Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect 10–30% of survivors of COVID-19, and post-acute sequelae of COVID-19 (PASC)-pulmonary fibrosis is a long-term outcome associated with major morbidity. Data from prior coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome) suggest that pulmonary fibrosis will contribute to long-term respiratory morbidity, suggesting that PASC-pulmonary fibrosis should be thoroughly screened for through pulmonary function testing and cross-sectional imaging. As data accumulates on the unique pathobiologic mechanisms underlying critical COVID-19, a focus on corollaries to the subacute and chronic profibrotic phenotype must be sought as well. Key aspects of acute COVID-19 pathobiology that may account for increased rates of pulmonary fibrosis include monocyte/macrophage–T-cell circuits, profibrotic RNA transcriptomics, protracted elevated levels of inflammatory cytokines, and duration of illness and ventilation. Mechanistic understanding of PASC-pulmonary fibrosis will be central in determining therapeutic options and will ultimately play a role in transplant considerations. Well-designed cohort studies and prospective clinical registries are needed. Clinicians, researchers and healthcare systems must actively address this complication of PASC to minimise disability, maximise quality of life and confront a post-COVID-19 global health crisis.

Objectives: Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course. Design: Retrospective cohort study. Setting: Northwestern Memorial Hospital ICUs. Patients: All patients intubated for coronavirus disease 2019 between March 2020 and June 2020. Interventions: Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Measurements and Main Results: Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments). Conclusions: The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation.

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Interstitial lung disease (ILD) is an inflammatory and fibrotic infiltrative process of the lung that is often associated with collagen vascular disease in women. Untreated, it results in collagen deposition in the lung interstitium that can lead to a slow suffocating death. Pregnancy planning is often not discussed with women who have ILD due to concerns about potentially aggravating the disease process, or due to lack of knowledge about the safety of medications used to treat ILD. With improved understanding of the pathophysiology of both autoimmune disease and ILD, it has become clear that safe, planned pregnancies are possible in most women with ILD. In this article, our aim is to review diagnosis, treatment, and disease course of ILD in women who are planning a pregnancy or are pregnant. Better understanding of the disease process and knowledge of safe treatments will likely lead to improved pregnancy planning in women with ILD.

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OBJECTIVES: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2020. DATA SOURCES: The Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update group screened 36 journals monthly for impactful publications. STUDY SELECTION: The group reviewed a total of 119 articles during 2020 according to relevance for practice. DATA EXTRACTION: Articles were selected with consensus and importance to clinical practice from those included in the monthly Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. The group reviewed articles according to Grading of Recommendations, Assessment, Development, and Evaluations criteria. Articles with a 1A grade were selected. DATA SYNTHESIS: Several trials were summarized, including two meta-analyses and five original research trials. Original research trials evaluating vitamin C, hydrocortisone, and thiamine versus hydrocortisone in sepsis, the use of nonsedation strategies, dexmedetomidine in cardiac surgery, remdesivir for severe acute respiratory syndrome coronavirus 2, and thrombectomy in acute ischemic stroke. Two meta-analyses determining the impact of norepinephrine initiation in patients with septic shock and the use of corticosteroids in severe acute respiratory syndrome coronavirus 2 was included. CONCLUSIONS: This clinical review provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2020.

Rationale: Immunologic risk factors contribute to endothelial dysfunction and development of pulmonary vascular disease (PVD). Immune checkpoint inhibitors (ICIs), used as immunotherapies for malignancies, have a wide range of reported immune related adverse events (irAEs). We retrospectively describe the impact of ICI’s on the development of pulmonary vascular injury and right ventricular dysfunction as compared across both computed tomography (CT) and transthoracic echocardiography (TTE). Methods: 24 of 389 patients treated with ICIs at a single academic center between 2015 to 2019 had post-treatment echocardiographic and CT data within 1 year of starting ICI therapy. Echocardiographic measures were abstracted and application of right ventricular free wall longitudinal systolic strain (RVfwLS) were applied in a blinded fashion using TomTec software. A blinded analysis of CT scans was performed. Statistical analyses were performed with GraphPad Prism v8.0 and STATA v16.1 software Results: Thirteen (54%) patients were treated with anti-PD-1 therapy, 8 (33%) with anti-PD-L1 therapy, and 3 (13%) with combination anti-PD-1 and anti-CTLA-4 therapy. At a median of 85 days of ICI therapy, RVfwLS significantly increased from -20.6 to -16.7 (p=0.002). After a median of 59 days of ICI therapy, median PA/Ao ratio worsened from 0.83 to 0.89 (p=0.03). There was an association of duration of ICI therapy (β= -0.574, p=0.003) with percent change in RVfwLS. Patients who received anti-PD1 therapy (β = -0.796, p=0.001) showed the greatest association of duration of ICI therapy with percent change in RVfwLS. Conclusions: Exposure to ICIs correlate with RV dysfunction and vascular changes as measured by strain and computed tomography, respectively. Duration of exposure was most strongly associated with changes in RV strain. The large correlation coefficient associated with anti-PD-1 therapy raises interesting questions about the differential effect of ICI therapies on the pulmonary vasculature.

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