Hyperventilation syndrome in patients with prolonged dyspnea after a mild COVID-19 infection

Introduction: Both post-COVID-19-syndrome and hyperventilation syndrome (HVS) are disputed concepts with a wide range of symptoms, where increased dyspnea is among the most common symptoms in both syndromes. The long-term prognosis for patients with post-COVID-19-syndrome is largely unknown. The Nijmegen questionnaire was suggested before the COVID-19 pandemic as a self-assessment score to detect HVS, with higher scores meaning more symptoms. A low end-tidal partial pressure of CO2 (PETCO2) despite normal diffusing capacity of the lungs for carbon monoxide (DLCO) has been suggested as a physiological marker of HVS, indicating an inappropriate increase of ventilation even at rest. Methods: Nineteen subjects (12 women, 7 men) aged 24-61 years (median 45 years) with laboratory test verified mild (non-hospitalized) infection with COVID-19 and subsequent increased dyspnea for ≥3 months, were included. All were never-smokers without any previous airway disease. Subjects performed 6-minute walk test (6MWT), spirometry, DLCO test, measurement of PETCO2 and were assessed with the Nijmegen questionnaire at inclusion. A second 6MWT and Nijmegen scoring was performed 6 months after inclusion. Results: Eighteen subjects had PETCO2 at rest below the normal range, one subject had a normal PETCO2 (median for all subjects 83% of predicted). All had a normal spirometry and test of DLCO. Median total Nijmegen score at inclusion was 22.5 (range 5-49). Walking distance on 6MWT was negatively correlated with Nijmegen questionnaire score (r=-0.67, p=0.02). Nijmegen scores had not decreased at the 6 months follow-up (median 26) and the 6MWT showed unchanged walking distance (median 575 m vs. 540 m). Discussion: Prolonged increased dyspnea after mild COVID-19 infection could be due to an HVS. The previously suggested HVS self-assessment score Nijmegen seems to correlate with physical capacity as measured by a 6MWT. Our subjects did not improve in self-assessed symptoms or physical capacity over a period of 6 months.