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Case: Wiskott-Aldrich Syndrome (WAS) is a rare X-linked inborn error of immunity caused by mutations in the WAS gene. It is classically characterized by immunodeficiency, eczema, and micro-thrombocytopenia. It has been known since the 1960s that patients with WAS have an increased risk of lymphoproliferative disease though the exact incidence remains unknown in the American population. Limited case reports have discussed EBV-related lymphoproliferative disease in patients with WAS. We present a case of a 9-year-old boy with known WAS complicated by eczematous rash, thrombocytopenia, recurrent ear infections, and monoclonal gammopathy who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. Family had been offered treatment with hematopoietic stem cell transplant but declined multiple times in the past. Earlier in the year, he presented with possible MIS-C with negative SARS-CoV-2 PCR. He presented to our hospital with mastoiditis and lymphadenopathy. Physical examination showed severe eczema on hands and tender right mastoid. Laboratory evaluation showed thrombocytopenia, elevated IgG of 6290, IgA of 744, IgE of 827, low IgM of 41, and 14% response to pneumococcal titers. He was empirically treated with intravenous antibiotics. ENT performed right postauricular incision and drainage and the culture grew Hemophilus influenza. Throughout his hospital stay, his submandibular lymphadenopathy became more prominent despite treatment. Core needle biopsy of right submandibular lymph node was suggestive of EBV-associated lymphoid hyperplasia. EBV PCR and antibodies were both positive. CT chest, abdomen, and pelvis revealed multifocal pulmonary lymphadenopathy and a diffuse, bilateral nodularity as well as retroperitoneal and mesenteric lymphadenopathy. He was given four doses of weekly Rituximab, which successfully decreased EBV viremia below linear detectability. Immunoglobulin replacement therapy (IgRT) was initiated. Bronchoalveolar lavage and lung biopsy were performed and are results are currently pending. Discussion(s): We present a case of a 9-year-old boy with known WAS awaiting transplant who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. While lymphoproliferative disease is a known complication of WAS, EBV-related lymphoproliferative disease in WAS patients has only been reported as case reports and remains a rare but known complication of patient with WAS.Copyright © 2023 Elsevier Inc.
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The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.
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Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.
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Background: Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Method(s): We obtained cross-sectional paired blood and lung biopsy samples from patients (n=30) undergoing lung resection for various reasons and assigned them to one of four groups: I.) uninfected unvaccinated individuals (n=5), II.) unvaccinated long-term SARS-CoV-2 convalescent individuals (between 6.0-10.5 months post-infection;n=9), III.) uninfected and long-term vaccinated individuals (between 6.0-7.7 months after the second or third dose;n=10), and IV.) uninfected and short-term vaccinated individuals (between 1.3-1.8 months after the third or fourth dose;n=6). We determined the presence of SARS-CoV-2-specific CD4+ and CD8+ T cells in blood and lung samples after exposure of cells to M, N, and S peptide pools, followed by flow cytometry to detect TRM cells expressing interferon (IFN)gamma and/or CD107a, as a degranulation marker. Result(s): We found that the frequency of CD4+ T cells secreting IFNgamma in response to S-peptides was variable but detectable in blood and lung up to 8 months after mRNA vaccination. Moreover, the IFNgamma response of CD4+ T cells in the lung of mRNA-vaccinated patients was similar to the response found in convalescent patients. However, in mRNA-vaccinated patients, lung responses presented less frequently with a TRM phenotype compared to convalescent infected individuals and, strikingly, polyfunctional CD107a+ IFNgamma+ TRM were virtually absent in vaccinated patients. Conclusion(s): mRNA vaccines might induce memory responses within the lung parenchyma in some patients, potentially contributing to the overall disease control. However, the robust and broad TRM response established in convalescent-infected individuals may offer advantages at limiting disease if the virus is not blocked by initial mechanisms of protection, such as neutralization. Our results warrant investigation of mucosal vaccine-induced resident T cell responses in establishing superior site-specific protective immunity.
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The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.
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The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.
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Since the emergence of coronavirus disease 2019, a large spectrum of clinical manifestations following this acute viral infection has been reported especially autoimmune manifestations and inflammatory disorders. However, a causal link has not yet been established. Herein, we reported a case of pulmonary mediastinal sarcoidosis following coronavirus disease 2019 infection. A 41-year-old woman with no clinical or radiographic symptoms or signs of sarcoidosis prior to coronavirus disease 2019 infection developed dyspnea, cough, and fatigue, a few months after discharge. A chest thoracic scan performed 3 months after hospital discharge showed regression of ground-glass opacities with the appearance of pulmonary micronodules. Clinical examination and spirometry were normal. The evolution was marked by progressive worsening of dyspnea and significant weight loss. A chest thoracic scan performed 6 months after discharge showed bilateral and symmetrical hilar and mediastinal and paratracheal lymphadenopathy. Bronchoalveolar lavage with cell count showed a lymphocytosis of 19.5% and a CD4/CD8 T cell ratio of 2.2. Endobronchial lung biopsy revealed noncaseating epithelioid granulomas. Sputum culture excluded tuberculosis. The diagnosis of pulmonary-mediastinal sarcoidosis was made. She was treated with an oral corticosteroid. The patient showed significant improvement during the 3-month follow-up period. Post-coronavirus disease sarcoidosis is very rare. Complementary studies are needed to discern the link between these diseases.Copyright © Author(s).
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The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.
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Background: 49 patients underwent Lung Biopsy due to different indications and Post-COVID Pulmonary Fibrosis(PCPF) was suspected in 25 patients. Objective(s): To document the evidence of PCPF in patients with history of suspected COVID 19 infection (in past oneyear) through Transbronchial Lung Biopsy(TBLB)with flexible bronchoscopy. PFT and HRCT gave variedpresentation. Method(s): we have evaluated patients who underwent Lung Biopsy on flexible Bronchoscopy between 08/07/2021 till31/01/2022 at Metro Hospitals and Heath Institute, Meerut, UP, India. The history of exposure to COVID 19 infectionwas taken. Most of these patients underwent Echocardiography (ECHO) for Left Ventricular Ejection Fraction (LVEF)and Pulmonary Artery Pressure (PAH), Pulmonary Function Test (PFT) and High Resolution CT Scan Chest (HRCTChest). Result(s): 49 patients underwent Lung Biopsy. 25 patients gave the history of exposure to COVID 19 infection with complaint of breathlessness and chest discomfort in the last 1 year. HRCT chest was suggestive of Atelectasis in 3 patients, Interstitial Lung Disease (ILD) in 6, Fibrosis in 8, Pulmonary Nodules in 4 and HRCT was not done in 4 patients. PFT showed Mixed Ventilator Defect in 8, Obstructive in 3, Restrictive in 7, small airway disease in 1 and 6 patients couldn't perform PFT. PAH was normal for 6,mild for 16, moderate for 2 and 1 severe. 4 patients had Coronary Artery Disease. 2 patients had major complications like pneumothorax who underwent TBLB. Conclusion(s): PCPF was detected with the help of TBLB in the patients with history of exposure to COVID 19 infection. However, TBLB may cause major complication like pneumothorax seen in 8% cases.
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Current knowledge of histopathological changes in Covid-19 pneumonia is mainly based on autopsy findings. There are few data on dynamics of lung lesions in vivo after acute phase of disease. The aim of this study was to determine histopathologic changes during the long/post-Covid stage in patients who had suffered from moderate to severe Covid-19 pneumonia. Bronchoscopy with transbronchial lung biopsy was performed in patients with HRCT lesions involving >40% of lung parenchyma, at least 4 weeks after discharge. Additional criteria were restrictive pattern in lung function tests and signed informed consent. Histopathologic analyses were performed using H&E, MSB, MOVAT, TTF1, CD34 and CD68 staining. Research was approved by the Hospital Ethical Committee. Among 26 patients that met inclusion criteria, adequate biopsy samples were obtained from 24. The mean time from the onset of disease to biopsy was 13 weeks. We found 4 histopathologic patterns: diffuse alveolar damage-DAD with vascular abnormalities, nonspecific interstitial inflammation, organizing pneumonia and interstitial fibrosis in 11, 9, 2 and 2 patients, respectively. Vascular abnormalities included capillary thrombi, dilated venules and dissection of small pulmonary arteries. Given the duration of disease, DAD and vascular abnormalities were detected up to the 12 week from the onset of symptoms. All patients biopsied after 12th weeks had some degree of tissue inflammation without vascular changes. Our findings show rather slow recovery of lung tissue after Covid-19 pneumonia. Long lasting DAD with vascular abnormalities may explain prolonged dyspnea and exercise intolerance and should be taken into consideration when planning further rehabilitation.
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Introduction: The onset of the COVID-19 pandemic, with urgent implementation of safety protocols limiting the number of on-site personnel, curtailed the utilization of rapid on-site evaluation (ROSE) for CT-guided lung biopsies at our institution. The pandemic, therefore, created an opportunity to examine the role of ROSE in diagnostic adequacy and ancillary testing yield for CT-guided lung biopsies. Material(s) and Method(s): We retrospectively identified all CT-guided lung biopsies performed from 2017-2021. The utilization of ROSE, adequacy of final diagnoses, and ancillary testing yield (PD-L1 immunohistochemistry, next generation sequencing) were ed from pathology reports and compared between 2017-2019 and 2020-2021. Cases were considered nondiagnostic if a definitive neoplastic diagnosis could not be rendered (e.g., atypical or suspicious diagnoses) or the histologic features did not explain imaging findings. Chi-square tests of independence were performed to examine relations between variables. Result(s): 766 CT-guided lung biopsies were performed from 2017-2021;174 (23%) utilized ROSE. The use of ROSE had been steadily decreasing prior to the pandemic and essentially ceased at the onset of the pandemic and never returned to pre-pandemic volumes (Figure 1). Overall (2017-2021), ROSE was more likely to be associated with an adequate final diagnosis (p=.003) and successful molecular testing (p=.013). ROSE was not associated with adequacy of PD-L1 results (p=.797). Comparing the periods 2017-2019 and 2020-2021 (with decreased utilization of ROSE in the latter), there was a trend towards a higher percentage of inadequate final diagnoses (17 vs. 24%, p=.08). Conclusion(s): Overall, ROSE was associated with higher diagnostic and molecular testing yields for CT-guided lung biopsies. The COVID-19 pandemic markedly reduced ROSE use during these procedures;evaluation of the impact on clinical care is ongoing with further studies investigating lesion size, number of passes, and need for repeat procedures.
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In patients recovering from coronavirus disease 2019 (COVID-19) pneumonia, respiratory symptoms and radiographic pneumonic infiltrate occasionally persist for many weeks even after viral clearance; thereby, making it difficult to decide on an appropriate treatment. Here, we describe a 46-year-old woman with COVID-19 pneumonia who had persistent radiographic pneumonic infiltration and respiratory symptoms for almost 4 weeks after illness onset, despite viral clearance, and was subsequently diagnosed with secondary organizing pneumonia (SOP) using video-assisted thoracoscopic (VATS) wedge lung biopsy. Intravenous methylprednisolone was administered at an initial dose of 50 mg/day (1 mg/kg) for 7 days and was tapered to a dose of prednisolone 30 mg/day following improvement in the patient's respiratory symptoms and chest radiographic findings. The patient was discharged from the hospital 14 days after the initiation of corticosteroid treatment. The dose of prednisolone was tapered monthly to 20, 15, 10, and 5 mg/day, respectively, at the outpatient clinic for a total duration of 6 months; nearly resolved pneumonic infiltrations were observed in a follow-up computed tomography scan approximately 2 months after she was admitted. To the best of our knowledge, this is the first case report of a COVID-19 associated SOP that was pathologically confirmed through VATS wedge lung biopsy in Korea. SOP should be considered in the differential diagnosis of patients with COVID-19 pneumonia with persistent respiratory symptoms and radiographic pneumonic infiltrations during the recovery phase to avoid the redundant use of antimicrobial or antiviral agents. Furthermore, histological confirmation is essential for the definitive diagnosis of SOP to avoid unnecessarily prolonged corticosteroid treatment.
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Clinicians face a significant obstacle when attempting to diagnose interstitial lung disease (ILD) patients. However, a thorough clinical examination together with the proper imaging and diagnostic techniques may provide a reliable diagnosis of a particular kind of ILD, and invasive tests such as rigid bronchoscopy or surgical lung biopsy may not be necessary. The aim of this study is to determine the histologic outcomes of an ILD transbronchial lung biopsy (TBLB) carried out at the university hospital in Aleppo. Methods: This retrospective cohort research was done between 1 January 2020 and 18 April 2022 at the pulmonary department of Aleppo University Hospital, Syria, using patient records. In our study, 174 patients were examined. We included patients over the age of 18 who were referred or admitted to our department at Aleppo University Hospital after being diagnosed with diffuse parenchymal lung disease based on high-resolution computed tomography and clinical symptoms, while excluding other respiratory diseases such as tuberculosis and coronavirus disease 2019. Results: Patients in the research were 53±7.1 years old on average. Cough and dyspnea were the most common clinical complaints among the patients, which accounted for 79.12 and 78.16%, respectively. A significant fraction of ground-glass opacity was detected on the high-resolution computed tomography, amounting to 102 (58.62%) and 74 (42.53%) for the reticular lesions, respectively. As a complication there were 40 patients with bleeding, of whom 24 had moderate bleeding, and 11 had major bleeding. We also had three patients with pneumothorax. The diagnostic yield of the TBLB in our ILD patients was 66.66%. Conclusion: An adequate diagnostic accuracy (66.66%) was detected in the TBLB in confirming the diagnosis of ILD; in addition, the bleeding was the most prevalent complication of this procedure. More interventional studies are needed to compare the diagnostic accuracy of this procedure with other invasive and noninvasive diagnostic methodologies of ILD.
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Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.
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Introduction: Coronavirus disease-2019 (COVID-19) infection can result in pulmonary complications ranging from mild illness to severe life-threatening disease. There are limited studies correlating the association between the clinical course of COVID-19 and histopathological findings. This study aimed to examine the postmortem histopathological changes in lung tissue of COVID-19-positive patients and to correlate those changes with disease severity. Materials and methods: This prospective observational study was conducted in adult COVID-19-positive patients. Postmortem core needle biopsy (CNB) of the lung was done using ultrasonography guidance within 1 hour of death. Histopathological analyses were performed by two expert pulmonary pathologists. The demographic and clinical data of the patients were recorded to correlate them with histopathological findings. Results: In total, 48 patients were assessed for inclusion, and 21 patient relatives consented for the study. The median duration of illness was 21 (range 9-38) days, the predominant histopathological finding was diffuse alveolar damage (DAD) in most patients (19/21), followed by pneumonia (13/21). Exudative, intermediate, and advanced DAD patterns were seen in 9.5%, 52.4%, and 28.6% of cases, respectively. Advanced DAD was associated with a longer duration of disease. The pneumonia findings were associated with positive respiratory and blood cultures. The microvascular thrombus was seen only in one patient. Conclusion: The predominant pathological findings in our patients were DAD and pneumonia. The DAD type correlated with the duration of illness, and we attributed pneumonia findings to secondary infection. The incidence of microvascular thrombi was low, and it might reflect the effect of treatment with anticoagulation. How to cite this article: Maddani SS, Rao R, Deepa HC, Noronha AK, Chaudhuri S, Vishwas P. Pathological Lung Patterns of COVID-19 and its Clinical Correlation to Disease Severity. Indian J Crit Care Med 2022;26(12):1285-1292.
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Purpose: Lung transplant recipients (LTRs) are less likely than other solid organ transplant recipients (SOTRs) to develop an antibody response to SARS-CoV-2 vaccination. Mycophenolate has been associated with impaired humoral response to SARS-CoV-2 vaccination, leaving these patients vulnerable to infection. Perivaccination antimetabolite hold has been an effective strategy for some patients with rheumatic and musculoskeletal diseases. In this study, we describe the safety and efficacy of a peri-vaccination antimetabolite hold in LTRs on SARS-CoV-2 anti-spike protein development following a third vaccine dose. Method(s): We studied LTRs on mycophenolate or azathioprine based antimetabolite therapy (AMT) >1-year post-LT with no history of acute cellular or humoral rejection who received SARS-CoV-2 vaccine Dose 3 (D3) May-October 2021. Patients were instructed to hold AMT 1 week before and 2 weeks after D3. Antibody titers were measured pre- and post-D3 (Roche Elecsys or DiaSorin Liaison anti-S EIA). Safety was evaluated using donor specific antibody (DSA) trend and lung biopsy results. Result(s): Of 40 participants, 30 held AMT and 10 did not hold AMT. Median (IQR) time since transplant was 3.9 years (1.9-7.3). Median (IQR) time between vaccine dose 2 and D3 was 163 days (143- 180). Among participants seronegative pre-D3, seroconversion post-D3 occurred in 52% (12/23) who held AMT vs. 57% (4/7) who did not hold AMT (p>0.9). Among patients with pre- and post-D3 DSA levels (N=19), increasing or de novo positive DSA was seen in 8.3% (1/12) of patients who held AMT vs. 0% of patients who did not hold AMT. For patients who underwent lung biopsy post-D3 (N=8), abnormal biopsy was seen in 0% (0/1) of patients holding AMT vs. 28.6% (2/7) not holding AMT. Conclusion(s): A three-week AMT hold by LTRs was not associated with increased rejection but also showed no significant difference in seroconversion compared to LTRs who did not hold AMT, suggesting this hold protocol is safe but not effective. Further investigation of alternative strategies is needed to protect LTRs from COVID-19 infection who do not mount effective immunoprotection following SARS COV-2 vaccination. (Table Presented).
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SESSION TITLE: Challenges in Cystic Fibrosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Pulmonary involvement in Systemic Lupus Erythematosus (SLE) is seen in 30-50% of patients (most commonly Nonspecific Interstitial Pneumonitis) but cystic lung disease is extremely rare (1). Lymphoid interstitial pneumonia (LIP) is an inflammatory lung disease that is characterized by infiltration of lymphocytes and plasma cells (2), and associated with lung cysts. Oftentimes, it is associated with HIV, lymphoma, and primary Sjogren's Syndrome (SS) (2), however there are rare reports of LIP associated with SLE (1). We present a case of a young male with incidental lung cysts who was found to have a new diagnosis of SLE. CASE PRESENTATION: A 24-year-old male with a past medical history of premature birth at 5 months and prior mild COVID-19 infection presented with 3 weeks of abdominal pain, nausea, vomiting, fever, and unintentional 15-pound weight loss. He endorsed dry mouth, frequent cavities, and a new rash involving his chest, face, and lower extremities. Physical exam was significant for malar rash and dry mucous membranes. Labs revealed pancytopenia, sedimentation rate 61 mm/hour and C-reactive protein 5.54 mg/L. Computed tomography (CT) of the chest showed several thin-walled cysts in all bilateral lung lobes (predominant in right upper lobe) and bilateral axillary lymph nodes [Figure 1]. CT abdomen and pelvis was unremarkable. Autoimmune work-up resulted in a positive antinuclear antibody >1:1280, double stranded DNA antibody elevated at 34, elevated SSA and SSB antibodies (>8.0 and 1.4 respectively), and decreased Complement 3 (59.5 mg/dl) and 4 (10.1 mg/dl) levels. Peripheral smear, right axillary lymph node and bone marrow biopsies were negative for malignancy. He was started on prednisone and Plaquenil with symptomatic improvement. There is high suspicion of LIP given the clinical and radiological findings. He will follow up in clinic to obtain PFTs and schedule a lung biopsy. DISCUSSION: Interstitial lung disease in SLE presents in middle-aged patients at a later part of their disease course, with a female preponderance (2,3). An initial presentation of SLE and secondary SS in a young male and associated cystic lung disease is rare. The suspicion for LIP in association with SLE is high in our patient given variable size and distribution of lung cysts and coexisting secondary Sjogren's syndrome, although no ground glass or nodular opacities were found on CT chest as reported in typical LIP (3). Though this patient has no pulmonary symptoms, cysts/LIP in SLE tend to progress and have a high incidence of developing lymphomas, gammaglobulinemia and amyloidosis (2,3). CONCLUSIONS: It is important to establish a histopathological diagnosis and obtain baseline PFTs to monitor pulmonary disease manifestations. In addition to controlling the primary disease with antirheumatic drugs, steroids have been found to be useful in acute pulmonary flares (2). Reference #1: Maeda R, Isowa N, Miura H, Tokuyasu H. Systemic lupus erythematosus with multiple lung cysts. Interact Cardiovasc Thorac Surg. 2009 Jun;8(6):701-2. doi: 10.1510/icvts.2008.200055. Epub 2009 Mar 12. PMID: 19282324. Reference #2: Yood RA, Steigman DM, Gill LR. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus. Lupus. 1995 Apr;4(2):161-3. doi: 10.1177/096120339500400217. PMID: 7795624. Reference #3: Filipek MS, Thompson ME, Wang PL, Gosselin MV, L Primack S. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus: radiographic and high-resolution CT findings. J Thorac Imaging. 2004 Jul;19(3):200-3. doi: 10.1097/01.rti.0000099464.94973.51. PMID: 15273618. DISCLOSURES: No relevant relationships by Matthew Fain No relevant relationships by Christina Fanous No relevant relationships by Rathnavali Katragadda No relevant relationships by CHRISELYN PALMA
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SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by low serum IgG, IgA and/or IgM, and poor specific antibody production. CVID is estimated to affect as many as 1 in 25,000 individuals. Chronic lung disease is a common problem in patients with CVID. About 10-20% of patients have lymphocytic infiltrates and/or sarcoid-like granulomas, with several histological findings, termed granulomatous and lymphocytic interstitial lung disease (GLILD). CASE PRESENTATION: Patient is a 61-year-old Caucasian woman with a history significant for CVID in remission who presented to the Pulmonary Clinic with a chief compliant of dyspnea of exertion (DOE). Patient was not suffering from any respiratory complaints until the diagnosis of severe COVID-19 pneumonia 4 months prior. For the following months, patient was slowly improving but was still suffering from severe DOE that has negatively impacted her quality of life. Patient has a remote history of smoking, having quit 10 years ago. Patient denied any joint pain, stiffness, swelling, skin rash, muscle ache, or weakness. No known history of SLE, Rheumatoid Arthritis, or other collagen vascular disorders had been reported. Patient denied any exposure to birds. Physical exam was significant only for bilateral basal rales with no wheezing or crackles. No skin rash, joints deformities, or clubbing was noticed. Laboratory studies revealed ESR was 17 with a CRP of 10.6. Negative ANA, SM, RNP, and SSA/SSB antibodies. Her Immunoglobulins levels were low with IgG 382 (nl > 610) and IgA < 2 (nl > 85). Her PFT revealed severe restrictive process with TLC 46% of predicted and severe reduction in DLCO at 35%. CT chest revealed diffuse central groundglass opacities, and interstitial thickening with traction bronchiectasis. Lung biopsy via VATS revealed lung parenchymal with focal, noncaseating granulomas, foci of focal interstitial lymphocytic infiltration and fibrosis;features consistent with Granulomatosis-Lymphocytic Interstitial Lung Disease (GLILD). Systemic steroid initiated and for the following weeks patient reports significant improvement in DOE. Her PFT at 3 month follow up showed significant improvement in FVC (5% increase), TLC (11% increase), and DLCO (5% increase). DISCUSSION: The respiratory manifestations of CVID follow two main mechanisms: injury due to acute or recurrent infections and damage due to poorly understood immune-mediated processes. Severe COVID-19 results in dysregulated immune and inflammatory response that can worsen an underlying lung disease. Previous cases have been reported about CVID with GLILD complicated with COVID-19 infection but not vice versa. CONCLUSIONS: To our knowledge, this is a rare case of CVID complicated by GLILD triggered by recent COVID-19 infection. However, little is known about the association between COVID-19 infection and GLILD and further investigation is needed. Reference #1: Ho HE, Mathew S, Peluso MJ, Cunningham-Rundles C. Clinical outcomes and features of COVID-19 in patients with primary immunodeficiencies in New York City. J Allergy Clin Immunol Pract. 2020;S2213–2198(20):31102–8. Reference #2: Prasse A, Kayser G, Warnatz K. Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med. 2013;19:503–9. Reference #3: Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48. DISCLOSURES: No relevant relationships by husam nayef No relevant relationships by Arshia Vahabzadeh No relevant relationships by Zaid Yaqoob No relevant relationships by Mohammad Zalt