Are there any long-term sequelae of infection with COVID-19? 

Posted on April 18, 2020 by Kate Jackson

Summary

There is currently little existing research regarding long-term sequelae of COVID-19. However, early evidence from recovered COVID-19 patients, as well as follow-up of patients infected with other novel coronaviruses, suggests that there may be long-term effects on the cardiac, respiratory, and metabolic systems. 

I.   BACKGROUND

  • In addition to respiratory disease, COVID-19 has also been found or proposed to affect the cardiac, vascular, renal, and gastrointestinal systems (1).
  • Given that SARS-Cov-2 is a novel pathogen in humans, there is currently very little research regarding long-term sequelae of infection. 
  • Long-term follow-up of patients infected with other novel coronaviruses (e.g. Middle Eastern Respiratory Virus [MERS], Severe Acute Respiratory Syndrome [SARS]) suggest a potential for long-term respiratory, cardiac, and metabolic sequelae (see below). 

II.   EARLY EVIDENCE FROM COVID-19 PATIENTS

Cardiac

  • A retrospective study of patients with COVID-19 admitted to hospital in Wuhan, China in January 2020 found that 12% of survivors experienced new or worsening heart failure that remained clinically significant at the time of discharge (1). 
  • Risk factors for cardiac events after pneumonia include older age, pre-existing cardiovascular disease, and greater severity of pneumonia at presentation (1).

Metabolic

  • A cohort of hospitalized patients with COVID-19 had impairments in amino acid metabolism after meeting criteria for hospital discharge, which the authors hypothesize may be related to persistent liver dysfunction (2).

III.   EVIDENCE FROM OTHER VIRAL PNEUMONIAS

Cardiac

  • The clinical effects of viral pneumonia have been linked to increased risk of cardiovascular disease up to 10-year follow-up (3). This effect is thought to be due to heightened systemic inflammatory and pro-coagulant activity that persists after the index event. 
  • However, findings are inconsistent and may depend on the specific viral pathogen. For example, cardiac abnormalities observed during hospitalisation in a study of patients with H7N9 influenza returned to normal at 1-year follow-up (4). 

Metabolic

  • Lipid metabolism remained disrupted 12 years after clinical recovery in a metabolomic study amongst 25 SARS survivors. Researchers hypothesized that high-dose pulses of methylprednisolone that patients received during treatment may have caused long-term systemic damage associated with serum metabolic alterations (5).

Respiratory

  • A 15-year follow-up study of patients diagnosed with SARS in 2002 found that one-third of recovered patients had mildly impaired diffusion function after three years. This mild diffusion impairment remained stable at 15-year follow-up (6).
  • In one follow-up study of MERS patients, one-third had pulmonary fibrosis that persisted after resolution of illness (mean duration of follow-up = 43 days). Patients with lung fibrosis had significantly greater number of ICU admission days, older age, and higher peak lactate dehydrogenase levels when compared to patients without lung fibrosis (7).
  • The extent of long-term respiratory compromise may be dependent on disease severity: a follow-up study of patients with MERS found that those with more severe pneumonia had reduced diffusing capacity one year after infection compared to those with mild disease. The authors also note that pre-existing lung disease is likely a strong mediator in this relationship (i.e. those with impaired lung function at baseline are more likely to develop severe pneumonia) (8).

Questions? Comments? Does this need to be updated? Do you have valuable points to add ? Please email ask.reakt@ubc.ca.

References

  1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet [Internet]. 2020 Mar; Available from: https://www.thelancet.com/pb-assets/Lancet/pdfs/S014067362305663.pdf
  2. Wu D, Shu T, Yang X, Song J-X, Zhang M, Wen L, et al. Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19. 2020 Apr 7 [cited 2020 Apr 18]; Available from: https://www.medrxiv.org/content/10.1101/2020.04.05.20053819v1
  3. Xiong T-Y, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. European Heart Journal [Internet]. 2020 Mar 18 [cited 2020 Apr 18]; Available from: https://academic.oup.com/eurheartj/article/doi/10.1093/eurheartj/ehaa231/5809453#200884134
  4. Wang J, Xu H, Yang X, Zhao D, Liu S, Sun X, et al. Cardiac complications associated with the influenza viruses A subtype H7N9 or pandemic H1N1 in critically ill patients under intensive care. The Brazilian Journal of Infectious Diseases [Internet]. 2017 Jan [cited 2020 Apr 18];21(1):12–8. Available from: http://www.scielo.br/scielo.php?pid=S1413-86702017000100012&script=sci_arttext
  5. Wu Q, Zhou L, Sun X, Yan Z, Hu C, Wu J, et al. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection. Scientific Reports [Internet]. 2017 Aug 22 [cited 2020 Apr 18];7(1). Available from: https://www.nature.com/articles/s41598-017-09536-z
  6. Zhang P, Li J, Liu H, Han N, Ju J, Kou Y, 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 Research [Internet]. 2020 Feb 14 [cited 2020 Apr 18];8(1). Available from: https://www.nature.com/articles/s41413-020-0084-5
  7. Das K, Lee E, Singh R, Enani M, Al Dossari K, Van Gorkom K, et al. Follow-up chest radiographic findings in patients with MERS-CoV after recovery. Indian Journal of Radiology and Imaging [Internet]. 2017 [cited 2020 Apr 18];27(3):342. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644332/
  8. Il Jun K, Park WB, Kim G, Choi J-P, Rhee J-Y, Cheon S, et al. Long-term Respiratory Complication in Patients with Middle East Respiratory Syndrome: 1-year Follow-up After the 2015 Outbreak in South Korea. Open Forum Infectious Diseases [Internet]. 2017 [cited 2020 Apr 18];4(suppl_1):S577–S577. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107210/

Disclaimer

The above is intended to serve as a rapidly-created, accessible source of information curated by medical students and healthcare professionals. It is for educational purposes only and is not a complete reference resource. It is not professional medical advice, and is not a substitute for the discretion, judgment, and duties of healthcare professionals. You are solely responsible for evaluating the information above.