COVID-19 in tobacco users.

Smoking is a significant social problem threatening the population's health, especially during the coronavirus pandemic. Due to the problem's urgency, we present a clinical case of SARS-CoV-2 infection in a patient with 10 years of smoking and concomitant chronic obstructive pulmonary disease (chronic bronchitis and peribronchial pneumosclerosis). Patient L.K., 42 years old, on 13.10.2022, was hospitalized for several hours at the Emergency Hospital of the Ministry of Health of Chuvashia (Cheboksary) with a severe new coronavirus infection. Secondary diagnosis: Chronic obstructive pulmonary disease Case history: for about two to three weeks, the patient noted an increase in body temperature to 37.2-37.4 degreeC and a cough. He has smoked for about 10 years, 1 pack per day. Computed tomography showed signs of bilateral COVID-associated pneumonitis, alveolitis with 85% involvement and consolidation sites, signs of chronic bronchitis, and peribronchial pneumosclerosis. The diagnosis of COVID-19 was confirmed by a polymerase chain reaction in a nasopharyngeal smear. The NEWS2 score was 9. After the treatment started, the patient died. Histological examination showed perivascular sclerosis, peribronchial pneumosclerosis, atrophic changes in the ciliated epithelium, and structural and functional alteration of the bronchial mucosa. In addition, areas of hemorrhage and inflammatory infiltrate in the bronchial wall were found. Coronavirus is known not to cause bronchitis but bronchiolitis. In the presented case, the patient showed signs of transition of bronchitis to the acute stage. Therefore, it can be assumed that the coronavirus acts as a complicating factor. In addition to the described changes, signs of viral interstitial pneumonia, pulmonary edema, and early development of acute respiratory distress syndrome were identified.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Housing and respiratory health: Exposures, health effects and interventions

Housing quality and affordability are well established as social determinants of health through direct and indirect mechanisms. Respiratory illnesses related to housing are nearly all the result of housing disrepair that allows intrusion into the home of environmental agents that are directly or indirectly associated with disease. Structural deficiencies such as leaks, cracks in the foundation or holes in the home's exterior can facilitate the presence of mould, which is causally linked to the development of asthma and is associated with exacerbation of asthma symptoms in children and adults. Indoor cleanliness can also contribute to the presence of mice and cockroaches. Proper ventilation can improve air quality, reducing exposure to PM, VOCs and infectious respiratory agents. Disparities in exposure to the housing conditions associated with respiratory disease are readily apparent across socioeconomic lines. Low-income families are less likely to be able to afford the costs of maintaining a home, which prevents them from making repairs that could improve respiratory health.Copyright © ERS 2023.

Unsupervised Clustering and Binary Classification Analysis for Predicting COVID Syndrome (LONG COVID) in US Adults

Objectives: This study investigated the risk factors of developing COVID Syndrome and identified potential disease profiles that may exist among those who have contracted COVID-19. Method(s): Data on 13,953 adults who had experienced COVID-19 at any time were analyzed from the 2022 US National Health and Wellness Survey. XGBoost binary classification with 10-fold cross-validation was used to predict long COVID among those who reported experiencing COVID-19 and to extract feature importance. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance in the outcome variable. Variable selection was conducted based on SHAP values. Fifty variables including demographic characteristics, COVID-19 symptoms, comorbidities, and health characteristics were used in the final model. Parameters were tuned using AUC. Among the 2,665 respondents who were diagnosed with long COVID, k-medoids clustering with t-SNE dimensionality reduction was implemented to determine whether distinct symptom profiles exist. Average silhouette score was used to determine the optimal number of clusters. Result(s): The XGBoost binary classification for predicting long COVID among those with COVID-19 had an AUC of 0.9145, accuracy of 0.9072, sensitivity of 0.9630, specificity of 0.8328, and Brier score of 0.0928. The most important features in predicting long COVID were age, smoking habits, COVID-19 vaccination status, certain COVID-19 symptoms experienced, and certain comorbidities. Among those diagnosed with long COVID, the clustering analysis found nine unique clusters of symptoms. The cluster that experienced the most severe symptoms was older, female, lower income, lower vaccination rate, and had more comorbidities like asthma, chronic bronchitis, and allergies. Conclusion(s): In a broadly representative US adult population, XGBoost model identified a selection of risk factors for developing long COVID. K-medoids clustering identified clusters of patients that were at risk for developing severe symptoms.Copyright © 2023

COVID-19 in tobacco users.

Smoking is a significant social problem threatening the population's health, especially during the coronavirus pandemic. Due to the problem's urgency, we present a clinical case of SARS-CoV-2 infection in a patient with 10 years of smoking and concomitant chronic obstructive pulmonary disease (chronic bronchitis and peribronchial pneumosclerosis). Patient L.K., 42 years old, on 13.10.2022, was hospitalized for several hours at the Emergency Hospital of the Ministry of Health of Chuvashia (Cheboksary) with a severe new coronavirus infection. Secondary diagnosis: Chronic obstructive pulmonary disease Case history: for about two to three weeks, the patient noted an increase in body temperature to 37.2-37.4 degreeC and a cough. He has smoked for about 10 years, 1 pack per day. Computed tomography showed signs of bilateral COVID-associated pneumonitis, alveolitis with 85% involvement and consolidation sites, signs of chronic bronchitis, and peribronchial pneumosclerosis. The diagnosis of COVID-19 was confirmed by a polymerase chain reaction in a nasopharyngeal smear. The NEWS2 score was 9. After the treatment started, the patient died. Histological examination showed perivascular sclerosis, peribronchial pneumosclerosis, atrophic changes in the ciliated epithelium, and structural and functional alteration of the bronchial mucosa. In addition, areas of hemorrhage and inflammatory infiltrate in the bronchial wall were found. Coronavirus is known not to cause bronchitis but bronchiolitis. In the presented case, the patient showed signs of transition of bronchitis to the acute stage. Therefore, it can be assumed that the coronavirus acts as a complicating factor. In addition to the described changes, signs of viral interstitial pneumonia, pulmonary edema, and early development of acute respiratory distress syndrome were identified.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Synergistic effects of COVID-19 and Pseudomonas aeruginosa in chronic obstructive pulmonary disease: a polymicrobial perspective.

This article discusses the connection between the novel coronavirus disease 2019 (COVID-19) caused by the coronavirus-2 (SARS-CoV-2) and chronic obstructive pulmonary disease (COPD). COPD is a multifaceted respiratory illness that is typically observed in individuals with chronic exposure to chemical irritants or severe lung damage caused by various pathogens, including SARS-CoV-2 and Pseudomonas aeruginosa. The pathogenesis of COPD is complex, involving a variety of genotypes and phenotypic characteristics that result in severe co-infections and a poor prognosis if not properly managed. We focus on the role of SARS-CoV-2 infection in severe COPD exacerbations in connection to P.  aeruginosa infection, covering pathogenesis, diagnosis, and therapy. This review also includes a thorough structural overview of COPD and recent developments in understanding its complicated and chronic nature. While COVID-19 is clearly linked to emphysema and chronic bronchitis at different stages of the disease, our understanding of the precise interaction between microbial infections during COPD, particularly with SARS-CoV-2 in the lungs, remains inadequate. Therefore, it is crucial to understand the host-pathogen relationship from the clinician's perspective in order to effectively manage COPD. This article aims to provide a comprehensive overview of the subject matter to assist clinicians in their efforts to improve the treatment and management of COPD, especially in light of the COVID-19 pandemic.

CHLORINE GAS EXPOSURE AND OBSTRUCTIVE AIRWAY DISEASE: A CASE REPORT AND CASE-BASED DISCUSSION

SESSION TITLE: Occupational and Environmental Lung Disease Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Chlorine gas is a pulmonary irritant with pungent odor that damages the respiratory tract. Chlorine gas exposure occurs in industrial or household exposures,Chlorine gas has two forms either a liquid or gas, toxicity of chlorine gas depends on the dose and duration of exposure. Chlorine gas used in manufacturing products like paper, insecticides, Chlorine is used to treat bottled and swiming pool water. CASE PRESENTATION: A 37 Y.O Male, no PMH presents with progressive dyspnea for three days worse with activity,decreases with rest, denied cough fever or chest pain he is vaccinated for COVID,no smoking history. The patient worked at a chlorine gas factory in the Dominican Republic for 15 years. Exam: Vitals: BP 124/72 mmHg. HR 100 BPM. RR 21 BPM. SpO2 84%. General: acute distress. Heart: normal S1, S2. RRR. Lung: wheeze bilaterally. Abdomen: Soft. Musculoskeletal: no pitting edema. he was placed on 6 LPM NC saturation improved to 90%. CBC and Chemistry were unremarkable, he was started on steroid, breathing treatment with antibiotics. ABG showed hypoxemia. he was placed on Venturi mask and his saturation improved to 95%.CTA was negative for PE. EKG, troponin were unremarkable. A proBNP normal. The antibiotics were discontinued because of a negative workup. A TTE study was normal. HRCT scan of the chest, showed atelectasis and infiltrates of lower lobes. No interstitial fibrosis.A PFT showed obstructive airway disease. He was discharged on oral and inhaled steroids.Hi new onset obstructive airway could be due to chlorine gas exposure. DISCUSSION: Chlorine gas causes cellular injury through oxidative damage but further damage results from activation and recruitment of inflammatory cells with subsequent release of oxidants and proteolytic enzymes. Humans can detect chlorine gas odor at a concentration between 0.1-0.3 ppm. At 1-3 ppm,it causes irritation of oral,eye mucosal membranes. At 30-40 ppm causes cough, chest pain, and SOB. At 40-60 ppm, toxic pneumonitis and pulmonary edema and can be fatal at 430 ppm concentration or higher within thirty minutes. Chronic exposure to chlorine gas lead to chest pain, cough, sore throat, hemoptysis, recurrent asthma. Physical exam findings include tachypnea cyanosis, wheezing, intercostal retractions, decreased breath sounds. Pulmonary function tests may reveal obstructive lung function disease. Chronic exposure to a low level was found to be associated with an increased risk of asthma in swimmers. CONCLUSIONS: Chlorine exposure results in direct chemical toxicity to the airways with acute airways obstruction or airways hyperreactivity, presentation varies from acute overwhelming intoxication with acute lung injury and or death, occupational exposure increase the likelihood of chronic bronchitis or isolated wheezing attacks. Treatment for chlorine exposure is largely supportive. Reference #1: 1- Center of disease control and prevention website/emergency preparedness and response/ https://emergency.cdc.gov/agent/chlorine/basics/facts.asp Reference #2: 2- C- Morim A, Guldner GT. Chlorine Gas Toxicity. [Updated 2021 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537213/. Reference #3: A- Gummin DD, Mowry JB, Beuhler MC, et al. 2020 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021;59(12):1282-1501. doi:10.1080/15563650.2021.1989785 DISCLOSURES: No relevant relationships by Abdallah Khashan No relevant relationships by Samer Talib no disclosure on file for Matthew Yotsuya;

CIRCULATING DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPS) AS PROGNOSTIC MARKERS OF DISEASE SEVERITY IN PATIENTS WITH COVID-19 ARDS IN THE ICU

SESSION TITLE: Biological Markers in Patients with COVID-19 Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Pandemic SARS-CoV-2 infection (COVID-19), like other respiratory viruses, caused a massive incidence of acute respiratory distress syndrome (ARDS). Prior literature showed that influenza infection results in a significant increase in the level of circulating High Mobility Group Box 1 (HMGB1) in infected mice, cotton rats, and in humans;and a small molecule inhibitor of HMGB1 blocked lung pathology and lethality in influenza-infected mice and cotton rats. Moreover, HMGB1 has also been shown to be elevated in the serum of patients with ARDS and is an indicator of increased mortality. Gastrin Releasing Peptide (GRP) has been implicated in bronchopulmonary dysplasia, chronic obstructive pulmonary disease, chronic bronchitis, emphysema, and fibrosis. In addition to HMGB1, GRP represents a novel DAMP that, when targeted therapeutically in influenza-infected mice, is highly protective. The interaction between GRP and HMGB1 is currently under study. We examined if these DAMPS are associated with poor clinical outcomes in patients with COVID-19 ARDS. METHODS: Deidentified patient plasma and serum samples were obtained from discarded, clinical blood samples from 100 patients with COVID-19 admitted to UMMC's intensive care unit (ICU). Demographic and clinical data were collected from the patient’s electronic medical record. HMGB1 and GRP ELISA kits were used to analyze their concentrations in patients’ sera at Day 1 of admission to ICU. Cox proportional hazards models were used to examine the relationship between risk factors and severity of hypoxemia (P/F ratio), need for mechanical ventilation, and need for mechanical circulatory support (VV-ECMO). RESULTS: The average age of study participants was 59.1 years of which 59.2% were men and 57.1% were African American. The mean BMI was 34.3 kg/m2. The prevalence of hypertension, hyperlipidemia, diabetes, pulmonary and cardiovascular disease was 57.1%, 26.5%, 42.9%, 32.7%, and 42.9%, respectively. We found that GRP concentration was associated with worsening hypoxemia (mild 31.9, mod. 42.7, severe 79.0 ng/ml;p=0.014), requirement for mechanical ventilation (No 40.1, Yes 61.5 ng/ml;p=0.063), and need for VV-ECMO (No 48.6, Yes 93.1 ng/ml;p=0.026). HMGB1 concentration was associated with worsening hypoxemia (mild 24.4, mod. 55.1, severe 40.9 ng/ml;p=0.021) but did not correlate with other outcomes. CONCLUSIONS: GRP and HMGB1 have been previously implicated in the pathogenesis of viral infections, such as influenza, and ARDS in animal models and human. Our results suggest that these DAMPs maybe associated with severity of disease in critically ill patients with COVID-19 infection. CLINICAL IMPLICATIONS: Future studies should elucidate the specific cellular and biochemical pathways implicated in pathogenesis of ARDS, identify whether HMGB1 and GRP could be potential biomarkers for severe illness outcomes, and test novel anti-HMGB1 and GRP therapeutics in ARDS. DISCLOSURES: No relevant relationships by Fahid Alghanim no disclosure on file for Jeffrey Hasday;Consultant relationship with Guidepoint Please note: $1-$1000 by Carl Shanholtz, value=Consulting fee stock holder relationship with Teva Pharmaceuticals Please note: $1001 - $5000 by Carl Shanholtz, value=stock iinvestor relationship with illumina Please note: $1001 - $5000 by Carl Shanholtz, value=options No relevant relationships by Kari Ann Shirey No relevant relationships by Mohan Tulapurkar No relevant relationships by Stefanie Vogel

MACROGLOSSIA IN THE SETTING OF COVID-19

SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Macroglossia is a rare but life-threatening symptom that disrupts a person's ability to talk, swallow, and can also compromise their airway. Although not very well studied, there are several case reports describing a possible association between COVID-19 infection and macroglossia in people with African ancestry. We present an African American man who developed significant macroglossia several days after testing positive for COVID-19. CASE PRESENTATION: A 59 y/o African American male with a history of chronic bronchitis and tobacco use presented with 4 days of dyspnea. Sars-Cov-2 PCR was positive. Chest x-ray revealed bilateral, diffuse lung infiltrates. He had an elevated CRP of 295 and a d-dimer of 265. He became lethargic and hypercapnic requiring intubation which was nontraumatic. He was sedated, paralyzed, and proned. He received steroid therapy, broad spectrum antibiotics and a dose of Sarilumab. About a week later, he developed macroglossia that worsened over the course of days. Side effect profiles of each of his medications did not reveal any increased likelihood of macroglossia. C1Q complement cascade was mildly elevated and C1 esterase inhibitor level was normal. Diagnosis and treatment was necessary at this point as concerns for tongue central necrosis were raised and baseline tongue size would be required for proper evaluation and surgical intervention if necessary. He was given 4 units of FFP for possible angioedema with no improvement. CT Neck W/ contrast revealed edema and protrusion of the tongue without a discrete mass. Workup for acromegaly, sarcoidosis, amyloidosis, and hypothyroidism were negative. A pressure ulcer developed on his tongue due to the endotracheal tube and so he underwent tracheostomy. His tongue was draped in Chlorhexidine soaked gauze as well as Vashe wound solution. As he recovered from COVID-19 pneumonia, his respiratory status improved as well as his macroglossia. His tracheostomy was decannulated and his tongue returned to its baseline size. DISCUSSION: Macroglossia can lead to complications including airway compromise, dysphagia, or speech difficulties. It has been heavily proposed in the literature that COVID-19 infection can lead to postinfectious inflammatory peripheral nerve injury secondary to immune driven mechanisms. It was also previously proposed in literature based on immune-histochemical analysis of a tongue tissue sample taken from a COVID-19 patient that tongue muscle atrophy occurs as well as macrophage infiltration similar to that of nerve injury repair which can eventually lead to macroglossia. CONCLUSIONS: As the effects of COVID-19 are becoming better studied overtime, macroglossia, especially in those with African ancestry, is increasingly coming under the radar. This case report seeks to educate clinicians on this possible sequela and encourage supportive treatment in hopes that the tongue will recover. Reference #1: McCrossan S, Martin S, Hill C. Tongue Reduction for Macroglossia. J Craniofac Surg. 2021;32(5):1856-1859. doi:10.1097/SCS.0000000000007276 Reference #2: Colombo D, Del Nonno F, Nardacci R, Falasca L. May macroglossia in COVID-19 be related not only to angioedema?. J Infect Public Health. 2022;15(1):112-115. doi:10.1016/j.jiph.2021.10.026 Reference #3: Fernandez CE, Franz CK, Ko JH, et al. Imaging Review of Peripheral Nerve Injuries in Patients with COVID-19. Radiology. 2020;298 (3). https://doi.org/10.1148/radiol.2020203116 DISCLOSURES: No relevant relationships by Megan Devine No relevant relationships by Devin Haney No relevant relationships by Es-Haq Hassanin No relevant relationships by Nadim Islam No relevant relationships by Alyssa Weyer

COVID-19 DISEASE SEVERITY AND RISK OF 12-MONTH CKD PROGRESSION

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been in our daily practice for almost 2 years now. Since the beginning of the pandemic, we have aimed to study its most immediate effects on patients to find the best line of treatment or, at least, mitigate its worst outcomes. Nevertheless, we also know some long-term health consequences such as fatigue, sleep difficulties, headache, among others, but its long-term kidney effects are not entirely clear yet. The aim of this study was to describe if coronavirus disease's (COVID- 19) severity increases the risk of chronic kidney disease (CKD) progression after a previous hospitalization and observe if there are any additional risk factors that could help us predict this outcome. METHOD: In this study, a sample of consecutive patients who required admission due to COVID-19 during the first wave of the pandemic (from March to May of 2020) was recruited. Patients were followed for 12 months since initial admission. The composite outcome of the study included either death or CKD progression. CKD progression was defined as incremental progression to a higher KDIGO CKD stage compared to baseline pre COVID-19 renal function [(in mL/min/1.73 m2): estimated glomerular filtration rate (eGFR) ≥60;stage 3a: 45-59;stage 3b: 30-44;stage 4: 15-29;stage 5: <15], or dialysis initiation. Cardiovascular disease was defined as a history of myocardial infarction, stroke, or peripheral vascular disease. Chronic lung diseases included asthma, chronic obstructive pulmonary disease and chronic bronchitis. RESULTS: The sample was composed of 93 patients, of which 14 (15.1%) died during follow-up. Of those alive 12 months after initial admission, 17 (21.5%) suffered CKD progression. No patient required renal replacement therapy. Patients that suffered the composite outcome presented a higher prevalence of cancer, tended to be slightly older and suffered from additional comorbidities more frequently (Table). In multivariate logistic regression analysis, previous history of CKD [odds ratio (OR): 1.066 (0.433- 2.624);P = 0.889], severe or critical COVID-19 on admission [OR: 0.657 (0.24-1.8);P =0.414] or ICU admission [OR: 0.986 (0.082-11.898);P = 0.991] failed to predict the composite outcome. CONCLUSION: Our main hypothesis was that COVID-19 sequelae should be due to an exaggerated activation of the immune system against the virus. Thus, patients that suffered severe COVID-19 should be expected to develop more long-term health consequences of the infection when compared with those with milder disease. However, we failed to prove any link between COVID-19 severity and long-term CKD progression. History of CKD or ICU admission was also unable to predict the composite outcome. Previous studies have described a relationship between COVID-19 severity and adverse renal outcomes, a relationship that we failed to observe. These discrepancies could be due to the small sample size of our study and the different definition of CKD progression applied. In addition, age could act as a potential modifier of CKD progression after admission due to COVID. More studies are required to further clarify the mechanisms and long-term renal consequences of COVID-19 and define potential lines of treatment. (Table Presented).

People With Chronic Bronchitis Are at More Risk of Getting Covid-19

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is the seventh-generation corona virus family causing viral pandemic corona virus disease (COVID-19) across globe affecting millions of people. In this time the COVIDS-19 corona virus pandemic is worldwide problem they affect 10.8M people on 3 Feb. 2021. The cases of COVID-19 are increase daily and they are affecting our physical, mental and also social-economic condition. The recent outbreak of corona virus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) poses an enormous threat to global public health and economies. Corona viruses (CoVs) are important RNA viruses that affect respiratory, gastrointestinal and urinary system of human being and birds. These viruses originated from the subfamily Coronavirinae which genetically includes Alphacoronavirus, Beta corona virus, Gamma corona virus and Delta corona virus. The genome sequencing study shows that SARS-CoV-2-induced COVID-19 belongs to the genus Beta corona virus and IBV-induced avian infectious bronchitis belongs to the genus Gamma corona virus. A chronic bronchitis is respiratory disease affect our both upper or lower respiratory track so it is increase the high risk of COVID-19. In this systematic review we are review the articles related to COVID-19 and CHRONIC bronchitis. A systematic search was observe to describe studies reporting occurrence of bronchitis in relation patients with confirm COVID-19. We performed a systematic literature review with meta-analysis using four databases to assess clinical, laboratory and confirmed outcomes of COVID-19.We report a low prevalence of bronchitis patients in COVID-19 case series compared to the latest bronchitis prevalence rate in India. We are assess the articles review the patient who have confirmed COVID-19 wi1th a chronic bronchitis and found that the, chronic bronchitis is it more high risk of COVID-119, by the use of collected review articles, data information. © The Electrochemical Society

The use of phytopreparations in the treatment of bronchopulmonary diseases: evidence base and practical experience

Respiratory diseases take the lead in the infectious pathology pattern of various organs and systems and are the most common. Acute bronchitis is inflammation of the bronchi due to a viral infection and is characterized by a persistent cough that can be productive or dry. The authors consider the use of herbal preparations as an effective symptomatic product for the treatment of cough of various origins. Medicinal herbs are widely used in medicine due to many useful properties and do not have any serious side effects. Ivy leaf (Hedera helix) extract preparations are common cough medicines available over the counter that are approved by the European Medicines Agency (EMA). Ivy (Hedera helix) leaves contain various biologically active components, but saponins are the main substance. Saponins are natural compounds that have a variety of biological effects. According to literature data, the action of saponins is determined not only by their bronchodilator and mucolytic properties: among additional therapeutic options of saponins are high anti-inflammatory activity, as well as antimicrobial, antifungal and antiviral effects. The article shows the potential for use of ivy saponins as carriers of pharmaceutical substances, which can significantly reduce the effective doses of certain drugs. Preparations containing ivy leaf extract are safe and approved for use even in new-borns. Also, herbal preparations with antiviral, immunomodulatory and anti-inflammatory potential become the object of study as a new strategy for treating COVID-19. © 2022, Remedium Group Ltd. All rights reserved.

Role of IL-13-induced Th2 inflammation in host responses to SARSCoV-2

Background: Chronic lung inflammation affects the response to respiratory viruses such as SARS-CoV-2 in airway epithelia. Based on the pattern associated with disease endotype, airway inflammation can be simplified into type 2 and type 17. Half of asthmatics have type 2 high endotype driven by IL-13/IL-4 cytokine signaling that induces goblet cell metaplasia. Other inflammatory diseases such as cystic fibrosis, chronic bronchitis, and sarcoidosis are associated with the type 17 cytokines IL-17 and TNF-α. Recent case-control studies have suggested that asthma may protect against or at least not worsen SARS-CoV-2 infection. However, the effect of inflammation on COVID-19 outcomes is unclear. Although interferons and cytokine-driven inflammation may modulate antiviral response, epithelial remodeling might also affect susceptibility to viruses.We applied a singlecell RNA-seq approach to investigate responses to SARS-CoV-2 in primary human airway epithelia treated with inflammatory cytokines. We hypothesized that IL-13-induced type 2 inflammation and IL-17-induced type 17 inflammation would respond differently to SARS-CoV-2-infected human airway epithelia and that IL-13 would protect the epithelia from SARS-CoV-2 infection through goblet cell-secreted factors Methods: We infected primary human airway epithelia (n = 3 donors) grown at the air–liquid interface with 0.1 multiplicity of infection of SARSCoV- 2 and obtained viral titers and single-cell suspensions at 6 and 72 hours after infection. The epitheliawere pretreated with IL-13 or IL-17 plus TNF-α for a short (4 days) or long (56 days) course to differentiate the early effects of cytokine response from late goblet cell metaplasia that develops over weeks. We then performed single-cell RNA-seq to analyze viral transcripts Results: We found that IL-13, but not IL17 plus TNF-α, protected epithelia from SARS-CoV-2 at 72 hours after infection. Moreover, the protection seemed to be independent of interferons because interferon-stimulated genes, induced by short IL-13 exposure, failed to protect the epithelia from viral infection. Our analysis shows that the genes with the largest expression change in long-course IL-13-treated epithelia were mediated by the appearance of goblet cells andwere goblet-specific genes. Using our single-cell RNA-seq data, we analyzed how cytokines change response in each cell type after viral infection. We found that, when cells become infected, their response is not abnormal. Conclusion: IL-13 protects human airway epithelia from SARS-CoV-2 infection in vitro;the protective mechanism may involve secreted products from goblet cells. IL-13-treated airway epithelial cells have an otherwise normal response to SARS-CoV-2. Our findings suggest that products secreted by goblet cells may have potential therapeutic applications for respiratory viral diseases.