Mueller, M; Dalidowicz, M. Long COVID: What does it mean for the healthcare system and programs to? 2021 Oct 21, Document no.: EOC021901v2 ESR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2021. 70 p. (CEST rapid review report).
Williams-Roberts, H; Groot, G; Mueller, M; Dalidowicz, M. Long COVID: What does it mean for the healthcare system and programs? 2021 Oct 29. Document no.: EOC021901v2 RR Table. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2021. (CEST Table).
In October, WHO released a consensus definition of post COVID-19 condition that includes 12 domains. This development should lead to better standardization of reporting and contribute to more precise prevalence estimates and better understanding of associated risk factors.
The effects of Variants of Concern (VoC) and COVID vaccination on progression of Long COVID symptoms remains unclear.
Risk factors for developing Long COVID symptoms were similar but limited evidence suggests that pre-pandemic psychological distress and poor general health were associated with developing persistent symptoms. Evidence is too limited to determine whether vaccination reduces the risk of developing Long COVID among persons with breakthrough infections.
Given the protean manifestations of Long COVID symptoms, the underlying causes are likely multifactorial; however, strong evidence to substantiate the theories of causation remains limited.
Research related to longer-term consequences of SARS CoV-2 infections in pediatric populations is growing but remains limited.
Key Findings
March 15, 2021
There is a lack of consensus around the clinical definition of Long COVID which in turn causes challenges with understanding the incidence and prevalence as well as the potential impact for the health care system
Information about the natural history of Long COVID is incomplete but limited evidence suggests that the immune response trajectories differ for those with few or no symptoms compared to those with severe disease. Individuals with severe disease are more likely to exhibit immunological marker abnormalities but anyone can experience functional limitations.
The mechanisms underlying the development of persistent symptoms in Long COVID remain an enigma. Despite multiple theories, there is little empirical evidence for specific immunological and or biochemical abnormalities in samples of individuals with symptoms consistent with Long COVID.
Risk factors for Long COVID include female gender, older age, higher body mass index, pre-existing asthma and the number of symptoms.
Few studies explored the short-term impact of Long COVID on health care utilization patterns and found a higher impact for those with severe disease compared with mild disease.
Williams-Roberts, H; Groot, G; Mueller, M; Dalidowicz, M. Long COVID: What does it mean for the healthcare system and programs? 2021 Oct 29. Document no.: EOC021901v2 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2021. 14 p. (CEST rapid review report).
Young, C; Howell-Spooner, B. What is the evidence that runny nose or sneezing are symptoms of COVID-19? 2020 Sep 25; Document no.: EOC092401-01 ESR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 37 p. (CEST evidence search report)
· The significance of rhinorrhea as a presenting/predictive clinical feature of COVID-19 is unclear at this time with rates ranging from as low as 2% to as high as 60% in the published literature
· Rhinorrhea generally associated with less severe disease
· No reports of sneezing as a clinical symptom of COVID-19
Badea, A; Groot, G; Howell-Spooner, B; Young, C. What is the evidence that runny nose or sneezing are symptoms of COVID-19? 2020 Sep 29; Document no.: EOC092401 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 16 p. (CEST rapid review report)
Hammond, B; Badea, A; Groot, G; Reeder, B; Howell-Spooner, B; Mueller, M. What is the incidence and duration of long COVID cases? 2022 Mar 31, Document no.: EPM210601v2 RR Table. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2022. CEST Table
Howell-Spooner, B; Mueller, M. What is the incidence and duration of long COVID cases? 2022 Mar 03, Document no.: EMP210601v002 ESR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2022. 100 p. (CEST evidence search report).
Since the previous rapid review, a large amount of new research and reviews are available to draw upon. Many studies have addressed aspects previously identified as limitations such as the use of validated questionnaires, documenting pre-COVID health status, and control cohorts. Many studies now include only participants with RT-PCR verified infections and also focus on a range of disease severities from severe (hospitalized) to mild (managed in the community); PCR-validated infections ensure a higher quality of comparison between test-positive and control groups. Studies involving control groups contributed illuminating findings about prevalence and incidence of long COVID, which is lower than previous thought when compared to control groups. Comorbidities/factors that potentially indicate increased risk of developing long COVID-19 have been identified and widely agreed-upon, such as diabetes, cardiovascular diseases, obesity, and gender (female).
A case definition for long COVID has yet to be adopted but is commonly defined as COVID-related symptoms that persist or emerge beyond 4 weeks of infection with two subsequent phases: “ongoing symptomatic COVID-19 (OSC; signs and symptoms from 4 to 12 weeks from initial infection) and 2) post-COVID-19 syndrome (PCS; signs and symptoms beyond 12 weeks) with respect to symptomatology, abnormal functioning, psychological burden, and quality of life”. Long COVID includes both OSC and PCS.
It is estimated that 32% of non-hospitalized and 51% of hospitalized people experience Long COVID symptoms within 12 weeks of infection; however, higher estimates up to 92% have been reported in studies with a greater proportion in persons who were previously hospitalized. More than 200 symptoms affecting 10 organ systems have been identified in various reports or systematic reviews. Many patients (49%), experience at least one COVID-related symptom 12 months after infection (compared to 68% at 6 months).
For many persons, symptoms improve over time while others experience persistent and/or new symptoms. At 3 months post-infection the most frequently reported symptoms are fatigue (up to 98%), dyspnoea (up to 88%), headache (up to 91%) and taste/smell disorders (up to 58%).
Mechanism(s) leading to long COVID remain unclear, but these comorbidities/factors have been found to indicate potentially increased risk of developing long COVID:
o Age (60+)
o Greater number of symptoms during the acute phase of illness (typically 5+)
o Manifestation of specific symptoms
o Diabetes
o Cardiovascular disease
o Obesity or high BMI
o Gender (female)
There is limited evidence to support the contention that vaccination lowers incidence of long COVID.
Key Findings
July 9, 2021
The frequency of Long COVID symptoms varies widely across studies based on populations studied, duration of follow up and methods of assessment of symptoms.
It is estimated that 1 in 50 persons experience Long COVID symptoms after 12 weeks; however, higher estimates up to 80% have been reported in studies with a greater proportion of persons who were previously hospitalized. A recent study of a mixed cohort of 96 persons found that only 22.9% had no symptoms at 12 months post diagnosis.
A wide range of symptoms affecting multiple organ systems has been reported. For many persons symptoms improve over time while others experience persistent and/or new symptoms. Among studies with the longest duration of follow up, the most frequently reported symptoms included fatigue (up to 65%), dyspnea (up to 50%), headache (up to 45%), anosmia/ageusia (up to 25%), cognitive memory/concentration (up to 39.6%) and sleep disorders (up to 26%).
Few studies estimated the duration of symptoms with estimates ranging from 2.2% for 6 months and 27% for 7-9 months.
The mechanism(s) leading to Long COVID remain unclear but those experiencing post acute sequelae tend to be older, have a greater number of symptoms during the acute phase of illness or manifest specific symptoms and live with multiple comorbid conditions such as obesity.
The lack of consensus on a definition of Long COVID contributes to marked variations in robust prevalence estimates.
Notes
A significant amount of evidence was produced since the previous review. This updated review was rewritten with extensive changes which have not been identified in red.
Hammond, B; Badea, A; Groot, G; Reeder, B; Howell-Spooner, B; Mueller, M. What is the incidence and duration of long COVID cases? 2022 Mar 31, Document no.: EPM210601v2 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2022. 18 p. (CEST rapid review report).
Badea, A; Groot, G; Dalidowicz, M; Young, C; Miller, L. What is the prevalence of sore throat as a symptom of COVID-19? 2020 Apr 7; Document no.: EOC040201 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 8 p. (CEST rapid review report)
Dalidowicz, M; Young, C; Miller, L. What is the prevalence of sore throat as a symptom of COVID-19? 2020 Apr 7; Document no.: EOC040201-01 ESR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 16 p. (CEST evidence search report)