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The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject.
Overview
When the COVID-19 pandemic began, initial symptomology descriptions focused on the clinical presentations of patients in the acute, inpatient setting. Now, information on the presentation of patients with mild disease (Gandhi, April 2020) as well as information on the fairly common occurrence of asymptomatic disease are also available (Moriarty, March 2020; Kimball, April 2020; Wei, April 2020; He, April 2020).
Data has also emerged about some patients who continue to experience symptoms related to COVID-19 after the acute phase of infection. Terminology used to describe this condition includes “long COVID,” “post-COVID syndrome” and “post-acute COVID-19 syndrome.” Among the lay public, the phrase “long haulers” is also used.
While the definition of “post-acute COVID-19 syndrome” is evolving, the term is commonly described in current literature as the persistence of symptoms 3 or 4 weeks after the onset of acute COVID-19 infection (Datta, November 2020; Greenhalgh, August 2020). This syndrome is further divided into two periods: (1) clinical and laboratory abnormalities that persist 4–12 weeks beyond acute COVID-19; and (2) clinical and laboratory abnormalities persisting 12 weeks beyond acute COVID-19 and not attributable to alternative diagnoses (Shah, January 2021).
The mechanism of post-acute COVID-19 syndrome is not well understood, but is hypothesized to be secondary to virus-specific pathophysiologic changes, prolonged inflammatory response to the acute infection, and sequelae of post-intensive care illness (Hosey, July 2020; Inoue, April 2019).
Here we review the current literature on post-acute symptoms in patients with COVID-19, using the term “post-acute COVID-19 syndrome.”
Guidelines
CDC, IDSA and the World Health Organization have not yet released guidelines on the treatment of post-acute COVID-19 syndrome.
In the U.K., guidelines for managing post-acute COVID-19 syndrome have been jointly issued by the National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network and Royal College of General Practitioners.
Key Literature
In summary: Reports indicate some patients may develop “post-acute COVID-19 syndrome” in which they experience persistent symptoms after recovering from their initial illness. The syndrome appears to affect those with mild as well as moderate-to-severe disease. The incidence, natural history and etiology of these symptoms is currently unknown.
Burden of post-COVID-19 syndrome and implications for health care service planning: A population-based cohort study (Menges, July 2021).
Overall, in this large population-based prospective cohort study, a significant proportion of patients with COVID-19 developed long-term health consequences after the acute infection.
Study population:
- Population-based prospective cohort of 431 patients in Switzerland.
- Eligibility criteria included a positive RT-PCR test result and age of 18 years or older.
- Positive RT-PCR test result between Oct. 6, 2020 and Jan. 26, 2021, at a median of 7.2 months after their diagnosis.
Primary endpoint:
- Self-reported presence of the following outcomes: fatigue, long-term respiratory complications, depression, anxiety and stress symptoms, health-related quality of life and health care service utilization.
Key findings:
- 26% of participants reported that they had not fully recovered at 6 to 8 months after initial COVID-19
- 55% of participants experienced fatigue, 25% reported shortness of breath and 26% had symptoms of depression.
- 40% of participants reported at least one general practitioner visit related to COVID-19 after their acute illness.
- Post COVID-19 symptoms were more often reported by females and hospitalized patients.
Limitations:
- Most participants included in the study were enrolled early in the pandemic, which likely selected for a sicker population due to testing capacity constraints.
- Self-selection bias may have also occurred.
- Sensitivity analysis by time periods was limited.
- Baseline (pre-COVID-19) assessment was not performed, so it is unclear if symptoms reported are new or attributable to COVID-
Post-COVID syndrome in non-hospitalized patients with COVID-19: a longitudinal prospective cohort study (Augustin, May 2021).
Overall, in this longitudinal study, post-acute COVID-19 syndrome was more frequently associated with female sex, lower-serum IgG titers, anosmia and diarrhea at disease onset.
Study population:
- Longitudinal, prospective analysis of health consequences in 958 patients in Germany with confirmed mild or asymptomatic COVID-19.
- 97.1% of study participants did not require hospitalization.
- Median age was 43 years; 46.5% were male.
Primary Endpoint:
- Presence of one of four symptoms (anosmia, ageusia, fatigue or shortness of breath) at month 4 and 7 after acute COVID-19 diagnosis.
Key findings:
- 27.8% of participants (123/442) experienced at least one symptom (anosmia, ageusia, fatigue or shortness of breath) at 4 months after acute COVID-19 infection; 34.8% (123/353) experienced at least one symptom at 7 months.
- At 4 months, 6% of patients experienced shortness of breath, 12.4% reported anosmia, 11.1% reported ageusia and 9.7% had fatigue.
- At 7 months, symptom distribution was similar with 13.6% experiencing shortness of breath, 14.7% reporting anosmia,0% reporting ageusia and 14.7% with fatigue.
- The presence of post-acute COVID-19 symptoms was more frequently associated with female sex (male sex 0.59 (0.36–0.98)), lower serum IgG titers 1.90 (1.13–3.18), and diarrhea at disease onset 1.50 (0.78–2•91).
Limitations:
- High drop-out rate suggests that true incidence of post-acute COVID-19 syndrome is likely lower as asymptomatic patients are more likely to not show up for follow-up visits.
Post-acute COVID-19 Syndrome Incidence and Risk Factors: A Mediterranean Cohort Study (Perez, January 2021).
Overall, in this prospective cohort study, post-acute COVID-19 syndrome was reported in almost half of the patients who recovered from acute infection.
Study population:
- Prospective cohort study of 277 adult patients who recovered from mild (34.3%) or severe (65.7%) COVID-19 infection and were evaluated 77 days after disease onset.
- Systematic assessment 10 to 14 weeks after disease onset.
Primary Endpoint:
- Post-acute COVID-19 syndrome was defined as the persistence of at least one clinically relevant symptom or abnormalities in spirometry or chest radiology.
Key findings:
- 50.9% (141/277) patients developed symptoms consistent with post-acute COVID-19 syndrome.
- Alterations in spirometry were noted in 9.3% of patients (25/269); alterations in radiographs were noted in 18.9% (51/277).
- Symptoms are mostly mild and improved with time, and with no identified predictors.
- Post-acute COVID-19 syndrome is not limited to severe acute COVID-19 patients.
Additional Literature
Post-acute COVID-19 Syndrome (Nalbandian, March 2021): This comprehensive review of the current literature on post-acute COVID-19 syndrome, its pathophysiology and its organ-specific sequelae includes a table summarizing findings from clinical studies on the prevalence of post-acute COVID-19 syndrome.
Post-acute COVID-19 Syndrome and its Prolonged Systematic Review (Malik, May 2021 - preprint, not peer-reviewed): This systematic review estimates the demographics, clinical characteristics and prevalence of post-acute COVID-19 symptoms.