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Introduction: Patient with chronic obstructive lung disease (COPD) have an increased risk of severe Coronavirus disease (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation accompanied with limited access to health care systems might influence the outcome of patients with severe COPD negatively. Methods: Data from COPD and pneumonia patients at Charité-Universitätsmedizin, Berlin and the volume of endoscopic lung volume reduction (ELVR) from the German lung emphysema registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to pandemic (2020 and 2021) period. In addition, 52 patients with COPD GOLD IV status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results: Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction of ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during pandemic. Increasing proportions of COPD patients with GOLD III and GOLD IV status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time-period. Summary: This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during pandemic, but a slight increase of mortality among patients hospitalized with COPD irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status probably caused by their very strict compliance to lockdown measures.
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive. METHODS: Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used to validate ex vivo results. RESULTS: We provide evidence that alveolar ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus. Instead, ex vivo infected human lungs and COVID-19 autopsy samples showed that alveolar macrophages were frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake and a related inflammatory and anti-viral activation, especially in "inflammatory alveolar macrophages", comparable to those induced by SARS-CoV and MERS-CoV, but different from NL63 or influenza virus infection. CONCLUSIONS: Collectively, our findings indicate that severe lung injury in COVID-19 probably results from a macrophage-triggered immune activation rather than direct viral damage of the alveolar compartment.