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Background: Severe COVID-19 and obesity are characterized by higher inflammation. We aimed to examine early inflammatory patterns in people with (Ob) and without (NOb) obesity and COVID-19 and how they relate to COVID-19 disease severity Methods: Ob (BMI >30 Kg/m2) and NOb with COVID-19 matched for age, sex and WHO disease severity provided blood early after diagnosis. Immunoassays measured 57 plasma biomarkers reflecting innate immune and endothelial activation, systemic inflammation, coagulation, metabolism and microbial translocation (Fig 1). Between-group differences were assessed by Mann- Whitney. Associations between subsequent maximal COVID-19 severity (mild vs moderate/severe/critical) and biomarkers were explored by logistic regression adjusted for age, sex, hypertension (HTN) and diabetes (DM). Data are median pg/mL [IQR] or n [%] unless stated Results: Of 100 subjects (50 Ob and 50 Nob) presenting between April 2020 and March 2021, characteristics (Ob vs Nob) included: age 65 [23-91] vs 65 [21-95];female sex 27 (48%) vs 28 (56%);BMI 33.7 [30.0-71.8] vs 23.3 [15.3-25.9];disease severity mild 22 [48%] vs 23 [46%], moderate 15 [30%] vs 13 [26%], severe 6 [12%] vs 7 [14%];HTN 30 (60%) vs 17 (34%);DM 19 [38%] vs 6 [12%];days from symptom onset 7 [2-17] vs 8 [1-15];vaccinated 3 (6%) vs 0 (0%). Compared to NOb, Ob had higher IFN-alpha (1.8 [0.6;11] vs 0.9 [0.1;4.7]), CRP (10 mAU/mL [9.6;10.2] vs 9.7 [7.2;10]), IL-1RA (197 [122;399] vs 138 [88;253]), IL-4 (288 AU/mL [161;424] vs 205 [82;333]), vWF (252 [166;383] vs 163 [96;318]), Zonulin (114 ng/mL [77;131] vs 57 [18;106]), Resistin (956 [569;1153] vs 727 [712;1525]), Leptin (3482 [1513;5738] vs 848 [249;2114]), and lower Adiponectin (1.12 mg/L [0.09;1.5] vs 1.5 [1.18;1.93]), all p< 0.05. In both groups higher, proinflammatory IL-18 and lower levels of antiinflammatory CCL22 and IL-5 were associated with higher odds of disease severity, and lower E-selectin with higher disease severity only in Ob. However, in NOb higher type 3 interferons (IL-28A), macrophage activation (sCD163, CCL3) and vascular inflammation markers (ICAM-1, VCAM-1), along with higher S100B, GM-CSF and leptin were also associated with disease severity, a pattern not observed in Ob (Fig 1) Conclusion(s): Although Ob had higher overall levels of inflammation than NOb, few biomarkers predicted subsequent COVID-19 severity in Ob. These differential inflammatory patterns suggest dysregulated immune responses in Ob with COVID-19. (Figure Presented).
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Background: Previous longitudinal studies (n=6) of objective olfaction performance post-acute COVID-19 have a maximum follow-up of 6-month and do not often test biomarkers. Although olfactory dysfunction appears to improve within two months of symptom onset, 4/6 longitudinal studies show persistent olfactory impairment. Method(s): PCR-confirmed COVID-19 patients in the prospective ADAPT cohort (Sydney, Australia) were assessed across 18 acute symptoms and hospitalization status: 40% mild, 50% moderate, 10% severe/hospitalised - none deceased). Blood samples were taken 2 (N=179), 4 (N=148) and 12-month (N=118) post-diagnosis. The NIH Odor Identification Test (OIT) and the Cogstate brief cognitive battery were performed. 58 also had an olfaction test at 24-month. The OIT raw data were transformed into demographically-corrected T-scores. OIT's attrition was completely random and only initial age (40+/-15 versus 47+/-15) differed between patients lost to follow-up and those in the study at 24-month. We tested peripheral neurobiomarkers (NFL, GFAP, S100B, GM-CSF) and immune markers (Interleukin-IL panel: 1-beta, 1Ralpha, 4, 5, 6, 8, 10, 12p40, 12p70, 13, and MCP-1, TNF-alpha and INF-gamma), analyzed as Log transformed and elevated/normal range using published references. Our previous analyses had shown no relationship with the kynurenine pathway, but an association of impaired olfaction and impaired cognition at 2-month only. Linear mixed effect regressions with time effect (months) tested olfaction trajectories (random subject effect) and their association with the biomarkers (main and time interaction). Result(s): At 2 months post-diagnosis 30% had impaired olfaction and those who had acute severe disease were more likely to be impaired (54% versus 26%, p=.009). 21%, 31% and 37% had impaired olfaction at 4, 12 and 24-months. Olfactory performance declined over time (p< .0001), which was dependent on the initial performance (Fig 1). Neurobiomarkers were within the normal range. IFN-gamma, IL-1Ralpha, IL-13 and TNF-alpha increased across time, p< .03-p< .0005. TNF-alpha and IFN-gamma showed a time covariance with poorer olfaction performance. Conclusion(s): Post-acute mild to moderate COVID-19 is associated with a declining olfactory performance up to 2-yr post-diagnosis, especially when initially impaired with the provisio of attrition although random. Olfactory performance decline may be mediated by upregulated immune parameters which are distinct from those driving cognitive changes. (Figure Presented).
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Background: COVID-19, the disease caused by SARS-CoV-2, has resulted in devastating morbidity and mortality worldwide. Alarming evidence indicates that long-term adverse outcomes of COVID-19 can affect all major systems of the body, including the immune, respiratory, cardiovascular, and neurological systems. While acute COVID-19 pathology does not appear to be markedly different by HIV status, long-term outcomes of COVID-19 in People with HIV (PWH) are unknown and require further investigation. This study evaluates the inflammatory profile longitudinally up to three months after COVID-19. In addition, markers of the blood-brain barrier (BBB) integrity and vascular dysfunction were also evaluated. Method(s): Plasma samples were collected from 15 males and 6 females with COVID-19 and HIV infection (COVID+/HIV+) and 9 males and 14 females with COVID-19 without HIV infection (COVID+/HIV-) between March 2020 and March 2021. Baseline samples were obtained approx. 10 days after COVID-19 diagnosis (T=0) and three months after (T=3). Mean age group for COVID+/HIV-was 45.4+/-17.8 years for males and 39.7+/-15.3 for females and for COVID+/HIV+ was 52.1+/-12.3 for males and 48.7+/-1 for females (N=15 and 6, respectively). 27 inflammatory molecules were measured by Bio-Plex Multiplex Immunoassay (Bio-Rad) and two markers of BBB and vascular dysfunction (soluble ICAM1 and S100beta) by ELISA. Result(s): Out of 27 inflammatory analytes, 20 had detectable signals. Eotaxin (CCL11) and G-CSF levels were differentially upregulated in the COVID+/HIV+ group as compared to the COVID+/HIV-group in both time point studied (Table 1). IFN-g showed sustained increased levels at T=3 in the COVID+/HIV+ group, whereas there was a significant reduction over time in the COVID+/HIV-group. At T3, inflammatory markers (IL-4, IL-8, IL-13, basic FGF, TNF-alpha, MIP-1alpha, and CCL2) either decreased or remained unchanged in both groups. In contrast, the markers of the BBB disruption and vascular dysfunction, such as S100beta and soluble ICAM-1 increased in the COVID+/HIV+ group, suggesting long-term progressive BBB and vascular alterations. Conclusion(s): HIV-1 may potentiate long COVID-19-induced neuropathology, with progressive BBB breakdown and sustained increase in eotaxin-1 and G-CSF. Plasma inflammatory markers in COVID-19 patients with or without HIV-1 co-infection.
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SESSION TITLE: Invasion of the Pleura SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: Schwannoma is a well circumscribed encapsulated solitary neoplasm arising from myelin producing cells of peripheral nerve sheaths. Pleural schwannomas represent only 1-2% of thoracic tumors and rarely present with pleural effusion. To our knowledge only six cases of benign pleural schwannoma have presented with a pleural effusion to date. We present a rare case of a pleural schwannoma with bilateral serosanguinous pleural effusions complicated by necrotizing pneumonia. CASE PRESENTATION: 54 year old smoking male with no past medical history was transferred from an outside hospital after two weeks of worsening acute hypoxemic respiratory failure while being treated for necrotizing pneumonia, right sided loculated pleural effusion, and a right paramediastinal mass. His only presenting symptom was worsening dyspnea for three days. Upon arrival to our hospital, the patient was on maximal ventilator settings with two right sided chest tubes draining blood tinged pleural fluid. CTA of the chest showed a large cavitary consolidation in the right upper lobe with destruction of the lung parenchyma. Additionally, there was an intrapleural heterogenous mass in the posterior aspect of the right lung apex which abut the mediastinum measuring 9.7 x 7.5 x 10.3 cm. He was treated with zosyn for positive sputum cultures growing beta hemolytic strep group F. Patient underwent a flexible bronchoscopy with EBUS-TBNA of mediastinal lymphnodes and lung mass which was non-diagnostic. A CT guided biopsy revealed a spindle cell neoplasm with a Ki-67 of 10-20%. Immunohistochemical analysis demonstrated positive staining of the tumor cells for S-100 protein. The final pathological diagnosis was benign schwannoma. He underwent a tracheostomy and PEG and was sent to a rehab center with outpatient follow-up with cardiothoracic surgery for tumor removal. DISCUSSION: Pleural schwannomas are slow growing, rarely progress to malignancy, and are often located in the posterior mediastinum. Patients are usually asymptomatic but can present with symptoms associated with obstructive pneumonia. It is very rare for a benign pleural schwannoma to present with a pleural effusion. Literature review has revealed only six cases of benign schwannoma presenting with a pleural effusion, all of which were blood stained. Spontaneous tumor hemorrhage or cyst rupture has been a theory of etiology for the effusions. Prognostically, once the pleural schwannomas are surgically resected there is minimal chance of recurrence. CONCLUSIONS: Our case represents a benign pleural schwannoma that caused extrinsic compression on the right upper lobe bronchus leading to a necrotizing pneumonia along with bilateral serosanguinous pleural effusions. A pleural schwannoma should be considered in the differential diagnosis of intrathoracic tumors even when presenting with pleural effusions. Reference #1: Shoaib D, Zahir M, Khan S, et al. Difficulty Breathing or Just a Case of the Nerves? Incidental Finding of Primary Pleural Schwannoma in a Covid-19 Survivor. Cureus. 2021. 13(8): e17511. Reference #2: Bibby A, Daly R, Internullo E, et al. Benign Pleural Schwannoma Presenting with a Large, Blood Stained Pleural Effusion. Thorax. 2018. 73:497-498. Reference #3: Nosrati R, Annissian D, Ramezani F, et al. Benign schwannoma of posterior mediastinum accompanied by blood pleural effusion misdiagnosed as solitary fibrous tumor: A Case report. Casplan J Intern Med. 2019. 10:468-471. DISCLOSURES: No relevant relationships by Brittany Bass No relevant relationships by Oleg Epelbaum No relevant relationships by Theresa Henson No relevant relationships by Yasmin Leigh No relevant relationships by Ester Sherman No relevant relationships by Sally Ziatabar