Half of recovered COVID-19 patients report lingering fatigue

Nov. 12, 2020

Fatigue is recognized as one of the most common presenting complaints in individuals infected with SARS-CoV-2, the cause of the current COVID-19 pandemic, according to a study published in Plos One.

Over half of individuals in the current study demonstrated symptoms consistent with severe fatigue a median of 10 weeks after their initial illness, while almost one-third of those previously employed had not returned to work. Most interestingly, fatigue was not associated with initial disease severity, and there were no detectable differences in pro-inflammatory cytokines or immune cell populations. Pre-existing diagnosis of depression is associated with severe post-COVID fatigue. Based on the Clinical Frailty Scale -CFQ-11 case definition, 52.3 percent (67/128) met the criteria for fatigue.

This study highlights the burden of fatigue, the impact on return to work and the importance of following all patients diagnosed with COVID, not merely those who required hospitalization. There are enormous numbers of patients recovering from SARS-CoV-2 infection worldwide. A lengthy post-infection fatigue burden will impair quality of life and will have significant impact on individuals, employers and healthcare systems. These important early observations highlight an emerging issue.

These findings should be used to inform management strategies for convalescent patients and allow intervention to occur in a timely manner. In early reports on the clinical characteristics of those infected, fatigue was listed as a presenting complaint in 44–69.6 percent. Further studies were followed by meta-analyses, with 34–46 percent of those infected presenting with fatigue. While the presenting features of SARS-CoV-2 infection have been well-characterized, with symptoms ranging from mild taste and smell disturbance to dyspnoea and respiratory failure, the medium and long-term consequences of SARS-CoV-2 infection remain unexplored. In particular, concern has been raised that SARS-CoV-2 has the potential to trigger a post-viral fatigue syndrome.

Patients acutely infected with SARS-CoV-2 demonstrate decreased lymphocyte counts, higher leukocyte counts with an elevated neutrophil-to-lymphocyte ratio (NLR) in addition to decreased percentages of monocytes, eosinophils and basophils. It has also been reported that both helper and suppressor T cells are decreased in those with SARS-CoV-2.

In one of the few reports to assess the long-term consequences of the severe acute respiratory syndrome (SARS) epidemic (caused by the novel coronavirus SARS-CoV), a subset of patients in Toronto experienced persistent fatigue, diffuse myalgia, weakness and depression one year after their acute illness and could not return to work. In a similar follow-up study amongst 233 SARS survivors in Hong Kong, over 40percent of respondents reported a chronic fatigue problem 40 months after infection.

In those affected by the subsequent Middle-Eastern Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, prolonged symptoms and fatigue were reported up to 18 months after acute infection. Similarly, prominent post-infectious fatigue syndromes have been reported following Epstein-Barr Virus (EBV), Q-Fever and Ross River Virus (RRV) infections, as well as rickettsiosis. It has also been reported following HHV-6 infection and in HIV infection. Whether or not infection with SARS-CoV-2 has the potential to result in post-viral fatigue, both in the medium and long-term, is currently unknown.

Persistent fatigue lasting 6 months or longer without an alternate explanation is termed chronic fatigue syndrome (CFS). This may be observed after several viral and bacterial infections. There have also been links between CFS and depression, although it remains unclear whether one diagnosis precedes the onset of the other.

Studies of post-viral fatigue and CFS often focus on immune system alterations, but robust data to indicate causation or association is absent.

Led by researchers at Trinity College Dublin, the study involved taking blood samples from and administering the Chalder Fatigue Scale (CFQ-11) assessment to 128 patients visiting an outpatient post-coronavirus care clinic at St. James's Hospital in Dublin. CFQ-11 rates fatigue on a scale of nine to 63 based on a nine-item questionnaire, with a higher score indicating more fatigue.

Sixty-seven of 128 participants (52.3 percent) reported fatigue, a common symptom of acute COVID-19 infection, a median of 10 weeks after recovery, while 54 (42.2 percent) said they had recovered their full health.

According to the CFQ-11 case definition, 67 of 128 participants (52.3 percent) met the criteria for fatigue, with a mean score of 20. While participants' physical and psychological fatigue levels after COVID-19 were higher than those of the general population, they were lower than scores indicating chronic fatigue syndrome, a complex illness causing extreme fatigue for at least 6 months unrelated to any underlying disease.

Before their illness, 105 participants (82 percent) had worked outside the home, but 33 (31 percent) of them still had not returned to employment by the time of study participation. "This is of particular concern, given that it is recommended that post-viral infection return to work should take place after four weeks to prevent deconditioning," the researchers wrote.

Seventy-one of 128 patients (55percent) had been hospitalized for treatment of COVID-19, 35 (49 percent) of them receiving the antimalarial drug hydroxychloroquine, and six (8.5 percent) of that subgroup also receiving the corticosteroid prednisolone.

There was no link between persistent fatigue and the need for hospitalization, supplemental oxygen, or critical care or concentrations of laboratory biomarkers of inflammation or cell turnover. However, women and those previously diagnosed as having depression or anxiety or reporting use of antidepressant drugs made up a disproportionate number of those with lingering fatigue.

Of the 128 patients, 66 (51.6 percent) were healthcare workers, but there was no association between occupation and lasting fatigue. "The large number of healthcare workers in our cohort is reflective of the overall demographics of Irish data and our institution, where 50 percent of positive SARS-CoV-2 cases involved healthcare workers," the authors said. "The high proportion of healthcare workers infected by COVID-19, not just in our cohort but internationally, means that this will have a significant impact on healthcare systems."

•     Mean participant age was 49.5 years; the study findings were independent of age.

•      Impaired quality of life, health system function

The authors noted that the rates of persistent fatigue in the study were much higher than those reported in a 2006 study of patients after recovery from Epstein-Barr virus, Q fever, or Ross River virus, but that a 2009 study reported that 40 percent of patients had fatigue one year after recovery from infection with the coronavirus that causes severe acute respiratory syndrome (SARS).

"A lengthy post-infection fatigue burden will impair quality of life and will have significant impact on individuals, employers and healthcare systems," the authors said. "This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention."

Plos One has the research article.

More COVID-19 coverage HERE.