Dysautonomia and Postural Orthostatic Syndrome of Hypocapnia in Long COVID Syndrome

Background: Long COVID syndrome (LCS) affects at least 10% of COVID-19 survivors. Dysautonomia and orthostatic intolerance (OI) are recognised manifestations of long COVID syndrome (LCS). Postural orthostatic syndrome of hypocapnia (POSH) is among the most frequently identified physiological markers of orthostatic intolerance in this patient population. This study aims to evaluate the prevalence of OI and POSH in a cohort of patients with LCS and then treat patients with LCS and evidence of dysfunctional breathing and hypocapnia with targeted respiratory rehabilitation to evaluate the response in physiology and symptoms. Methods: Adults (>18 years) with a diagnosis of long COVID syndrome (LCS) underwent a NASA lean test (NLT) in our dedicated long COVID clinic. The NLT consists of measurements of respiratory rate, heart rate, blood pressure, oxygen saturation, end-tidal carbon dioxide (ETCO2), and symptoms taken over a 10 min period in the supine position, followed by repeated measurements in the leaning position. Patients with evidence of LCS, dysfunctional breathing and hypocapnia from the lean test were referred for targeted respiratory rehabilitation using the Papworth method. Results: A representative sample of patients with LCS (N = 50) underwent the NLT. Orthostatic symptoms were elicited in 50.0% of patients (n = 25) during the NASA Lean Test. Supine or orthostatic hypocapnia was identified in 64.0% of patients (n = 32), while postural orthostatic tachycardia and postural orthostatic hypotension were each observed in 32.0% of patients (n = 16). A total of 62.0% (n = 31) of patients with LCS who had persistent dyspnoea or evidence of OI as supported by supine or orthostatic hypocapnia were referred for targeted respiratory rehabilitation. Of the group referred, 41.9% (13 of the 31) completed respiratory rehabilitation. Comparing mean pre- and post-physiotherapy respiratory rehabilitation values, there was a significant improvement in the Malmö POTS score and the breathing pattern assessment tool (BPAT) (5.7 ± 1.9 vs. 2.1 ± 1.0, p < 0.0001) without a corresponding improvement in end-tidal CO2. Conclusions: These findings provide additional evidence supporting the presence of dysautonomia and OI in patients with long COVID syndrome (LCS). The NLT is a test for OI that can be easily performed in the clinic. Respiratory rehabilitation can improve symptoms related to dysfunctional breathing and OI in LCS. Although hypocapnia has been implicated in orthostatic cerebral vasoconstriction and was postulated as a treatable target in LCS, improvement in the symptoms that we observed were independent of changes in end-tidal CO2 on lean testing.