The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting

Abstract

Background Post-COVID-Fatigue (PCF) is one of the most reported symptoms following SARS-CoV-2 infection. Currently, research on persistent symptoms focuses mainly on severe infections, while outpatients are rarely included in observations. Objective To investigate whether the severity of PCF is related to the number of acute and persistent symptoms due to mild-to-moderate COVID-19 and to compare the most common symptoms during acute infection with the persistent symptoms in PCF patients. Methods A total of 425 participants were examined after COVID-19 treated as an outpatient (median 249 days [IQR: 135; 322] after acute disease) at the site of University Hospital Augsburg, Germany. The Fatigue Assessment Scale (FAS) was used to quantify the severity of PCF. The number of symptoms (maximum 41) during acute infection and persistent symptoms (during the last 14 days before examination) were added up to sum scores. Multivariable linear regression models were used to show the association between the number of symptoms and PCF. Results Of the 425 participants, 37% (n = 157) developed PCF; most were women (70%). The median number of symptoms was significantly higher in the PCF group than in the non-PCF group at both time points. In multivariable linear regression models, both sum scores were associated with PCF (acute symptoms: β-estimate per additional symptom [95%-CI]: 0.48 [0.39; 0.57], p < 0.0001); persistent symptoms: β-estimate per additional symptom [95%-CI]: 1.18 [1.02; 1.34], p < 0.0001). The acute symptoms strongest associated with PCF severity were difficulty concentrating, memory problems, dyspnea or shortness of breath on exertion, palpitations, and problems with movement coordination. Conclusion Each additional symptom that occurs in COVID-19 increases the likelihood of suffering a higher severity of PCF. Further research is needed to identify the aetiology of PCF. Trial registration: Nr. NCT04615026. Date of registration: November 4, 2020.

Symptom Clusters in Acute SARS-CoV-2 Infection and Long COVID Fatigue in Male and Female Outpatients

“…The finding that a higher number of symptoms during SARS-CoV-2 infection is more likely to result in later fatigue is also confirmed by the results of Stavem et al, who examined non-hospitalized patients (n = 458), who answered a questionnaire at a median of 117.5 days after acute infection [12]. Results from our previous work confirmed these findings: outpatients in the Long COVID fatigue group had a higher median number of acute SARS-CoV-2 symptoms [17]. Finally, Whitaker et al formed clusters at the onset of symptoms, and re-clustered the symptoms assessed 84 days after acute SARS-CoV-2 infection.…”

“…Only a few studies investigated the situation in outpatients [ 3 ]. An earlier report from our group found an association between the number of symptoms in acute infection and the risk of Long COVID fatigue in outpatients [ 17 ]. SARS-CoV-2 symptoms can be clustered into distinct symptom clusters, and these clusters are differently associated with fatigue.…”

Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity

“…We used a ≥22 cut-off value to indicate substantial fatigue, categorizing patients into fatigued and non-fatigued groups. This value is derived from studies examining sarcoidosis-related fatigue and is also used to indicate fatigue in patients with other conditions, including long COVID ( 4 , 39 , 40 ). Patients filled out a symptom questionnaire (Corona Symptom Checklist [CSC], Supplementary Methods ) to assess the presence of new or worsened symptoms following acute SARS-CoV-2 infection on a binary scale (yes or no).…”