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Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.
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Background & Aim: Ricin is one of the most lethal toxins, particularly if inhaled, and is considered a biological threat agent due to its wide availability and ease of production. Pulmonary ricin intoxication manifests in ARDS, cytokine storm, immune infiltration, and severe edema. Passive immunization is the preferred measure against pulmonary ricinosis, but only if administered shortly after exposure. Despite their potential to remedy pulmonary injury and inflammation, mesenchymal cell (MSC) therapies were never investigated in ricinosis. Here, we report the potential for treating pulmonary ricinosis with MesenCure, a professionalized allogeneic MSC therapy shown to reduce the mortality of patients suffering from severe pulmonary manifestations of COVID by 68%. Methods, Results & Conclusion(s): Preliminary studies demonstrated positive MesenCure effects in a sub-lethal pulmonary ricinosis model in CD1 mice. This model is regarded as highly translational due to the broad heterogeneity of these outbred mice. Positive effects included a reduction in excess protein content of the bronchoalveolar lavage fluid (BALF) by 45% when MesenCure was injected intravenously (IV) at 125k cells/animal, 48h post-exposure (PE) and evaluated one day later (p<0.05, Fig. 1A). Moreover, we found up to 52% reduction in the excess BALF leukocytes, when MesenCure was injected IV, 24h PE using the same dose (p<0.05, Fig. 1B) or 6h PE using a double dose (p<0.01, Fig. 1C), and evaluated two days PE. Optimizing the dose and administration route further improved the therapeutic outcome of MesenCure applied 6h PE as assessed by weight loss. As shown in Fig. 1D-E, IV injection of 250k-500k MesenCure cells/animal slightly protected the intoxicated animals against weight loss (p for treatment x time interaction <0.01 or <0.05 for 250k and 500k cells/animal, respectively). Interestingly, one million cells IV resulted in a lesser effect (not shown), however when injected subcutaneously (SC), 1M cells were very effective (p<0.001, Fig. 1F), seemingly even more effective than 2M cells/animal SC (Fig. 1G). Surprisingly, 2M thawed cells/animal injected SC protected the animals against weight loss almost completely (p<0.0001, Fig. H). In conclusion, we provide evidence for the potential of SC MSCs, specifically MesenCure, for treating pulmonary ricinosis and possibly other forms of ARDS. In agreement with Giri and Galipeau (2020), we provide further evidence for the dependency of MSC outcomes on their specific state and administration route. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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The COVID-19 outbreak has fashioned to severe threat to each and every individual in social and economic aspects in the country. This required improved wisdom to know how it is different and dominant, to diagnose and determine effective vaccines to avoid the transmission of these deadly causative agents. From this review, the probable property of these deadly transmissible viruses is related to that of SARS-CoV-2 as a fright zone of viruses. It also provides some sparks about effective and accurate diagnosis and treatment strategies. The effective management and control of panic zone of virus (PZV) and SARS-CoV-2 are more important to reduce the pandemic situation.Copyright © 2023 Inderscience Enterprises Ltd.
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Towards the end of 2019 a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) caused the ongoing global pandemic. The virus surface consists of spike proteins that mediate SARS-CoV-2 entry into cells through its receptor-binding domain (RBD) that attaches to the human receptor Angiotensin- Converting Enzyme 2 (ACE2). Upon infection with foreign material, like viruses and bacteria, the human immune system responds by producing a humoral response specific to the viral antigen. Cells from the innate immune system and antibodies generated in the humoral response work to destroy and block infectious antigens from causing damage to the human cells. The S protein of SARSCoV- 2 is the key protein that stimulates the immune system to generate neutralizing antibodies. To safely test and investigate SARS-CoV-2 in BSL-2 lab setting, we propagated a surrogate pseudo typed virus to evaluate the ability of antibodies to reduce viral cell entry and replication in SARS-CoV-2 infected mice model. Quantifying the functional ability of neutralizing antibodies would help us understand how they influence reinfection in recovered individuals. We hypothesize that antibodies generated in SARS-CoV-2 infected mice models will induce a protective immune response against the SARSCoV- 2 infection. To detect and quantify the protective immune response generated in mice, we performed two different serological assays and identified antibodies endpoint titers. Mice were infected with Delta and Beta at time points Day 3 and Day 4. We performed a SARS-CoV-2 Spike pseudo virus neutralization assay and measured luminescence to determine the percentage neutralization of functional antibodies induced in mice serum samples upon infection. Utilizing indirect ELISAs,' we measured absorbance for IgA antibodies in Bronchoalveolar lavage fluid (BALF) serum and total IgG antibodies in cardiac bleeds. Our results showed we did not obtain neutralizing activity of antibodies in mice serum samples taken at early time points, 24 hrs and 4 days, after infection with the Delta variant of SARS CoV2 virus using both the pseudo viruses Omicron andWA spike.We obtained 100% neutralizing activity in mice serum samples taken at day 21 and infected with Beta variant of SARS CoV2 virus using both the pseudo viruses Omicron and WA spike demonstrating that there is cross-neutralization against various variants of concern. Antibodies (IgA, IgM, IgG) generated in mice 3 weeks post infection with SARS CoV2 (Beta) virus are capable of neutralizing and inhibiting the entry of WA spike and Omicron pseudo viruses in human HEK293 T Ace2 cells. Moving forward utilizing samples with timepoints surpassing 3 weeks could possibly yield higher concentrations of IgA and IgM antibodies that can neutralize the SARS-CoV-2 pseudo virus. Thank you to Dr. Rhea Coler, the entire Coler lab, National Institutes of Health (NIH), and Seattle Children's Research Institute.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Objective To explore the application value of Biofire Filmarry pneumonia panel (PN) in detection of secondary and concomitant pathogen among critically ill patients with coronavirus disease 2019(COVID-19). Methods We consecutively included and analyzed the clinical data of critically ill patients with COVID-19 transferred to the ICU from February to April 2020 in the Sino-French Campus of Wuhan Tongji Hospital. Samples of Bronchoalveolar lavage fluid obtained by bedside bronchoscopy were sent for Biofire Filmarray PN and standard culture concomitantly. We compared the results of two methods and evaluated their concordance. Results In total, 21 critically ill patients with COVID-19 were included and 54 samples were tested, including 33 (61.1%) Biofire Filmarray PN tests (21 patients) and 21 (38.9%) standard cultures (14 patients), in which 19 pairs (38 samples) underwent both tests simultaneously. In Biofire Filmarray PN group, the turnaround time was about 1 hour. There were 74 positive results in 32 samples (97.0%) from 20 patients, including 29 cases(39.2%) of Acinetobacter baumannii complex, 21 cases (28.4%) of Pseudomonas aeruginosa, 16 cases (21.6%)of Klebsiella pneumoniae, 5 cases (6.8%) of Escherichia coli, 1 case (1.4%)each of Enterobacter cloacae, Haemophilus influenzae, and respiratory syncytial virus. In the standard culture group, the turnaround time was about 3 days. 19 positive results returned in 16 (76.2%) samples from 11 patients, including 8 cases (42.1%) of Pseudomonas aeruginosa, 6 cases (31.6%) of Acinetobacter baumannii, 4 cases (21.1%) of Stenotrophomonas malt and 1 case (5.3%) of Myxobacterium. Among the 19 pairs of "back-to-back" specimens, 15 pairs were concordant, and the agreement ratio was 78.9%. Conclusions Acinetobacter baumannii and Pseudomonas aeruginosa may be the common pathogens of secondary or concomitant infection in critically ill patients with COVID-19. Biofire Filmarray PN is a rapid diagnostic test and has application value in such patients;its sensitivity and accuracy require further investigation with larger sample sizes.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.
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Introduction: The most widely used marker for the diagnosis of invasive aspergillosis (IA) is the detection of galactomannan by ELISA. This study describes the evaluation of the results obtained by Euroimmun Aspergillus antigen ELISA (EIA-GM-E) in serum samples and bronchoalveolar lavage fluid (BAL) from patients at risk of IA, and compares these results with those obtained by Bio-Rad Galactomannan EIA (EIA-GM-BR). Method(s): Anonymous retrospective case-control comparative study in 64 serum samples and 28 BAL from 51 patients. Result(s): Overall agreement of the results of the two assays was observed in 72 of 92 samples (78.3%). The sensitivity of EIA-GM-BR and EIA-GM-E in serum samples was 88.9% and 43.2%, respectively, and 100% and 88.9% for BAL. The specificity of EIA-GM-BR and EIA-GM-E in serum samples was 91.9% for both assays, and 68.4% and 84.2% in BAL. There were no statistically significant differences in the results of both assays. Conclusion(s): Both methods show good results for the discrimination of patients with IA when BAL is tested, or serum in case of EIA-GM-BR.Copyright © 2021 Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica
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Introduction: Instillations with balcillus Calmette - Guerin (BCG) are established adjuvant therapy for superficial bladder cancer. Although generally safe and well tolerated, they may cause a range of different, local, and systemic complications. Case description: We present a patient treated with BCG instillations for three years, who was admitted to our hospital due to fever and progressive dyspnea. Blood test revealed elevated CRP and liver function tests. On CT scan massive bilateral ground glass opacities in the middle and lower parts of the lungs, parenchymal infiltrations, bronchial walls thickening, and hilar lymphadenopathy were visible. PCR test for SARS-CoV-2 as well as sputum, blood, and urine cultures were negative. Initial empiric antibiotic therapy was ineffective and respiratory failure progressed with the need of oxygen supplementation of 15l/min. Finally, positive cultures for M. tuberculosis ssp. bovis (BCG) were available from sputum and bronchoalveolar lavage fluid. Antituberculous treatment (rifampin, isoniazid, etambuthol) was implemented together with systemic corticosteroids resulting in the quick improvement of the patient's clinical condition. Due to hepatotoxicity and finally reported resistance of the BCG strain to isoniazid, it was replaced with levofloxacin with a good tolerance. Follow up CT scan showed partial resolution of the infiltrates. The patient was discharged home and continued treatment without further side effects. Conclusion(s): The diagnosis of BCG infection in the lungs must be taken into consideration in every patient treated with BCG instillations and symptoms of unexplained infection.
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A significant number of patients suffer from persistent symptoms following COVID-19 infection. However, data regarding the immunopathological mechanisms and potential biomarkers are limited. We investigated the differential cell count in the bronchoalveolar lavage fluid (BALF) in a post-COVID cohort. Patients presenting at the Vienna General Hospital within six months of a COVID-19 infection were enrolled. All patients underwent pulmonary function tests (PFT) and low-dose HRCT at baseline and at 6 and 12 months after a COVID-19 infection. Patients with pathological findings on HRCT or impairment in PFT were offered a bronchoscopy with BALF differential cell count via FACS analysis. Out of the 305 patients enrolled, 29 underwent bronchoscopy with bronchoalveolar lavage. After a median of 84 days following initial diagnosis of COVID-19, 25 showed persistent symptoms including dyspnoea (62.1%), fatigue (10.3%) and chest pain (10.3%). 24 patients showed pathological findings on HRCT consistent with COVID-19. While 11 patients developed a restrictive lung disease defined as TLC < LLN, 18 patients showed a reduced diffusion capacity defined as DLCO < 80%. Differential cell counts revealed that some patients showed lymphocytosis (7/29), increased eosinophil counts (5/29) and elevated neutrophils counts (2/29) in the BALF. Our preliminary data show that 34.5% of patients with persistent changes on HRCT have an elevated immune cell count with lymphocytosis being the predominant pattern. The degree of alveolar lymphocytosis might correlate with the severity of restrictive lung disease and might facilitate treatment decisions in patients with persistent symptoms following COVID-19.
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. There is no effective medication for COVID-19 as of now, so it would be good to take preventive measures that not only boost our immunity but also fight against infections. The use of traditional Chinese medicine in China to treat COVID-19 patients sets the prototype demonstrating that traditional medicines can contribute to prevention and treatment successfully. In India, the Ministry of AYUSH (Ayurveda, Yoga, Unani, Siddha, Homeop-athy) released a self-care advisory during the COVID-19 crisis as a preventive aspect. This review article discusses the therapeutic potential and clinical relevance of some herbs [(Tulsi (Ocimum sanctum), Haridra (Curcuma longa), Tvaka (Cinnamon), Maricha (Piper longum), Shunthi (Zingi-ber officinale), Munakka (Dried grapes), Lavang (Syzigiumaromaticum), Pudina (Mentha arvensis), and Ajwain (Trachyspermum ammi)] advised by AUYSH to take during COVID-19 infection. They are effective in COVID-19 management, therefore, authors have discussed their detailed traditional uses as therapeutics and spotted scientific insight and clinical significance of the herbs mentioned above along with their mechanistic viewpoint, adequately, on a single platform. Provided information could be a treasure to open up a new research arena on natural products to manage human health crises effectively, caused not only by COVID-19 but also by other infectious diseases.Copyright © 2023 Bentham Science Publishers.
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Objective To investigate drug resistance gene in Mycoplasma pneumoniae (MP) and the distribution of 13 respiratory pathogens in bronchoalveolar lavage fluid(BALF) of children with Mycoplasma pneumoniae pneumonia(MPP). Methods A total of 100 BALF of children with MPP in Peking University Third Hospital and Peking University First Hospital from January 2018 to January 2019 were collected. Fluorogenic quantitative PCR was used to detect nucleic acid and it's drug resistance gene of MP and multiple PCR method was adopted to detect influenza A virus, influenza A virus - H1 N1, influenza A virus - H3 N2, influenza B, human parainfluenza virus, adenovirus, human bocavirus, human rhino virus, Chlamydia pneumoniae, human metapneumovirus, MP, human corona virus, and respiratory syncytial virus gene, and the results were compared by using Chi square test. Results In 100 BALF samples, MP and drug resistance gene were detected by fluorogenic quantitative PCR. Totally, 83 cases (83. 00%) were MP positive and 78 cases (93. 98%) were drug resistant. All of them had the point mutations A2063G in V region of 23S rRNA domain. A total of 13 kinds of respiratory pathogens were detected by multiplex PCR method, and 89 cases (89. 00%) were positive. Totally, 79 cases (79. 00%) were MP positive, of which 74 cases (74. 00%) detected only MP, and 5 cases (5. 00%) detected MP combined with other pathogens. Other pathogens were detected in 10 cases (10. 00%). The virus detection rate of 0-4 years old group was higher than that of > 4-6 years old group (P - 0. 042) and > 6 years old group (P =0. 002), and the differences were statistically significant. Conclusions MP can be detected in most BALF samples of MPP children, the drug resistance phenomenon is serious, and the main point mutation is A2063G. There were other respiratory pathogens and 2 or 3 pathogens were detected in a small number of BALF samples.Copyright © 2022 Authors. All rights reserved.
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Background: Systemic and pulmonary uncontrolled activation of pro-inflammatory pathways following severe acute respiratory syndrome coronavirus 2 (Sars-Cov-2) infection can lead to development of serious short- and long-term complications such as ARDS and lung fibrosis. Mounting evidence reveals a positive correlation between cytokine overexpression in bronchoalveolar lavage fluid (BALF) and the severity of respiratory involvement in Sars-Cov-2 patients. We aimed to compare levels of metalloprotease 9 (MMP9) and fibrogenic Growth factors (VEGF, a-CTGF, FGF, PDGF) in BALF of intermediate medicine ward (IMW) Sars-Cov-2 and Intensive Care Unit (ICU) mechanically ventilated patients. Method(s): Sars-Cov-2 infection was diagnosed by Reverse transcriptase-polymerase chain reaction (RT-PCR) on respiratory samples. 10 IMW and 10 ICU patients were enrolled. ELISA assay was used to quantify growth factors and MMP9 on UV rays inactivated BAL fluid samples. Result(s): BALFs collected from ICU patients showed higher levels of Connective Tissue Growth Factor (CTGF;p<0.05) and MMP-9 (p<0,05) whereas inward patients with moderate pneumonia displayed higher titles of Vascular Endothelial Growth Factor (VEGF;p<0,05). FGF values were below detection limit in 90% of samples. No statistical difference in Platelet Derived Growth Factor (PDGF) levels were found between the two groups. Conclusion(s): Analogously to what observed for pro-inflammatory cytokines, early alveolar expression of MMP9 and CTGF are associated to a more severe outcome and might play a role in determining fibrotic evolution while VEGF does not seem to play a major role.
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Objective To study the anti-coronavirus effect of Qingre Xiaoyanning Tablet (), and provide experimental basis for evaluating its prevention and treatment of coronavirus infection. Methods A total of 96 BALB/c mice with half male and half female were randomly divided into control group, model group, Lianhua Qingwen Capsules (, 0.546 g/kg) group and Qingre Xiaoyanning Tablet (8.72, 17.44, 34.89 g/kg) groups with 16 mice in each group. BALB/c mice were infected with ip cyclophosphamide combined with HCoV-229E coronavirus to establish a model of coronavirus infection. The therapeutic effect of Qingre Xiaoyanning Tablet was evaluated by body weight, lung index, viral load, hemagglutination titer and pathological changes in lung tissue of mice;Levels of interleukin-1beta (IL-1beta), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and vascular cell adhesion molecule-1 (VCAM-1) in alveolar lavage fluid were detected by ELISA;The proportion of macrophages, lymphocytes (CD3+, CD4+) and NK cells in lung tissue was detected by flow cytometry;Western blotting was used to detect Toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), inhibitor kappa B kinase-beta (IKK-beta), inhibitor kappa B (IkappaB) and p-IkappaB protein expressions in lung tissue. Results Compared with model group, Qingre Xiaoyanning Tablet significantly increased the body weight of virus infected mice (P < 0.05, 0.01), decreased lung index and hemagglutination titer (P < 0.01), improved lung disease (P < 0.05), and significantly inhibited viral mRNA expression (P < 0.01);TNF-alpha, IL-1 beta and VCAM-1 levels in alveolar lavage fluid were decreased (P < 0.05, 0.01), IFN-gamma level was increased (P < 0.05);The percentage of macrophages was significantly decreased (P < 0.05, 0.01), percentage of CD3+, CD4+ lymphocytes and NK cells was increased (P < 0.01);MYD88, TLR4, IkappaB and IKK-beta protein expressions in lung tissue were significantly down regulated (P < 0.05, 0.01). Conclusion Qingre Xiaoyanning Tablet can inhibit the replication of coronavirus in vivo, reduce inflammatory reaction, protect lung tissue, and has obvious anti-coronavirus effect in vivo. Its mechanism may be related to the regulation of TLR4/MyD88/IKK/IkappaB signal pathway and improving immunity.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.
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Neutrophils (Neu) play a pathogenic role in COVID19 by releasing Neutrophils Extracellular Traps (NETs) or HNE. Being HNE inhibited by a1AT, supplementation of this protein has been proposed. We aim to study a1AT/HNE balance in BALf from ICU admitted COVID19 patients. To assess HNE, a1AT and HNE/a1AT complexes, 33 COVID 19 BALf samples were analysed by means of ELISA or gel-Electrophoresis + Western Blot. Proteins bound to a1AT or HNE were identified by Liquid chromatography-mass spectrometry. NETs release (PMA stimulated Neu +/- a1AT) was analysed by confocal microscopy. Both HNE and a1AT were clearly detectable in BALf at high levels. Contrary to what previously observed in other settings (Bronchiolits obliterans) (Cagnone, M. et al. High Throughput 2019;8(1):5) we couldn't detect any HNE/ a1AT complex in COVID19 even when purified HNE was added to samples (Fig 1a). HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free a1AT to bind to histones. Although this binding was confirmed, a1AT wasn't able to inhibit NETs formation (Fig 1b). Despite the finding of a high burden of free and bound HNE in COVID 19 BALf, the formation of HNE/ a1AT inhibitory complex is prevented. Furthermore, a1AT binds to histones but does not prevent NETs formation and their noxious activity.
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Introduction: Sarcoidosis is a rare granulomatosis. The absence of well-defined criteria for definition and the existence of differential diagnosis makes the positive diagnosis difficult. Method(s): We report a case of sarcoidosis that illustrates the difficulty of this diagnosis in the presence of atypical clinical manifestations and a strong suspicion of tuberculosis. Ultimately, renal histology allowed the positive diagnosis and the response to corticosteroids confirmed it retrospectively. Result(s): Our patient was a 66 years-old female with a history of hypertension who presented with a sensory and motor polyneuropathy a couple of months after a mild COVID-19 pneumonia, hospitalized for exploration of a worsening renal function due to a tubulointerstitial neuropathy (creatinine upon admission at 250 micromol/l, eGFR = 16 ml/min/1,73m2 -MDRD). Kidney biopsy revealed an interstitial infiltrate of monocytes and fibrosis alongside non-necrotic and giant-cell epithelioid interstitial granulomas. Extra-renal signs consisted of the above-mentioned neuropathy, bilateral mediastinal adenopathies with no signs of a pulmonary disease at the bodyscan, a hepatomegaly, splenomegaly, a pleural and pericardial effusion of low abundance, and a peritoneal thickening. Bronchoscopy and bronchoalveolar washing found no evidence for malignancies and screening for mycobacterial infections by polymerase chain reaction was negative. No granulomas were found at the hepatic biopsy. Digestive tract endoscopy and biopsies showed no abnormalities. During hospitalization, the patient presented an episode of acute polyradiculonevritis confirmed by cerebral-spine fluid study and nerve conduction study results. Our patient received intraveinous immunoglobulins (IgIV) with a favorable outcome but relapsed one month later, showing signs of respiratory failure. Upon the second relapse of the chronic polyradiculonevritis and based on the absence of bacteriological and histological evidence for a mycobacterial infection and the results or the renal biopsy, the patient received high-dose corticosteroids alongside a second course of IgIV. The neuropathy regressed totally within a month with a decrease of creatinine level to 140 micromol/l (eGFR = 35ml/min/1,73m2) alongside the polyserositis and organomegaly. The final diagnosis was that of a sarcoidosis with pulmonary and renal involvement. Although the neuropathy could be considered a manifestation of sarcoidosis, its origin was intricated as post-viral original could not be formally excluded. Conclusion(s): The etiological diagnosis for granulomatous interstitial nephropathies can be challenging due to similar clinical presentations and the need to start specific treatments especially in the presence of life-threatening situations and the absence of clear criteria defining sarcoidosis further enhances the level of difficulty. No conflict of interestCopyright © 2023
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The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged â½ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
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Oxidative stress by reactive oxygen species (ROS) has been hypothesized to be the major mediator of SARS-CoV-2-induced pathogenesis. During infection, the redox homeostasis of cells is altered as a consequence of virus-induced cellular stress and inflammation. In such scenario, high levels of ROS bring about the production of pro-inflammatory molecules like IL-6, IL-1ß, etc. that are believed to be the mediators of severe COVID-19 pathology. Based on the known antioxidant, anti-inflammatory, mucolytic and antiviral properties of NAC, it has been hypothesized that NAC will have beneficial effects in COVID-19 patients. In the current study efforts have been made to evaluate the protective effect of NAC in combination with remdesivir against SARS-CoV-2 induced lung damage in the hamster model. The SARS-CoV-2 infected animals were administered with high (500 mg/kg/day) and low (150 mg/kg/day) doses of NAC intraperitoneally with and without remdesivir. Lung viral load, pathology score and expression of inflammatory molecules were checked by using standard techniques. The findings of this study show that high doses of NAC alone can significantly suppress the SARS-CoV-2 mediated severe lung damage (2 fold), but on the contrary, it fails to restrict viral load. Moreover, high doses of NAC with and without remdesivir significantly suppressed the expression of pro-inflammatory genes including IL-6 (4.16 fold), IL-1ß (1.96 fold), and TNF-α (5.55 fold) in lung tissues. Together, results of this study may guide future preclinical and clinical attempts to evaluate the efficacy of different doses and routes of NAC administration with or without other drugs against SARS-CoV-2 infection.
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Background. Coinfections, both bacterial and viral, occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. Methods. We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance platform to investigate the occurrence of viral and bacterial coinfections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection during March 2020 and February 2022. Patients receiving additional standard of care (SOC) molecular testing for viral pathogens (14 days prior to admission or 7 days after), including respiratory syncytial virus, rhinovirus/enterovirus (RV/EV), influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and endemic coronaviruses, were included. SOC testing for clinically relevant bacterial pathogens (7 days before admission or 7 days after) from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. Results. Among 2,654 adults hospitalized with COVID-19 and tested for all 7 virus groups, another virus was identified in 3.1% of patients. RV/EV (1.2%) and influenza (0.4%) were the most commonly detected viruses. Half (17,842/35,528, 50.2%) of hospitalized adults with COVID-19 had bacterial cultures taken within 7 days of admission, and 1,092 (6.1%) of these had a clinically relevant bacterial pathogen. A higher percentage of those with a positive culture died compared to those with negative cultures (32.3% vs 13.3%, p< 0.001). Staphylococcus aureus was the most common isolate overall;Pseudomonas aeruginosa was the second most common respiratory isolate This figure includes 1,408 bacterial cultures from 1,066 individuals. Deep respiratory sites include endotracheal aspirate, bronchoalveolar lavage fluid, bronchial washings, pleural fluid, and lung tissue. Commensal organisms were excluded. Conclusion. Consistent with previous studies, a relatively low proportion of adults hospitalized with COVID-19 had concomitantly identified viral or bacterial infections. Identification of a bacterial infection within 7 days of admission is associated with increasedmortality among adults hospitalized with COVID-19. Conclusions about the clinical relevance of bacterial infections is limited by the retrospective nature of this study.
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Background. Secondary infections are common among severe COVID-19 patients, increasing complications and mortality risk. These infections are not well characterized in Latin America and the Caribbean. Methods. A cross-sectional observational study of adult patients with COVID-19 admitted to the hospital Fundacion Valle del Lili in Cali-Colombia from March 2020 to March 2021. Demographic data, clinical characteristics, laboratory parameters, and clinical outcomes were collected. We describe secondary infection, antibiotic therapy, and antibiotic resistance profiles. Secondary infection was defined if the diagnosis occurred >=48 hours after hospital admission for COVID-19. Results. A total of 2138 patients with COVID-19 were analyzed;350 (16.3%) presented secondary infection. 60% were male;the median age was 65 years [IQR: 55-72]. Glucocorticoid therapy was indicated in 335 patients (96.3%). 281 received high doses and 54 low doses. Bacterial infections were the most common, affecting 81.3 % of patients, followed by fungal (14.4%) and viral (4.3%) infections. Most bacterial isolates were orotracheal secretion, blood, urine, and bronchoalveolar lavage fluid culture. The three most frequently identified bacteria were Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. Most of the initial isolates were not antibiotic-resistant (75-89.7%). Empiric antibiotic therapy was indicated in 346 patients (98.9%), 268 received carbapenems (76.6%), 267 Vancomycin (76.3%), and 233 cefepime (66.6%). Of the 350 patients, 327 (93.4%) required management in the intensive care unit, and overall mortality was 35.4% (124/350). Conclusion. Our results showed a lower frequency of secondary infection than previous reports;However, a high frequency of broad-spectrum antibiotics usage was found despite a high prevalence of non-resistant bacteria. Further studies are needed to establish the best approach for antibiotics therapy.
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Objective To investigate drug resistance gene in Mycoplasma pneumoniae (MP) and the distribution of 13 respiratory pathogens in bronchoalveolar lavage fluid(BALF) of children with Mycoplasma pneumoniae pneumonia(MPP). Methods A total of 100 BALF of children with MPP in Peking University Third Hospital and Peking University First Hospital from January 2018 to January 2019 were collected. Fluorogenic quantitative PCR was used to detect nucleic acid and it's drug resistance gene of MP and multiple PCR method was adopted to detect influenza A virus, influenza A virus - H1 N1, influenza A virus - H3 N2, influenza B, human parainfluenza virus, adenovirus, human bocavirus, human rhino virus, Chlamydia pneumoniae, human metapneumovirus, MP, human corona virus, and respiratory syncytial virus gene, and the results were compared by using Chi square test. Results In 100 BALF samples, MP and drug resistance gene were detected by fluorogenic quantitative PCR. Totally, 83 cases (83. 00%) were MP positive and 78 cases (93. 98%) were drug resistant. All of them had the point mutations A2063G in V region of 23S rRNA domain. A total of 13 kinds of respiratory pathogens were detected by multiplex PCR method, and 89 cases (89. 00%) were positive. Totally, 79 cases (79. 00%) were MP positive, of which 74 cases (74. 00%) detected only MP, and 5 cases (5. 00%) detected MP combined with other pathogens. Other pathogens were detected in 10 cases (10. 00%). The virus detection rate of 0-4 years old group was higher than that of > 4-6 years old group (P - 0. 042) and > 6 years old group (P =0. 002), and the differences were statistically significant. Conclusions MP can be detected in most BALF samples of MPP children, the drug resistance phenomenon is serious, and the main point mutation is A2063G. There were other respiratory pathogens and 2 or 3 pathogens were detected in a small number of BALF samples. © 2022 Authors. All rights reserved.
ABSTRACT
Background: Immunothrombosis resulting from the crosstalk between activation of the innate immune system, coagulation and inflammation is thought to play an important role in severe COVID-19 pathogenesis. Activation of the NLRP3 inflammasome inducing caspase-1 activation and IL-1b processing, constitutes an important step of the inflammatory cascade and may be central in COVID-19 hyperinflammation and immunothrombosis. Aim(s): We evaluated NLRP3 inflammasome activation in lung tissues and broncho-alveolar lavage fluid (BALF) during severe COVID-19 and studied its association with lung vasculopathy. Method(s): Postmortem lung biopsies from 40 patients deceased of acute respiratory distress syndrome (ARDS) complicating SARS-Cov 2 infection were collected. Histological analysis and activated caspase-1 expression by immunohistochemistry, were performed. In another cohort of 19 COVID-19 patients with ARDS, soluble NLRP3, activated caspase-1 and inflammatory cytokines were measured by ELISA in BALF collected within 48 h of admission and compared with BALF of patients with lung cancer. Result(s): Among lung biopsies, 33 presented evidence of vasculopathy consisting in thrombo-embolism (n = 9), thrombotic microangiopathy (n = 9), endothelitis (n = 15), intima fibrosis (n = 19) and intima edema (n = 11). Among them, 16 expressed activated caspase-1, which appeared specifically located into endo-alveolar macrophages. Higher concentrations of soluble NLRP3, activated caspase-1, IL-1B, and IL-1Ra were observed in BALF from patients with COVID-19 ARDS compared to controls (p < 0.0001). Conclusion(s): We observed NLRP3 inflammasome activation in endo-alveolar macrophages of COVID-19 patients with ARDS and high inflammatory cytokine secretion associated with lung vasculopathy. These observations suggest that NRLP3 inflammasome may constitute a therapeutic target in severe COVID-19.