COVID-19

Long Haulers: The Post-Acute Sequelae of SARS-CoV-2 (PASC) That Last

The majority of patients with COVID-19 experience mild to moderate symptoms, with only 10% to 15% of patients progressing to severe illness and 5% progressing to critical illness.1 Generally, recovery usually takes about 2 weeks for mild cases of COVID-19 and about 6 weeks for severe cases.1

But what about the patients who do not recover as quickly?

Some patients experience symptoms that are drawn out for weeks or months, regardless of the severity of the of COVID-19 infection.1 Patients experiencing these symptoms initially coined themselves as “long-COVID” or “COVID-long haulers”2. Now the official term is post-acute sequelae of SARS-Cov-2 (PASC), as defined by the director of the National Institutes of Health (NIH) Dr. Francis S. Collins, M.D., PhD and reiterated by the director of the National Institute of Allergy and Infectious Disease (NIAID) Dr. Anthony Fauci, M.D. in a White House press briefing on February 24, 2021.3,4  There is no globally recognized definition for PASC. The general consensus is that any patient experiencing symptoms that extend beyond 3 weeks from first symptoms onset are considered to have “post-acute COVID-19,” and patients with symptoms extending beyond 12 weeks are considered to have “chronic COVID-19.”5  

In a study of patient-reported data, the most common lingering COVID-19 symptoms include:6

  • Fatigue
  • Cough/congestion/shortness of breath
  • Loss of taste and/or smell
  • Headache
  • Body aches
  • Diarrhea
  • Nausea
  • Chest or abdominal pain
  • Confusion

 

Of the patients with COVID-19, 35% report not being at their usual state of health 2 to 3 weeks following the diagnosis.6 Approximately 25% of individuals aged 18 to 34 years who were in good health prior to COVID-19 infection reported prolonged symptoms.6

PASC can occur regardless of comorbid health conditions, although it is about 2 times more common in women as in men.7 Additional risk factors for persistent symptoms include high blood pressure, obesity, and mental health conditions.6

COVID-19 can affect multiple body systems, causing tissue damage and organ failure amongst other serious adverse health events, including:1

  • Heart: damage to muscle, heart failure
  • Lungs: tissue damage, restrictive lung failure
  • Brain and nervous system: loss of smell, thromboembolic events, cognitive impairment
  • Mental health: anxiety, depression, post-traumatic stress disorder, sleep disturbance
  • Musculoskeletal: joint pain, muscle pain, fatigue

 

Little is known regarding the clinical course of mild COVID-19 illness. The most common PASC symptoms for individuals who experience a mild infection are cough, low-grade fever, and fatigue.5 These symptoms are reported to relapse and remit over time.5

Severe cases of COVID-19 are more likely to occur in older patients, who are already at a greater risk for developing many of the conditions associated COVID-19 organ damage.8 A study from the United Kingdom found an increased degree of cognitive underperformance related to severity of COVID-19.9 Patients who were hospitalized and placed on a ventilator had a -0.57 standard deviation regarding general cognitive deficit compared with patients who were not placed on a ventilator.7 The British Thoracic Society Guidelines report that patients with more severe COVID-19 pneumonia have a greater risk for developing post-viral lung fibrosis and pulmonary thromboembolism.10

With just over a year of research since the COVID-19 pandemic began, the long-term consequences of COVID-19 infection are unknown. Until more is known, researchers are looking to data on SARS to provide some indication as to how symptoms may progress and linger. In one study, researchers found that 38% of patients who had SARS still had reduced lung function 15 years after infection.11 Preliminary data are suggesting a similar pattern for COVID-19. In a small study of 70 patients, 74% (66 patients) had some form of residual disease when discharged from the hospital for COVID-19 pneumonia.12

While there appears to be a correlation between severity of illness and associated PASC symptoms, so much is still unknown. As studies continue and more data are gathered, this information may change. Moving forward, COVID-19–specific data needs to be collected focusing on long-term effects, why persistent symptoms occur, how this affects patients, and the clinical course to full recovery.1

—Audrey Amos

References

  1. What we know about long-term effects of COVID-19. Coronavirus Update 36. World Health Organization. Updated September 9, 2020. Accessed March 2, 2021. https://www.who.int/docs/default-source/coronaviruse/risk-comms-updates/update-36-long-term-symptoms.pdf
  2. Mendelson M, Nel J, Blumberg L, et al. Long-COVID: an evolving problem with an extensive impact. S Afr Med J. 2021;111(1):10-12. doi:10.7196/SAMJ.2021.v111i1.15433   
  3. NIH launches new intitative to study "Long COVID". National Institutes of Health. February 23, 2021. Accessed March 16, 2021. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid
  4. Press Briefing by White House COVID-19 Response Team and Public Health Officials. The White House. Press Briefing. February 24, 2021. Accessed March 16, 2021. https://www.whitehouse.gov/briefing-room/press-briefings/2021/02/24/press-briefing-by-white-house-covid-19-response-team-and-public-health-officials-7/
  5. Greenhalgh T, Knight M, A’Court C, et al. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026ia. https://doi.org/10.1136/bmj.m3026
  6. Tenforde MW, Kim SS, Lindsell CJ, et al; IVY Network Investigators and CDC COVID-19 Response Team. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network – United States, March – June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(30):993-998. http://dx.doi.org/10.15585/mmwr.mm6930e1 
  7. Nabavi N. Long covid: how to define it and how to manage it. BMJ. 2020;370:m3489. https://doi.org/10.1136/bmj.m3489
  8. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-2629. https://doi.org/10.1172/JCI137244
  9. Hampshire A, Trender W, Chamberlain SR, et al. Cognitive deficits in people who have recovered from COVID-19 relative to controls: an N=84,285 online study. medRxiv. Preprint posted online October 21, 2020. https://doi.org/10.1101/2020.10.20.20215863
  10. British Thoracic Society guidance on respiratory follow up of patients with a clinic-radiological diagnosis of COVID-19 pneumonia. Updated May 11, 2020. Accessed March 4, 2021. https://www.brit-thoracic.org.uk/document-library/quality-improvement/covid-19/resp-follow-up-guidance-post-covid-pneumonia/
  11. Zhang P, Li J, Liu H, et al. Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study. Bone Res. 2020;8(8). https://doi.org/10.1038/s41413-020-0084-5
  12. Wang Y, Dong C, Hu Y, et al. Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study. Radiology. 2020;296(2):E55-E64. https://doi.org/10.1148/radiol.2020200843