This briefing note examines the research and jurisdictional reports on post COVID-19 condition for: 1) the general population; and 2) working age adults and low-income populations. In particular:

• General Population: Definitions; underlying causes; prevalence and associated symptoms and sequelae; risk factors and mitigation; health system utilization; functional limitations; use of long- term disability and employment; and expected burden for Ontario.
• Working Age/Low-Income Populations: Symptom prevalence by body system (e.g., neurological, respiratory); symptom duration and intensity over time; acuity level of illness; quality of life (QoL) and activities of daily living impacts; work-related impacts (e.g., leaves of absence); health care services received; and analysis/modelling considerations. 

This briefing note is an update of RAEB’s Evidence Synthesis Briefing Note on Long COVID (Oct 29, 2021) and a Science Advisory Table’s (SAT) report on Understanding the Post-COVID-19 Condition (Long COVD) and the Expected Burden for Ontario (Sept 14, 2021). The literature search was limited to sources published from October 1, 2021 to April 2022; however, where applicable, information was included outside of this date range if it was not present in the previously completed RAEB’s Evidence Synthesis Briefing Note or SAT report listed above. 

• Most of the information identified on general aspects of post COVID-19 condition (i.e., definitions, method of diagnosis, prevalence, and risk factors) are largely unchanged from the RAEB and SAT reports listed above. 
• There are no standardized definitions and diagnostic criteria (e.g., validated self-reported questionnaires versus clinical assessments) used across studies. In particular: 
  • A report (Mar 16, 2022) by Public Health Ontario noted that study populations, follow-up periods, outcome measures, and analysis methods were highly heterogeneous across systematic reviews and primary studies,making direct comparisons challenging.
  • A report (2021) by the World Health Organization (WHO) indicated that there are multiple names in use in the literature to refer to post COVID-19 condition, 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. This Briefing Note will apply the term post COVID-19 condition.
• There was limited information identified on the following topics: 
  • The impact of post COVID-19 condition on health system utilization, work- and disability-related impacts, and expected burdens across jurisdictions, including Ontario. 
  • The impact of post COVID-19 condition on working age and low-income populations. For example, this was emphasized in the following studies:
    • A review (Oct 2021) on the acute and post‑acute neurological manifestations of COVID‑19 reported that population data from low- and middle-income countries are scarce, leading to uncertainties in measuring neurological impacts.
    • A US study (Apr 2022) on Black, Indigenous, and Latinx communities noted few studies address inequities in outcomes associated with post COVID-19 condition.
  • The impact of vaccination on post COVID-19 condition. In particular: 
    • A Canadian Agency for Drugs and Technologies in Health (CADTH) draft scoping review (Mar 16, 2022) on the clinical classification and interventions for post COVID-19 condition did not identify many published studies assessing the impact of COVID-19 vaccination on post COVID-19 condition. The scoping review did not identify many studies of individuals who received the COVID-19 vaccine, making it unclear whether receiving a COVID-19 vaccine before or after developing post COVID-19 condition will impact symptoms.
• The clinical recommendations and/or methodological quality of most of the sources identified are unclear as the Research, Analysis, and Evaluation Branch does not have the expertise to make such assessments; methodological assessments published by other research groups are reported where available. 

This section below summarizes the scientific evidence and jurisdictional experiences on post COVID-19 condition among the general population, low-income populations, and working age population.

Scientific Evidence

Definitions

• Definitions of post COVID-19 condition have been defined by many studies and share similar components, such as persistent symptoms and/or delayed symptoms of SARS-CoV-2 infection beyond four weeks from symptom onset, and signs and symptoms that develop during or after SARS-CoV-2 infection that are not explained by an alternative diagnosis, and continue for three weeks; beyond four weeks; or, at tleast two months.

Prevalence

• Since the official name and definition for the condition are not yet established, determining an overall prevalence of post COVID-19 condition among COVID-19 survivors remains challenging. There is high heterogeneity in prevalence estimates.
  • Prevalence at Follow-up Periods: Eight identified systematic reviews (SRs) reported on post COVID-19 condition prevalence at multiple follow-up points, ranging from four to 12 weeks after COVID-19 diagnosis to 12 months after symptom onset. For example:
    • A SR (Dec 16, 2021) reporting on post COVID-19 condition prevalence estimated that 59% of people withconfirmed COVID-19 had symptoms at 12 weeks and 62% had symptoms at >12 weeks.
    • A preprint SR (Nov 3, 2021) reporting on 36 studies estimated that 83% of people with confirmed COVID-19 had symptoms four weeks after diagnosis and 56% experienced symptoms after 12 weeks.
    • A SR (Oct 13, 2021) reported on post COVID-19 condition prevalence at three follow- up periods: one month(54%); two to five months (55%); and six months (54%).
  • Global Prevalence: A preprint SR (Nov 16, 2021), reporting on 29 studies comprising 886,388 COVID-19 positive patients, estimated a global pooled prevalence of post COVID-19 condition at 43% of all cases (57% among patients hospitalized). Reports from North America had the lowest pooled prevalence at 30%. Overall, the SR estimated that about 100 million people had or are still living with post COVID-19 condition worldwide.

Symptomatology

• Emerging evidence about the type of symptoms and long-term health effects post COVID-19 condition suggests that many adults can experience a range of symptoms after their initial COVID-19 infection. 
  • Common Symptoms: The most common symptoms reported are: chronic fatigue, dysosmia (disordered smell perception), dyspnea (e.g., shortness of breath), taste dysfunction, headache, pain (e.g., chest, joint, muscle), poor sleep quality, and reduced exercise capacity. In addition, persistent symptoms also affect the cognitive, musculoskeletal, respiratory, nervous, gastrointestinal, cardiac, and psychological systems (e.g., post-traumatic stress disorder, anxiety, depression). For example:
    • Neuropsychiatric Symptoms: A SR and meta-analysis (Dec 17, 2021) on the persistent neuropsychiatric symptoms associated with post COVID-19 condition across 51 studies and 18,917 patients assessed at least 20 days after acute COVID-19 infection. The neuropsychiatric symptoms included cognitive dysfunction (20.2%, 10.3–35.7), and psychological outcomes, such as: sleep problems (27.4%), anxiety (19.1%), post traumatic stress disorder (PTSD) (15.7%), and depression (12.9%).

Risk Factors

• The identified literature reported that having five symptoms in the first week of illness (i.e., fatigue, headache, shortness of breath, hoarse voice, and myalgia) may increase the risk for post COVID-19 condition. The following factors also may increase the risk for the condition.
  • Number of symptoms during acute SARS-CoV-2 infection; severe/critical acute infection; female sex; older age; obesity; hospital admission at symptom initiation, and dyspnea or abnormal chest auscultation.

Quality of Life (QoL)

• Two identified studies investigated how post COVID-19 condition impacted QoL outcomes for patients, reporting that the symptoms led to a decreased QoL in the general population.
  • A SR (Dec 16, 2021) of 39 studies examined post COVID-19 condition symptoms at >12 weeks after initial infection. Overall, 57% of the study samples reported a decreased QoL at 12 weeks after initial infection. The prevalence of QoL were identified for: 1) pain or discomfort (36%); 2) mobility issues (32%); 3) depression or anxiety (27%); 4) decrease in usual activities (23%); and 5) issues with self-care (10%).
  • A SR and meta-analysis (Aug 31, 2022) on symptoms of post COVID-19 condition reported that an overall prevalence result was reported for poor QoL. Additionally, the study reported prevalence results of individual factors in the EQ-5D-5L questionnaire (higher scores represent more problems with the specified factor): 1) mobility (36%); 2) personal care (8%); 3) usual activities (28%); 4) pain/discomfort (42%); and 4) anxiety/depression (38%). Poor QoL was significantly higher among post COVID-19 patients with admission to intensive care unit and fatigue.

Activities of Daily Living

• A review (Jan 27, 2021) on the epidemiology of post COVID-19 condition among a general population reported that the need for care assistance significantly increased (52.4%) after COVID-19 infection compared to before (7.7%); 41.1% of cases who were not dependent previously were at least partially dependent on others in the performance of daily activities subsequently.

Impact on the Working Age Population

• Prevalence: A SR (Oct 16, 2021) of 13 studies on post COVID-19 condition among working age patients (aged 15-67 years) reported that the prevalence of the condition ranged from 16% to 87% of workers.
• Work Absences: A review (Mar 15, 2022) on post COVID-19 condition stated that almost 50% of 102 primary studies reported some degree of social and family-life impairment, long absence periods off work, adjusted workloads, and loss of employment. For example, the review reported on study findings on work-related implications:
  • In studies on previously hospitalized participants, absence from work due to post COVID-19 condition was reported in 9%-40% of those previously employed at two to three months after discharge.
  • Research on primarily mild-to-moderate and non-hospitalized SARS-CoV-2 cases reported that about 12%-23% remained absent from work (or had long absence periods) at three to seven months after acute disease.
  • A study with a mixed sample (hospitalized and non-hospitalized) reported that 70% of participants were absent from work for a period of 13 weeks or more, while another study (hospitalized and non-hospitalized) reported that 31% were still out of work at six weeks after acute illness.
• Workload Adjustments: The review (Mar 15, 2022) also reported that many of those living with post COVID-19 condition are forced to adjust or reduce their workload. For example:
  • Two studies (July, 2020; Nov, 2021) included in the review followed up on previously hospitalized participants for two months and reported that their employed participants adjusted their employment to their current circumstances. In the UK study (July, 2020), 15% percent of hospitalized patients remained off-sick from work at the two-month follow-up. The US study (Nov, 2021) reported that 40% of their employed participants had reduced hours and/or modified duties upon their return to work.
  • Three studies (Feb, 2021; April, 2021; Jul, 2021) reported that, at follow-ups of three to eight months, the proportions of hospitalized participants (mild to moderate cases) who adjusted or reduced their workloads ranged from 8%-45%.
  • Two studies (Jan, 2021; Aug, 2021) reported permanent employment loss in relation to deteriorating health, with one reporting that 11% and the other 13.8% of their previously employed participants were unemployed at two months after acute disease.

Impact of Low-Income Populations

• Limited Data: A US study (Apr, 2022) on Black, Indigenous, and Latinx communities noted few studies addressing inequities in post COVID-19 condition outcomes in the context of material resource deprivation caused by low socio-economic status, chronic stress brought on by racial/ethnic discrimination, or place-based risk. Moreover, the overall lack of complete data for cases, deaths, and vaccine uptake by race and ethnicity complicates the ability to understand the etiology and factors associated with mitigation of post COVID-19 condition in the US.
  • Recommendations: The study recommended jurisdictions use the Centers for Disease Control and Prevention(CDC) Social Vulnerability Index (SVI) to mitigate the impact of systemic racism and socioeconomic adversity, which correlate with the disproportionately higher rates of COVID-19 morbidity, mortality, and transmission in black, Indigenous, and Latinx communities.
• Symptomatology: A review (Oct, 2021) on acute and post‑acute neurological manifestations of COVID‑19 indicated that data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19.

• QoL: A review (Oct 28, 2021) on the impact of COVID-19 on health-related quality of life (HQoL) of patients reported that the impact on HRQoL was considerable among patients with post COVID-19 condition. In patients from low-income countries, there was a greater impact on HRQoL. The study noted that a higher HRQoL among COVID-19 patients in high-income countries (e.g., United Kingdom, Norway) may be due to better health services of the countries rather than other factors compared to low-and-middle income countries (e.g., Iran).

International Scan

Definition

• A WHO (Oct 6, 2021) study on standardizing the clinical case definition for long-term symptoms associated with COVID-19 uses the term post COVID-19 condition; however, the study 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.

Prevalence

• The Office for National Statistics (Aug 5, 2021) in the United Kingdom reported that approximately 40% of all people with post COVID-19 condition will continue living with sequelae for over 12 months.

Canadian Scan

Definition

• A Government of Canada report (Sept 24, 2021) on post COVID-19 condition defined it as having COVID-19 symptoms for weeks or months after their initial recovery and may occur in some people after infection.

Prevalence

• A living systematic review (Dec 4, 2021) on care models for long COVID reported that, at the time of writing, Canadian prevalence data were unavailable. Based on findings in a preprint SR (Nov 16, 2021) on the global prevalence of post-acute sequelae of COVID-19, the living review estimated that upward of 500,000 Canadians may need to seek care for long COVID.

Symptomatology

• The Government of Canada report (Sept 24, 2021) on post COVID-19 condition reports that for adults the most common symptoms are different for adults and children:
  • Adults: Fatigue, memory problems, sleep disturbances, shortness of breath, anxiety and depression, general pain and discomfort, difficulty thinking or concentrating, and PTSD.
    • There have been reports of more than 100 symptoms or difficulties with everyday activities. About 80% of adults reported one or more symptoms in the short-term (four to 12 weeks after their initial COVID-19 infection).
    • About 60% of adults reported one or more symptoms in the long-term (more than 12 weeks after their initial COVID-19 infection) and 10% said that they were also unable to return to work in the long-term.
  • Children: The most common symptoms that are reported in children include fatigue, headaches, weight loss, muscle pain, sleep disturbances, stuffy or runny nose, and difficulty thinking or concentrating.
    • Approximately 58% of children had one or more symptoms four weeks or more after their initial COVID-19 infection.
    • These symptoms can be mild to severe and can sometimes disappear and reappear. Some patients report that over-exertion (both mental and physical) may make the condition worse.

Risk Factors

• The Government of Canada report (Sept 24, 2021) states that people are at risk of developing post COVID-19 condition if they were hospitalized or needed intensive care during recovery; or had a mild to severe infection with symptoms or even mild infection without symptoms.

Ontario Scan

• No information identified.

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: 

• Canadian Agency for Drugs and Technologies in Health. (March 2022). Clinical Classification and Interventions for Post–COVID-19 Condition: A Scoping Review (Draft). CADTH. 
• Decary, S., Dugas, M., Stefan, T., Langlois, L., Skidmore, B., Bhéreur, A., & LeBlanc, A.(December 4, 2021). Care Models for Long COVID – A Living Systematic Review. First Update – December 2021. SPOR Evidence Alliance, COVID-END Network.
• Public Health Ontario. (March 16, 2022). Post-Acute COVID-19 Syndrome (PACS) in Adults –What We Know So Far (Confidential). Public Health Ontario.