TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS最新文献

{"title":"Physical Properties of COVID-19 Acute Respiratory Distress Syndrome (ARDS) Sputum","authors":"A. Pacheco-Navarro, M. Kratochvil, G. Kaber, J. Roque, C. Blish, Samuel Yang, K. Nadeau, S. Heilshorn, C. Milla, A. Rogers, P. Bollyky","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1293","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1293","url":null,"abstract":"Introduction: COVID-19 respiratory infections are associated with copious, adherent respiratory secretions that prolong chronic ventilation and contribute to the morbidity and mortality caused by the disease. To target thinning these secretions requires understanding the physical properties that contribute to these tenacious secretions. Methods: We received surrogate consent from 11 patients with COVID-19 ARDS to collect an undiluted tracheal aspirate obtained as part of routine care. All samples were frozen at-80C immediately after collection and heat inactivated at 65C for 30 minutes to render them noninfectious prior to further analyses. These were compared with sputum collected from 4 patients with Cystic Fibrosis and 15 healthy controls. Clinical phenotypes of COVID patients included ARDS severity, treatments related to sputum clearance, and patient outcomes including length of mechanical ventilation and mortality. Sputum was characterized for percent solids, double strand DNA, and hyaluronin content. Results: Sputum samples were collected from 11 patients intubated with COVID-19 ARDS, with aspirates sampled between 2-18 days into their course. 63% of patients had thick secretions described by respiratory therapy, 81% had moderate or severe ARDS, and 90% had prolonged mechanical ventilation > 14 days. We found that the physical characteristics of COVID-19 sputum are similar to CF sputum, with markedly higher percent solid, hyaluronin, and double strand DNA content than that seen in sputum from healthy controls (Figure 1). Conclusion: In this proof of concept study, we show the feasibility of measuring numerous physical characteristics of COVID-19 sputum. As expected, we found that percent solids, DNA content and hyaluronin were similar to the known thick secretions of CF, and markedly increased in comparison to sputum of healthy controls. We were unable to identify differences in outcomes in this small cohort, with collection of additional samples ongoing to improve power. Figure 1. Physical characteristics of COVID sputum are much more similar to CF than normal sputum.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133676774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Therapeutics on the Modulation of ACE2 Expression in Airway Epithelium: Implications for COVID-19","authors":"G. Singhera, T. Guo, J. Leung, D. D. Sin, D. Dorscheid","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1283","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1283","url":null,"abstract":"RATIONALE: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV2). SARS-CoV-2 uses the receptor angiotensin-converting enzyme 2 (ACE2) to gain entry to host cells in the respiratory tract epithelium. Clinical features post viral infection include symptoms of viral pneumonia, fever, cough, chest discomfort, and in severe cases dyspnea and bilateral lung infiltration. Adults with any age are at risk of getting COVID-19, however co-morbidities like hypertension, COPD, smoking, type 2 diabetes, asthma, obesity etc. increase infection susceptibility. Modern day therapeutics to control aforementioned health conditions include angiotensin II receptor blockers (ARBs), ACE inhibitors (ACEi), and anti-inflammatory drugs such as dexamethasone and hydroxychloroquine. Since binding of viral spike protein with receptor ACE2 initiates viral entry in the host, hence ACE2 has been one of the main candidates to understand the mechanism of viral infection. In this study our aim was to investigate if ACE2 expression levels can be modulated with therapeutic interventions. Methods: In an in vitro model of monolayer cultures, human airway epithelial (1HAEo-) cell lines were treated with losartan and telmisartan (ARB), captopril (ACEi), and hydroxychloroquine at half-log concentrations from 1 to 100 μM, and fluticasone, ciclesonide, and dexamethasone (steroids) at half-log concentrations from 0.3 to 10 μM. Whole cell lysates were obtained at 24hr post-treatment to quantify ACE2 expression via western blotting. Statistical analysis was performed using one-way ANOVA and Dunnett's multiple comparison test. Results: The in vitro experiments have shown that total ACE2 protein expression in 1HAEo-cells is modulated in response to certain drugs. Compared to untreated control cells, losartan treatment showed ∼45 % significant increase in ACE2 expression at both 3 μM and 10 μM concentrations (p< 0.01), whereas dexamethasone showed ∼ 40% significant increase at 10 μM dose (p< 0.001). Captopril treatment showed ∼35% decrease at 30 and 100 μM (p<0.01), whereas ciclesonide treatment demonstrated statistically significant decrease in ACE2 expression with all tested concentrations. No difference in ACE2 expression was observed with telmisartan and hydroxychloroquine treatments. Conclusion: Our findings suggest that daily medications like losartan, captopril, dexamethasone and ciclesonide for certain pre-existing conditions may modulate ACE2 protein levels in airway epithelium hence possibly priming for COVID19 infections if exposed. This affect susceptibility for COVID19 infection and severity of illness in vulnerable populations. Hence basic understanding of mechanism of action for daily standard of care prophylactic therapies can reduce or prevent SAR-CoV-2 infection in at-risk individuals.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125411114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitotriosidase Activity in Lung Injury Associated with Coronavirus Disease 2019 (COVID-19)","authors":"A. Skvortsov, A. Balakhonov, A. Panferov","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1288","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1288","url":null,"abstract":"RATIONALE: Chitotriosidase (CHIT1) is an enzyme secreted by activated macrophages. The role of CHIT1 in the pathogenesis of some pulmonary diseases such as pulmonary fibrosis, bronchial asthma, chronic obstructive pulmonary disease, pulmonary infections and pulmonary sarcoidosis was reported. The potential role of CHIT1 in Coronavirus disease 2019 (COVID-19) remains unclear. The present study aimed to determine if serum CHIT1 activity is elevated in a group of COVID-19 patients. METHODS: The single-center case-control study included 40 patients hospitalized for COVID-19 associated pneumonia confirmed by high-resolution CT and 40 non-COVID-19 patients with no signs of lung damage as a control group. We compared the serum CHIT1 activity levels between the two groups. Nonparametric Mann-Whitney U test and Spearman's ρ were used for statistical processing. RESULTS: The groups were comparable in age, sex and body mass index. The median of lung involvement percentage was 36.50% (15.0-48.0%). The median of serum CHIT1 activity level in COVID-19 patients was 42.50 U/ml (27.25-70.00) that is significantly higher than 30.00 U/ml (15.50-45.00) in the control group (U=543, p=0.013). There was no correlation between CHIT1 activity and the percentage of lung tissue damage. A moderate negative correlation between serum CHIT1 activity and the duration of illness was found (ρ=-0.502, p=0.001). CONCLUSIONS: Present study did not confirm the interrelation between the activity of CHIT1 and the severity of lung damage. Still, due to CHIT1 taking part in cytokine release syndrome, it could be an early marker of macrophage activation in COVID-19.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123370937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferons and Potential Consequences for SARS-CoV-2 Infection","authors":"M. Conway, D. Francisco, B. Sierra, Hirokazu Kimura, M. Kraft","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1274","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1274","url":null,"abstract":"RATIONALE: Severe acute respiratory syndrome 2 (SARS-CoV-2) and resulting coronavirus disease 2019 (COVID-19) have been associated with several symptoms including fever, chills, cough, fatigue, loss of taste or smell, sore throat, and congestion. Moderate cases may require hospitalization and severe cases have resulted in death. Interferons (IFNs) are a class of immune molecules typically involved in the anti-viral response. Their role in SARS-CoV-2 infection is controversial as IFNs may increase angiotensin-converting enzyme 2 (ACE2) expression, the receptor for SARS-CoV-2, yet also enhance viral clearance. IFN-α2 stimulation increases gene expression of Interleukin-6 (IL-6), a cytokine that activates STAT proteins and is associated with poor hospital outcomes in COVID-19 patients. Meanwhile, surfactant protein A (SP-A), an immunomodulatory respiratory protein, is known from our work to bind to cytokine receptors such as IL-13α1 and IL-13 ligand (Francisco et al, JI 2020). Therefore, we hypothesized that SP-A binds to ACE2 and IL-6, making it a possible novel regulator of SARS-CoV-2 infection that potentially impacts disease severity.Methods: Normal human bronchial epithelial cells (NHBE) and asthmatic diseased bronchial human epithelial cells (DHBE) were cultured at air liquid interface for 2 weeks and stimulated with increasing doses of IFN-α2 (0.1, 1, and 10 ng/ml) for 48 hours. RT-PCR was performed and gene expression for ACE2 and IL-6 was assessed by normalizing to PPIA. Binding assays were performed using a 96-well, immunosorbent assay coated with either IL-6, IL-6Rα, GP130, ACE2, IFN-α2 or the negative control, EGFR and incubated with increasing concentrations of full-length SP-A (0-5000 ng/ml) and a SPA-HRP conjugated antibody. In separate experiments, western blotting was used to detect levels of total and phosphorylated STAT-1 in primary asthmatic bronchial epithelial cells treated for 30 minutes with IL-6 (10 ng/ml) in the presence and absence of SP-A2 (20 ug/ml) peptide.Results: Stimulation with 10 ng/ml IFN-α2 significantly increased ACE2 and IL-6 gene expression in NHBE and DHBE cells (p<.05). Full length SP-A was found to bind ACE2, both IL-6 receptors (IL-6Rα and GP-130), and to a lesser extent, IL-6 cytokine. SP-A did not bind to IFN-α2 or EGFR. Asthmatic primary human lung epithelial cells treated with IL-6 resulted in phosphorylation of STAT-1, and pre-treatment with SP-A2 peptides reduced this activation by approximately 45%.Conclusion: While IFNs may play a role in viral clearance, our data suggest potential dysregulation of mechanisms affecting the response to SARS-CoV-2. SP-A may be protective based upon its effects on ACE2 and IL-6.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126757435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of the COVID-19 Lockdown on Severe Asthma in Patients Taking Biologic Therapy and Air Pollution","authors":"H. Al-Jahdali, Mohammad A Khan, R. Rajkumar, M. Al-Gamedi, H. Al-Hayyan, A. Al-Harbi","doi":"10.1164/ajrccm-conference.2021.203.1_MeetingAbstracts.A1290","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2021.203.1_MeetingAbstracts.A1290","url":null,"abstract":"Background: The curfews and lockdowns imposed during the COVID 19 pandemic may decreased volume of traffic and reduced air pollution. In addition, social distancing measures may contribute to reduce infection and asthma exacerbation. Objective: To assess asthma control and asthma medication use among sever asthmatics on biologics before and after COVID-19 pandemic Method: This is a cross-sectional survey study of patients with severe asthma receiving biologic therapy at King Abdulaziz Medical City-Riyadh (KAMC-R), Saudi Arabia. We looked at the effects of the COVID19 lockdown on this cohort of sever asthmatics on biologic therapy from March till June 2020 over a period of 12 weeks. We investigated changes in patients symptoms and asthma control using the asthma control test (ACT) score and other parameters including, emergency department (ED) visits, hospitalizations, use of oral prednisolone, changes in inhaler therapy, frequency of bronchodilators use and patient perception of their symptoms before and after the lockdown period. Results: A total of 56, Female 39;(69%0;mean age ± SD 47.4 ± 13.8 years. The duration of bronchial asthma since diagnosis range from 4-30 years. Most patients had been treated with Omalizumab (47;84%);the rest received Mepolizumab (7;12.5%) and Dupilumab (2;3.6%). All these patients had been on biologic therapy for 5 months, range from 5 to 120 months. Most of the patients (45;80.4%) agreed that their symptoms of asthma had improved with biologic therapy. Most of the patients felt overall asthma symptoms is better after curfew and lockdown 28 (50%). Less use of bronchodilators post curfew reported in 38% of the patients. Asthma control (≥20) using ACT score was significantly higher among patients in post curfew and lockdown period compared to pre curfew period 34(61.7%) and 23 (41%), (p.0.001) respectively. Conclusion: Asthma control was better post curfew and lockdown. Decrease in air pollution and social distances may be contribute factor.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115812513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Clinical Characteristics of COVID-19 Patients With or Without Evidence of Allergic Asthma","authors":"R. Kaner, T. Murphy, C. Holweg, Y. Rajput, K. Raimundo, A. Seetasith, C. S. Meyer, A. Iqbal, W. Busse","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1275","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1275","url":null,"abstract":"RATIONALE: ACE2, a critical SARS-CoV-2 entry receptor, has reduced expression in those with allergic sensitizations. Consequently, SARS-CoV-2 infections may impact patients with allergic asthma (AA) or no evidence of allergic asthma (NEAA) differently. We explore demographics of SARS-CoV-2-infected AA and NEAA patients. METHODS: Retrospective data were obtained from the US-representative COVID-19 Optum Electronic Health Record dataset through 10/15/2020. Index was the earliest date of presumed diagnosis or laboratory-confirmed SARS-CoV-2 infection (CDC guidelines) from 02/20/2020, defined as (1) diagnosis code of U07.1/U07.2, or (2) positive diagnostic test for SARS-CoV-2, (3) diagnosis code of B97.29 without a negative molecular SARS-CoV-2 test within a 14-day window (+/-7 days). Patients SARS-CoV-2-positive with evidence of moderate-to-severe asthma at any time (ICD-10 J45.4X or J45.5X) were included. AA was defined as positive specific IgE (≥0.35 kU/L) serum test or skin prick test (code 95004) ordered by a specialist (eg, allergist, pulmonologist, dermatologist) or omalizumab use. NEAA was defined as failing to meet the AA definition and patients with allergic comorbidities were excluded. Baseline demographic and clinical characteristics were obtained 6-12 months before COVID-19 diagnosis. RESULTS: The database included 242,280 SARS-CoV-2-positive patients;569 (0.2%) had evidence of comorbid AA and 3137 (1.3%) had asthma and NEAA. For AA patients, mean (SD) age at index was 48.2 (18.2) years;70.3% were female, with 54.3% White, 26.4% Black, and 12.5% Hispanic (Table 1). Most AA patients were from the US Midwest and Northeast (80.5%). NEAA patients had similar demographics: mean (SD) age at index was 50.7 (19.5) years;67.6% female;with 60.0% White, 21.5% Black, and 13.0% Hispanic;and 81.5% were from the US Midwest and Northeast. A greater proportion of patients had severe asthma in AA versus NEAA groups (220/569 [38.7%] versus 457/3137 [14.6%]). More patients with AA versus NEAA used asthma biologic treatment (62/569 [10.9%] vs 27/3137 [0.9%]). Comorbid conditions (hypertension, diabetes, pregnancy, chronic obstructive pulmonary disease, and Charlson Comorbidity Index), body mass index, and smoking history were comparable between groups. A higher proportion of NEAA patients were current smokers. CONCLUSIONS: A smaller proportion of patients with SARS-CoV-2 infection in this retrospective analysis had comorbid AA versus NEAA, whereas patient demographics and comorbidities were generally comparable between groups. Differences included the proportion of patients with severe asthma and biologic treatment use (greater in AA), and current smoking (lower in AA). The observed lower prevalence of AA versus NEAA in SARS-CoV-2-positive patients warrants further investigation.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132252041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19 Pandemic on Incidence of Asthma Exacerbations and Hospitalizations in US Specialist-Treated Patients with Severe Asthma: Results from the CHRONICLE Study","authors":"W. Moore, D. Ledford, D. Carstens, C. Ambrose","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1289","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1289","url":null,"abstract":"RATIONALE: The impact of the COVID-19 pandemic on disease control in patients with severe asthma (SA) has not been described. Anecdotal reports suggest that social distancing, exposure avoidance, and restrictions on travel may have impacted the incidence of asthma exacerbations. Methods: CHRONICLE is an observational study of specialist-treated US adults (aged ≥18 years) with SA. At enrollment, patients must be: (1) receiving FDAapproved monoclonal antibody therapy for SA;(2) receiving systemic corticosteroids (SCS) or other systemic immunosuppressants for ≥50% of the prior 12 months;or (3) persistently uncontrolled while treated with highdosage inhaled corticosteroids and additional controllers. Specialists report all exacerbations and asthma hospitalizations for enrolled patients from 12 months prior to enrollment, with updates provided every 6 months. To describe the effect of the COVID-19 pandemic, we calculated the incidence of these events by month from July 2018 to May 2020 (latest month with complete data) among patients enrolled through November 2020. Results: Among enrolled patients (N=2633), specialist-reported exacerbations and asthma hospitalizations declined significantly in April and May 2020, following varying state/local COVID-19-related stay-at-home orders and social distancing recommendations. Relative to the average rates from July 2018 to March 2020, exacerbations (Figure panel A) and asthma hospitalizations (Figure panel B) were 47% and 57% lower, respectively, in April 2020 and 72% and 74% lower, respectively, in May 2020. Relative to the same months in 2019, exacerbations and asthma hospitalizations were 49% and 58% lower, respectively, in April 2020 and 67% and 74% lower, respectively, in May 2020. Conclusions: There was a notable decline in exacerbations and asthma hospitalizations among US patients with SA coincident with COVID-19-related stay-at-home orders and social distancing recommendations. Reasons for these declines are likely multifactorial and may be explained by reduced viral infections due to reduced social contact, altered patient behavior, and possibly reduced access to care. Rates in later months will be evaluated as data become available.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"192 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116142723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon Responses by Differentiated Primary Bronchial Airway Epithelial Cells to SarsCoV2 Are Less Robust Than to Human Rhinovirus16","authors":"E. Vanderwall, K. Barrow, L. M. Rich, M. White, S. Ziegler, J. Rathe, J. Debley","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1292","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1292","url":null,"abstract":"RATIONALE: Common human alphacoronaviruses and rhinoviruses (HRV) induce IFN I/III responses important to limiting viral propagation in the airway epithelium. In contrast, highly pathogenic human betacoronaviruses (e.g. SARS-CoV, circa 2002) may evade or antagonize RNA-induced IFN I/III responses. Aim: 1) Compare IFN I/III responses by bronchial AECs from children and adults between infection with SARS CoV2 and HRV-16. 2) Determine if pre-infection of AEC cultures with HRV-16, or pretreatment with IFN-β or IFN-λ, modifies SARS-CoV-2 replication. Methods: Bronchial AECs from children and adults (n=15;ages 8-75 yrs.) were differentiated ex vivo at an air-liquid interface to generate organotypic cultures. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 isolate USA-WA1/2020 or HRV-16 at a multiplicity of infection (MOI) of 0.5. At 96 hrs. following infection, RNA and protein were isolated. Expression of IFNB1, IFNL2, and interferon stimulated genes (ISGs) IFITM1, IFITM3, and OAS1 was measured by qPCR in SARS-CoV-2-infected, HRV-16-infected, and uninfected AEC cultures. In additional experiments AECs were pre-infected with HRV-16 (MOI=0.5), or pre-treated with recombinant IFN-β1 (1ng/mL in media) or IFN-λ2 (10ng/mL), 72 hrs. before SARS-CoV-2 infection. Recombinant IFNs were refreshed with each media change. SARS-CoV-2 replication was assessed by qPCR, and quantified as viral copy number/ng RNA. Results: SARS-CoV-2 induced less robust increases then HRV-16 in expression of IFNB1 (median 1.4-fold increase, 95% CI 1.2-1.7, vs. 3.8-fold, 95% CI 2.3-6.6, p<0.01), IFNL2 (median 11-fold increase, 95% CI 3-17, vs. 23-fold, 95% CI 12-62, p<0.01), IFITM1 (median 3-fold increase, 95% CI 1.8-5.4, vs. 6.8-fold, 95% CI 3.9-16, p=0.001), IFITM3 (median 1.6-fold increase, 95% CI 1.2-2, vs. 2.5-fold, 95% CI 2.2-4, p=0.003), and OAS1 (median 1.9-fold increase, 95% CI 1.4-3.5, vs. 3.8-fold, 95% CI 2.8-7.8, p<0.001). SARS-CoV-2 replication was significantly reduced when AECs were pre-infected with HRV-16 (median 2126 viral copies/ng RNA, 95% CI 204-11,080, vs. 92 viral copies/ng RNA, 95% CI 24-289, p=0.002). SARS-CoV-2 replication was also significantly reduced when AECs were treated with recombinant IFN-β1 (median 2126 viral copies/ng RNA, 95% CI 204-11,080, vs. 81 viral copies/ng RNA, 95% CI 3-172, p=0.005) or IFN-λ2 (median 2126 viral copies/ng RNA, 95% CI 204-11,080, vs. 48 viral copies/ng RNA, 95% CI 26-143, p=0.001). Conclusion: SARS-CoV-2 elicits a less robust IFN I/III response by primary bronchial AECs than HRV-16. Pre-infection of AECs with HRV-16, or pre-treatment with recombinant IFN-β1 or IFN-λ2 markedly reduces SARS-CoV-2 replication.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129774974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 Related Stress and Uncontrolled Asthma Among Adults","authors":"K. Eldeirawi, S. Nyenhuis, L. Huntington-Moskos, B. Polivka","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1282","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1282","url":null,"abstract":"RATIONALE: The COVID-19 pandemic has been associated with detrimental effects on mental as well as physical health. Studies on the impact of the psychosocial stress associated with the pandemic on adults with asthma are limited. We examined the associations of COVID-19 related stress with asthma control in adults. Methods: An online cross-sectional study was conducted with US adults with asthma. Study invitations were shared with potential participants via social media and email lists. Stress was measured using a 5-point Likert scale to capture participants' responses to 8 questions on being worried, sad vs. happy, relaxed vs. nervous, not fidgety vs. extremely fidgety, not fatigued vs. fatigued, focused vs. unfocused, not irritable vs. extremely irritable, and not lonely vs. extremely lonely. Responses were summed for a score ranging from 8-40 with higher values indicating higher stress. Stress scores were categorized into 4 levels (low: 8-16, moderate:17-24, high: 25-32, very high: 33-40). Participants also completed the asthma control test (ACT), answered questions about health care utilization during the pandemic, and reported the level of life changes they and their families experienced due to the pandemic. Results: Participants (N=909) were mostly female (82%), white (80%), from urban areas (61%), with at least a college degree (69%), and had a mean age of 44±15 years. Of participants, 13% and 15% were put into self-quarantine with and without symptoms, respectively;14% lost their job;and 21% had reduced ability to earn money. Less educated, non-white, and those who rent or live with family were more likely to experience significantly higher levels of stress in the 2 weeks before the survey. Almost 58% had an asthma exacerbation since the pandemic and 43% had uncontrolled asthma (ACT≤19). In adjusted multiple logistic regression models, we observed a significant dose-response (p trend<0.0001) direct relationship of COVID-19 related stress levels with the odds of uncontrolled asthma. Compared to participants with low stress score, the odds of having uncontrolled asthma were 1.58 (95% CI=1.04,2.41), 2.74 (95% CI=1.72,4.37), and 6.46 (95% CI=3.18,13.12) for those at moderate, high, and very high levels of stress, respectively, after adjusting for covariates. Conclusions: Adults with asthma are significantly impacted by the pandemic. Our findings show a significant and dose-response detrimental effect of COVID-19 related stress on asthma control. Health care providers should attempt to assess the psychosocial impact of COVID-19 on adults with asthma and provide the necessary mental health care and referrals.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122450367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Responses to S1-RBD and Nucleocapsid Antigens Elevate at Initial COVID-19 Infection and Remain Elevated at 12 Weeks Post Hospital Discharge","authors":"S. Kates, J. Owen, T. Thatcher, P. Sime","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1291","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A1291","url":null,"abstract":"RATIONALE:COVID-19 was first reported in Wuhan, China in December 2019 as a viral pneumonia and was found to be caused by a novel Coronavirus SARS-CoV-2. Diagnosis has included a nasopharyngeal swab examined with PCR. Immunodominant antigens have been identified for SARS-CoV-2-the Nucleocapsid and Spike-protein antigens with known genetic sequences. It is presumed that most infected with SARS-CoV-2 will develop measurable antibody titers against the Nucleocapsid and/or Spike-protein antigens as they recover from the disease. We have developed a custom Luminex assay to measure these antibodies. We hypothesize that patients undergoing treatment for COVID-19 will develop varying levels of anti-SARS-CoV-2 antibody levels after infection suggesting an acquired immunity to SARS-CoV-2.Methods:Following institutional review board approval, inpatients were recruited at the time of admission for COVID-19 care. Serum was collected at the time of hospital admission (Baseline, B, n=34) and at timepoints following hospital discharge: 2-weeks (2W, n=9), 6-weeks (6W, n=7), and 12-weeks (12W, n=4). Pooled convalescent serum from 5 PCR+ patients was used for positive control (POSCTRL) and serum collected prior to December 2019 from healthy preoperative patients (preCOVIDCtrl, n=48) were used for negative controls. IgG serum antibodies were measured via custom Luminex assay using SARSCoV-2 Spike S1 (S1-RBD) and Nucleocapsid human chimeric antibodies (HC2001 and HC2003, Genscript USA, Inc., Piscataway, NJ) to generate 5PL standard curves to convert Luminex median fluorescent intensity measurements into antibody concentrations. Concentrations for the different groups were analyzed using nonparametric comparisons for each group pair via Wilcoxon method. Statistical significance for all tests was set at p<0.05.Results:Concentrations of S1-RBD and Nucleocapsid varied widely at time of admission (B) but were significantly higher than preCOVIDCtrl (Figure 1). Elevations at later timepoints remained significantly higher for S1-RBD and Nucleocapsid than Baseline. S1-RBD concentrations were higher at 2W and 6W than Baseline. Nucleocapsid concentrations were higher at 2W than Baseline. Later timepoints for both antibodies did not differ from POS-CTRL.Conclusions:Wide variation in anti-SARS-Cov-2 antibody levels at the time of hospital admission suggest patients were in different stages of response to the infection. Antibody levels were seen to be more uniformly elevated by 2 weeks post discharge and remained elevated consistently at the 6 and 12-week time points. The negative control sera suggest no prior exposure to the SARS-CoV-2 S1-RBD antigen.","PeriodicalId":320542,"journal":{"name":"TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123034504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}