Deep phenotyping in long COVID: Pulmonary microangiopathy in non-hospitalized patients

Patients with persistent long COVID symptoms with low diffusion capacity (DLCO) can have abnormalities in perfusion on lung imaging: this may reflect vascular damage. We describe patients with non-segmental perfusion defects on VQ-SPECT (n=41), dual energy CT (n=25) or both (56%) 11.9 (range 3.9-17.6) months after COVID. Patients with pulmonary emboli or interstitial lung disease were excluded. Patients were 44.7±11.6 years, 87.8% female, BMI 22.9±4.3 kg/m2, non-smokers (in 35, 85%). Raynaud’s symptoms in n=10. HRCT were normal or non-significant changes (n=5). Symptoms included exercise intolerance in 39, 95.1%, dysautonomia (n=5); myopericarditis in 19 (46.3%). Echocardiography suggested no pulmonary hypertension. Bloods included elevated ACE and antiphospholipid antibodies. Baseline FEV1 107.4+-15.2% predicted, FVC 112.8+-16.2% pred., DLCO mean 74.7±11 % pred. (75 (52-96% median, range). KCO 75.3+-11.1% pred., VA 103.8+-11.5% pred. SaO2 97.9+-0.92 %. Physiotherapy features of breathing pattern disorder were noted. Cardiopulmonary exercise testing (CPET) was performed in 17 (41%) patients at baseline. Peak VO2 was 26.8+-10.8ml/kg/min, 90.4+-33.4% predicted. Peak exercise Aa gradient and Vd/Vt were elevated in 9 (40%) and 5 patients (38%) respectively. Lung function at 9.2±5.8 months, DLCO improved 70.4±8.9 to 74.4± 9.4, p=0.004 and KCO 71.9±9.7 to 74.4±9.4, p=0.093, most (n=26) treated with apixaban. We describe a cohort of symptomatic patients after COVID with abnormal perfusion, a ‘pulmonary microangiopathy’ phenotype, with low DLCO and abnormalities in gas exchange. Although symptoms and DLCO at lung function significantly improved over time, not to normal values. Potential therapeutics, longer term recovery, and relevance to future pulmonary vascular disease is unknown.