Persistence of fatigue in the absence of pathophysiological mechanisms in some patients more than 2 years after the original SARS‐CoV‐2 infection

Figures

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  FIGURE 1. Mean (± SD) values of the eight general health domains (i.e., physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to emotional problems, mental health, social functioning, vitality, and general health perceptions) covered by the MOS 36‐Item Short‐Form Health Survey (SF‐36) in patients with (Long COVID) or without (Control) persistent long COVID symptoms. Scores for each domain were transformed to a 0–100% scale, with a higher score defining a more favourable health state.

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  FIGURE 2. (a) Mean values (±SD) of blood flow in the common femoral artery at rest and in response to 1‐min passive leg movement (PLM), in patients with some persistent long COVID symptoms (Long COVID) and in control participants (Control). The vertical dashed line indicates the onset of PLM. (b) Individual and mean (±SD) values of baseline blood flow (Baseline), peak blood flow (Peak), changes from baseline to peak blood flow (∆peak) and area under the blood flow versus time curve (AUC) in response to 1‐min PLM, in patients with some persistent long COVID symptoms (Long COVID, n = 10) and in control participants (Control, n = 11).

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  FIGURE 3. (a) NIRS‐obtained muscle V˙O2 (V˙O2m) recovery kinetics for a representative participant for each group (Control and Long COVID) following the moderate‐intensity constant work rate exercise. The fitted functions and the calculated time constant (τ) values are also shown. (b) Individual and mean (± SD) values of τ (time constant) and k (velocity constant, k = 1/τ), in patients with persistent long COVID symptoms (Long COVID, n = 6) and in control participants (Control, n = 8).

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  FIGURE 4. Individual and mean (±SD) values of the slope of pulmonary ventilation versus CO2 output (V˙E/V˙CO2 slope) below RCP, V˙E/V˙CO2 at the gas exchange threshold (V˙E/V˙CO2 at GET), ventilatory equivalents for CO2 (EqCO2) and end‐tidal CO2 partial pressure (PETCO2) at peak exercise in patients with some persistent long COVID symptoms (Long COVID) and in patients with no symptoms (Control). A subgroup (n = 4) of Long COVID patients with higher values of V˙E/V˙CO2 slope and EqCO2 and a trend towards lower values of PETCO2 compared to the rest of patients is circled with a dotted line.

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  FIGURE 5. (a) Mean (± SEM) values of pulmonary ventilation (V˙E) (grouped for discrete tidal volume (V T) intervals) as a function of V T in Control and Long COVID during the incremental exercise. (b) The ventilatory pattern for Long COVID patients with ventilatory inefficiency (i.e., high V˙E/V˙CO2 slope, n = 4) was also shown. Iso‐respiratory frequency (f R) lines (dashed lines, departing from the origin) and the exponential functions fitting the data points were also reported in both graphs.