A study of glycemic perturbations following two doses of COVID-19 vaccination for patients with diabetes: the impacts of vaccine type and anti-diabetes drugs.

BACKGROUND: Glycemic monitoring has become critical during the COVID-19 pandemic because of poor prognosis in diabetes. Vaccines were key in reducing the spread of infection and disease severity but data were lacking on effects on blood sugar levels. The aim of the current study was to investigate the impact of COVID-19 vaccination on glycemic control. METHODS: We performed a retrospective study of 455 consecutive patients with diabetes who completed two doses of COVID-19 vaccination and attended a single medical center. Laboratory measurements of metabolic values were assessed before and after vaccination, while the type of vaccine and administrated anti-diabetes drugs were analyzed to find independent risks associated with elevated glycemic levels. RESULTS: One hundred and fifty-nine subjects received ChAdOx1 (ChAd) vaccines, 229 received Moderna vaccines, and 67 received Pfizer-BioNtech (BNT) vaccines. The average HbA1c was raised in the BNT group from 7.09 to 7.34% (P = 0.012) and non-significantly raised in ChAd (7.13 to 7.18%, P = 0.279) and Moderna (7.19 to 7.27%, P = 0.196) groups. Both Moderna and BNT groups had around 60% of patients with elevated HbA1c following two doses of COVID-19 vaccination, and the ChAd group had only 49%. Under logistic regression modeling, the Moderna vaccine was found to independently predict the elevation of HbA1c (Odds ratio 1.737, 95% Confidence interval 1.12-2.693, P = 0.014), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) was negatively associated with elevated HbA1c (OR 0.535, 95% CI 0.309-0.927, P = 0.026). CONCLUSIONS: Patients with diabetes might have mild glycemic perturbations following two doses of COVID-19 vaccines, particularly with mRNA vaccines. SGLT2i showed some protective effect on glycemic stability. Hesitancy in having vaccinations should not be indicated for diabetic patients with respect to manageable glycemic change. TRIAL REGISTRATION: Not applicable.

Impact of lockdown policies during the COVID-19 outbreak on a trauma center of a tertiary hospital in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a major and costly public health emergency. AIM: To investigate the impact of China's lockdown policies during the COVID-19 outbreak on the level I trauma center of a tertiary comprehensive hospital of Traditional Chinese Medicine. METHODS: All patients admitted to our trauma center during a lockdown in 2020 and the same period in 2019 were enrolled. We collected data on demographics, daily visits, injury type, injury mechanism, injury severity score, and patient management for comparative analysis. RESULTS: The total number of patients in the trauma center of our hospital decreased by 50.38% during the COVID-19 Lockdown in 2020 compared to the same period in 2019. The average number of trauma visits per day in 2019 was 47.94, compared to 23.79 in 2020. Comparing the patients' demographic data, loss of employment was the most predominate characteristic in 2020 compared to 2019, while there was no significant difference in gender, age, and marital status between both periods. During the lockdown period, the proportion of traffic accident-related injuries, injuries due to falls greater than 1.5 m, and mechanical injuries decreased significantly, whereas the proportion of injuries caused by falls less than 1.5 m, cuts, assault, bites, and suicidal tendencies and other injuries increased relatively. In addition, the proportion of patients with minor injuries increased and serious injuries decreased during the lockdown. The hospitalization rate increased significantly, and there was no significant difference in emergency surgery and death rates. CONCLUSION: The lockdown policies during the COVID-19 outbreak significantly altered the number and mechanism of traumatic events in our hospital, which can be monitored regularly. Our results suggest that mandatory public health prevention and control measures by the government can reduce the incidence of traumatic events and the severity of traumatic injuries. Emergency surgery and mortality rates remain high, increased because of factors such as family injury and penetrating injury, and hospitalization rates have increased significantly. Therefore, our trauma center still needs to be fully staffed. Finally, from the perspective of the injury mechanism, indoor trauma is a major risk during a lockdown, and it is particularly important to develop prevention strategies for such trauma to reduce the medical burden of the next catastrophic epidemic.

Wireless and Multi‐Person Respiration Monitoring using Facemask‐Integrated Flexible Meta‐Antennas

Respiration monitoring of a large population is important in containing the spread of viral respiratory infections such as the coronavirus disease 2019 (COVID‐19). Current technologies, however, lack the ability in respiration monitoring of multiple human subjects in a long‐term, robust, and low‐cost manner. Herein, wireless respiration monitoring of multiple human subjects using facemask‐integrated flexible meta‐antennas is demonstrated. The flexible meta‐antenna has an architecture of multi‐layered anisotropic hole‐array, which is optimized by theory and simulations to achieve high performances including good antenna gain, robustness against body interferences, and high air permeability favorable for facemask integration. A person's respiration patterns and respiration rates are wirelessly obtained by the meta‐antenna integrated with a temperature‐sensor‐embedded chip. Respiration monitoring of multiple subjects in long range and long term during daily activities is simultaneously demonstrated. In addition, a real‐time data processing system is introduced in which a local server, a cloud server, and an application layer are implemented for the real‐time display of respiration patterns and automatic recognition of abnormal status. The design of flexible meta‐antennas may lead to a distinct class of physiological sensors over a large population for applications in pandemic control and personalized healthcare. [ABSTRACT FROM AUTHOR] Copyright of Advanced Materials Technologies is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Humoral and Cellular Response of Transplant Recipients to a Third Dose of mRNA SARS-CoV-2 Vaccine: A Systematic Review and Meta-analysis.

BACKGROUND: High rates of nonresponse to 2 doses of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine have been reported in transplant recipients. Several studies have investigated the efficacy of a third dose in this population. However, efficacy remains unclear, as response rates vary across studies. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy of a third dose of any mRNA SARS-CoV-2 vaccine in transplant recipients. METHODS: Preferred Reporting Items for Systematic Review and Meta-Analysis reporting guidelines (PROSPERO:CRD42021281498) were followed. Medline, Embase, and CENTRAL were searched from inception to December 2, 2021, without restrictions. All full-text studies reporting on the efficacy of a third dose of any mRNA SARS-CoV-2 vaccine in pediatric and adult transplant recipients were included. The National Institutes of Health quality assessment tool for case series and the Cochrane risk of bias tool determined study quality. Meta-analysis was performed via the DerSimonian-Laird random-effect model. RESULTS: Of 84 records, 12 studies totaling 1257 patients met inclusion criteria. One study was a randomized controlled trial, whereas all other studies were observational. Across 7 studies (801 patients), humoral response after 3 doses was observed in 66.1% (95% confidence interval, 62.8%-69.4%; I2 = 0%) of transplant recipients. Triple immunosuppression, mycophenolate, antiproliferatives, and belatacept use were associated with reduced odds of humoral response in studies reporting multivariate analyses. Transplant recipients receiving a third dose displayed higher levels of neutralizing antibodies to SARS-CoV-2 variants (Alpha, Beta, and Delta) compared with placebo. CONCLUSIONS: A third dose SARS-CoV-2 mRNA vaccine should be strongly considered in transplant recipients. Limitations included lack of controlled studies and clinically relevant thresholds to determine response to vaccination.

Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry.

The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.

Correction: Lee et al. The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b. Pharmaceutics 2022, 14, 1511.

In the original publication [...].

Transmission roles of symptomatic and asymptomatic COVID-19 cases: a modelling study.

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.

Physical Activity, Dietary Behavior, and Body Weight Changes during the COVID-19 Nationwide Level 3 Alert in Taiwan: Results of a Taiwanese Online Survey.

This cross-sectional study aimed to explore the influence of the COVID-19 pandemic on physical activity (PA) and dietary habits, and their impact on body weight changes during the Level 3 alert period that resulted in the lockdown in Taiwan. The study was conducted between 1 July 2021 and 15 July 2021, using a Google Forms online survey platform. Personal data, anthropometric information, PA information, and dietary habit information were collected before and during the alert period. Exactly 374 respondents, aged between 20 and 66, were included in the study. The results indicate that the lockdown during the alert period negatively impacted all levels of PA, including vigorous and moderate activities and walking. Additionally, respondents showed a sedentary lifestyle, with an increased daily sitting time of 22%. However, body weight and dietary behavior were not significantly affected, and some dietary questions achieved significant differences, including eating three meals less regularly, among others. During the pandemic, exercise was still one of the most important ways to maintain health; therefore, we hope to bring more attention to the prevention of sedentary lifestyles and dietary abnormalities in Taiwan during a pandemic.

Reply to Crimi, C.; Cortegiani, A. Comment on "Liu et al. Application of High-Flow Nasal Cannula in COVID-19: A Narrative Review. Life 2022, 12, 1419".

Thanks for Crimi et al.'s comment [...].

Application of High-Flow Nasal Cannula in COVID-19: A Narrative Review.

BACKGROUND: During the first wave of COVID-19, the large influx of severely ill patients led to insufficient availability of beds in intensive care units and a shortage of ventilators. The shortage of ventilators, high mortality of intubated patients, and high risk of infections among healthcare workers involved in intubation were the main factors that led to the prevalence of noninvasive respiratory support during the pandemic. The high-flow nasal cannula (HFNC) is a commonly used, popular form of noninvasive respiratory support. Due to its unique physiological effects, HFNC can provide a high fraction of humidified oxygen and is satisfactorily comfortable for patients with COVID-19. However, before the COVID-19 era, there was little evidence on the application of HFNC in patients with acute respiratory failure caused by viral infection. AIM: This narrative review provides an overview of recent studies on the use of HFNC in patients with COVID-19-related acute hypoxemic respiratory failure. The main topics discussed include the probability of successful use of HFNC in these patients, whether late intubation increases mortality, the availability of convenient and accurate monitoring tools, comparison of HFNC with other types of noninvasive respiratory support, whether HFNC combined with the prone position is more clinically useful, and strategies to further reduce the infection risk associated with HFNC. The implication of this study is to identify some of the limitations and research gaps of the current literature and to give some advice for future research.

Disease-Specific Factors Associated with Readmissions or Mortality After Hospital Discharge in COVID-19 Patients: a Retrospective Cohort Study.

BACKGROUND: Understanding the implications of disease-specific factors beyond baseline patient characteristics for coronavirus disease 2019 (COVID-19) may allow for identification of indicators for safe hospital discharge. OBJECTIVE: Assess whether disease-specific factors are associated with adverse events post-discharge using a data-driven approach. DESIGN: Retrospective cohort study. SETTING: Fifteen medical centers within Kaiser Permanente Southern California. PARTICIPANTS: Adult patients (n=3508) discharged alive following hospitalization for COVID-19 between 05/01/2020 and 09/30/2020. INTERVENTIONS: None. MAIN MEASURES: Adverse events defined as all-cause readmission or mortality within 14 days of discharge. Least absolute shrinkage and selection operator (LASSO) was used for variable selection and logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (CI). KEY RESULTS: Four variables including age, Elixhauser index, treatment with remdesivir, and symptom duration at discharge were selected by LASSO. Treatment with remdesivir was inversely associated with adverse events (OR: 0.46 [95%CI: 0.36-0.61]), while symptom duration ≤ 10 days was associated with adverse events (OR: 2.27 [95%CI: 1.79-2.87]) in addition to age (OR: 1.02 [95%CI: 1.01-1.03]) and Elixhauser index (OR: 1.15 [95%CI: 1.11-1.20]). A significant interaction between remdesivir and symptom duration was further observed (p=0.01). The association of remdesivir was stronger among those with symptom duration ≤10 days vs >10 days at discharge (OR: 0.30 [95%CI: 0.19-0.47] vs 0.62 [95%CI: 0.44-0.87]), while the association of symptom duration ≤ 10 days at discharge was weaker among those treated with remdesivir vs those not treated (OR: 1.31 [95%CI: 0.79-2.17] vs 2.71 [95%CI 2.05-3.59]). CONCLUSIONS: Disease-specific factors including treatment with remdesivir, symptom duration, and their interplay may help guide clinical decision making at time of discharge.

Comparison of safety and outcomes related to remdesivir treatment among dialysis patients hospitalized with COVID-19.

Background: Patients with end-stage kidney disease (ESKD) are highly susceptible to coronavirus disease 2019 (COVID-19) infection and its complications. Remdesivir has improved outcomes in COVID-19 patients but its use has been limited among ESKD patients due to insufficient data regarding safety outcomes. We sought to evaluate the safety of remdesivir among dialysis patients hospitalized with COVID-19. Methods: This retrospective cohort study was conducted among patients age ≥18 years on maintenance dialysis and hospitalized with COVID-19 between 1 May 2020 and 31 January 2021 within an integrated health system who were treated or not treated with remdesivir. The primary outcome was 30-day all-cause mortality. Secondary outcomes were intensive care unit (ICU) stay, and transaminitis (AST/ALT >5× normal). Pseudo-populations were created using inverse probability of treatment weights with propensity scoring to balance patient characteristics among the two groups. Multivariable Poisson regression with robust error was performed to estimate 30-day mortality risk ratio. Results: A total of 486 (407 hemodialysis and 79 peritoneal dialysis) patients were hospitalized with COVID-19, among which 112 patients (23%) were treated with remdesivir [median treatment four days (interquartile range 2-5)]. The 30-day mortality rate was 24.1% among remdesivir-treated and 27.8% among non-treated patients. The estimated 30-day mortality rate was 0.74 (95% confidence interval 0.52-1.05) among remdesivir treated compared with non-treated patients. Liver injury and ICU admission rates were 1.8% and 14.3% among remdesivir-treated patients compared with 2.4% and 16% among non-treated patients. Conclusion: Among dialysis patients hospitalized with COVID-19, remdesivir was not associated with higher rates of liver injury or ICU admissions, and demonstrated a trend toward lower 30-day mortality.

Rejection of Acellular Porcine Corneal Stroma Transplantation During Coronavirus Disease 2019 Pandemic.

ABSTRACT: To report 2 successfully managed cases of graft rejection with acellular porcine corneal stroma (APCS) transplantation in patients with fungal corneal ulcer. Two patients were diagnosed with fungal corneal ulcer and received APCS transplantation. Graft rejection developed due to the lost follow-up during the period of coronavirus disease 2019 outbreak. Amniotic membranes transplantation and cauterization of neovascularization was performed, respectively. The graft failure resolved successfully after the procedure. To the best of our knowledge, amniotic membranes transplantation and cauterization of new vessels are the firstly reported in treating APCS graft failure. Amniotic membranes transplantation or cauterization of neovascularization appear to be a safe and costeffective method for treating graft failure.

Safety and immunogenicity of MVC-COV1901 vaccine in older adults: Phase 2 randomized dose-comparison trial.

INTRODUCTION: Older adults are subject to higher COVID-19 infection and mortality rates. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine have been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age, however, older adults were under-represented. METHODS: A double-blind, randomized, multi-center study compared safety and immunogenicity of high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart in 420 participants of 65 years and older. The results have been stratified by the comorbidity status. RESULTS: Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities. CONCLUSION: Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommend high dose for immunization of elder adults with MVC-COV1901. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04822025).

Outcomes Among Hospitalized Patients With COVID-19 and Acute Kidney Injury Requiring Renal Replacement Therapy.

IntroductionAcute kidney injury (AKI) occurs in up to 10%-30% of coronavirus disease 2019 (COVID-19) patients. AKI patients who require renal replacement therapy (RRT) often have concurrent respiratory failure and represent a high-mortality-risk population. The authors sought to describe outcomes in hospitalized COVID-19 patients with AKI requiring RRT and determine factors associated with poor outcomes. MethodsA retrospective cohort study of hospitalized COVID-19 patients with AKI requiring RRT during the period from March 14, 2020, to September 30, 2020, was performed at Kaiser Permanente Southern California. RRT was defined as conventional hemodialysis and/or continuous renal replacement therapy. The primary outcome was hospitalization mortality, and secondary outcomes were mechanical ventilation, vasopressor support, and dialysis dependence among discharged patients. Hospitalization mortality risk ratios were estimated up to 30 days from RRT initiation. ResultsA total of 167 hospitalized COVID-19 patients were identified with AKI requiring RRT. The study population had a mean age of 60.7 years and included 71.3% male patients and 60.5% Hispanic patients. Overall, 114 (68.3%) patients died during their hospitalization. Among patients with baseline estimated glomerular filtration rate (eGFR) values of ≥ 60, 30-59, and < 30 mL/min, the mortality rates were 76.8%, 78.1%, and 50.0%, respectively. Among the 53 patients who survived to hospital discharge, 29 (54.7%) continued to require RRT. Compared to patients with eGFR < 30 mL/min, the adjusted 30-day hospitalization mortality risk ratios (95% CI) were 1.38 (0.90-2.12) and 1.54 (1.06-2.25) for eGFR values of 30-59 and ≥ 60, respectively. ConclusionAmong a diverse cohort of hospitalized COVID-19 patients with AKI requiring RRT, survival to discharge was low. Greater mortality was observed among patients with higher baseline kidney function. Most of the patients discharged alive continued to be dialysis-dependent.

Tyrphostin AG1024 Suppresses Coronaviral Replication by Downregulating JAK1 via an IR/IGF-1R Independent Proteolysis Mediated by Ndfip1/2_NEDD4-like E3 Ligase Itch.

JAK1 depletion or downregulation was previously reported to account for coronavirus inhibition. Here, we found that AG1024, an IR (insulin receptor) and IGF-1R (insulin-like growth factor 1 receptor) inhibitor, diminishes JAK1 protein levels and exerts anti-coronaviral activities with EC50 values of 5.2 ± 0.3 µM against transmissible gastroenteritis coronavirus (TGEV) and 4.3 ± 0.3 µM against human flu coronavirus OC43. However, although the IR and IGF-1R signaling pathways are activated by insulin or IGF-1 in swine testis cells, they are not triggered upon TGEV infection. AG1024, therefore, inhibits coronaviral replication and downregulates JAK1 protein levels independently of IR and IGF-1R. Moreover, JAK1 proteolysis caused by AG1024 was found through activation of upstream Ndfip1/2 and its effector NEDD4-like E3 ligase Itch. In addition, ouabain, which was reported to mediate JAK1 proteolysis causing anti-coronaviral activity by activation of Ndfip1/2 and NEDD4 E3 ligase, additively inhibited anti-coronaviral activity and JAK1 diminishment in combination with AG1024. This study provides novel insights into the pharmacological effects of AG1024 and Itch E3 ligase mediated JAK1 proteolysis and identified Ndfip1/2 as a cognate effector for JAK1 proteolysis via the diversified E3 ligases NEDD4 and NEDD4-like Itch. These findings are expected to provide valued information for the future development of anti-viral agents.

The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b.

Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 by increasing IκBα protein levels and significantly decreasing p65 nuclear translocation. Furthermore, we found that the combination of ciclesonide and dbq33b, a potent tylophorine-based coronavirus inhibitor that affects coronavirus-induced NF-κB activation a little, additively and synergistically decreased coronavirus-induced IL-6, IL-8, and MCP-1 cytokine levels, and synergistically inhibited the replication of both HCoV-OC43 and SARS-CoV-2. Collectively, the combination of ciclesonide and dbq33b merits consideration as a treatment for COVID-19 patients who may otherwise be overwhelmed by high viral loads and an NF-κB-mediated cytokine storm.

SARS-CoV-2 testing, infection and outcomes among Ontario physicians: a descriptive population-based cohort study.

BACKGROUND: Health care workers have a higher risk of acquiring SARS-CoV-2 infection than the general population. Our study reports on SARS-CoV-2 testing, infection and associated outcomes in Ontario physicians before SARS-CoV-2 vaccination became available on Dec. 14, 2020. METHODS: We conducted a descriptive, population-based cohort study of physicians in Ontario, Canada, from Jan. 25 to Dec. 31, 2020. We included physicians and postgraduate medical trainees who were residents of Ontario and registrants with the College of Physicians and Surgeons of Ontario during the study period. We examined the proportion of physicians tested for SARS-CoV-2 infection, the proportion who tested positive, and how testing and infections varied by certain physician characteristics. We reported on clinical outcomes associated with infection, including hospital admission and death. RESULTS: Of 41 208 physicians (mean age 47 yr; 56.1% male), 19 116 (46.4%) were tested at least once for SARS-CoV-2 infection; 358 tested positive (0.9%). No physicians died within 30 days of testing positive; however, 20/358 (5.6%) were admitted to hospital. By specialty, the proportion tested was highest among postgraduate medical trainees (2531/4125 [61.4%]), emergency physicians (281/478 [58.8%]), infectious disease physicians (33/67 [49.3%]) and family physicians (8857/18 553 [47.7%]). The proportion who tested positive was highest among internal medicine physicians (44/3499 [1.3%]), postgraduate medical trainees (47/4125 [1.1%]) and family physicians (171/18 553 [0.9%]). Of 2290 physicians who worked in long-term care, 1636 (71.4%) were tested and 25 (1.1%) tested positive. INTERPRETATION: During the prevaccination period of the COVID-19 pandemic in Ontario, nearly half of all physicians in the province were tested at least once for SARS-CoV-2 infection, 0.9% tested positive and none died. These findings may reflect the public health measures that were implemented in the province during this period.

Performance Evaluation of a Novel Ultrafast Molecular Diagnostic Device Integrated With Microfluidic Chips and Dual Temperature Modules.

Ultrafast, portable, and inexpensive molecular diagnostic platforms are critical for clinical diagnosis and on-site detection. There are currently no available real-time polymerase chain reaction (PCR) devices able to meet the demands of point-of-care testing, as the heating and cooling processes cannot be avoided. In this study, the dual temperature modules were first designed to process microfluidic chips automatically circulating between them. Thus, a novel ultrafast molecular diagnostic real-time PCR device (approximately 18 and 23 min for DNA and RNA detection, respectively) with two channels (FAM and Cy5) for the detection of 12 targets was developed. The device contained three core functional components, including temperature control, optics, and motion, which were integrated into a portable compact box. The temperature modules accurately control temperature in rapid thermal cycles with less than ±0.1 °C, ±1 °C and ±0.5 °C for the temperature fluctuation, uniformity, and error of indication, respectively. The average coefficient of variation (CV) of the fluorescence intensity (FI) for all 12 wells was 2.3% for FAM and 2.7% for Cy5. There was a good linear relationship between the concentrations of fluorescent dye and the FIs of FAM and Cy5(R 2 = 0.9990 and 0.9937), and the average CVs of the Ct values calculated by the embedded software were 1.4% for FAM and Cy5, respectively. The 100 double-blind mocked sputum and 249 clinical stool samples were analyzed by the ultrafast real-time PCR device in comparison with the DAAN Gene SARS-CoV-2 kit run on the ABI 7500 instrument and Xpert C. difficile/Epi, respectively. Among the 249 stool samples, the ultrafast real-time PCR device detected toxigenic C. difficile in 54 samples (54/249, 21.7%) with a specificity and positive predictive values of 99.0 and 96.3%, which were higher than the Xpert C. difficile/Epi values of 94.4 and 88.1% (p > 0.05). The ultrafast real-time PCR device detected 15 SARS-CoV-2 positive samples, which has a 100% concordance with that obtained by the DAAN Gene SARS-CoV-2 kit. This study demonstrated that the ultrafast real-time PCR device integrated with microfluidic chips and dual temperature modules is an ultrafast, reliable, easy-to-use, and cost-effective molecular diagnostic platform for clinical diagnosis and on-site testing, especially in resource-limited settings.

Rejection of Acellular Porcine Corneal Stroma Transplantation During Coronavirus Disease 2019 Pandemic

: To report 2 successfully managed cases of graft rejection with acellular porcine corneal stroma (APCS) transplantation in patients with fungal corneal ulcer. Two patients were diagnosed with fungal corneal ulcer and received APCS transplantation. Graft rejection developed due to the lost follow-up during the period of coronavirus disease 2019 outbreak. Amniotic membranes transplantation and cauterization of neovascularization was performed, respectively. The graft failure resolved successfully after the procedure. To the best of our knowledge, amniotic membranes transplantation and cauterization of new vessels are the firstly reported in treating APCS graft failure. Amniotic membranes transplantation or cauterization of neovascularization appear to be a safe and costeffective method for treating graft failure.