Acute eosinophilic pneumonia-like syndrome post-initiation of vortioxetine.

A man in his mid-30s presented to the emergency department with a 1-week history of fatigue, loss of appetite, fever and productive (yellow) cough. This progressed to requiring admission to intensive care needing a oxygen therapy via high-flow nasal cannula for acute hypoxaemic respiratory failure. He had recently started vortioxetine for major depressive disorder, and his acute symptoms correlated with an increase in the dose of vortioxetine. For more than 20 years, rare but consistent reports of serotonergic medications have been implicated in eosinophilic pulmonary conditions. During this same period, serotonergic medications have become a mainstay solution for a wide range of depressive symptoms and disorders. This is the first report of an eosinophilic pneumonia-like syndrome occurring while consuming the novel serotonergic medication vortioxetine.

Respiratory virus infections of the lower respiratory tract elevate bronchoalveolar lavage eosinophil fraction: a clinical retrospective study and case review.

BACKGROUND: Eosinophilic airway inflammation caused by respiratory virus infection has been demonstrated in basic research; however, clinical investigations are lacking. To clarify the extent to which respiratory virus infection induces airway eosinophilic inflammation, we reviewed the results of bronchoalveolar lavage (BAL) and respiratory virus testing performed at our hospital. METHODS: Among the BAL procedures performed at the University of the Ryukyu Hospital from August 2012 to September 2016, we collected cases of acute respiratory disease in which multiplex polymerase chain reaction (PCR) was used to search for respiratory viruses. The effect of respiratory virus detection on BAL eosinophil fraction was analyzed using statistical analysis. A case study was conducted on respiratory virus detection, which showed an elevated BAL eosinophil fraction. RESULTS: A total of 95 cases were included in this study, of which 17 were PCR-positive. The most common respiratory virus detected was parainfluenza virus (eight cases). The PCR-positive group showed a higher BAL eosinophil fraction than the PCR-negative group (p = 0.030), and more cases had a BAL eosinophil fraction > 3% (p = 0.017). Multivariate analysis revealed that being PCR-positive was significantly associated with BAL eosinophil fraction > 1% and > 3%. There were nine PCR-positive cases with a BAL eosinophil fraction > 1%, of which two cases with parainfluenza virus infection had a marked elevation of BAL eosinophil fraction and were diagnosed with eosinophilic pneumonia. CONCLUSIONS: Cases of viral infection of the lower respiratory tract showed an elevated BAL eosinophil fraction. The increase in eosinophil fraction due to respiratory virus infection was generally mild, whereas some cases showed marked elevation and were diagnosed with eosinophilic pneumonia. Respiratory virus infection is not a rare cause of elevated BAL eosinophil fraction and should be listed as a differential disease in the practice of eosinophilic pneumonia.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database.

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

BNT162b2 coronavirus disease-2019 vaccination accelerated rheumatoid arthritis disease activity in chronic eosinophilic pneumonia: A case report.

RATIONALE: The relationship between rheumatoid arthritis (RA) and eosinophilic inflammation is unclear. According to recent studies, it has been suggested that T helper 2 cell responses play a role in the inhibition of RA. It is unclear how the immunological response after coronavirus disease-2019 (COVID-19) vaccination affects T cell immune reactions. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of an 88-year-old woman diagnosed with RA and chronic eosinophilic pneumonia (CEP). She was diagnosed with CEP about 20 years ago, and, through steroid treatment, she improved and had no relapse for 16 years. At the time of diagnosis of CEP, the rheumatoid factor (RF) was increased; however, there were no joint symptoms. After receiving the COVID-19 vaccine, joint and respiratory symptoms gradually worsened. Laboratory examinations showed increased RF, anti-cyclin citrullinated peptide antibody, and peripheral absolute eosinophil count. Musculoskeletal ultrasonography showed synovitis. INTERVENTION AND OUTCOME: Methylprednisolone pulse therapy improved respiratory and joint symptoms immediately; RA and CEP stabilized with no relapses. LESSONS: Eosinophilic and rheumatoid reactions following COVID-19 vaccination were an-reported adverse events. Eosinophilic inflammation might be reflected on an anti-inflammatory reaction in initial phase of RA.

Prophylactic Vaccine Targeting TLR3 on Dendritic Cells Ameliorates Eosinophilic Pneumonia in a Mouse SARS-CoV Infection Model.

Putative subcomponent vaccines of severe acute respiratory syndrome coronavirus spike protein and ARNAX (TLR3-specific adjuvant for priming dendritic cells) were examined and compared with spike protein + Alum in a mouse BALB/c model. Survival, body weight, virus-neutralizing Ab titer in the blood, and viral titer in the lung were evaluated for prognosis markers. The infiltration degrees of eosinophils in the lung were histopathologically monitored at 10 d postinfection. The results were: (1) adjuvant was essential in vaccines to achieve a complete recovery from infection, (2) ARNAX displayed optimal body weight recovery compared with Alum, (3) ARNAX was optimal for the amelioration of eosinophilic pneumonia, and (4) the eosinophil infiltration score was not associated with the neutralizing Ab titer in the blood or viral titer in the lung. Although the pathological link between the TLR3 vaccine and lung eosinophil infiltration remains unclear, severe acute respiratory syndrome-mediated eosinophilic pneumonia can be blocked by the prior induction of dendritic cell priming by ARNAX.

Money, Power, and Radical Honesty: A Look At Members of Congress' Use of Information for Financial Gain (preprint)

Cleared of wrongdoing due to lack of evidence, Senators Kelley Loeffler and David Perdue continued their bids for re-election, and control of the Senate, in the Georgia run-off. Both Senators Loeffler and Perdue traded stocks in the run-up to the COVID-19 crisis after receiving classified briefings. These are just two of many instances of members of Congress profiting after receiving classified information. While the American public remained uninformed as to the true crisis looming as COVID-19 spread, members of Congress received private briefings and quietly sold securities such as travel and hotel related interests, and purchased other securities, such as remote-work software and medical equipment related interests.Many members of Congress also profit from federal money earmarked to increase the value of their personal land deals, from access to IPOs, and from corporate board seats. While corporate executives, members of the executive branch, and ordinary citizens are subject to strict insider trading laws, members of Congress sail through loopholes and exceptions that are hand-crafted for their benefit. This article reviews proposals for fixing the problem before proposing a comprehensive solution focused on limiting the financial opportunities for members of Congress and strict reporting requirements.While many proposals to address this problem exist, none come close to preventing members of Congress from profiting in these often-nefarious ways. To ensure that members of Congress work on behalf of the American Public—and not their own pocketbooks—the comprehensive and drastic reform articulated in this article is required.

Eosinophil-mediated lung inflammation associated with elevated natural killer T cell response in COVID-19 patients.

BACKGROUND/AIMS: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory syndrome. The mechanisms underlying the different degrees of pneumonia severity in patients with COVID-19 remain elusive. This study provides evidence that COVID-19 is associated with eosinophil-mediated inflammation. METHODS: We performed a retrospective case series of three patients with laboratory and radiologically confirmed COVID-19 pneumonia admitted to Chosun University Hospital. Demographic and clinical data on inflammatory cell lung infiltration and cytokine levels in patients with COVID-19 were collected. RESULTS: Cytological analysis of sputum, tracheal aspirates, and bronchoalveolar lavage fluid (BALF) samples from all three patients revealed massive infiltration of polymorphonuclear cells (PMNs), such as eosinophils and neutrophils. All sputum and BALF specimens contained high levels of eosinophil cationic proteins. The infiltration of PMNs into the lungs, together with elevated levels of natural killer T (NKT) cells in BALF and peripheral blood samples from patients with severe pneumonia in the acute phase was confirmed by flow cytometry. CONCLUSION: These results suggest that the lungs of COVID-19 patients can exhibit eosinophil-mediated inflammation, together with an elevated NKT cell response, which is associated with COVID-19 pneumonia.

Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab.

Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies.

Diffuse alveolar haemorrhage in the setting of eosinophilic pneumonia.

A 65-year-old woman who presented with a constellation of symptoms, including cough with haemoptysis, fever, chills and hypoxia along with weight loss, was found to have diffuse alveolar haemorrhage. After a myriad of investigations returned normal, an open lung biopsy was performed, which revealed the diagnosis to be subacute eosinophilic pneumonia. This is one of its kind of rare presentations where eosinophilic pneumonia presents as diffuse alveolar haemorrhage and has been reported only five times prior to this.

COVID-19 mimics on chest CT: a pictorial review and radiologic guide.

Chest imaging is often used as a complementary tool in the evaluation of coronavirus disease 2019 (COVID-19) patients, helping physicians to augment their clinical suspicion. Despite not being diagnostic for COVID-19, chest CT may help clinicians to isolate high suspicion patients with suggestive imaging findings. However, COVID-19 findings on CT are also common to other pulmonary infections and non-infectious diseases, and radiologists and point-of-care physicians should be aware of possible mimickers. This state-of-the-art review goal is to summarize and illustrate possible etiologies that may have a similar pattern on chest CT as COVID-19. The review encompasses both infectious etiologies, such as non-COVID viral pneumonia, Mycoplasma pneumoniae, Pneumocystis jiroveci, and pulmonary granulomatous infectious, and non-infectious disorders, such as pulmonary embolism, fat embolism, cryptogenic organizing pneumonia, non-specific interstitial pneumonia, desquamative interstitial pneumonia, and acute and chronic eosinophilic pneumonia.

Identification of Complex Pneumonia during the Outbreak of COVID-19: Bacterial Pneumonia Combined with Acute Eosinophilic Pneumonia in Patients with Maintenance Hemodialysis.

It is of crucial importance to diagnose patients in a timely and clear manner during the outbreak of COVID-19. Different causes of pneumonia makes it difficult to differentiate COVID-19 from others. Hemodialysis patients are a special group of people in this outbreak. We present a successfully treated case of a patient with maintenance hemodialysis from acute eosinophilic pneumonia for using meropenem when treating bacterial pneumonia, avoiding possible panic and waste of quarantine materials in dialysis centers.

Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Alum Induces Protective Immunity and Reduces Immune Enhancement (preprint)

We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high-level neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ∼ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.View Full Text

The Potential Role of Th17 Immune Responses in Coronavirus Immunopathology and Vaccine-induced Immune Enhancement (preprint)

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.