Symptom variation, correlations, and relationship to physical activity in Long Covid: intensive longitudinal study

Abstract

Background People with Long Covid (Post-Acute Sequelae of Covid-19) describe multiple symptoms which vary between and within individuals over relatively short time intervals. We aimed to describe the real-time associations between different symptoms and between symptoms and physical activity at the individual patient level. Methods and Findings Intensive longitudinal study of 82 adults with self-reported Long Covid (median duration 12-18 months). Data collection involved a smartphone app with 5 daily entries over 14 days and continuous wearing of a wrist accelerometer. Data items included 7 symptoms (Visual Analog Scales) and perceived demands in the preceding period (Likert scales). Activity was measured using mean acceleration in the 3-hour periods preceding and following app data entry. Analysis used within-person correlations of symptoms pairs and both pooled and individual symptom networks derived from graphical vector autoregression. App data was suitable for analysis from 74 participants (90%) comprising 4022 entries representing 77.6% of possible entries. Symptoms varied substantially within individuals and were only weakly auto-correlated. The strongest between-subject symptom correlations were of fatigue with pain (partial coefficient 0.5) and cognitive difficulty with light-headedness (0.41). Pooled within-subject correlations showed fatigue correlated with cognitive difficulty (partial coefficient 0.2) pain (0.19) breathlessness (0.15) and light-headedness (0.12) but not anxiety. Cognitive difficulty was correlated with anxiety and light-headedness (partial coefficients 0.16 and 0.17). Individual participant correlation heatmaps and symptom networks showed no clear patterns indicative of distinct phenotypes. Symptoms, including fatigue, were inconsistently correlated with prior or subsequent physical activity: this may reflect adjustment of activity in response to symptoms. Delayed worsening of symptoms after the highest activity peak was observed in 7 participants. Conclusion: Symptoms of Long Covid vary within individuals over short time scales, with heterogenous patterns of symptom correlation. The findings are compatible with altered central symptom processing as an additional factor in Long Covid.

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“…Long-COVID is a term used to describe symptoms that persist in the months and years following confirmed or probable infection with COVID-19 [ 1 ]. The clinical characterisation and treatment of Long-COVID are complex [ 2 ] because there is a wide range of symptoms (most commonly fatigue and shortness of breath) with varying levels of severity [ 3 , 4 , 5 ]. Long-COVID is a growing burden upon global healthcare services with reports suggesting that over 144 million patients are living with multi-dimensional, episodic, and disabling symptoms that broadly impact functional status and quality of life [ 6 , 7 , 8 ].…”