Long-term Pulmonary Sequelae Research Articles

Long-term pulmonary sequelae in adolescents post-SARS-CoV-2 infection.

RationaleSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes long‐term pulmonary sequelae in adults, but little is known about pulmonary outcomes in pediatrics.Objective(s)The aim of this study was to describe long‐term subjective and objective pulmonary abnormalities after SARS‐CoV‐2 infection in pediatric populations.MethodsSingle‐center, retrospective cohort of patients seen in post‐coronavirus disease 2019 (COVID‐19) pulmonary clinic in 2021. Subjects evaluated had persistent pulmonary symptoms 4 weeks or more after initial infection. Clinical testing included a 6‐min walk test (6MWT), chest X‐ray, pre‐ and postbronchodilator spirometry, plethysmography, and diffusion capacity. Patients were followed 2‐to‐3‐months after the initial visit with repeat testing. The primary outcome was the presence of abnormal pulmonary function testing. Secondary measures included variables associated with pulmonary outcomes.ResultsEighty‐two adolescents were seen at a median of 3.5 months postinfection, with approximately 80% reporting two or more symptoms at clinic presentation (cough, chest pain, dyspnea at rest, and exertional dyspnea). At follow‐up (~6.5 months) exertional dyspnea persisted for most (67%). Spirometry was normal in 77% of patients, but 31% had a positive bronchodilator response. No abnormalities were noted on plethysmography or diffusion capacity. Clinical phenotypes identified included inhaled corticosteroid responsiveness, paradoxical vocal fold motion disorder, deconditioning, and dysautonomia. Multivariable modeling demonstrated that obesity, anxiety, and resting dyspnea were associated with reduced 6MWT, while female sex and resting dyspnea were associated with higher Borg Dyspnea and Fatigues scores.ConclusionsThis is the largest study to date of pediatric patients with long‐term pulmonary sequelae post‐COVID‐19. Identified clinical phenotypes and risk factors warrant further study and treatment.

COVID-19: Some unresolved issues.

Two years after the COVID-19 pandemic, many uncertainties persist about the causal agent, the disease and its future. This document contains the reflection of the COVID-19 working group of the Official College of Physicians of Madrid (ICOMEM) in relation to some questions that remain unresolved. The document includes considerations on the origin of the virus, the current indication for diagnostic tests, the value of severity scores in the onset of the disease and the added risk posed by hypertension or dementia. We also discuss the possibility of deducing viral behavior from the examination of the structure of the complete viral genome, the future of some drug associations and the current role of therapeutic resources such as corticosteroids or extracorporeal oxygenation (ECMO). We review the scarce existing information on the reality of COVID 19 in Africa, the uncertainties about the future of the pandemic and the status of vaccines, and the data and uncertainties about the long-term pulmonary sequelae of those who suffered severe pneumonia.

Pulmonary evaluation of post-COVID-19 patients: an Ecuadorian experience

BackgroundDespite the growing concerns related to the potential of long-term pulmonary sequelae due to COVID-19, data about intermediate and long-term changes in the respiratory function of patients who recover is relatively sparse, particularly in developing countries.ObjectivesTo assess the characteristics and pulmonary function at follow-up in a sample of Ecuadorian patients that recovered from the virus.MethodsWe conducted a cross-sectional study that included 43 patients after symptomatic COVID infection, who were evaluated by spirometry, single breath DLCO, and 6MWT. For statistical analysis we performed point biserial correlations, and chi squared tests.ResultsOverall, 30.3% of patients (n = 13) reported persistent symptoms, with fatigue being the most common (23.3%, n = 10). Around 34.9% (n = 15) of the sample had a restrictive spirometry pattern, 18.6% (n = 8) had an abnormally decreased adjusted DLCO. A restrictive spirometry pattern was associated with an abnormally low adjusted DLCO (χ2(2) = 11,979, p = 0.001).ConclusionWe found that a considerable proportion of patients presented with persistent symptoms and alterations in pulmonary function following COVID-19, mainly a restrictive respiratory pattern and abnormally low DLCO. Further studies are needed to determine which patients may benefit from the follow-up with specific pulmonary function tests.

Chest CT of Lung Injury 1 Year after COVID-19 Pneumonia: The CovILD Study.

BackgroundThe long-term pulmonary sequelae of COVID-19 is not well known.PurposeTo characterize patterns and rates of improvement of chest CT abnormalities 1 year after COVID-19 pneumonia.Materials and MethodsThis was a secondary analysis of a prospective, multicenter observational cohort study conducted from April 29 to August 12, 2020, to assess pulmonary abnormalities at chest CT approximately 2, 3, and 6 months and 1 year after onset of COVID-19 symptoms. Pulmonary findings were graded for each lung lobe using a qualitative CT severity score (CTSS) ranging from 0 (normal) to 25 (all lobes involved). The association of demographic and clinical factors with CT abnormalities after 1 year was assessed with logistic regression. The rate of change of the CTSS at follow-up CT was investigated by using the Friedmann test.ResultsOf 142 enrolled participants, 91 underwent a 1-year follow-up CT examination and were included in the analysis (mean age, 59 years ± 13 [SD]; 35 women [38%]). In 49 of 91 (54%) participants, CT abnormalities were observed: 31 of 91 (34%) participants showed subtle subpleural reticulation, ground-glass opacities, or both, and 18 of 91 (20%) participants had extensive ground-glass opacities, reticulations, bronchial dilation, microcystic changes, or a combination thereof. At multivariable analysis, age of more than 60 years (odds ratio [OR], 5.8; 95% CI: 1.7, 24; P = .009), critical COVID-19 severity (OR, 29; 95% CI: 4.8, 280; P < .001), and male sex (OR, 8.9; 95% CI: 2.6, 36; P < .001) were associated with persistent CT abnormalities at 1-year follow-up. Reduction of CTSS was observed in participants at subsequent follow-up CT (P < .001); during the study period, 49% (69 of 142) of participants had complete resolution of CT abnormalities. Thirty-one of 49 (63%) participants with CT abnormalities showed no further improvement after 6 months.ConclusionLong-term CT abnormalities were common 1 year after COVID-19 pneumonia.© RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leung in this issue.

Prenatal Diagnosis and Outcome of Scimitar Syndrome: A Case Series of Six Patients.

Scimitar syndrome is a rare disease characterized by hypoplasia of the right lung and partial anomalous pulmonary venous drainage to the inferior vena cava. All cases with a prenatal diagnosis of scimitar syndrome with or without associated malformations in an 18-year period (2000–2018) in two large tertiary referral centers (University of Bonn and University of Cologne, Germany) were retrospectively reviewed for the intrauterine course and postnatal outcome. Six cases were diagnosed in the study period. All presented with hypoplasia of the right lung, right-sided mediastinal shift, and abnormal pulmonary venous drainage to the inferior vena cava. Systemic arterial blood supply to the right lung, albeit postnatally present in all cases, could not be detected prenatally. Major associated anomalies were present in all cases and included atrial septal defect (n = 5), coarctation (n = 3), diaphragmatic hernia (n = 2), and VACTERL association (n = 1). Half of the cohort died within 6 months after birth and all three survivors suffer from long-term pulmonary sequelae. The primary hint to the prenatal diagnosis of scimitar syndrome is the abnormal position of the heart in the chest. If searched for, abnormal venous drainage can be identified prenatally and confirms the diagnosis. The prognosis depends on the presence of associated major anomalies and the need for neonatal intervention.

High-Resolution Computed Tomography Scores in Cases of Bronchopulmonary Dysplasia.

Background Bronchopulmonary dysplasia (BPD) carries a risk of long-term pulmonary sequelae. High-resolution computed tomography (HRCT) is a method of detecting such structural changes. This study is aimed at characterizing structural abnormalities associated with BPD and at evaluating the clinical findings in the newborn period associated with HRCT scores. Methods 28 patients born with a mean gestation age of 30 ± 2.9 weeks and diagnosed as BPD in their neonatal period were reevaluated when they were between the postnatal ages of 6 and 12 months. HRCT was performed in 20 patients with a history of moderate and severe BPD. Scans were interpreted by one radiologist using a scoring system. Results Patients were 9.8 ± 2.3 months at the time of reevaluation. The average HRCT score of patients was, respectively, 7.20 ± 4.05 with moderate and 7.40 ± 2.84 with severe BPD. The difference between them was not significant (p = 0.620). When moderate and severe groups were collected as a whole on the basis of physical findings and drug treatment, 6 had normal physical examination findings, no oxygen and no drug requirement; 14 had at least one finding at the time of reevaluation. No significant difference was detected in terms of HRCT score between the two groups (6.50 ± 3.83 versus 7.64 ± 3.30). Conclusions More studies are needed in terms of the role of HRCT in the assessment of BPD prognosis. A contemporary definition of BPD that correlates with respiratory morbidity in childhood is needed. Also, a new lung ultrasound technique for predicting the respiratory outcome in patients with BPD can be used instead of HRCT.

Characteristics and Prognostic Factors of Pulmonary Fibrosis After COVID-19 Pneumonia.

BackgroundFew is known about the long-term pulmonary sequelae after COVID-19 infection. Hence, the aim of this study is to characterize patients with persisting pulmonary sequelae at follow-up after hospitalization. We also aimed to explore clinical and radiological predictors of pulmonary fibrosis following COVID-19.MethodsTwo hundred and 20 consecutive patients were evaluated at 3–6 months after discharge with high-resolution computed tomography (HRCT) and categorized as recovered (REC) or not recovered (NOT-REC). Both HRCTs at hospitalization (HRCT0), when available, and HRCT1 during follow-up were analyzed semiquantitatively as follows: ground-glass opacities (alveolar score, AS), consolidations (CONS), and reticulations (interstitial score, IS).ResultsA total of 175/220 (80%) patients showed disease resolution at their initial radiological evaluation following discharge. NOT-REC patients (45/220; 20%) were mostly older men [66 (35–85) years vs. 56 (19–87); p = 0.03] with a longer in-hospital stay [16 (0–75) vs. 8 (1–52) days; p < 0.0001], and lower P/F at admission [233 (40–424) vs. 318 (33–543); p = 0.04]. Moreover, NOT-REC patients presented, at hospital admission, higher ALV [14 (0.0–62.0) vs. 4.4 (0.0–44.0); p = 0.0005], CONS [1.9 (0.0–26.0) vs. 0.4 (0.0–18.0); p = 0.0064], and IS [11.5 (0.0– 29.0) vs. 0.0 (0.0–22.0); p < 0.0001] compared to REC patients. On multivariate analysis, the presence of CONS and IS at HRCT0 was independent predictors of radiological sequelae at follow-up [OR 14.87 (95% CI: 1.25–175.8; p = 0.03) and 28.9 (95% CI: 2.17–386.6; p = 0.01, respectively)].ConclusionsIn our population, only twenty percent of patients showed persistent lung abnormalities at 6 months after hospitalization for COVID-19 pneumonia. These patients are predominantly older men with longer hospital stay. The presence of reticulations and consolidation on HRCT at hospital admission predicts the persistence of radiological abnormalities during follow-up.

The relationship between the sugammadex use and postoperative reintubation in the absence of neuromuscular monitoring

Background: Evidences show that sugammadex may facilate extubation after surgery. Applying neuromuscular monitoring in general anesthesia may prevent postoperatrive reintubation. However, routine general anesthesia does not always include neuromuscular monitoring. Therefore, we investigated the relationship between the sugammadex use and postoperative reintubation in the absence of neuromuscular monitoring. Methods: We conducted a retrospective analysis of the incidence of postoperative reintubation in the operating room (OR) or postanesthesia care unit following sugammadex use in the absence of neuromuscular monitoring that involved a large number of patients over 4 years (from January 2017 to August 2020). Postoperative reintubation was applied for patients who had peripheric oxygen saturation <90% despite being given 6 L/min oxygen with a face mask. Patients with perioperative neuromuscular monitoring, renal or hepatic failure, electrolyte imbalance, body mass index over 35, incomplete data, and age under 20 years were excluded. All data from the ORs' database and anesthesia records were analyzed. Results: Of 6582 patients receiving sugammadex, 6313 were included in this study. Two confirmed cases of postoperative reintubation were detected, with an incidence of 0.03% (2 of 6,313). As of the type of surgery, a 34 years old male received elective thoracic surgery, and another 66 years old male received elective urological surgery. No long-term pulmonary sequelae were found. Conclusion: This study suggests that the occurrence of postoperative reintubation following sugammadex (2–4 mg/kg) use is rare even in the absence of neuromuscular monitoring. Further large prospective studies are required to validate the findings of this study.

CT Lung Abnormalities after COVID-19 at 3 Months and 1 Year after Hospital Discharge.

BackgroundData on the long-term pulmonary sequelae in COVID-19 are lacking.PurposeTo assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up.Materials and MethodsAdult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used.ResultsEighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95–141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360–366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%–40%).ConclusionCT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up.ClinicalTrials.gov identifier: NCT04459351.© RSNA, 2022 Online supplemental material is available for this article.

BULLOUS LUNG DISEASE COMPLICATING COVID-19 PNEUMONIA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The long-term pulmonary sequelae and mechanism of lung injury seen in COVID-19 pneumonia are still under investigation, but have consistently been characterized by tissue destruction due to a hyperinflammatory state [1]. We discuss a case of bullous disease as a consequence of severe COVID 19 infection. CASE PRESENTATION: 71-year-old never smoker male presented with dyspnea, fevers and myalgias diagnosed with COVID-19 infection and admitted to the intensive care unit for acute hypoxemic respiratory failure due to acute respiratory distress syndrome (ARDS). On examination, he was noted to be in respiratory distress, with decreased breath sounds and crackles noted at the lung bases. Commuted Tomography (CT) chest revealed ground glass opacities (GGO), peripheral consolidative opacities affecting all five lobes, intralobular septal thickening in upper lobes, and traction bronchiectasis (Figure 1). His inflammatory markers were significantly elevated: C-reactive protein 384.8 mg/L, ferritin 2803 ng/mL, and D-dimer >20,000 ng/mL. His persistent hypoxemia due to COVID-19 infection was managed with high flow nasal cannula, prolonged course of corticosteroids, convalescent plasma and remdesivir. Follow up CT chest without IV contrast one month after hospitalization showed a new 8 cm bulla at the apex of the right lung with new focal emphysematous-type changes in the upper lobes, improved GGOs, traction bronchiectasis and subpleural fibrosis (Figure 2). Unfortunately, his recovery was complicated by readmission to the hospital for large right sided pneumothorax which required definitive management with surgical pleurodesis. DISCUSSION: Biopsies of lung tissue affected by severe COVID-19 pneumonia have shown interstitial inflammatory infiltrates and predominant findings consistent with diffuse alveolar damage, which is the primary histopathology of acute respiratory distress syndrome [2]. The formation of bullae after disruption of normal lung morphology is an established complication of ARDS and this underlying pattern of acute lung injury [3]. This case is unique in its description of development and recognition of significant bullous disease in a patient with COVID-19 infection without prior history of lung disease. To our knowledge, this is only the second reported case of bulla formation prior to observed pneumothorax in COVID-19 infection. There are otherwise an increasing number of cases reporting incidental bullous lung disease seen on CT imaging after readmission for spontaneous pneumothorax following index hospitalization for COVID-19 pneumonia. CONCLUSIONS: Although the precise etiologic mechanism is unclear, development of bullous lung disease as a consequence of COVID-19 infection is important to recognize and could represent an interval finding prior to presentation with spontaneous pneumothorax. REFERENCE #1: Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255-2273. REFERENCE #2: Hariri LP, North CM, Shih AR, et al. Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review. Chest. 2021;159(1):73-84. REFERENCE #3: Gattinoni L, Caironi P, Pelosi P, Goodman LR. What has computed tomography taught us about the acute respiratory distress syndrome?. Am J Respir Crit Care Med. 2001;164(9):1701-1711. DISCLOSURES: No relevant relationships by Raymond Foley, source=Web Response No relevant relationships by Ashita Mittal, source=Web Response No relevant relationships by Simrina Sabharwal, source=Web Response

Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study

Background: Long-term pulmonary sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia are not yet confirmed; however, preliminary observations suggest a possible relevant clinical, functional, and radiological impairment. Objectives: The aim of this study was to identify and characterize pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. Methods: In this multicentre, prospective, observational cohort study, patients hospitalized for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only,” “continuous positive airway pressure,” and “invasive mechanical ventilation”) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6-min walking test, chest X-ray, physical examination, and modified Medical Research Council (mMRC) dyspnoea score were collected. Results: Between March and June 2020, 312 patients were enrolled (83, 27% women; median interquartile range age 61.1 [53.4, 69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥1, or showed restrictive ventilatory defects (9%). In the logistic regression model, having asthma as a comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalization appeared as a protective factor. The need for invasive ventilatory support during hospitalization was associated with chest imaging abnormalities. Conclusions: DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with the coronavirus disease 2019 (COVID-19) during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Post-Acute Sequelae of COVID-19 Pneumonia: Six-month Chest CT Follow-up.

BackgroundThe long-term post acute pulmonary sequelae of COVID-19 remain unknown.PurposeTo evaluate lung injury in patients affected by COVID-19 pneumonia at six-month follow-up compared to baseline chest CT.MethodsFrom March 19th,2020 to May 24th,2020, patients with moderate to severe COVID-19 pneumonia and baseline Chest CT were prospectively enrolled at six-months follow-up. CT qualitative findings, semi-quantitative Lungs Severity Score (LSS) and well-aerated lung quantitative Chest CT (QCCT) were analyzed. Baseline LSS and QCCT performances in predicting fibrotic-like changes (reticular pattern and/or honeycombing) at six-month follow-up Chest CT were tested with receiver operating characteristic curves. Univariable and multivariable logistic regression analysis were used to test clinical and radiological features predictive of fibrotic-like changes. The multivariable analysis was performed with clinical parameters alone (clinical model), radiological parameters alone (radiological model) and the combination of clinical and radiological parameters (combined model).ResultsOne-hundred-eighteen patients, with both baseline and six-month follow-up Chest CT, were included in the study (62 female, mean age 65±12 years). At follow-up Chest CT, 85/118 (72%) patients showed fibrotic-like changes and 49/118 (42%) showed GGOs. Baseline LSS (>14), QCCT (≤3.75L and ≤80%) showed an excellent performance in predicting fibrotic-like changes at Chest CT follow-up. In the multivariable analysis, AUC was .89 (95%CI .77-.96) for the clinical model, .81 (95%CI .68-.9) for the radiological model and .92 (95%CI .81-.98)for the combined model.ConclusionAt six-month follow-up Chest CT, 72% of patients showed late sequelae, in particular fibrotic-like changes. Baseline LSS and QCCT of well-aerated lung showed an excellent performance in predicting fibrotic-like changes at six-month Chest CT (AUC>.88). Male sex, cough, lymphocytosis and QCCT well-aerated lung were significant predictors of fibrotic-like changes at six-month with an inverse correlation (AUC .92).See also the editorial by Wells and Devaraj.

Pulmonary Sequelae at 4 Months After COVID-19 Infection: A Single-Centre Experience of a COVID Follow-Up Service.

IntroductionAt the end of the first year of the COVID-19 pandemic, more than 78 million known survivors were recorded. The long-term pulmonary sequelae of COVID-19 remain unknown.MethodsWe performed a retrospective analysis of a post-COVID follow-up service to estimate the burden of persistent pulmonary morbidity in hospitalised COVID survivors.ResultsA total of 221 patients were followed-up: 44 intensive care unit (ICU) and 177 ward patients. Further investigations were planned as per British Thoracic Society Guidelines: For all ICU patients (n = 44) and for 38 of 177 (21%) ward-based patients who had persistent symptoms and/or persistent radiographic changes on CXR at their initial 8-week follow-up visit. In the ward-based cohort, statistically significant associations with persistent symptoms were being an ex- or current smoker, having pre-existing diabetes, and having a longer length of stay. In patients requiring further investigations, pulmonary function tests (PFTs; n = 67) at an average of 15 weeks post-discharge showed abnormalities in at least one PFT parameter in 79% (equating to 24% of the entire cohort). The most common abnormality was an abnormal diffusion capacity of carbon monoxide (TLCO), highest in the ICU cohort (64% ICU vs. 38% non-ICU). TLCO correlated negatively with length of stay and with maximum inspired FiO2 in the patient group as a whole. In ICU patients, TLCO correlated negatively with maximum inspired positive airway pressure. Computed tomography scans (n = 72) at an average of 18 weeks post-discharge showed evidence of persistent ground glass opacities in 44% and fibrosis in 21% (equating to 7% of the entire cohort).ConclusionOur data add to the growing evidence that there will be pulmonary sequelae in a proportion of COVID survivors, providing some insight into what may become a significant chronic global health problem.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01833-4.

Long-Term Pulmonary Sequelae After Inhalation Injury: A Retrospective Case-Control Study.

Inhalation injury (INHI) has strong associations with increased rates of in-patient mortality and pneumonia. This study's aim is to review long-term pulmonary outcomes in INHI patients. We present a retrospective cohort of burn patients admitted to an ABA-certified burn unit. Burn patients with or without medically confirmed INHI who were admitted were studied. The control groups were ventilated patients (V) and nonventilated patients (NV). Primary study outcomes were rates of postdischarge pulmonary sequelae, including ineffective airway clearance, infections, shortness of breath, and malignancy. Secondary outcomes included rates of postdischarge surgeries and readmission, postdischarge nonpulmonary sequelae, and postdischarge days to pulmonary/nonpulmonary sequelae. The study population included 33 INHI, 45 V, and 50 NV patients. There were no significant differences in age (P = .98), sex (P = .68), % TBSA (P = .18), pulmonary comorbidity (P = .5), or smoking status (P = .92). Outpatient pulmonary sequelae were significantly higher for both INHI and V groups as compared to NV (21% and 17% vs 4%, P = .023, .043). The number of days from discharge to pulmonary sequelae was significantly shorter in the INHI group vs the V group (162 ± 139 vs 513 ± 314 days, P = .024). All other measures were not significant when comparing INHI to V or NV (P > .05). Both INHI and V groups resulted in higher rates of outpatient pulmonary sequelae independent of inpatient course as compared to NV. While outpatient pulmonary sequelae were not significantly different between INHI and V, the INHI patients presented with complaints earlier.

17 Long-Term Pulmonary Sequelae After Inhalation Injury: A Retrospective Cohort Study

Abstract Introduction Inhalation injury (INHI) has strong associations with increased rates of in-patient mortality and pneumonia. Data describing long-term health outcomes after inhalation injury are scarce and the true sequelae are largely unknown. The aim of the study is to review long-term pulmonary outcomes in inhalation injury patients. We hypothesize that INHI patients are at greater risk of developing long-term pulmonary sequelae. Methods We present a retrospective case-control of burn patients admitted to an ABA certified facility. We included burn patients with or without medically confirmed INHI who were admitted between 06/2016 to 11/2019 and were part of the regional Department of Health Services (DHS) system. The experimental group was patients with bronchoscopy confirmed INHI. The control groups were ventilated patients with confirmed non-inhalation injury (V) and non-ventilated patients with confirmed non-inhalation injury (NV). These were matched for age, TBSA, sex, previous comorbid pulmonary disease, and smoking status. Primary study outcomes were rates of post-discharge pulmonary sequelae, including ineffective airway clearance, infections, shortness of breath, and malignancy. Secondary outcomes included rates of post-discharge surgeries and readmission, post-discharge non-pulmonary sequelae, and post-discharge days to pulmonary/non-pulmonary sequelae. Results The study population included 33 INHI, 45 V, and 50 NV patients. There were no significant differences in age (P=.98), sex (P=.68), TBSA (P=.18), pulmonary comorbidity (P=.5), or smoking status (P=.92). Outpatient pulmonary sequelae were significantly higher for both INHI and V groups as compared to NV (21% and 17% vs 4%, P=.023, .043). The number of days from discharge to pulmonary sequelae was significantly shorter in the INHI group versus the V group (162±139 days vs 513±314 days, P=.024). Multinomial logistic regression for both INHI and V groups using the variables comorbid pulmonary disease, smoking status, and inpatient course and complications, indicated no effect on post-discharge pulmonary sequelae (all P &amp;gt;.05). All other measures were not significant when comparing INHI to V or NV (all P &amp;gt;.05). Conclusions Both INHI and V groups resulted in higher rates of outpatient pulmonary sequelae independent of inpatient course as compared to NV. While outpatient pulmonary sequelae were not significantly different between INHI and V, the INHI patients presented with complaints earlier. Thus one can conclude that ventilation alone is a significant contributing factor for the long-term pulmonary sequelae reported in this patient population.

Pulmonary Function and Radiologic Features in Survivors of Critical COVID-19: A 3-Month Prospective Cohort

BackgroundMore than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear.Research QuestionWhat are the major long-term pulmonary sequelae in critical patients who survive COVID-19?Study Design and MethodsConsecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging.ResultsOne hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID-19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay.InterpretationThree months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID-19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.

Follow-Up Study of the Chest CT Characteristics of COVID-19 Survivors Seven Months After Recovery.

Background: It has remained a concern whether any long-term pulmonary sequelae exist for COVID-19 survivors.Methods: Forty-one patients (22 men and 19 women, 50 ± 14 years) confirmed with COVID-19 performed follow-up chest CT and cardiopulmonary exercise testing at 7 months after discharge. Patients were divided into fibrosis group and non-fibrosis group according to the evidence of fibrosis on follow-up CT. The clinical data and the CT findings were recorded and analyzed.Results: The predominant CT patterns of abnormalities observed at 7 months after discharge were parenchymal band (41%), interlobular septal thickening (32%), and traction bronchiectasis (29%). Sixty-one percent of the patients achieved complete radiological resolution, and 29% of patients developed pulmonary fibrosis. Compared with the patients in the non-fibrosis group, the patients in the fibrosis group were older, with a longer hospital stay, a higher rate of steroid and mechanical ventilation therapy, lower levels of lymphocyte and T cell count, higher levels of D-dimer and lactic dehydrogenase, and higher quantitative CT parameters (opacity score, volume of opacity, and percentage of opacity) at discharge. Besides, oxygen consumption and metabolic equations were decreased and ventilatory equivalent for carbon dioxide was increased in patients in the fibrosis group. Logistic regression analyses revealed that age, steroid therapy, presence of traction bronchiectasis on chest CT at discharge, and opacity score at discharge, were independent risk factors for developing pulmonary fibrosis at 7 months after discharge. Receiver operating characteristic analysis revealed that the combined clinical-radiological model was better than the clinical-only model in the prediction of pulmonary fibrosis.Conclusions: The chest CT lesions could be absorbed without any sequelae for most patients with COVID-19, whereas older patients with severe conditions are more prone to develop fibrosis, which may further lead to cardiopulmonary insufficiency. The combined clinical-radiological model may predict the formation of pulmonary fibrosis early.

Medium-term chest computed tomography (CT) follow-up of COVID-19 pneumonia patients after recovery to assess the rate of resolution and determine the potential predictors of persistent lung changes

BackgroundThe data on medium-term follow-up of coronavirus disease-19 (COVID-19) pneumonia survivors is scarce. Medium-term follow-up will generate knowledge and help in devising a structured follow-up plan and to facilitate enrolment in clinical trials assessing the role of antifibrotic drugs in modifying the course of disease in order to avert long-term pulmonary sequelae of disease. The study was aimed to evaluate the lung findings on a medium-term follow-up (3 months or more) chest computed tomography (CT) in COVID-19 pneumonia survivors, assess the rate of resolution or persistence of lung abnormalities and to identify the initial demographic, clinical, and imaging characteristics that could potentially predict the persistence of lung abnormalities on follow-up.ResultsOut of the total study cohort of 81 patients, 46 (56.8%) demonstrated complete resolution of lung findings and the remaining 35 (43.2%) had residual lung opacities on follow-up CT. The most common type of residual abnormality was ground glass opacity (GGO) (16/35; 45.7%), followed by parenchymal bands (9/35; 25.7%), mixed pattern of GGO and parenchymal bands (6/35; 17.2%), bronchiectasis (6/35; 17.2%), and interlobular septal thickening (4/35; 11.4%). Patients with residual abnormalities were older, had higher BMI, more comorbidities, lower SpO2, longer hospital stay, higher rate of intensive care unit (ICU) admission, higher WBC count, a higher CT severity score, and lower rate of steroid administration with all p values < 0.05.ConclusionNearly half of post-COVID-19 survivors had residual lung abnormalities after ≥ 3 months of follow-up. Certain clinico-radiological characteristics have the potential to identify the individuals at risk of having residual lung abnormalities on medium-term follow-up.

386. Long-term Complications Associated with COVID-19 Infection

BackgroundIn Michigan, 44,964 (68%) of the 66,269 COVID-19 patients have recovered. However, there is concern that COVID-19 infection may lead to long-term sequelae, including pulmonary defects, cardiac complications, blood clots, and neurocognitive impairment. This study describes the 30-day outcomes of patients who had recovered.MethodsFrom 3/16/2020 to 5/19/2020, a follow-up was attempted for patients who were discharged alive from Henry Ford Hospital in Detroit and had recovered. Recovery was defined as being alive 30 days post symptom-onset. A telephone survey was conducted 30 days post-index admission and recorded in electronic medical records. Oxygen (O2) requirements, symptoms, readmissions and the need for antibiotics for secondary bacterial infections were evaluated.Results585 patients met inclusion criteria and were contacted by phone; 303 answered their phone (Table 1), but only 266 (45%) completed a full telephone encounter and were included in the final analysis (Table 2). The majority were female (53%), black (80%), and discharged to home (84%). The clinical characteristics of those who completed the survey were as follows: 11% presented with O2 saturation < 90%, 16% had underlying lung pathology, and 57% had a BMI above 30. Patients’ average age was 61 ± 14.3 years. At 30 days post-index admission, 49% were still symptomatic. Of the symptomatic patients, 86% had dyspnea on exertion and 15% required O2 supplementation. 18% of patients were readmitted within 30 days, and 9% developed a secondary infection prior to the phone encounter. No statistically significant differences in demographics or comorbidities were found between symptomatic and asymptomatic cohorts (Tables 1, 2). ConclusionIn our study, almost half of the discharged patients remained symptomatic after 30 days with a substantial proportion experiencing pulmonary symptoms. A better understanding of the long-term pulmonary sequelae following COVID-19 infection is needed to design interventions to reduce post-infectious morbidity.Disclosures Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau)

Acute and chronic effects of intravitreal bevacizumab on lung biomarkers of angiogenesis in the rat exposed to neonatal intermittent hypoxia

Purpose/Aim Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used to treat severe retinopathy of prematurity (ROP) in extremely low gestational age neonates (ELGANs). ELGANs who are at the highest risk for developing severe ROP often experience brief intermittent hypoxia (IH) episodes which may cause oxidative damage. We tested the hypothesis that intravitreal Avastin leaks into the systemic circulation during exposure to IH and has adverse effects on biomarkers of pulmonary microvascular maturation, thus leading to pulmonary hemorrhage and long-term pulmonary sequelae. Methods Neonatal rats at postnatal day (PN) 0 (birth) were exposed to either: 1) hyperoxia (50% O2) or 2) neonatal IH (50% O2 with brief episodes of 12% O2) from PN0 to PN14. Room air (RA) littermates served as controls. At PN14, the time of eye opening in rats, a single dose of Avastin (0.125 mg in 5 µL) was injected into the vitreous cavity of the left eyes. A control group received equivalent volume saline. At PN23 and PN45, blood gases, lung-to-body weight ratios, histology, immunofluorescence, and lung biomarkers of angiogenesis were examined. Results At PN23, Avastin increased lung VEGF, nitric oxide derivatives (NOx), and hypoxia-inducible factor (HIF)1a in the hyperoxia-exposed groups, but decreased soluble VEGFR-1 (sVEGFR-1). At PN45, lungs from animals exposed to neonatal IH and treated with Avastin were severely hemorrhagic with morphologic changes in lung architecture consistent with chronic lung disease. This was associated with higher VEGF and NOx levels, and lower insulin-like growth factor (IGF)-I and sVEGFR-1. Conclusions These findings prove our hypothesis that intravitreal Avastin penetrates the blood–ocular barrier in IH and alters lung biomarkers of angiogenesis. Avastin targeting of VEGF could affect normal lung development which may be exaggerated under pathologic conditions such as IH, ultimately leading to vascular permeability, vessel rupture, and pulmonary hemorrhage.