[EPIPEN INSTRUCTIONS FOR ANAPHYLAXIS PATIENTS DURING DISPENSING: FACTORS RELATED TO THE QUALITY OF PHARMACISTS' INSTRUCTIONS].

BACKGROUND AND AIM: We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered a questionnaire survey to pharmacists with experience handling EpiPen prescriptions. We investigated the relationship between the questionnaire results and the factors in the pharmacists' background regarding the explanation and guidance to patients. RESULTS: The percentage of pharmacists working in pharmacies who provided guidance using visual information and demonstrations was insufficient. Moreover, this figure decreased after the second guidance session. Objective confirmation of patient understanding was also insufficient. The results indicated that self-examination and participation in drug information sessions were important background factors for pharmacists who provided detailed guidance to patients. DISCUSSION: For appropriate long-term management of their condition, An patients must master the EpiPen technique. Pharmacists' guidance plays a critical role in this regard. A support system should be established for proper instruction of pharmacy patients by improving pharmacists' self-education and other educational opportunities.

Involvement of Muscarinic M3 Receptor in the Development of M2 Macrophages in Allergic Inflammation.

INTRODUCTION: The muscarinic M3 receptor antagonist, tiotropium, has a bronchodilatory effect on asthma patients. Additionally, tiotropium inhibits allergic airway inflammation and remodeling in a murine asthma model. However, the underlying mechanisms of this M3 receptor antagonist remain unclear. Therefore, we investigated the effect of muscarinic M3 receptor blockage on M2 macrophage development during allergic airway inflammation. METHODS: BALB/c mice were sensitized and challenged with ovalbumin to develop a murine model of allergic airway inflammation mimicking human atopic asthma. During the challenge phase, mice were treated with or without tiotropium. Lung cells were isolated 24 h after the last treatment and gated using CD68-positive cells. Relm-α and Arginase-1 (Arg1) (M2 macrophage markers) expression was determined by flow cytometry. Mouse bone marrow mononuclear cell-derived macrophages (mBMMacs) and human peripheral blood mononuclear cells (PBMCs)-derived macrophages were stimulated with IL-4 and treated with a muscarinic M3 receptor antagonist in vitro. RESULTS: The total cells, eosinophils, and IL-5 and IL-13 levels in BAL fluids were markedly decreased in the asthma group treated with tiotropium compared to that in the untreated asthma group. The Relm-α and Arg1 expression in macrophages was reduced considerably in the asthma group treated with tiotropium compared to that in the untreated asthma group, suggesting that the development of M2 macrophages was inhibited by muscarinic M3 receptor blockage. Additionally, muscarinic M3 receptor blockage in vitro significantly inhibited M2 macrophage development in both mBMMacs- and PBMCs-derived macrophages. CONCLUSIONS: Muscarinic M3 receptor blockage inhibits M2 macrophage development and prevents allergic airway inflammation. Moreover, muscarinic M3 receptors might be involved in the differentiation of immature macrophages into M2 macrophages.

Superconductivity in a van der Waals layered quasicrystal.

Van der Waals layered transition-metal chalcogenides are drawing significant attention owing to their intriguing physical properties. This group of materials consists of abundant members with various elements, having a variety of different structures. However, they are all crystalline materials, and the physical properties of van der Waals layered quasicrystals have never been studied to date. Here, we report on the discovery of superconductivity in a van der Waals layered quasicrystal of Ta1.6Te. The electrical resistivity, magnetic susceptibility, and specific heat of the quasicrystal unambiguously validate the occurrence of bulk superconductivity at a transition temperature of ~1 K. This discovery can promote new research on assessing the physical properties of novel van der Waals layered quasicrystals as well as two-dimensional quasicrystals; moreover, it paves the way toward new frontiers of superconductivity in thermodynamically stable quasicrystals.

Prevalence and Impact of Social Frailty in Patients with Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) are more inclined to have a high level of social vulnerability due to their physical and psychological burden. However, to date, there have been no study on social frailty in patients with COPD. This study aimed to investigate the prevalence, characteristics, and impact of social frailty in patients with COPD. Methods: Social frailty was assessed using five items in a questionnaire. A patient was diagnosed with social frailty if responses to two or more items were positive. Four hundred and five patients with COPD were assessed for social frailty, dyspnea, and appetite. We also prospectively examined the number of acute exacerbation and unexpected hospitalization for 1 year. Results: Thirty-six percent of patients with COPD had social frailty. They had reduced appetite and more severe dyspnea [Simplified Nutritional Appetite Questionnaire score: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.69‒0.95, p < 0.01; modified Medical Research Council score: OR 1.42, 95% CI 1.05‒1.93, P = 0.02] than patients without social frailty. Social frailty was not a risk factor for moderate acute exacerbation of COPD but a risk factor for severe acute exacerbation and all-cause unexpected hospitalization (severe acute exacerbation: ß, standardized regression coefficient: 0.13, 95% CI 0.01‒0.25, P = 0.04, unexpected hospitalization: ß 0.17, 95% CI 0.05‒0.29, P = 0.01). Conclusion: The prevalence of social frailty is 36%; however, social frailty has a marked clinical impact in patients with COPD.

[SURVEY OF KNOWLEDGE ABOUT ANAPHYLAXIS AND GUIDANCE WHEN DISPENSING EPIPEN FOR PHARMACISTS WORKING IN PHARMACIES].

BACKGROUND/PURPOSE: Anaphylactic shock is a serious and life-threatening condition, and affected patients should be quickly and effectively treated with an EpiPen. Although the correct use of an EpiPen is greatly affected by a user's proficiency level and the instructions accompanying the EpiPen, there has been almost no investigation into the knowledge of the EpiPen and the actual situation of the accompanying instructions for use. Therefore, we conducted this nationwide survey to elucidate these issues. METHODS: A questionnaire survey was conducted among pharmacists registered as members of the system of a research company outside the university and working at pharmacies with experience in handling EpiPen prescriptions. RESULTS: Many of the pharmacists surveyed knew that the EpiPen is the first-line treatment for anaphylactic shock. However, they did not have sufficient knowledge of administration routes and candidates for second-line treatment. Both their occasions and experiences of dealing of EpiPen were found to be low. CONSIDERATION: It is desirable to learn at conferences regarding allergology/clinical allergy and seminars for medical professionals including pharmacists in order to acquire the skills and knowledge to consult with patients with allergic diseases, including action plans presented by doctors in preparation for recurrence of anaphylaxis.

Effect of linezolid on platelet count in critically ill patients with thrombocytopenia.

INTRODUCTION: Linezolid (LZD) is one of the antibiotics used to treat methicillin-resistant Staphylococcus aureus. In Japan, the dose of LZD is not generally adjusted by renal function or therapeutic drug monitoring and is readily available for critically ill patients. The adverse effects of LZD include pancytopenia, especially thrombocytopenia. We investigated the effect of LZD on platelet counts in critically ill patients with thrombocytopenia during admission to the intensive care unit (ICU). METHODS: Fifty-five critically ill patients with existing thrombocytopenia (platelet count < 100 ×103 /µL) who received LZD for five days or more during the period from January 2011 to October 2018 were included. Changes in platelet count and frequency of platelet concentrate (PC) transfusion were evaluated retrospectively. RESULTS: Mean (± standard error) platelet count prior to initiation of LZD was 47 ± 4 ×103 /uL, which increased significantly to 86 ± 13 ×103 /uL on day 15 (p<0.01). Median [interquartile range] duration of LZD therapy was 9 [8-12] days. Thirty-two patients (58.2%) required PC transfusion in the 15-day study period. The daily rate of PC transfusion decreased from 30.2% on days 1-5 to 18.2% on days 11-15. Similar tendencies were observed in patients with non-hematological and hematological disease. CONCLUSION: Thrombocytopenia in critically ill patients in the ICU did not worsen after initiation of LZD therapy, and may be considered for the treatment of MRSA in this setting.

High Phase-Purity and Composition-Tunable Ferromagnetic Icosahedral Quasicrystal.

We discovered a ferromagnetic Au-Ga-Dy icosahedral quasicrystal (i QC), not only with high phase purity but also with tunable composition. The isothermal magnetization of the polycrystalline ferromagnetic i QC was closely investigated and the mean-field-like nature of the ferromagnetic transition is elucidated. Moreover, the maximum Weiss temperature (θ_{p}) of the i QCs was found at the electrons-per-atom (e/a) ratio of 1.70 being well consistent with those of ACs, validating tunability of the magnetic properties of i QCs on the basis of θ_{p}-e/a scheme for the first time. Thus, the present work provided direct evidence that the magnetism of the i QCs depends on the e/a ratio or the Fermi energy, paving the way for future studies on various exotic magnetic textures formed on a quasiperiodic lattice through the e/a ratio.

Observation of a critical charge mode in a strange metal.

Understanding the strange metallic behavior that develops at the brink of localization in quantum materials requires probing the underlying electronic charge dynamics. Using synchrotron radiation-based Mössbauer spectroscopy, we studied the charge fluctuations of the strange metal phase of ß-YbAlB4 as a function of temperature and pressure. We found that the usual single absorption peak in the Fermi-liquid regime splits into two peaks upon entering the critical regime. We interpret this spectrum as a single nuclear transition, modulated by nearby electronic valence fluctuations whose long time scales are further enhanced by the formation of charged polarons. These critical charge fluctuations may prove to be a distinct signature of strange metals.

Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema.

Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change.

Serum cystatin C and CRP are early predictive biomarkers for emergence of hypoxia in COVID-19.

BACKGROUND: In Japan, during the coronavirus disease 2019 (COVID-19) pandemic, patients with non-hypoxia are recommended to recuperate at home or in pre-hospital facilities. However, it was observed that unexpected hypoxia may occur and become severe subsequently in patients whose symptoms were initially expected to improve naturally. The aim of this study is to validate biomarkers that can predict at an early stage the emergence of hypoxia in COVID-19 patients without hypoxia. METHODS: We retrospectively enrolled 193 patients with COVID-19, excluding patients with hypoxia and severe disease from the onset. Participants were classified into two groups according to the emergence of hypoxia during the clinical course, and the laboratory data were compared to identify biomarkers that could predict early the emergence of hypoxia. RESULTS: The areas under the curve for serum cystatin C (CysC) and C-reactive protein (CRP) levels for the emergence of hypoxia during the clinical course were higher than those for other biomarkers (CysC, 0.84 and CRP, 0.83). Multivariate analysis showed that high serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course. CONCLUSIONS: Elevated serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course in COVID-19 patients without hypoxia. These findings may help determine the need for hospitalization in initially non-hypoxic COVID-19 patients.

Serum IL-28A/IFN-λ2 is linked to disease severity of COVID-19.

Type III interferons (IFNs) play an important role in respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to determine whether the expression of serum type III IFNs predicted disease severity among patients with the coronavirus disease (COVID-19). A retrospective cohort study was conducted of patients admitted to a single hospital between March 21, 2020, and March 31, 2021. Patients were divided into mild to moderate I (MM) and moderate II to severe (MS) groups based on the COVID-19 severity classification developed by the Japanese Ministry of Health, Labor and Welfare. A total of 257 patients were included in the analysis. Human interleukin-28A (IL-28A/IFN-λ2) expression was significantly lower, and interleukin (IL)-6 expression was significantly higher in the MS group than in the MM group (both p < 0.001). In addition, IL-28A/IFN-λ2 was statistically significantly inversely correlated with the time from disease onset to negative SARS-CoV-2 PCR results (p = 0.049). Multivariable logistic regression analysis showed that IL-28A/IFN-λ2 was an independent predictor of disease severity (p = 0.021). The low expression of IL-28A/IFN-λ2 may serve as a serum biomarker that predicts the severity of COVID-19, possibly through the mechanism of delayed viral elimination.

Comprehensive Gene Expression Signature Using RNA-Seq in Airways of Mouse Model of Severe Asthma with Fungal Sensitization.

INTRODUCTION: Inhalation of fungal allergens induces airway epithelial damage following airway inflammation and excessive mucus secretion, which can lead to severe asthma with fungal sensitization (SAFS). Comprehensive gene expression analysis in Alternaria-exposed mouse airways, a model of SAFS, has not been conducted. METHODS: BALB/c mice received intranasal administration of Alternaria extract or phosphate-buffered saline twice a week for 6 weeks. Lung sections and bronchoalveolar lavage fluid were obtained to assess airway inflammation. RNA-Seq in the central airway was performed, and gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted for pathway analyses. An in vitro experiment using human airway epithelial cell 16HBE14o- was performed to validate the RNA-Seq findings. RESULTS: Eosinophilic airway inflammation with mucus overproduction and airway remodeling was observed in mice exposed to Alternaria. RNA-Seq analysis revealed 403 upregulated and 108 downregulated genes in airways of Alternaria-exposed mice. In GO analysis, the functions of immunoglobulin (Ig) receptor binding, Ig production, inflammatory response, and T-cell activation were upregulated, while those of keratinization and defense response to other organisms were downregulated. GSEA revealed positive enrichment in T-cell receptor complex, immunological synapse, antigen binding, mast cell activation, and Ig receptor binding, and negative enrichment in keratinization and cornification in Alternaria-exposed mice relative to control. Alternaria exposure to 16HBE14o- cells validated the downregulation of epithelial keratinization-related genes, including SPRR1A, SPRR1B, and KRT6B. CONCLUSION: RNA-Seq analysis showed that Alternaria exposure induced inflammatory response and impaired defense mechanisms in mice airway epithelium, which might be therapeutic targets for SAFS.

Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products.

INTRODUCTION: Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. METHODS: This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. RESULTS: Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p<0.05). The logistic regression analysis model showed that a younger age and higher education level were associated with the use of HTP (age OR=0.83; higher education level OR=4.63; p<0.05). Many of the current smokers displayed smoking behaviors that are not guaranteed to be safe, such as reducing smoking or switching to lighter cigarettes or HTP. CONCLUSIONS: Patients with COPD who continue smoking tended to have low appetite as well as smoking behaviors that are not guaranteed to be safe. Physicians should provide appropriate guidance to these patients on smoking cessation.

Experimental Observation of Long-Range Magnetic Order in Icosahedral Quasicrystals.

Quasicrystals (QCs), first discovered in 1984, generally do not exhibit long-range magnetic order. Here, we report on long-range magnetic order in the real icosahedral quasicrystals (i QCs) Au-Ga-Gd and Au-Ga-Tb. The Au65Ga20Gd15 i QC exhibits a ferromagnetic transition at TC = 23 K, manifested as a sharp anomaly in both magnetic susceptibility and specific heat measurements, along with an appearance of magnetic Bragg peak below TC. This is the first observation of long-range magnetic order in a real quasicrystal, in contrast to the spin-glass-like behaviors observed for the other magnetic quasicrystals found to date. Moreover, when Gd is replaced by Tb, i.e., for the Au65Ga20Tb15 i QC, a ferromagnetic behavior is still retained with TC = 16 K. Although the sharp anomaly in the specific heat observed for the Au65Ga20Gd15 i QC becomes broadened upon Tb substitution, neutron diffraction experiments clearly show marked development of magnetic Bragg peaks just below TC, indicating long-range magnetic order for the Au65Ga20Tb15 i QC also. Our findings can contribute to the further investigation of exotic magnetic orders formed on real quasiperiodic lattices with unprecedented highest global symmetry, i.e., icosahedral symmetry.

A novel LRP6 variant in a Japanese family with oligodontia.

Congenital tooth agenesis is a common anomaly in human development. We performed exome sequence analysis of genomic DNA collected from Japanese patients with tooth agenesis and their relatives. We found a novel single-nucleotide insertion in the LRP6 gene, the product of which is involved in Wnt/ß-catenin signaling as a coreceptor for Wnt ligands. The single-nucleotide insertion results in a premature stop codon in the extracellular region of the encoded protein.

Acute Exacerbation of Idiopathic Interstitial Pneumonia Triggered by Cardiac Ablation: The First Case Report.

Acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) is associated with invasive procedures and respiratory infections. However, there have been no reports of AE-IIP triggered by catheter ablation. We herein report a case of AE-IIP after catheter ablation for atrial fibrillation in an 82-year-old man who was diagnosed with IIP. Cardiac ablation has become an increasingly common procedure for managing patients with arrhythmias. Considering that catheter ablation causes AE-IIP, a detailed clinical interview, physical examination, and chest radiography are necessary before catheter ablation. We should additionally consider AE-IIP as a differential diagnosis of respiratory failure after catheter ablation.

Cardiac Failure Requiring Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) Management in a Refeeding Syndrome Patient with Diabetic Ketoacidosis: A Case Report.

BACKGROUND Refeeding syndrome is a complex metabolic disorder that develops following rapid nutritional administration after a long period of undernutrition. The onset mechanism involves intracellular transport of phosphorus, potassium, and water, in association with rapid glucose administration. The resulting hypophosphatemia is extremely dangerous and can cause severe heart failure and fatal arrhythmia. We successfully used extracorporeal cardiopulmonary support to manage a case of refeeding syndrome that occurred during the course of treatment of diabetic ketoacidosis. There are only a few reports of the use of cardiopulmonary support for the treatment of refeeding syndrome. CASE REPORT A 72-year-old man was admitted to the hospital for treatment of diabetic ketoacidosis. Despite receiving insulin and nutrition therapy, QT prolongation and ventricular fibrillation appeared on the electrocardiogram. Although coronary angiography was performed in consideration of the possibility of ischemic heart disease, no significant stenosis of the coronary arteries was identified. Due to persistent hypotension and recurrence of ventricular fibrillation, extracorporeal cardiopulmonary support was commenced in the ICU. His serum phosphorus level showed a marked decrease on his first day in the ICU, for which daily replacement therapy was administered during his ICU stay. No fatal arrhythmia developed thereafter. He was weaned off extracorporeal cardiopulmonary support on the fourth day of his ICU stay and was subsequently discharged from the hospital. CONCLUSIONS We suggest vigilant monitoring of electrolytes, including phosphate levels, in diabetic ketoacidosis patients, and active circulatory support, as required, in patients with refeeding syndrome.

Immune-Associated Proteins Are Enriched in Lung Tissue-Derived Extracellular Vesicles during Allergen-Induced Eosinophilic Airway Inflammation.

Studying the proteomes of tissue-derived extracellular vesicles (EVs) can lead to the identification of biomarkers of disease and can provide a better understanding of cell-to-cell communication in both healthy and diseased tissue. The aim of this study was to apply our previously established tissue-derived EV isolation protocol to mouse lungs in order to determine the changes in the proteomes of lung tissue-derived EVs during allergen-induced eosinophilic airway inflammation. A mouse model for allergic airway inflammation was used by sensitizing the mice intraperitoneal with ovalbumin (OVA), and one week after the final sensitization, the mice were challenged intranasal with OVA or PBS. The animals were sacrificed 24 h after the final challenge, and their lungs were removed and sliced into smaller pieces that were incubated in culture media with DNase I and Collagenase D for 30 min at 37 °C. Vesicles were isolated from the medium by ultracentrifugation and bottom-loaded iodixanol density cushions, and the proteomes were determined using quantitative mass spectrometry. More EVs were present in the lungs of the OVA-challenged mice compared to the PBS-challenged control mice. In total, 4510 proteins were quantified in all samples. Among them, over 1000 proteins were significantly altered (fold change >2), with 614 proteins being increased and 425 proteins being decreased in the EVs from OVA-challenged mice compared to EVs from PBS-challenged animals. The associated cellular components and biological processes were analyzed for the altered EV proteins, and the proteins enriched during allergen-induced airway inflammation were mainly associated with gene ontology (GO) terms related to immune responses. In conclusion, EVs can be isolated from mouse lung tissue, and the EVs' proteomes undergo changes in response to allergen-induced airway inflammation. This suggests that the composition of lung-derived EVs is altered in diseases associated with inflammation of the lung, which may have implications in type-2 driven eosinophilic asthma pathogenesis.

Specific substrates composed of collagen and fibronectin support the formation of epithelial cell sheets by MDCK cells lacking α-catenin or classical cadherins.

The effect of the extracellular matrix substrates on the formation of epithelial cell sheets was studied using MDCK cells in which the α-catenin gene was disrupted. Although the mutant cells did not form an epithelial cell sheet in conventional cell culture, the cells formed an epithelial cell sheet when they were cultured on or in a collagen gel; the same results were not observed when cells were cultured on collagen-coated cover glasses or culture dishes. Moreover, the cells cultured on the cell culture inserts coated with fibronectin, Matrigel, or vitronectin formed epithelial cell sheets, whereas the cells cultured on cover glasses coated with these proteins did not form the structure, implying that the physical and chemical features of the substrates exert a profound effect on the formation of epithelial cell sheets. MDCK cells lacking the expression of E- and K-cadherins displayed similar properties. When the mutant MDCK cells were cultured in the presence of blebbistatin, they formed epithelial cell sheets, suggesting that myosin II was involved in the formation of these sheets. These cell sheets showed intimate cell-cell adhesion, and electron microscopy confirmed the formation of cell junctions. We propose that specific ECM substrates organize the formation of basic epithelial cell sheets, whereas classical cadherins stabilize cell-cell contacts and promote the formation of structures.

Downregulation of type III interferons in patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) is globally rampant, and to curb the growing burden of this disease, in-depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID-19 patients, based on disease severity. We included 72 consecutive COVID-19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild-Moderate I (mild) and Moderate II-Severe (severe) groups based on the COVID-19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d-dimer, lactate dehydrogenase, C-reactive protein, ferritin, Krebs von den Lungen-6, surfactant protein (SP)-D, and SP-A than the mild group. Strikingly, the levels of interleukin (IL)-28A/interferon (IFN)-λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN-λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.