher acuity of COVID-19 infection or presence of many acute COVID-19 symptoms, having a higher body mass index (e.g., obesity), pre-existing comorbidities, psychiatric disorders, and being a health care worker. In addition:
- Severity of Acute Illness: The CADTH report (September 2021) states that multiple studies suggest that people who were hospitalized may have a higher risk of developing or having a more severe long COVID compared to those with milder symptoms. Acute illness severity may be associated with specific long COVID symptoms or with post-intensive care syndrome (PICS).
- Gender: Specific symptoms may vary by sex, and may change over time. Being female may be associated with higher risk of developing long COVID, although some research identified no correlation. For example, one review (January, 2021) suggested that women are twice as likely to develop symptoms of long COVID.
- Older Age: Research suggests older people (defined variably) are more likely to develop long COVID. One review (2021) suggests that patients with the condition are around four years older than those without. Symptoms may peak for people between ages 40 and 60 years.
- Comorbidities: CADTH (September 2021) reported that asthma, autoimmune disease, and obesity have been associated with greater risk of long COVID. A survey cohort study (July 2021) and a preprint cohort study (2021) reported that anxiety, depression, and neurologic disabilities may also be risk factors. However, another cohort study (November 2020) reported no association between comorbidities and the presence of COVID-19 condition.
- Symptoms in Acute Phase: People who experience specific symptoms in the acute phase, and a higher number of these, may be more likely to develop long COVID (e.g., fatigue, shortness of breath, headache, voice hoarseness, muscle aches and pains).
- Ethnicity and Socioeconomic Factors: These factors have been investigated but show mixed findings.
- Prevention: Two studies (April 2021; June 2021) of early rehabilitation clinics that treated people after the acute COVID-19 phase reported improvements in pulmonary symptoms and physical performance (e.g., six-minute walking distance) when comparing participants before and after completing rehabilitation. These studies were short, eight-week interventions for people who had been hospitalized. It is unclear how rehabilitation may affect people who had not been hospitalized, particularly people who present with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like symptoms such as post-exertional malaise.
- Rehabilitation Care Models: A rapid systematic review that focused on care models for long COVID identified several studies from the United States, United Kingdom, Spain, and Italy, with multiple common focuses across different models including: 1) principles (e.g., multidisciplinary teams, integrated care); 2) medical specialists (e.g., pulmonary, cardiovascular, psychiatry); and 3) components (e.g., standardized symptom assessment, referral system). For more details on potential models of care for long COVID, see Table 5.
- Treatment and Management: CADTH (September 2021) described a study on long COVID (2021) that describes treatment of minor symptoms, etiology, and follow-up:
- Treatment of Minor Symptoms: Cough, pain, myalgia can be treated symptomatically with paracetamol (i.e., acetaminophen), cough suppressants, and oral antibiotics (if secondary bacterial infection is suspected).
- Etiology: Etiology behind the symptoms, (such as pulmonary embolism, cerebrovascular accident, coronary artery disease) if any, has to be treated as per the standard protocol; chest physiotherapy and neuro rehabilitation is important in patients with pulmonary and neuromuscular sequelae.
- Follow-up: The ideal frequency and duration of follow up is not clearly defined. In people with COVID-19 interstitial pneumonia, in the first 12 months, seven interactions with health care professionals (four face-to-face) are recommended, alongside four high-resolution CT scans, four six-minute walk tests (6MWT); four blood tests (including blood count and metabolic panel); and two SARS-CoV-2-IgG tests (i.e., antibody tests).
- Exercise: The CADTH report (September 2021) suggests the evidence about exercise rehabilitation for people with COVID-19 is mixed and requires further assessment. Exercise may help reduce fatigue – a common long COVID symptom – and may be helpful for people who had been bedridden (e.g., people treated in hospital or intensive care unit or people who had been hospitalized. However, limited research exists on the impact of exercise for people who had not been hospitalized.
- Vaccination: For people who have not been vaccinated and develop post-COVID-19 condition, the CADTH report (September 2021) states there is mixed evidence to suggest that receiving a COVID-19 vaccine after the acute infection phase may help to reduce their post-COVD-19 symptoms. For example, a 2021 survey from the LongCOVIDSOS group reported that, of the respondents who received at least their first dose, 57% reported an overall improvement of symptoms, 25% saw no change, and 19% saw their symptoms worsen. Another preprint study reported that in a group of people with post-COVID-19 condition who had received at least one dose, 23% saw an increase in symptom resolution compared to 15% in matched unvaccinated individuals.
- Economic Impact: The CADTH report (September 2021) suggests the economic impact and cost-effectiveness of long COVID treatment and care models are not yet established. The 2021 report described a rapid systematic review (2021) that assessed the economic impact of long COVID, which was focused on health care utilization outcomes and the proportion of people who were able to return to work. The systematic review (2021) stated that the United Kingdom had announced a total investment of $230 million CAD to care for an estimated 1.1 million long COVID cases. At scale for Alberta, projections could require a $6.7million investment for the 2021-2022 fiscal year. The review recommended additional research on the health care costs of various specialists.
- Demand for Health Care Services: A Canadian survey of 1,048 people with self-reported post-COVID-19 condition reported that nearly 50% of respondents visited a health care provider five times over the past year and nearly 30% of respondents visited more than 10 times. The CADTH report (September 2021) notes that as more people develop long COVID, a number of health care services could see increases in demand (e.g., primary care; multidisciplinary rehabilitation services; prescription drugs; mental health treatments and supports).
- Health Equity: The CADTH report (September 2021) summarizes research that suggests that people experiencing vulnerabilities (e.g., diverse ethnic backgrounds, lower income households, people with disabilities) may be disproportionately impacted by long COVID, as they may be more likely to: 1) work in jobs without sick leave or extended health benefits; 2) struggle financially; 3) have challenges accessing health services; or 4) be misdiagnosed or have long COVID symptoms dismissed.
- Diagnosis: The Mayo Clinic (2021), the National Institute for Health and Care Excellence (NICE) (November 2021), and a UK-based clinical practice guideline (August 2020) provide guidance on diagnosing long COVID.
- US: The Mayo Clinic recommends looking for symptoms affecting at least two of six major organ systems (general, cardiac, respiratory, gastrointestinal, musculoskeletal, and neurologic), as well as for a decrease in functional status.
- UK: NICE (November 2021) and UK-based clinical practice guidelines (August 2020) state that suspected previous COVID-19 illness (e.g., symptoms closely linked to COVID-19 infection) is sufficient to suspect long COVID as a cause for any new or ongoing symptoms beyond four weeks; diagnosis should not depend on positive COVID-19 tests or hospitalization due to COVID-19. In addition, symptoms may vary across specific populations (e.g., children, older adults). NICE recommends that health care providers:
- Test those suspected of having long COVID to assess if their symptoms stem from another condition; and
- Use a screening questionnaire to develop a clearer understanding of each person’s symptoms.
- Treatment and Management: The CADTH report (September 2021) describes the literature on treatment and management of long COVID vary across jurisdictions. For example:
- Self-Management: NICE (November 2021) and a multidisciplinary clinical panel from the UK recommend people with suspected long COVID be provided with education and support for self-management strategies (e.g., current information about the condition, goal setting, online support networks).
- Exercise: Long COVID guidelines from World Physiotherapy and the CDC recommend a cautious and conservative approach to exercise; exercise may be useful for treating certain syndromes but not others. Further research with be needed to determine who is most likely to benefit.
- Activity Management: World Physiotherapy guidelines for long COVID and the CDC’s guidelines for ME/CFS recommend pacing or activity management (i.e., balancing rest with activity, and staying within personal limits) to avoid worsening symptoms.
- Screening: The World Physiotherapy’s report suggests that before recommending exercise, people with long COVID should be screened for post-exertional symptom exacerbation.
- Exercise Rehabilitation: World Physiotherapy’s report also recommends against exercise rehabilitation for those with cardiac impairments, exertional oxygen desaturation (i.e., low oxygen levels during exertion), or autonomic nervous system dysfunction.
- Economic Impact: The UK’s National Health Service documented a nationwide investment in long COVID care. The total investment to establish 89 post-COVID clinics was CAD $58.6 million between December 2020 and April 2021.
- Health Equity: The CDC and health policy researchers have recommended a series of strategies for addressing health inequities that include: education, training for health service providers, and easy to navigate services. For example:
- Allocate resources to raise awareness of long COVID among marginalized groups and increase access to needed services;
- Provide training to health care providers surrounding sensitivity to and awareness of stigma, empathy, and the importance of completing full clinical evaluation; and
- Use telemedicine for easier scheduling, easier collection of information including symptoms, and improving access.
- Prevalence: An Alberta Health Services (AHS) framework (2021) on long COVID estimates that, based on international prevalence rates, it is conceivable that there could be over 36,500 Albertans who could benefit from rehabilitation services for five or six weeks after testing positive for COVID-19 and over 14,600 persons likely require a much longer course of rehabilitation support.
- Treatment and Management: The AHS framework (2021) did not identify specific treatments for long COVID compared to similar problems that occur to patients without COVID. The AHS recommend that people with long COVID should be assessed and treated using current standards of medical care.
- Rehabilitation Services: Reports from Alberta and Quebec describe existing and recommended rehabilitation responses:
- Alberta: Rehabilitation services vary across the five AHS Zones and there is no provincial coordination or planning. The AHS suggest a coordinated approach to rehabilitation along the continuum of care and using community care alternatives to potentially decrease emergency department visits. A multidisciplinary intervention based on personalized assessment and treatment might include: exercise training; education, and behavioural modification designed to improve the physical, cognitive, psychological, and social effects of long COVID.
- Quebec: Quebec’s Institut national d’excellence en santé et services sociaux (2021) produced a set of guidelines for the therapeutic management of long COVID for frontline workers, including: 1) medical management; 2) functional recovery; 3) social and psychological support; and 4) self-management of signs and symptoms.
- Prevalence: A 2021 Ontario COVID-19 Science Advisory Table brief reported that 57,000 to 78,000 Ontarians had or are currently experiencing long COVID, although prevalence estimates can vary widely depending on the case-definition applied.
- Health Care Utilization: Ontario Health data (October 2021) suggests there were 23,260 COVID-19 cases in Ontario that required hospitalization and 22% of these cases had an ICU admission; estimates suggest that approximately 17,000 people in Ontario will require specialist supports.
- 41% of COVID-19 inpatient cases were admitted to home and community care services in 2020 fiscal year. More analysis is needed to evaluate the rehabilitation use rate for this population.
- Local Health Integration Networks in Central West, Central, and Toronto Central had the highest hospitalization rates within the province. These three regions are known to have growing use of acute care use and three marginalization indexes (ethnic concentration, material deprivation, income dependency).
- Patient Care: Ontario Health (October 2021) indicated that equitable and patient-centered care for long COVID would require a coordinated provincial approach that would involve various providers/sectors. They recommended nine potential actions, such as:
- Create tools that assist primary care providers to integrate a long COVID clinical guidance document into electronic medical records applications;
- Fund regions to plan a coordinated approach to providing long COVID care;
- Leverage existing Primary Care and COVID-19 Community of Practice to share communications and support to primary care with the provision of long COVID care;
- Develop service delivery model recommendations based on best evidence to date and innovative models; and
- Develop funding calculations for ongoing future service delivery on a regional level.
Individual peer-reviewed articles and review articles were identified through PubMed, and Google Scholar. The search was limited to English sources and therefore may not capture the full extent of initiatives in non-English speaking countries. Full-text results extracted were limited to those available through Open Access or studies made available to the Ministry by our partners.
The COVID-19 Evidence Synthesis Network is comprised of groups specializing in evidence synthesis and knowledge translation. The group has committed to provide their expertise to provide high-quality, relevant, and timely synthesized research evidence about COVID-19 to inform decision makers as the pandemic continues. The following members of the Network provided evidence synthesis products that were used to develop this Evidence Synthesis Briefing Note:
- Decary, S., et al. (2021). Care models for Long COVID-19: A rapid systematic review. Toronto: SPOR Evidence Alliance. COVID-END Network. Accessed October 20, 2021;
- Evidence Synthesis Unit. (2021). Long COVID-19 clinics (Evidence Synthesis Network briefing note). Ontario Ministry of Health, Research, Analysis and Evaluation Branch;
- Razak, F., et al. (September 2021). Understanding the Post COVID-19 Condition (Long COVID) and the Expected Burden for Ontario. Science Briefs of the Ontario COVID-19 Science Advisory Table, 2 (44); and
- Vu, T., & McGill, S. (September 2021). CADTH Horizon Scan: An Overview of Post COVID-19 Condition (Long COVID). Canadian Journal of Health Technologies, 1 (9), pp. 31.