Lung pathology

The series of autopsies reported since the beginning of the pandemic have highlighted several patterns of lung damage, both isolated and combined. The factors influencing the occurrence of these different tissue responses to viral aggression by SARS-CoV-2 have not yet been determined. In asymptomatic patients or patients with respiratory symptoms who were not ventilated, lymphocyte pneumonia associated with type II pneumocyte atypical hyperplasia and a few hyaline membranes or focal lesions of acute fibrinous pneumonia have been observed. In critically ill patients, the most frequent pattern is diffuse alveolar damage with interstitial lymphoid infiltration, type II pneumocyte atypia and, very often, capillary or arteriolar microthromboses and/or endothelitis. The precise description of these lesions, which is becoming more and more consensual, makes it possible to understand the favourable effects of corticosteroid therapy in seriously ill patients and the evolution under ventilation towards fibrosis.Copyright © ERS 2021.

To What Extent do Social Determinants of Health Modulate Presentation, ITU Admission and Outcomes among Patients with SARS-COV-2 Infection? An Exploration of Household Overcrowding, Air Pollution, Housing Quality, Ethnicity, Comorbidities and Frailty.

Background: Internationally, researchers have called for evidence to support tackling health inequalities during the severe acute respiratory syndrome coronavirus 2 (COVID19) pandemic. Despite the 2020 Marmot review highlighting growing health gaps between wealthy and deprived areas, studies have not explored social determinants of health (ethnicity, frailty, comorbidities, household overcrowding, housing quality, air pollution) as modulators of presentation, intensive care unit (ITU) admissions and outcomes among COVID19 patients. There is an urgent need for studies examining social determinants of health including socioenvironmental risk factors in urban areas to inform the national and international landscape. Methods: An in-depth retrospective cohort study of 408 hospitalized COVID19 patients admitted to the Queen Elizabeth Hospital, Birmingham was conducted. Quantitative data analyses including a two-step cluster analysis were applied to explore the role of social determinants of health as modulators of presentation, ITU admission and outcomes. Results: Patients admitted from highest Living Environment deprivation indices were at increased risk of presenting with multi-lobar pneumonia and, in turn, ITU admission whilst patients admitted from highest Barriers to Housing and Services (BHS) deprivation Indies were at increased risk of ITU admission. Black, Asian and Minority Ethnic (BAME) patients were more likely, than Caucasians, to be admitted from regions of highest Living Environment and BHS deprivation, present with multi-lobar pneumonia and require ITU admission. Conclusion: Household overcrowding deprivation and presentation with multi-lobar pneumonia are potential modulators of ITU admission. Air pollution and housing quality deprivation are potential modulators of presentation with multi-lobar pneumonia. BAME patients are demographically at increased risk of exposure to household overcrowding, air pollution and housing quality deprivation, are more likely to present with multi-lobar pneumonia and require ITU admission. Irrespective of deprivation, consideration of the Charlson Comorbidity Score and the Clinical Frailty Score supports clinicians in stratifying high risk patients.

Diagnosis of community-acquired acute pneumonia in the emergency room and distinction between viral or bacterial etiology.

The current pandemic linked to the emergence of SARS-CoV-2 in 2019 has considerably changed the perception of doctors of the impact of respiratory viruses and their role in community-acquired acute pneumonia (CAP). While more than 25% of CAP in adults were of viral origin, respiratory viruses were often perceived as harmless pathogens. Faced with the challenge that the microbiological documentation of a CAP still represents today, the establishment of empirical antibiotic treatment is often carried out in the emergency room. The COVID-19 pandemic has primarily highlighted the decisive role of molecular biology and chest CT in the diagnostic algorithm of CAP. Indeed, a rapid and reliable diagnosis is the key to improve isolation decisions and reducing the unnecessary prescription of antibiotics. Due to significantly different treatments, it is necessary to distinguish the viral etiology from the bacterial of a CAP. Copyright © 2022 Lavoisier. All rights reserved.

Effect of magnesium on severity and mortality of COVID-19 patients: A systematic review

Unbalanced magnesium levels in the body, like other minerals, are a factor that is important in the severity and mortality of COVID-19. This study was designed to investigate the relationship between serum magnesium levels and clinical outcomes in COVID-19 patients. In this systematic review, a comprehensive search was performed in PubMed, Scopus, and Web of Science databases until September 2021 by using the keywords COVID-19, severe acute respiratory syndrome coronavirus 2, coronavirus disease, SARS- COV-infection 2, SARS-COV-2, COVID 19, and magnesium. End-Note X7 software was used to manage the studies. Articles that evaluated effect of magnesium on COVID-19 were included in the analysis. After reviewing several articles,12 studies were finally included in the ultimate analysis. The studies show that hypomagnesemia and hypermagnesemia are both factors that increase mortality in patients with COVID-19, even in one study, hypomagnesemia is the cause of doubling thedeaths in COVID-19 patients. Some studies have also found a negative correlation between magnesium deficiency and infectionseverity, while some others have reported no correlation between magnesium level and disease severity. According to the important role of magnesium in the body and its involvement in many physiological reactions, as well as differences in physical and physiological conditions of COVID-19 patients, in addition to the need for studies with larger sample sizes, monitoring and maintaining normal serum magnesium levels during the disease seems necessary as a therapeutic target, especially in patients admitted to the intensive care unit.

THE PANDEMIC'S FUNGAL REVENGE: COVID-19 ASSOCIATED PULMONARY ASPERGILLOSIS (CAPA)

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Since the start of the COVID-19 pandemic, COVID-19 Associated Pulmonary Aspergillosis (CAPA) has been on the rise. This superinfection, if not properly identified and treated, has shown to increase mortality up to 67% in COVID-19 patients. We are presenting a late presentation of CAPA after 4-month of COVID-19 infection and treated successfully. CASE PRESENTATION: A 57-year-old female patient with past medical history type 2 diabetes mellitus, hypertension and cardiomyopathy in addition to COVID-19 pneumonia treated for months ago with azithromycin, Bamlanivimab/Etesevimab, and Dexamethasone who presents to the hospital with massive hemoptysis and shortness of breath requiring intubation and mechanical ventilation. There was no reported history of recent travel, smoking, alcohol, or illicit drug use. Physical exam showed diminished lung sounds at the right lower lobe. Her labs showed mild leukocytosis, lactic acidosis and negative COVID-19 PCR. CT scan showed dense consolidation on right lower lobe consistent with lobar pneumonia and centrilobular ground glass opacities in the right upper lobe. Bronchoscopy showed complete obstruction of right bronchus intermedius and minimal blood clots in LLL. BAL respiratory culture, fungal smear, acid fast bacilli were non-diagnostic and negative for malignancy. Patient continued to have hemoptysis and bronchoscopy was repeated with negative cytology and cultures. The patient continued to have hemoptysis and she was transferred to tertiary center were bronchoscopy was repeated and confirmed right bronchus intermedius stenosis, blood clots, and suspicious right mainstem nodules with mucosal lesion. Biopsy results from bronchoscopy came back positive for the morphologic features of Aspergillus species. The patient was started on voriconazole with significant improvement in her symptoms. DISCUSSION: The recent literature of COVID-19 suggest association between COVID infection and invasive pulmonary Aspergillosis. COVID-19 virus causes damage in the airway epithelium and enable aspergillus to invade the pulmonary tract leading to serious infections with Aspergillus. It has also been known that Aspergillus infections are associated with diabetes mellitus and immune suppression which can be precipitated by steroid use and other treatments for COVID-19 infection like IL-6 inhibitors. Here in our patient with help of tissue biopsy we diagnosed CAPA, started treatment early and treated successfully. CONCLUSIONS: CAPA can be difficult to diagnose and needs high index of suspicion in the appropriate clinical scenario when dealing with post COVID respiratory complaints like hemoptysis. Bronchoalveolar lavage alone without tissue biopsy might miss the diagnosis in the context of invasive aspergillosis like the scenario we observed in our case. Doing tissue biopsy through bronchoscopy might add more clinical benefit when Aspergillus infections are suspected. Reference #1: Chih-Cheng Lai, Weng-Liang Yu, COVID-19 associated with pulmonary aspergillosis: A literature review, https://doi.org/10.1016/j.jmii.2020.09.004 DISCLOSURES: No relevant relationships by Haytham Adada No relevant relationships by Mahmoud Amarna No relevant relationships by Rishika Bajaj No relevant relationships by Camelia Chirculescu No relevant relationships by Sonia Dogra No relevant relationships by Azad Patel

BUT WHAT ABOUT THE RASH?

SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: This is a case of a patient 74-year-old immunosuppressed woman presenting with a one-week history of skin lesions. CASE PRESENTATION: A 74-year-old woman with Crohn's disease (on weekly adalimumab);pulmonary hypertension (RVSP 76 mmHg);OHS/OSA, on home BPAP 17/7 cmH2O;and morbid obesity presented with a one-week history of skin lesions. She was seen by her primary care physician two days prior with skin lesions, shortness of breath, and decreased vision. She was hypoxic during the visit and given doxycycline for empiric treatment of pneumonia. She denied recent travel or exposure to animals. On admission, she was afebrile (36.9C) and saturating 98% on 2 L nasal cannula. She appeared chronically ill with mouth ulcers and an eroded nodule with overlying hemorrhagic crusting and peripheral pustular area above her right eyebrow (figure 1). Throughout her skin, she had multiple erythematous papules, some with overlying vesicles/pustules. Labs were significant for a leukocytosis of 19.3 with left shift, lactate of 3.5, serum creatinine of 1.9 (likely higher than patient's previous baseline of 1.7 with previous history of recurrent AKIs on CKD), elevated inflammatory markers, and normal ALT/AST. Influenza and COVID were negative. A CT chest showed consolidations and numerous pulmonary nodules highly suspicious for an infectious or inflammatory process (figure 2). She was treated empirically with vancomycin, piperacillin-tazobactam, valacyclovir, and amphotericin B, the latter given the concern of blastomycosis. During her hospitalization, she had further respiratory failure requiring intubation and multiorgan failure. Disseminated blastomycosis was confirmed via a skin biopsy which demonstrated pyogranulomatous inflammation with numerous broad-based budding yeasts (figure 3) and supported with a bronchoalveolar lavage (BAL) culture growing the same. Given her continued decline, her medical decision maker decided to transition the patient to hospice care. DISCUSSION: Blastomycosis is a systemic pyogranulomatous infection that is caused from the inhalation of the conidia form of the dimorphic fungus. It can manifest as asymptomatic infection, acute or chronic pneumonia, or extrapulmonary disease. BAL yields a positive diagnosis in 92% of patients and definitive diagnosis requires growth of the organism from a clinical specimen. Without appropriate treatment of amphotericin B or one of the azole antifungals, the disease had a 90% mortality rate. CONCLUSIONS: Prompt recognition of multiorgan failure secondary to blastomycosis is important for early treatment and improved survival in immunocompromised patients Reference #1: 1)Chapman, S W et al. "Endemic blastomycosis in Mississippi: epidemiological and clinical studies.” Seminars in respiratory infections vol. 12,3 (1997): 219-28. Reference #2: 2)Saccente, Michael, and Gail L Woods. "Clinical and laboratory update on blastomycosis.” Clinical microbiology reviews vol. 23,2 (2010): 367-81. doi:10.1128/CMR.00056-09 Reference #3: 3)Chapman, Stanley W et al. "Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 46,12 (2008): 1801-12. doi:10.1086/588300 DISCLOSURES: No relevant relationships by Jennifer Duke No relevant relationships by Ashley Egan

COVID-19 and SARS-CoV-2. We learn that there's still so much more to learn

Background: Current COVID-19 pandemic exposes health staff to a new and potentially fatal disease Case history: Male, 37 yo, entered ER referring worsening asthenia, feeling non-specifically unwell for 7 days, recent history of SARSCoV- 2 infection with interstitial pneumonia requiring hospitalization two weeks prior admission. Blood tests showed severe anemia (Hb 4gr/dl), mild hyperbilirubinemia, markedly raised LDH, positive direct/ indirect Coombs' reaction. Autoimmune haemolytic anemia was suspected because of symptomatic anaemia, evidence of ongoing haemolysis on blood tests, history of a viral infection. Chest XRay and CT pulmonary angiogram were negative for features suggestive of Covid-19 but highlighted lower right lobar pneumonia. Nasopharyngeal molecular swab was negative, while antibody test showed high titer G Immunoglobulin, confirming recent infection. He was initially treated with high doses steroids (1 gr/Kg bw) as well as antibiotics for pneumonia;but, due to lack of efficacy, on the fourth day we started ev immunoglobulins, obtaining gradual improvement in Hb towards baseline and tests normalization. Discussion: SARS-CoV2 infection frequently meets complications;although the pathophysiology underlying COVID-19 remains poorly understood, evidence argues for hyperinflammatory syndrome and/or various autoimmune disorders, which may appear after pneumonia recovery, highlighting need of medium and longterm follow up, to identify possible presentations of COVID-19 complications.

Pathology of Double Lung Transplantation of 12 Cases Following COVID-19

Background: Pulmonary failure is one of the major causes of death in COVID-19 (SARS-CoV-2) patients. Lung transplantation has been evolving to rescue those patients' lives with promising success. Explanted native lungs post COVID-19 are valuable to understand the long-term pulmonary pathology of this deadly disease, as currently available data is very limited. Design: Lung transplantation cases post COVID-19 were collected through the pathology database in our institution from January 2020 through September 2021. Patient clinical courses, CT imaging data prior to transplantation and pathological findings are evaluated. Results: The cohort consisted of 12 male patients with a median age of 46.5 years (range 24 - 67). Co-morbidities were present in 6 patients including obesity, diabetes mellitus and hypertension. No prior known pulmonary specific disease was present in any of the patients. Extracorporeal membrane oxygenation (ECMO) was used in 10 of 12 patients for 54 - 130 days. CT imaging pretransplantation showed extensive bilateral consolidation (5 cases), extensive bilateral ground-glass (3 cases) or extensive infiltration/air space disease (4 cases). All patients survived post double lung transplantation (including one patient with concurrent heart transplantation) and no significant pathologic alteration was identified on most recent surveillance biopsies (26 - 183 days post transplantation). The most prominent pathological finding in the explanted lungs is nonspecific interstitial pneumonia (NSIP)- like interstitial fibrosis (100%, 12 cases). Other findings include collections of numerous hemosiderin-laden macrophages (8 cases), patchy diffuse alveolar damage (DAD) (hyaline membrane formation and/or organizing DAD) (5 cases), intrapulmonary small vessel thrombosis (5 cases), organizing pneumonia (5 cases), necrosis (2 cases), calcifications (5 cases), acute pneumonia (3 cases), peribronchiolar metaplasia (8 cases), and microscopic honeycombing (8 cases). No viral cytopathic changes were seen. The pathologic findings of the two patients who did not receive ECMO are similar to those in patients with variable length of ECMO treatment. Conclusions: Lung transplantation is a successful treatment option for eligible candidates with pulmonary fibrosis and failure post COVID-19. NSIP-like interstitial fibrosis is a universal finding, consistent with a sequala of DAD. A spectrum of acute, subacute, vascular and airway-related changes are also prominent findings in respiratory failure post COVID-19.

Histology-proven Post-COVID Lung Fibrosis

Background: Pulmonary fibrosis is a serious complication of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV2). COVID-19 is believed to trigger substantial fibrotic consequences during acute infection. However, the extent to which lung fibrotic change could last and the degree of lung fibrosis in patients with complete resolution of infection still remain ambiguous. A predominant majority of reports on post-COVID-19 pulmonary fibrosis were drawn from radio imaging studies. By contrast, histological evidences of post-COVID-19 pulmonary fibrosis are paradoxically in significant shortage whilst they have higher diagnostic values. We herein report postmortem autopsies focusing on lungs from six patients with resolved SARS-CoV-2 infection. Design: Eligible autopsy samples were collected from patients who died from diseases other than acute COVID-19 and who contracted SARS-CoV-2 virus but either had subsequent negative SARS-CoV-2 test (n=4) or the symptoms of COVID-19 no longer existed and died after at least 100 days after initial positive SARS-CoV-2 test (n=2). Results: These patients included 4 men and 2 women with a mean age of 63 years (range 28 - 79 years). Two patients died from cardiovascular compromise, one patient died from venous thrombosis, one patient died from acute pneumonia, one patient died from post-COVID lung fibrosis, and one patient died from metastatic prostatic adenocarcinoma. Histology of lungs from all six cases showed different degree of fibrosis (Table 1). Remarkably, three of six cases showed extensive patchy interstitial fibrosis. Three of four cases with imaging data reviewed revealed consistent findings in CXR or CT (Table 1). Case (79 yo male) who died from post-COVID lung complications at 410 days after initial positive SARS-COV2 test showed remarkably diffuse lung parenchyma damage with extensive fibrotic changes, honey combing, with an interstitial pattern (Figure 1). Conclusions: Post-COVID fibrotic lung change is present in some patients following resolution of COVID infection. The extent to which lung fibrotic change could last and the degree of lung fibrosis in patients with complete resolution of infection vary from case to case. However, the finding of significant histologically-proven fibrotic lung changes more than 400 days after the resolution of acute COVID-19 in the setting of autopsy provide insight into the pathogenesis and prognosis of long-lasting complications of COVID-19.

Hypoxic respiratory failure caused by osimertinib-induced acute fibrinous and organizing pneumonia

INTRODUCTION: Osimertinib is a molecular targeted antineoplastic tyrosine kinase inhibitor that is primarily used in the treatment of non-small cell lung cancer (NSCLC). It has been associated with the development of interstitial lung disease/pneumonitis that requires discontinuation of the drug and occurs usually within the first 2-3 months of therapy. Approximately 3% of patients treated with osimertinib will experience lung toxicity. Acute fibrinous and organizing pneumonia (AFOP) is a rare form of interstitial pneumonitis that has been associated with drug toxicity but to our knowledge has not yet been described in association with osimertinib. Here we present one such case. DESCRIPTION: A 77 year old woman with a history of EGFR+ stage IIB adenocarcinoma presented with two weeks of shortness of breath, fevers, and dry cough. She had been started on osimertinib two months prior to presentation. On admission she was noted to be hypoxic with new oxygen requirement of 4L nasal cannula. CT chest showed bilateral ground glass opacities. She was started on empiric vancomycin and zosyn without improvement in symptoms. She underwent bronchoscopy on hospital day 3 with lung biopsy pathology showing AFOP. Infectious workup including bronchoalveolar lavage, blood, and sputum cultures, as well as respiratory viral panel and COVID-19 test was negative. Transthoracic echocardiogram showed normal cardiac function with an ejection fraction of 64%. Given these findings she was started on methylprednisolone 1 mg/kg for TKI-induced pneumonitis on day 5. Her oxygen requirements increased during hospitalization and on day 7 she acutely desaturated and was intubated. Repeat chest CT was negative for pulmonary embolism but showed interval worsening of infiltrates and consolidation at lung bases. Her methylprednisolone was increased to 2 mg/kg on day 10. Her pulmonary function improved and she was extubated to nasal cannula on day 12. DISCUSSION: Molecular targeted antineoplastic agents have been associated with lung toxicity, which can be severe and even fatal. To our knowledge this is the first known case of osimertinib-induced AFOP, which improved with discontinuation of the drug and initiation of high-dose methylprednisolone.