What’s the connection between Covid-19 and persistent fatigue?

Fatigue is one of the most common symptoms in patients with Covid-19, both during the acute illness as well during the weeks or months that follows it. Depending on the study, fatigue has been reported in around 30%-80% of patients at 2-3 weeks to 6 months or longer after the onset of illness (1-4).

In a study of hospitalized patients with Covid-19, ~80% of patients complained of fatigue during the acute illness, with ~50% having persistent fatigue at a mean follow-up of 60 days following onset of illness (1). Persistent fatigue was the most common symptom during the post-Covid-19 period, followed by dyspnea, joint pain, chest pain and cough.

In another study, 52.3% of patients with Covid-19 complained of persistent debilitating fatigue at a median of 10 weeks after initial onset of symptoms, despite a negative test for the virus (2). Of interest, there was no association between severity of Covid-19 illness/need for hospitalization and post-covid fatigue.  No association was found between routine laboratory markers of inflammation, WBC profile, LDH, C-reactive protein or interleukin-6 levels and persistent fatigue.

A CDC survey of outpatients with Covid-19 patients at 14-21 days from test date found persistent fatigue in one-third of patients (3).   

A MedRxive study (pending peer review) of over 3700 patients with definite (27%) or probable diagnosis of Covid-19 from 56 countries (>90% not hospitalized) reported fatigue in 78% of patients after 6 months (4).

Although the true nature or course of persistent fatigue following Covid-19 has yet to be clearly defined, In some respects, it’s reminiscent of chronic fatigue syndrome associated with many acute viral infections, such as SARS, EBV, and enteroviruses (5-7).

Bonus pearl: Did you know that persistent fatigue following Covid-19 may be more frequent than that following influenza in which >90% of outpatients recover within about 2 weeks (3)?

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References

  1. Carfi A, Bernabei R, Landi. Persistent symptoms in patients after acute COVID-19.JAMA 2020;324:603-605. https://pubmed.ncbi.nlm.nih.gov/32644129/
  2. Townsend L, Dyer AH, Jones K, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLOS ONE 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240784   
  3. Tenforde MW, Kim SS, Lindsell CJ, et al. 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 2020;69:993-98. https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm
  4. Davis HE, Assaf GS, MCorkell L, et al. Characterizing long COVID in an international cohort:7 months of symptoms and their impact. MedRxive 2020. https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2.full.pdf
  5. Chia JKS, Chia AY. Chronic fatigue syndrome is associated with chronic infection of the stomach. Clin Pathol 2008;61:43-48. https://jcp.bmj.com/content/61/1/43
  6. Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case control study. BMC Neurol 2011;11:37. https://pubmed.ncbi.nlm.nih.gov/21435231/
  7. Hickie I, Davenport T, Whitfield D, et al. Post-infective and chronic fatigue syndrome precipitated by pathogens: prospective cohort study. BMJ 2006;333:575. https://jcp.bmj.com/content/61/1/43

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the connection between Covid-19 and persistent fatigue?

How does older people’s immune system place them at high risk of sepsis and death?

Increased risk of sepsis and death from infectious causes among the elderly is a well-known phenomenon—particularly as witnessed in the Covid-19 era— and is in part due to 2 major age-related alterations of their immune system: 1. Defective T and B cell functions in response to acute infections; and 2. Once infection sets in, inadequate control of sepsis-induced pro-inflammatory response and its attendant procoagulant state. Interestingly, the essential elements of the innate immunity (eg, neutrophils, dendritic cells, complements) are generally spared from the effects of aging.1,2

Increased susceptibility of the elderly to acute infections is in part caused by poorer T helper cell function and suboptimal B cell humoral response to neoantigens. Despite this, serum levels of pro-inflammatory cytokines such as IL-1, IL-6,TNF-alpha, and IFN-gamma are intact.  In fact, production of IL-6 and its duration of response is actually increased in the elderly.1,2

Poor control of the inflammatory state due to sepsis in older patients may be related to the difficulty in clearing a pathogen or dysfunction in the signaling by counter-regulatory cytokines, such as IL-10.2 Either way, unchecked inflammatory response is deleterious to the patient and is associated with increased risk of thrombosis and thromboembolism, multiorgan system failure, septic shock and death. 

Bonus Pearl: Did you know that even in the absence of infection, older people are more prone to thrombosis and thromboembolism , in part related to elevated plasma levels of fibrinogen, as well as factor VII, VIII, and IX, among others?2,3  

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 References

  1. Ticinesi A, Lauretani F, Nouvenne A, et al. C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med 2017;37:7-12. https://pubmed.ncbi.nlm.nih.gov/27594414/
  2. Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005;41: (Suppl 7) S504-12. https://pubmed.ncbi.nlm.nih.gov/16237654/
  3. Mari D, Coppola R, Provenzano R. Hemostasis factors and aging. Experimental Gerontology 2008;43:66-73. https://www.sciencedirect.com/science/article/abs/pii/S0531556507001404?via%3Dihub

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

How does older people’s immune system place them at high risk of sepsis and death?