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Rationale Patients with COPD who are afflicted with COVID-19 have an increased risk for adverse outcomes. Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations. Given the concern for increased viral shedding related to oral corticosteroids seen with the related coronaviruses MERS-CoV and SARS-CoV-1, our study analyzed the impact of ICS on COPD patients with COVID-19. Methods This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020. We used electronic health records (EHR) to gather patient data on the diagnosis of COPD, ICS use and clinical outcomes. Patients with a concurrent diagnosis of asthma and less than a 10 pack year smoking history, and those aged 35 and younger, were excluded to minimize bias and uncertainty about the diagnosis of COPD. Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased COVID-19 risk for infection and severe disease. Results Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive versus 47.2% who tested negative (p=0.033). Of those who tested positive for COVID-19 (n=1288), 371 (28.8%) required hospitalization. Comparing the groups of individuals with COPD treated with, and without ICS, there was no significant difference in terms of age (66.9+14.0 vs 67.1+15.0, p=0.92) or gender (38.3% [77/201] vs 46.7% [79/170] males, p=0.13) respectively. In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of sepsis (28.4% [57/201] vs 26.5% [45/170], p=0.77), shock (15.9% [32/201] vs 12.4% [21/170], p=0.41), ICU admission (36.8% [74/201] vs 31.2% [53/170], p=0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p=0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p=0.80). Multivariate logistic regression demonstrated that ICS therapy in patients with COPD was associated with less COVID-19 infection (adj OR 0.85, CI: 0.76-0.96);however, there were no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4l02), or mortality (OR: 0.80, CI: 0.43-1.49). Conclusions The lack of adverse outcomes from ICS therapy among individuals with COPD infected with COVID-19 infection as demonstrated in this study, and the known advantages of ICS therapy in lowering the risk of COPD exacerbations, support continuing ICS in individuals with COPD who meet the recommended criteria.

Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa.