Uniform Gold Nanostructure Formation via Weakly Adsorbed Gold Films and Thermal Annealing for Reliable Localized Surface Plasmon Resonance-Based Detection of DNase-I.

Deoxyribonuclease-I (DNase-I), a representative endonuclease, is an important biomarker for the diagnosis of infectious diseases and cancer progression. However, enzymatic activity decreases rapidly ex vivo, which highlights the need for precise on-site detection of DNase-I. Here, a localized surface plasmon resonance (LSPR) biosensor that enables the simple and rapid detection of DNase-I is reported. Moreover, a novel technique named electrochemical deposition and mild thermal annealing (EDMIT) is applied to overcome signal variations. By taking advantage of the low adhesion of gold clusters on indium tin oxide substrates, both the uniformity and sphericity of gold nanoparticles are increased under mild thermal annealing conditions via coalescence and Ostwald ripening. This ultimately results in an approximately 15-fold decrease in LSPR signal variations. The linear range of the fabricated sensor is 20-1000 ng mL-1 with a limit of detection (LOD) of 127.25 pg mL-1 , as demonstrated by spectral absorbance analyses. The fabricated LSPR sensor stably measured DNase-I concentrations from samples collected from both an inflammatory bowel disease (IBD) mouse model, as well as human patients with severe COVID-19 symptoms. Therefore, the proposed LSPR sensor fabricated via the EDMIT method can be used for early diagnosis of other infectious diseases.

Chronic Obstructive Pulmonary Disease is Associated with a More Symptomatic Burden and Severe Presentation of COVID-19: A Korean National COVID-19 Cohort Study.

Insufficient data are available on comprehensive evaluation of demographics, symptoms or signs, laboratory findings, and disease course in patients with coronavirus disease 2019 (COVID-19) and chronic obstructive pulmonary disease (COPD). We aimed to evaluate whether COPD patients are more prone to severe COVID-19 compared with those without COPD. We also investigate the clinical characteristics and disease course of COVID-19 in patients with COPD versus those without COPD. Patients were selected from a Korean nationwide cohort of 5,628 patients with confirmed COVID-19 and who had completed treatment or quarantine by April 30, 2020; 3,673 patients aged 40 years or older were included in this study. COPD was diagnosed using patient reports of physician-diagnosed COPD. During the study period, all patients with COVID-19 in Korea were hospitalized following the national health policy. Of the study participants, 38 (1.0%) had COPD. Regarding initial symptoms, COPD patients with COVID-19 showed greater sputum production (50.0% vs. 29.8%, p < 0.01) and dyspnea (36.8% vs. 14.9%, p < 0.01) than those without COPD. In addition, patients with COPD were more likely to receive oxygen therapy or non-invasive ventilation (29.0% vs. 13.7%, p = 0.01) and had a higher mortality (21.1% vs. 6.4%, p < 0.01) than those without COPD. After adjusting for age, sex, body mass index, and comorbidities, COPD patients showed increased risk of severe COVID-19 compared with those without COPD. Our nationwide study showed that COVID-19 patients with COPD have higher symptomatic burden and more severe disease course than those without COPD.

Recent Advances in Surface Plasmon Resonance Sensors for Sensitive Optical Detection of Pathogens.

The advancement of science and technology has led to the recent development of highly sensitive pathogen biosensing techniques. The effective treatment of pathogen infections requires sensing technologies to not only be sensitive but also render results in real-time. This review thus summarises the recent advances in optical surface plasmon resonance (SPR) sensor technology, which possesses the aforementioned advantages. Specifically, this technology allows for the detection of specific pathogens by applying nano-sized materials. This review focuses on various nanomaterials that are used to ensure the performance and high selectivity of SPR sensors. This review will undoubtedly accelerate the development of optical biosensing technology, thus allowing for real-time diagnosis and the timely delivery of appropriate treatments as well as preventing the spread of highly contagious pathogens.

Anti-SARS-CoV-2 Spike Protein RBD Antibody Levels After Receiving a Second Dose of ChAdOx1 nCov-19 (AZD1222) Vaccine in Healthcare Workers: Lack of Association With Age, Sex, Obesity, and Adverse Reactions

Response to vaccines generally varies according to individual factors of the vaccinated subjects such as demographics and immune status. While there are various reports of factors associated with immunogenicity of mRNA COVID-19 vaccines, little is known about those of adenovirus vector vaccines. We conducted a prospective observational study to assess the relationships of antibody level with age, sex, body mass index (BMI), and adverse reactions (ARs) to an adenovirus vector vaccine, ChAdOx1 nCoV-19. Healthcare workers who planned to receive both the first and second injections of the ChAdOx1 nCoV-19 vaccine at Hanyang University Hospital, Seoul, Korea, were enrolled in the study. Seven days after each injection, participants were asked to complete an online adverse reaction survey. In addition, anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody concentration was measured 4 weeks after the second injection. All participants (n = 447, 100%) showed serologic positivity (≥ 0.8 U/mL) 4 weeks after the second injection of ChAdOx1 nCoV-19 vaccine. Furthermore, the anti-SARS-CoV-2 S protein RBD concentration was similar among groups when stratified by age, sex, BMI, or presence and severity of AR;multivariable linear regression found no associations between antibody response to the ChAdOx1 nCoV-19 vaccine and age, BMI, sex, and vaccine-induced ARs. In conclusion, age, sex, obesity, and ARs were not associated with antibody responses after two doses of ChAdOx1 nCoV-19 vaccination.

Predicting Factors of Severe COVID-19 in Patients With Asthma: A Korean National Cohort Study.

As there are limited data on the disease course of and factors predicting severe coronavirus disease 19 (COVID-19) in patients with asthma, this study aims to perform a detailed analysis of the clinical course of asthmatic patients with COVID-19 and evaluate factors related to severe infection. Of the 5,628 patients confirmed with COVID-19, 128 (2.3%) had asthma. Among the 128 asthmatic patients, 32 (25%) had severe COVID-19 and 96 (75%) had non-severe COVID-19. Among asthmatic patients, those with severe COVID-19 were significantly older and had more dyspnea and fever, more comorbidities, and lower lymphocyte and platelet counts than those with non-severe COVID-19. In multivariable logistic regression analysis, chronic obstructive pulmonary disease (adjusted odds ratio [aOR], 6.49; 95% confidence interval [CI], 1.18-41.81), low lymphocyte proportion (aOR, 0.91; 95% CI, 0.86-0.97), and low platelet count (aOR, 0.99; 95% CI, 0.98-0.99) were independently associated with severe COVID-19.

Risk Factors for Grade 3 to Grade 4 Adverse Reactions to the ChAdOx1 nCoV-19 Vaccine (AZD1222) Against SARS-CoV-2.

Objective: Limited data are available regarding the rates and risk factors of severe to serious adverse reactions (ARs) to the ChAdOx1 nCoV-19 vaccine. Methods: Eligible participants were healthcare workers who received their first dose of the ChAdOx1 nCoV-19 vaccine in either of two university hospitals in Seoul, Korea. We evaluated the type and severity of ARs 7 days after the first dose of the ChAdOx1 nCoV-19 vaccine using a questionnaire survey delivered via a smartphone application link. Results: Among the 1,603 participants who completed the survey, 684 (42.7%) participants experienced any kind of grade 3 to grade 4 AR. Being young (adjusted odds ratio [OR] for age 21-30 years = 2.49, 95% confidence interval [CI] = 1.75-3.56; adjusted OR for 31-40 years = 1.78, 95% CI = 1.22-2.62; adjusted OR for 41-50 years = 1.47, 95% CI = 1.03-2.11), being female (adjusted OR = 2.16. 95% CI = 1.62-2.89), and being underweight (adjusted OR = 1.61, 95% CI = 1.02-2.55) were identified as risk factors for grade 3 to grade 4 ARs. Among comorbidities, only diabetes mellitus (adjusted OR = 2.36, 95% CI = 1.03-5.53) was identified as a risk factor. When stratified by the type of AR, being young and being female were risk factors for both local and systemic grade 3 to grade 4 ARs. Conclusions: Being young, female, or underweight and having diabetes mellitus were associated with an increased risk of developing grade 3 to grade 4 ARs after receiving the first dose of the ChAdOx1 nCoV-19 vaccine.

Medical student education through flipped learning and virtual rotations in radiation oncology during the COVID-19 pandemic: a cross sectional research.

BACKGROUND: The COVID-19 pandemic has stripped many medical students worldwide of their right to quality education. In response, we developed hybrid courses involving aspects of both online and in-person teaching for radiation oncology medical student clerkship. METHODS: We entitled students to customize their own rotation schedule using Google Forms and developed a flipped learning online class, which consisted of at least one video clip on basic knowledge of radiation oncology per day (yonsei-radonc.com). Students were instructed to watch online videos before the next day's discussion session. Required components of the medical education program (e.g., target drawing, site visits to treatment facilities) were also prepared and conducted in accordance with the appropriate level of social distancing measures. Finally, we conducted questionnaire surveys after the completion of the week-long course and clerkship. RESULTS: From March to June 2020, 110 fourth-year medical students undertook a clinical module in our 1-week radiation oncology program course. Each day, students completed the flipped learning prior to meeting with the educator and then participated in the online discussion session and conference. All activities were well performed as scheduled. Students' motivation was high, as was their overall satisfaction with the course. The students were satisfied with the online contents, flipped learning strategy, and instructors. CONCLUSIONS: We successfully integrated open and virtual educational platforms to improve access to and satisfaction with student clerkship. In the future "new normal," minimized face-to-face learning interactions, such as flipped learning, should be actively utilized for medical and other students' education.

Risk of Coronavirus Disease 2019 Occurrence, Severe Presentation, and Mortality in Patients with Lung Cancer.

PURPOSE: This study aimed to analyze whether patients with lung cancer have a higher susceptibility of coronavirus disease 2019 (COVID-19), severe presentation, and higher mortality than those without lung cancer. MATERIALS AND METHODS: A nationwide cohort of confirmed COVID-19 (n=8,070) between January 1, 2020, and May 30, 2020, and a 1:15 age-, sex-, and residence-matched cohort (n=121,050) were constructed. A nested case-control study was performed to compare the proportion of patients with lung cancer between the COVID-19 cohort and the matched cohort. RESULTS: The proportion of patients with lung cancer was significantly higher in the COVID-19 cohort (0.5% [37/8,070]) than in the matched cohort (0.3% [325/121,050]) (p=0.002). The adjusted odds ratio [OR] of having lung cancer was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR, 1.51; 95% confidence interval [CI], 1.05 to 2.10). Among patients in the COVID-19 cohort, compared to patients without lung cancer, those with lung cancer were more likely to have severe COVID-19 (54.1% vs. 13.2%, p < 0.001), including mortality (18.9% vs. 2.8%, p < 0.001). The adjusted OR for the occurrence of severe COVID-19 in patients with lung cancer relative to those without lung cancer was 2.24 (95% CI, 1.08 to 4.74). CONCLUSION: The risk of COVID-19 occurrence and severe presentation, including mortality, may be higher in patients with lung cancer than in those without lung cancer.

Noble Metal Nanomaterial-Based Biosensors for Electrochemical and Optical Detection of Viruses Causing Respiratory Illnesses.

Noble metal nanomaterials, such as gold, silver, and platinum, have been studied extensively in broad scientific fields because of their unique properties, including superior conductivity, plasmonic property, and biocompatibility. Due to their unique properties, researchers have used them to fabricate biosensors. Recently, biosensors for detecting respiratory illness-inducing viruses have gained attention after the global outbreak of coronavirus disease (COVID-19). In this mini-review, we discuss noble metal nanomaterials and associated biosensors for detecting respiratory illness-causing viruses, including SARS-CoV-2, using electrochemical and optical detection techniques. this review will provide interdisciplinary knowledge about the application of noble metal nanomaterials to the biomedical field.

Interstitial lung disease increases susceptibility to and severity of COVID-19.

BACKGROUND: There are limited data regarding the relationship between interstitial lung disease (ILD) and the natural course of COVID-19. In this study, we investigate whether patients with ILD are more susceptible to COVID-19 than those without ILD and evaluate the impact of ILD on disease severity in patients with COVID-19. METHODS: A nationwide cohort of patients with COVID-19 (n=8070) and a 1:15 age-, sex- and residential area-matched cohort (n=121 050) were constructed between 1 January 2020 and 30 May 2020 in Korea. We performed a nested case-control study to compare the proportions of patients with ILD between the COVID-19 cohort and the matched cohort. Using the COVID-19 cohort, we also evaluated the risk of severe COVID-19 in patients with ILD versus those without ILD. RESULTS: The proportion of patients with ILD was significantly higher in the COVID-19 cohort than in the matched cohort (0.8% versus 0.4%; p<0.001). The odds of having ILD was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR 2.02, 95% CI 1.54-2.61). Among patients in the COVID-19 cohort, patients with ILD were more likely to have severe COVID-19 than patients without ILD (47.8% versus 12.6%), including mortality (13.4% versus 2.8%) (all p<0.001). The risk of severe COVID-19 was significantly higher in patients with ILD than in those without ILD (adjusted OR 2.23, 95% CI 1.24-4.01). CONCLUSION: The risks of COVID-19 and severe presentation were significantly higher in patients with ILD than in those without ILD.

Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.

Bioinspired DNase-I-Coated Melanin-Like Nanospheres for Modulation of Infection-Associated NETosis Dysregulation.

The current outbreak of the beta-coronavirus (beta-Cov) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019. No specific antiviral treatments or vaccines are currently available. A recent study has reported that coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with neutrophil-specific plasma membrane rupture, and release excessive neutrophil extracellular traps (NETs) and extracellular DNAs (eDNAs). This mechanism involves the activation of NETosis, a neutrophil-specific programmed cell death, which is believed to play a crucial role in COVID-19 pathogenesis. Further progression of the disease can cause uncontrolled inflammation, leading to the initiation of cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. Herein, it is reported that DNase-I-coated melanin-like nanospheres (DNase-I pMNSs) mitigate sepsis-associated NETosis dysregulation, thereby preventing further progression of the disease. Recombinant DNase-I and poly(ethylene glycol) (PEG) are used as coatings to promote the lengthy circulation and dissolution of NET structure. The data indicate that the application of bioinspired DNase-I pMNSs reduce neutrophil counts and NETosis-related factors in the plasma of SARS-CoV-2 sepsis patients, alleviates systemic inflammation, and attenuates mortality in a septic mouse model. Altogether, the findings suggest that these nanoparticles have potential applications in the treatment of SARS-CoV-2-related illnesses and other beta-CoV-related diseases.