Inhalation Pneumonitis Caused by Nebulized Hydrogen Peroxide.

Hydrogen peroxide is a chemical commonly used as a household antiseptic for cleaning and disinfecting. No cases of acute hydrogen peroxide inhalation-induced lung injury are previously described. We present a case of acute chemical pneumonitis caused by mixing hydrogen peroxide in a nighttime continuous positive airway pressure device's humidifier used for obstructive sleep apnea to prevent COVID-19 infection. The patient endorsed mixing hydrogen peroxide with distilled water in his nighttime continuous positive airway pressure device's humidifier at a ratio of 1:3-1:2 for the previous week before admission based on a friend's advice in preventing COVID-19. The presenting chest X-ray showed new multifocal consolidations with interstitial markings and alveolar edema throughout both lungs. Chest computed tomography (CT) imaging demonstrated multifocal, bilateral, hazy consolidations with increased interstitial markings and bilateral pleural effusions. The patient was subsequently initiated on systemic glucocorticoid therapy, significantly improving hypoxemia and dyspnea. Inhalation of hydrogen peroxide may produce acute pneumonitis distinct from what has been described previously with chronic inhalation. Given this case, systemic glucocorticoid therapy may be considered a viable treatment option for acute hydrogen peroxide-associated inhalation lung injury causing pneumonitis.

Use of protracted CPAP as supportive treatment for COVID-19 pneumonitis and associated outcomes: a national cohort study.

BACKGROUND: Continuous positive airway pressure (CPAP) has been increasingly deployed to manage patients with COVID-19 and acute respiratory failure, often for protracted periods. However, concerns about protracted CPAP have been raised. This study aimed to examine the use of CPAP for patients with COVID-19 and the outcomes after protracted use. METHODS: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to December 25, 2021 who received CPAP. Protracted CPAP was defined as ≥ 5 continuous days of CPAP. Outcomes included CPAP failure rate (institution of invasive mechanical ventilation [IMV] or death), mortality, and outcomes after institution of IMV. Multivariable logistic regression was performed to assess the impact of protracted CPAP on mortality after IMV. RESULTS: A total of 1961 patients with COVID-19 received CPAP for COVID-19 pneumonitis, with 733 patients (37.4%) receiving protracted CPAP. CPAP failure occurred in 891 (45.4%): 544 patients (27.7%) received IMV and 347 patients (17.7%) died in critical care without IMV. Hospital mortality rate was 41.3% for the population. For patients who subsequently commenced IMV, hospital mortality was 58.7% for the standard duration CPAP group and 73.9% for the protracted duration CPAP group (P=0.003); however, there was no statistical difference in hospital mortality after adjustment for confounders (odds ratio 1.4, 95% confidence interval 0.84-2.33, P=0.195). CONCLUSIONS: Protracted CPAP was used frequently for managing patients with COVID-19. Whilst it was not associated with worse outcomes for those patients who subsequently required IMV, this might be due to residual confounding and differences in processes of care.

A CLINICAL CASE OF SARS-CoV-2 INFECTION COMPLICATED BY NEPHROGENIC PULMONARY EDEMA AND COVID-ASSOCIATED PNEUMONITIS, ALVEOLITIS.

COVID-19 is a highly transmissible disease with severe course especially in patients with nephrogenic hypertensive disease and chronic kidney disease due to a higher incidence of all-type infections than in the general population. The aim of the study is to describe a clinical case of SARS-CoV-2 infection complicated by nephrogenic pulmonary edema and COVID-associated pneumonitis, alveolitis. Description of the case. Patient K.S., born in 1975, was hospitalized 24 hours after symptom onset at emergency hospital due to complaints of increased blood pressure up to 180-200/110-120 mm Hg, temperature up to 38.7degreeC, dry cough, feeling of heaviness in the chest, change in urine color. PCR smear for SARS-CoV-2 was positive. Computed tomography revealed a pattern of bilateral COVID-associated pneumonitis, alveolitis, with 75% involvement. The electrocardiogram revealed signs of left ventricular myocardial hypertrophy. Ultrasound examination showed numerous cysts in the kidneys. Urinalysis at admission: leukocytes - 499, erythrocytes - 386. Glomerular filtration rate (CKD-EPI: 29 ml/min/1.73 m2) and corresponds to stage IV of chronic kidney disease. Coagulogram: fibrinogen: 32.3 (1.6-4.0) g/l, D-dimer: 663 (0-250). Despite the treatment, the patient's condition worsened, the phenomena of cardiopulmonary and renal insufficiency increased, which led to a fatal outcome. During a virological study of sectional material: SARS-CoV-2 coronavirus RNA was found in the lung and kidneys. Signs of bilateral COVID-associated pneumonitis, alveolitis with diffuse cellular infiltrates in combination with changes in the alveolar apparatus, signs of pulmonary edema were revealed. Heart-related signs - swelling of the interstitium, fragmented muscle fibers, some of them hypertrophied, a wave-like deformation of cardiomyocytes, blurring of the transverse striation. Arteries with thickened sclerosed walls. In the kidneys - diffuse damage to the proximal tubules of the nephron with areas of cortical and proximal necronephrosis, areas of fibrinoid swelling. Conclusion. The cause of death of a 45-year-old patient was a severe course of bilateral COVID-associated pneumonitis, alveolitis, which contributed to the development of renal medullary hypoxia and type 1 cardiorenal syndrome, which led to early nephrogenic pulmonary edema.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

When to panic about a panic attack: A challenging case of hypersensitivity pneumonitis.

The COVID-19 pandemic has created diagnostic difficulties with the increase in mental health illnesses that often present with nonspecific symptoms, like hypersensitivity pneumonitis. Hypersensitivity pneumonitis is a complex syndrome of varying triggers, onset, severity, and clinical manifestations that can be challenging to diagnose in many cases. Typical symptoms are nonspecific and can be attributed to other entities. There are no pediatric guidelines, which contributes to diagnostic difficulties and delays in treatment. It is particularly important to avoid diagnostic biases, have an index of suspicion for hypersensitivity pneumonitis, and to develop pediatric guidelines as outcomes are excellent when diagnosed and treated promptly. This article discusses hypersensitivity pneumonitis with a focus on the causes, pathogenesis, diagnostic approach, outcomes, and prognosis while using a case to illustrate the diagnostic difficulties worsened by the COVID-19 pandemic.

Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety.

BACKGROUND: Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients. METHODS: We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety. RESULTS: After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference -0.76%, 95% CI -6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events. CONCLUSIONS: The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP. TRIAL REGISTRATION MUMBER: NCT02958917.

Identification of Common Dysregulated Genes in COVID-19 and Hypersensitivity Pneumonitis: A Systems Biology and Machine Learning Approach.

A comprehensive knowledge on systems biology of severe acute respiratory syndrome coronavirus 2 is crucial for differential diagnosis of COVID-19. Interestingly, the radiological and pathological features of COVID-19 mimic that of hypersensitivity pneumonitis (HP), another pulmonary fibrotic phenotype. This motivated us to explore the overlapping pathophysiology of COVID-19 and HP, if any, and using a systems biology approach. Two datasets were obtained from the Gene Expression Omnibus database (GSE147507 and GSE150910) and common differentially expressed genes (DEGs) for both diseases identified. Fourteen common DEGs, significantly altered in both diseases, were found to be implicated in complement activation and growth factor activity. A total of five microRNAs (hsa-miR-1-3p, hsa-miR-20a-5p, hsa-miR-107, hsa-miR-16-5p, and hsa-miR-34b-5p) and five transcription factors (KLF6, ZBTB7A, ELF1, NFIL3, and ZBT33) exhibited highest interaction with these common genes. Next, C3, CFB, MMP-9, and IL1A were identified as common hub genes for both COVID-19 and HP. Finally, these top-ranked genes (hub genes) were evaluated using random forest classifier to discriminate between the disease and control group (coronavirus disease 2019 [COVID-19] vs. controls, and HP vs. controls). This supervised machine learning approach demonstrated 100% and 87.6% accuracy in differentiating COVID-19 from controls, and HP from controls, respectively. These findings provide new molecular leads that inform COVID-19 and HP diagnostics and therapeutics research and innovation.

COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea: A Nationwide Multicenter Survey.

BACKGROUND: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. METHODS: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. RESULTS: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. CONCLUSION: These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Vaccination for seasonal influenza, pneumococcal infection and SARS-CoV-2 in patients with solid tumors: recommendations of the Associazione Italiana di Oncologia Medica (AIOM).

Patients with cancer have a well-known and higher risk of vaccine-preventable diseases (VPDs). VPDs may cause severe complications in this setting due to immune system impairment, malnutrition and oncological treatments. Despite this evidence, vaccination rates are inadequate. The Italian Association of Medical Oncology [Associazione Italiana di Oncologia Medica (AIOM)] has been involved in vaccination awareness since 2014. Based on a careful review of the available data about the immunogenicity, effectiveness and safety of flu, pneumococcal and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we report the recommendations of the AIOM about these vaccinations in adult patients with solid tumors. The AIOM recommends comprehensive education on the issue of VPDs. We believe that a multidisciplinary care model may improve the vaccination coverage in immunocompromised patients. Continued surveillance, implementation of preventive practices and future well-designed immunological prospective studies are essential for better management of our patients with cancer.

Evolution of fibrotic interstitial lung diseases (ILD) after COVID-19

Introduction: Data about the impact of COVID-19 on patients with fibrotic ILD are limited. These patients have impaired lung function and increased risk of acute exacerbation driven by viral infection, so COVID-19 is of particular concern. Aim(s): To evaluate the impact of SARS-CoV-2 infection on patients with previous fibrotic ILD. Method(s): Single-center retrospective study including adult patients with previous fibrotic ILD and SARS-CoV-2 infection. Clinical, imaging, and respiratory functional data, pre and post infection, were revised. Result(s): A total of 49 patients (median age 68.4+/-11.1 years, 61.2% male) were analysed and major comorbidities included dyslipidaemia (69.4%), hypertension (53.1%) and obesity (29.9%). Hypersensitivity pneumonitis was the most frequent diagnosis (22.4%) followed by CTD-ILD (20.4%). Non-corticosteroid immunosuppression was present in 38.8% of the cases. Regarding COVID-19 severity, most cases were mild (55.1%) and 34.7% were severe disease requiring hospitalization. Fifteen patients died and 14 patients experienced progression of fibrosis, which was associated with a significant clinical (mean mMRC 0.86+/-0.53 vs 1.57+/-1.09, p=0.015) and DLCO decline (5.12+/-2.57 vs 4.54+/-2.96, p=0.002). Independent predictor of fibrotic worsening was the absence of non-corticosteroid immunosuppression (OR 0.072, p=0.019). Mortality correlated with OSA (p=0.011), heart failure (p=0.032), previous hypoxemic respiratory failure (p=0.013), severe COVID-19 disease (p<0.001) and hospitalization (p=0.004). Conclusion(s): Non-corticosteroid immunosuppression may have a protective role in fibrotic ILD patients. Mortality associated with COVID-19 severity, OSA, heart failure and previous hypoxemic respiratory failure.

Covid-19 in lung allograft recipients - better outcomes after vaccination?

Vaccination remains a main weapon against Coronavirus Disease 2019 (Covid-19). Although its efficacy is reduced in the immunocompromised population, we felt empirically that outcomes of Covid-19 in lung transplant recipients (LTRs) were better after widespread vaccination than in earlier phases of the pandemic. We aimed to compare outcomes of unvaccinated and vaccinated LTRs infected with SARS-CoV-2. All LTRs followed in our hospital were reviewed and those with a positive polymerase chain reaction test were included. We analysed disease severity (using World Health Organization criteria) and mortality rates in unvaccinated and fully vaccinated patients (pts). Twenty-four pts were included, two-thirds of which were male, with a mean age of 51 years. Main diagnoses were hypersensitivity pneumonitis (25%), chronic obstructive pulmonary disease (16,7%), idiopathic pulmonary fibrosis (12,5%) and cystic fibrosis (12,5%). Lung transplant was bilateral in 79,2% of pts, unilateral in 16,7% and lobar in one pt (4,1%). The most common immunosuppression regimen was tacrolimus, mycophenolate-mofetil and prednisolone. Thirteen pts were unvaccinated and 11 were vaccinated at time of infection, with a mean time since transplant of 746 and 1641 days, respectively. In the unvaccinated group 69,2% had mild disease, 30,8% had severe disease and mortality was 25%. No deaths occurred among fully vaccinated pts;disease was mild in 72,7%, moderate in 18,2% and severe in 9,1%. Neither the difference in severity (p=0,156) or mortality (p=0,089) reached statistical significance, presumably due to the small sample size. Nevertheless, we confirmed that, in our centre, vaccinated LTRs had better overall outcomes than unvaccinated pts.

Post COVID Lung function after mild to moderate disease: Good prognosis, but high prevalence of hyperventilation (HV)

Background: There is evidence of persistent symptoms after COVID-19 disease in more than 50 %. of patients (pts.). We hereby report our experience with lung function tests in Post-COVID pts. in an outpatient clinic. Method(s): Since spring 2020, we offered ambulatory control of lung function and imaging after COVID-19 disease. Lung function tests (LFT) including blood gas analysis were performed. Result(s): 66 consecutive pts. (39M, 27F, age 50+/-15.1 Y, BMI 29+/-6 kg/m2) without pulmonary pre-existing condition presented with persistent symptoms 168+/-122 days after COVID. 41 pts. were treated ambulatory and 25 pts. were hospitalized (none with prolonged ventilation). LFT's were normal (TLC 99+/-18 %, VC 91+/-20 %, FEV1/VC 80+/-10 %, pO2 86+/-10 mmHg, pCO2 37+/-4 mmHg), except in 6 pts., where LFT was slightly impaired: 2 showed moderate obstruction and 4 a restrictive pattern. Interestingly 22 pts. (34.9%) presented with a low pCO2, indicating different degrees of HV, inclining in F (M 7/39 vs. F 15/27, p=0.004). Also, 12 pts. with known pulmonary precondition diagnoses (6 sarcoidosis, 2 chronic hypersensitivity pneumonitis (HP), 1 non-specific interstitial pneumonia, 1 CTD-ILD, 1 asthma, 1 organizing pneumonia (OP) by primary biliary cirrhosis) presented after COVID-19 disease. In 8 of these pts. the LFT was comparable as before COVID-19 disease. One patient with HP showed prolonged recovery, one asthmatic needed intensified treatment, and one presented with a new episode of OP. Discussion(s): Our pts., who recovered from mild to moderate COVID-19 disease, presented with good prognosis with regard to LFT. HV could be one pathophysiologic mechanism for Post-COVID symptoms, particularly in F.

Arabincoside B isolated from Caralluma arabica as a potential anti-pneumonitis in LPS mice model.

Acute lung injury (ALI) is a life-threatening condition usually associated with poor therapeutic outcomes and a high mortality rate. Since 2019, the situation has worsened due to the COVID-19 pandemic. ALI had approximately 40% of deaths before COVID-19, mainly due to the dysfunction of the blood-gas barrier that led to lung edema, failure of gas exchange, and dyspnea. Many strategies have been taken to mitigate the disease condition, such as diuretics, surfactants, antioxidants, glucocorticoids, heparin, and ventilators with concomitant sedatives. However, until now, there is no available effective therapy for ALI. Thus, we are presenting a new compound termed Arabincoside B (AR-B), recently isolated from Caralluma arabica, to be tested in such conditions. For that, the lipopolysaccharide (LPS) mice model was used to investigate the capability of the AR-B compound to control the ALI compared to standard dexamethasone. The results showed that AR-B had a significant effect on retrieving ALI. A further mechanistic study carried out in the serum, lung homogenate, histological, and immunohistochemistry sections revealed that the AR-B either in 50 mg/kg or 75 mg/kg dose inhibited pro-inflammatory cytokines such as IL-6, IL-13, NF-κB, TNFα, and NO and stimulated regulatory cytokines IL-10. Moreover, AR-B showed a considerable potential to protect the pulmonary tissue against oxidative stress by decreasing MDA and increasing catalase and Nrf2. Also, the AR-B exhibited an anti-apoptotic effect on the lung epithelium, confirmed by reducing COX and BAX expression and upregulating Bcl-2 expression. These results pave its clinical application for ALI.

Role of vitamin D3 in selected pulmonary diseases with particular emphasis on lung fibrosis.

INTRODUCTION AND OBJECTIVE: For many years vitamin D3 was known only as a regulator of the calcium-phosphate and water-electrolyte balances. Recent studies have paid special attention to other biological effects of calcitriol (the bioactive form of vitamin D3) with particular emphasis on its influence on immune function. Thus, any alterations, especially deficiencies, in the physiological level of calcitriol have serious health consequences. The aim of the study was to summarise the current state of knowledge concerning the role of vitamin D3 in selected pulmonary diseases. REVIEW METHODS: The review was based on data obtained from articles published in PubMed between 2000-2022. Papers were reviewed for scientific merit and relevance. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: In the reviewed literature, much attention was paid to clinical studies focused on the role of vitamin D3 in the pathogenesis of selected respiratory diseases. As revealed in research over the last two decades, vitamin D3 deficiency increases the risk and worsens the course of asthma, cystic fibrosis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, as well as COVID-19. Surprisingly, vitamin D supplementation has not always proved to be an effective therapeutic strategy. The review also presents the unique concept of the possibility of using vitamin D3 in the prevention and treatment of pulmonary fibrosis in the course of hypersensitivity pneumonitis. SUMMARY: Due to the multiplicity and variety of factors that affect the metabolism of vitamin D3, effective counteracting, and even more eliminating the negative consequences of disorders in the level and activity of calcitriol in the respiratory tract, seems to be a breakneck action. On the other hand, only a deep understanding of the role of calcitriol in the pathogenesis of lung diseases provides the chance to develop an effective therapy.

COVID-19 and Early Post-Primary TB: Commonalities of Pathobiology in Pneumonitis and Therapies.

OBJECTIVE: Concurrent infection with COVID-19 and M. tuberculosis has been reported to be more severe than either alone, resulting in increased mortality. Our objective was to define the shared pathobiology of COVID-19 and the developmental stage of TB in the lung and explore adjunctive therapies to treat such commonalities. METHODS: Since morphoproteomics combines the disciplines of histopathology, molecular biology and protein chemistry to paint a portrait of the protein circuitry in diseased cells for the purpose of uncovering targets amenable to specific intervention [1], we used morphoproteomic analyses to study lung tissues of patients with early post-primary tuberculosis or COVID-19 infection. RESULTS: These studies showed co-localization of the COVID-19 virus and M. tuberculosis antigens with cyclo-oxygenase-2 and fatty acid synthase in the reactive alveolar pneumocytes and with programmed death-ligand 1 expression on the alveolar interstitium and alveolar pneumocytes. This was associated with accumulation of pro-infectious M2 polarized macrophages in the alveolar spaces. CONCLUSION: The commonalities in these pathways suggest that they might be susceptible to adjunctive therapies with metformin and vitamin D3. This is supported by published studies that metformin and vitamin D3 could reduce the severity of both COVID-19 and early post-primary TB infections.

Cytomegalovirus pneumonitis in infants: The challenge in diagnosis among pediatricians.

Cytomegalovirus (CMV) pneumonitis infections might present mild or severe illnesses and need sophisticated diagnostic tools, so it remains a diagnostic challenge. We reported five infants diagnosed with CMV pneumonitis who were initially and undiagnosed by the pediatrician in secondary private or public health hospitals with no improvement with standard and escalation of antibiotics treatment for bronchopneumonia as the initial diagnoses. As all cases occurred during the COVID-19 pandemic, they proved negative COVID-19 identified by polymerase chain reaction (PCR) SARS-CoV-2. We diagnosed acquired perinatal pneumonitis CMV in all claims based on clinical criteria, imaging studies, CMV serology, and PCR-CMV urinary tests as diagnostic tools. They showed clinical improvement after two weeks of valganciclovir therapy. Other organs' involvement was considered to be evaluated, including brain-evoked response audiometry (BERA) and eye examination. The physician should consider the possibility of CMV pneumonitis, who did not respond to standard and escalation of antibiotics treatment after initial diagnoses of bronchopneumonia.

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis.

INTRODUCTION: Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP). CASE REPORT: We report an unusual case of pneumonitis with atypical imaging in a patient who received pembrolizumab for metastatic p16-positive squamous cell carcinoma of the base of the tongue. We discuss the approach to the recognition and management of atypical CIP in patients on pembrolizumab with the intent to standardize workup and increase awareness among healthcare providers in the new era of immunotherapy. MANAGEMENT AND OUTCOME: Serologic workup including laboratory studies for complete blood count (CBC), lactate, procalcitonin, SARS-CoV-2 (COVID-19), Legionella, Cytomegalovirus (CMV), Coccidioides, Coxiella, and viral respiratory panel were negative for infectious processes. Since CIP was suspected, the patient was started on steroid therapy. Interval computed tomography (CT) of the chest without contrast showed a resolution of pneumonitis. DISCUSSION: In this case report, we discuss our workup of CIP and initial testing to rule out other possible causes of the patient's symptoms and radiographic findings, and management of the patient's diagnosis of atypical CIP which led to complete clinical recovery from CIP.

Immune checkpoint inhibitor-related pneumonitis and COVID-19: a case-matched comparison of CT findings.

OBJECTIVES: To compare the radiological findings of immune checkpoint inhibitor-related pneumonitis (IRP) and COVID-19 pneumonia, evaluating the potential of the CO-RADS score to differentiate between them. METHODS: Two readers blindly reviewed chest CTs from age- and sex-matched groups of 33 patients with IRP and 33 patients with COVID-19 pneumonia. Each examiner evaluated the presence of 13 CT features, semiquantitatively scored lung involvement, and assigned a CO-RADS score. Inter-reader reliability in the assessment of CT features and CO-RADS categories was evaluated with Cohen's κ. Distribution differences between groups were evaluated with the χ2, Fisher's, and Mann-Whitney U tests. RESULTS: Substantial or higher inter-reader reliability was found in CO-RADS assignments (κ = 0.664) and in the evaluation of CT features (κ ≥ 0.638), among which the sole feature found to significantly differentiate IRP from COVID-19 pneumonia was unilateral presentation (p < 0.001). Lung involvement semiquantitative scores and CO-RADS scores were significantly higher (p < 0.001) in COVID patients (median involvement score 4, IQR 4-6; median CO-RADS score 5, IQR 4-5) than in IRP patients (median involvement score 2.5, IQR 2-4; median CO-RADS score 3, IQR 3-4) but exploratory analysis of CO-RADS specificity revealed comparatively low values, ranging between 51.5% (Reader 1) and 54.6% (Reader 2). CONCLUSIONS: CT features of IRP and COVID-19 pneumonia frequently overlap, save for the extent of lung involvement and bilaterality. In the current SARS-CoV-2 pandemic, the low specificity of the CO-RADS score for the differential diagnosis of COVID-19 pneumonia and IRP may prompt to reconsider the role of imaging in IRP work-up.

Acute Respiratory Failure and the Risk Immunotherapy Related Pneumonitis during the Covid Pandemic

Background Immune checkpoint inhibitors are a newer modality of systemic cancer-directed therapy that is often more tolerable and has broader eligibility criteria than traditional cytotoxic chemotherapy. Unfortunately, pneumonitis is a feared complication of these drugs in around 5% of all patients, including a rare risk of death. Per professional guidelines, there are no pathognomonic features in radiology, clinical history, or laboratory testing to confirm pneumonitis. The global COVID-19 pandemic and the widespread utilization of these drugs have complicated this diagnostic challenge. We sought to develop a systematic method to measure the incidence of different etiologies of acute respiratory failure in the current landscape. Methods We developed a novel patient registry from a retrospective cohort of patients treated with an immune checkpoint inhibitor for cancer and then presented to the hospital after the onset of the COVID19 pandemic in this region. We created a novel case report template in REDCap that collected all relevant data from clinical documentation, imaging reports, and laboratory values during the hospitalization and follow-up. The template prompted the physician reviewer to attribute the respiratory failure based on diagnostic criteria from professional guidelines. Results Our retrospective cohort was made up of 110 patients who had 304 separate hospitalizations between March 2020 and June 2022. Nearly half of these encounters (n = 138, 45%) had a respiratory complaint noted on admission, and an additional 36 encounters (11%) had respiratory testing at any point during their hospitalization. Respiratory complaints were most commonly due to bacterial pneumonia (n = 52, 30.2%), COPD exacerbations (n = 20, 11.6%), pleural effusions (n = 18, 10.5%), malignant obstruction (n = 18, 10.5%), multiple etiologies (n = 16, 9.3%), other etiologies (n = 16, 9.3%), checkpoint inhibitor pneumonitis (n = 3, 2%) and COVID19 pneumonia (n = 2, 1%). Conclusions Our analysis found that respiratory evaluations occurred in most hospitalizations among patients receiving an immune checkpoint inhibitor for cancer. Although the current widespread use of these drugs and the COVID19 pandemic have altered the diagnosis and management of respiratory failure patients with cancer, most cases were still due to bacterial infections or malignant progression. Our study also provides proof-of-concept for a novel case report template form that can systematically collect and categorize data from these complicated hospitalizations.

Clozapine Toxicity in the Setting of COVID-19: A case of differential diagnosis

Introduction: Together with agranulocytosis, fever and immflamatory manifestations are clozapine side effects to be monitorized during initial treatment. In the context of COVID-19 pandemic, implied mechanisms, and symptomatology should be carefully controlled. Objective(s): To analyze the clinical analytic and inflammatory chracterisctics the resembles and differenciates clozapine immune response and SARS-CoV-2 infection. To describe a case of clozapine induced fever and pneumonitis during COVID-19 pandemic. Method(s): A case of clozapine-induced pneumonitis during COVID-19 pandemic is described.- A mini-review of clozapine inflamamtory effects, induced-pneumonitis and SARS-CoV-2 was performed. Result(s): A 33 year old afrolatin male started treatment with clozapine up to 250 mg daily. He developed fever and respiratory symptoms in the 11th day of treatment. The exploration revealed pulmonary sounds decreased and 91% basal saturation, making the probable causes viral infection (local incidence of SARS-CoV-2 >800/100000hab), nosocomial bacterial infection or pulmonary thromboembolism. The patient was isolated due to probable COVID-19. Blood tests showed leucocytosis (13400/mcL), Lymphocytopenia (11.8%), high PCR (14.4mg/dL), Ferritine (506.9ng/ mL), Fibrinigen (663.83 mg/dL), D-Dimer (1.61mg/dL), and Interleukin-9 /25.8pg/mL). The angioTC revealed a pleural efusion and ground glass infiltrates (figure1). Only after 2 weeks eosinophilia was discovered (88/mcL) After 2 negative consecutieve PCRs for SARS-CoV-2, no imrovement with ampirical antibiotics and all infectious pannels negative, we started decreasing clozapine with improvement of the symptoms and resolution after suspending clozapine completely. Conclusion(s): Clozapine may induce a generalize inflammatory response mediated by interleukin-6. Patients treated with clozapine may exhibit fever and rarely, insterstitial lung inflammation. The expression of induced pneumonitis resembles viral infections, particularly SARS-CoV-2.

Daptomycin-Induced Eosinophilic Pneumonia Mimicking Multifocal Pneumonia.

A 71-year-old female presented to the emergency department with worsening dyspnea, dry cough, malaise, weight loss, fever, chills, and diaphoresis for one week. The patient had been hospitalized four weeks prior with right knee methicillin-resistant Staphylococcus aureus (MRSA) bursitis and was initially treated with IV vancomycin but was switched to IV daptomycin at the time of discharge for convenience of dosing. On presentation to the ED, vitals were normal. Physical examination revealed bilateral scattered rhonchi and crepitations. Chest X-ray revealed new patchy bilateral interstitial and airspace opacities concerning for multifocal pneumonia. Labs were pertinent for mild peripheral eosinophilia. CT chest revealed moderate diffuse ground glass opacities involving both lungs, with subpleural predominance and some areas of septal thickening seen as well. Daptomycin-induced pneumonitis was suspected, and empiric antibiotics were discontinued. The patient subsequently underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsy. BAL fluid showed leukocytosis and eosinophilia of 25 mm3. Right upper lobe biopsy demonstrated foci of alveolar spaces with collections of eosinophils and histiocytes consistent with acute eosinophilic pneumonia. The patient was started on oral prednisone and albuterol breathing treatments with significant improvement after 48 hours from admission. She was discharged on albuterol inhalers and prednisone taper. Acute eosinophilic pneumonia (AEP) is a lung condition that can be rapidly progressive, leading to significant morbidity and mortality. Daptomycin-induced AEP can mimic community-acquired pneumonia, resulting in delayed diagnosis and management. Recognizing the temporal association between drug initiation and the development of symptoms is crucial in the diagnosis of drug-induced AEP. If it is recognized and treated in a timely manner, the prognosis is generally excellent, with rapid and complete clinical recovery as demonstrated by our case.