Figures
- FIGURE 1
Radiographic features of PASC. Representative radiographic findings from CT scans collected at least 30 days after COVID-19 infection collected from the Post-COVID Registry at our centre. a) Dense consolidations. b) Patchy ground consolidation and ground glass with atoll sign. c) Diffuse ground-glass opacities. d) Fibrosis with honeycomb changes in the left upper lobe. e) Ground glass and reticular changes. f) Ground glass, reticulation and a pneumatocele. COVID-19: coronavirus disease 2019; CT: computed tomography; PASC: post-acute sequelae of COVID-19.
- FIGURE 2
Temporal unfolding of primary COVID-19 infection, COVID-19 ARDS and PASC-pulmonary fibrosis. a) SARS-CoV-2 infects AEC-IIs and TRaMs. Infected TRaMs express T-cell and monocyte chemokines. CoV-reactive T-cells recognise SARS-CoV-2 antigens and secrete IFN-γ. b) This results in death of TRaMs, proliferation of CoV-reactive T-cells and recruitment of monocytes, which become MoAMs. MoAMs become infected with SARS-CoV-2 and form a loop with CoV-reactive T-cells to create a replenishing circuit. c) Prolonged disease, duration of mechanical ventilation and exposure to higher level of cytokines transition the acute process of alveolar damage to fibroproliferative injury. Fibroblasts respond to the chronically elevated levels of cytokines to expand the ECM with matrix proteins. A circuit between MoAMs and fibroblasts may exist to promote fibrosis and differentiation of fibroblasts to myofibroblasts. AEC-I: type 1 alveolar epithelial cells; AEC-II: type 2 alveolar epithelial cells; ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; CoV-reactive T-cell: COVID-reactive T-cell; ECM: extracellular matrix; IFN: interferon; MoAM: monocyte-derived alveolar macrophage; PASC: post-acute sequelae of COVID-19; RBC: red blood cell; TRaM: tissue resident alveolar macrophages.
- FIGURE 3
Avenues of future investigation into hallmarks of PASC-pulmonary fibrosis. Prospective future investigation should focus on the elucidating the contribution of unique pathobiologic factors (circuits between monocytes–T-cells, monocytes–fibroblasts), protracted elevations in cytokine levels, clinical factors (disease duration, NIV/IMV duration, secondary pneumonias) and use of adjunctive therapies for acute disease or PASC-organising pneumonia (immunomodulators such as glucocorticoids or anti-interleukin-6 antagonists) on the incidence, pathology and natural history of PASC-pulmonary fibrosis. IMV: invasive mechanical ventilation; NIV: noninvasive ventilation; PASC: post-acute sequelae of COVID-19.
- FIGURE 4
Our institutional protocol for endotyping the spectrum of respiratory PASC and prediction tools for PASC-pulmonary fibrosis. Patients referred for evaluation of respiratory PASC are phenotyped clinically and baseline cross-sectional images are obtained. Those with radiographic evidence of lung injury are offered bronchoscopy and nasal epithelial curettage. Those without radiographic lung injury are offered a research bronchoscopy as a control population. Follow-up cross-sectional images are obtained at pre-defined 6 month intervals and assessed quantitatively. Finally clinical, radiographic, and molecular data are integrated in an effort to study who will develop chronic lung diseases including PASC-pulmonary fibrosis. COVID-19: coronavirus disease 2019; CT: computed tomography; PASC: post-acute sequelae of COVID-19; scRNA: single-cell RNA sequencing.
Tables
- TABLE 1
Recommended screening for PASC-pulmonary fibrosis more than 1 month after acute COVID-19
Screening exam Severity of acute COVID-19 PFTs CXR HRCT Asymptomatic and no PASC + − − Mild disease and no PASC + +/− − Mild disease with PASC + − + Moderate/severe disease – regardless of PASC + − + We advocate for the use of screening PFT in all patients after COVID-19. In the instance of mild acute COVID-19 symptoms and no PASC symptoms, plain radiographs can be used to follow-up abnormal initial imaging. For those with moderate to severe acute COVID-19 disease (regardless of PASC symptoms), we recommend both PFT and cross-sectional imaging, often with the use of HRCT. PASC: post-acute sequelae of COVID-19; COVID-19: coronavirus disease 2019; PFT: pulmonary function testing, CXR: plain film chest radiograph, HRCT: high-resolution computed tomography.
