Mechanisms of gas transfer impairment utilizing nitric oxide following severe COVID-19 pneumonitis

Reduced carbon monoxide diffusing capacity (DL_CO) is common after recovery from severe COVID-19 pneumonitis. The extent to which this relates to alveolar membrane dysfunction as opposed to vascular injury is uncertain. Simultaneous measurement of nitric oxide diffusing capacity (DL_NO) and DL_CO can partition gas diffusion into its two components: alveolar-capillary membrane conductance (D_mCO) and capillary blood volume (V_C). We sought to evaluate D_mCO and V_C in the early and later recovery periods after severe COVID-19. Patients attended for post-COVID-19 clinical review and lung function testing including DL_NO/DL_CO. Repeat testing occurred when indicated and comparisons made using t-tests. Forty-nine (eight female) subjects (mean ± SD age: 58 ± 13, BMI: 34 ± 8) who had severe COVID-19 pneumonitis, WHO severity classification of 6 ± 1, and prolonged (21 ± 22 days) hospital stay, were assessed 2 months (61 ± 35 days) post discharge. DL_COadj (z-score -1.70 ± 1.49, 25/49 < lower limit of normal [LLN]) and total lung capacity (z-score -1.71 ± 1.30) were both reduced. D_mCO and V_C and were reduced to a similar extent (z-score -1.19 ± 1.05 and -1.41 ± 1.20, p = 0.4). Seventeen (one female) patients returned for repeat testing 4 months (122 ± 61 days) post discharge. In this subgroup with more impaired lung function, DL_COadj improved but remained below LLN (z-score -3.15 ± 0.83 vs. -2.39 ± 0.86, p = 0.01), 5/17 improved to >LNN. D_mCO improved (z-score -2.05 ± 0.89 vs. -1.41 ± 0.78, p = 0.01) but V_C was unchanged (z-score -2.51 ± 0.55 vs. -2.29 ± 0.59, p = 0.16). Alveolar membrane conductance is abnormal in the earlier recovery phase following severe COVID-19 but significantly improves. In contrast, reduced V_C persists. These data raise the possibility that persisting effects of acute vascular injury may contribute to gas diffusion impairment long after severe COVID-19 pneumonitis.