Risk factors for disease severity among children with Covid-19: a clinical prediction model.

BACKGROUND: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19. METHODS: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively. CONCLUSION: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.

Observed Interactions, Challenges, and Opportunities in Student-Led, Web-Based Near-Peer Teaching for Medical Students: Interview Study Among Peer Learners and Peer Teachers.

BACKGROUND: Near-peer teaching (NPT) is becoming an increasingly popular pedagogical tool in health professions education. Despite the shift in formal medical education from face-to-face teaching toward encompassing web-based learning activities, NPT has not experienced a similar transition. Apart from the few reports on NPT programs hastily converted to web-based learning in light of the COVID-19 pandemic, no studies to date have explored web-based learning in the specific context of NPT. OBJECTIVE: This qualitative study examined the nature of interactions among peer learners (PLs), peer teachers (PTs), and the learning content in a student-led, web-based NPT program for medical students. METHODS: A 5-month-long voluntary NPT program to support first- and second-year medical students' biomedical science learning in the undergraduate medical curriculum was designed by 2 senior-year medical students and delivered by 25 PTs with 84 PLs participating. In total, 9 PLs and 3 PTs underwent individual semistructured interviews at the end of the program to explore general NPT experience, reasons for joining NPT, the effectiveness of NPT, the demand and importance of NPT, and the feasibility of incorporating NPT in the formal curriculum. Interview transcripts were analyzed using a thematic analysis approach. RESULTS: The first general theme focused on the nature of student-student, student-teacher, and student-content interactions. Although PLs were engaged in web-based NPT, there was minimal interaction between students, as most PLs preferred to learn passively and remain anonymous. PLs believed the web-based NPT learning process to be a unidirectional transmission of knowledge from teacher to learner, with the teacher responsible for driving the interactions. This was in sharp contrast to PTs' expectation that both parties shared responsibility for learning in a collaborative effort. The second general theme identified the advantages and disadvantages of delivering NPT on a web platform, which were mainly convenience and teaching skills development and poor interactivity, respectively. CONCLUSIONS: Student-led, web-based NPT offers a flexible and comfortable means of delivering academic and nonacademic guidance to medical students. However, the web-based mode of delivery presents unique challenges in facilitating meaningful interactions among PLs, PTs, and subject content. A blended learning approach may be best suited for this form of student-led NPT program to optimize its efficacy.

Effect of MMR Vaccination to Mitigate Severe Sequelae Associated With COVID-19: Challenges and Lessons Learned.

Mortality in COVID-19 cases was strongly associated with progressive lung inflammation and eventual sepsis. There is mounting evidence that live attenuated vaccines commonly administered during childhood, also provide beneficial non-specific immune effects, including reduced mortality and hospitalization due to unrelated infections. It has been proposed that live attenuated vaccine-associated non-specific effects are a result of inducing trained innate immunity to function more effectively against broader infections. In support of this, our laboratory has reported that immunization with a live attenuated fungal strain induces a novel form of trained innate immunity which provides protection against various inducers of sepsis in mice via myeloid-derived suppressor cells. Accordingly, we initiated a randomized control clinical trial with the live attenuated Measles, Mumps, Rubella (MMR) vaccine in healthcare workers in the greater New Orleans area aimed at preventing/reducing severe lung inflammation/sepsis associated with COVID-19 (ClinicalTrials.gov Identifier: NCT04475081). Included was an outcome to evaluate the myeloid-derived suppressor cell populations in blood between those administered the MMR vaccine vs placebo. The unanticipated emergency approval of several COVID-19 vaccines in the midst of the MMR clinical trials eliminated the ability to examine effects of the MMR vaccine on COVID-19-related health status. Unfortunately, we were also unable to show any impact of the MMR vaccine on peripheral blood myeloid-derived suppressor cells due to several inherent limitations (low percentages of blood leukocytes, small sample size), that also included a collaboration with a similar trial (CROWN CORONATION; ClinicalTrials.gov Identifier: NCT04333732) in St. Louis, MO. In contrast, monitoring the COVID-19 vaccine response in trial participants revealed that high COVID-19 antibody titers occurred more often in those who received the MMR vaccine vs placebo. While the trial was largely inconclusive, lessons learned from addressing several trial-associated challenges may aid future studies that test the non-specific beneficial immune effects of live attenuated vaccines.

Cas12a-assisted RTF-EXPAR for accurate, rapid and simple detection of SARS-CoV-2 RNA.

Developing highly accurate and simple approaches to rapidly identify and isolate SARS-CoV-2 infected patients is important for the control of the COVID-19 pandemic. We, herein, reported the performance of a Cas12a-assisted RTF-EXPAR strategy for the identification of SARS-CoV-2 RNA. This assay combined the advantages of RTF-EXPAR with CRISPR-Cas12a can detect SARS-CoV-2 within 40 min, requiring only isothermal control. Particularly, the simultaneous use of EXPAR amplification and CRISPR improved the detection sensitivity, thereby realizing ultrasensitive SARS-CoV-2 RNA detection with a detection limit of 3.77 aM (∼2 copies/µL) in an end-point fluorescence read-out fashion, and at 4.81 aM (∼3 copies/µL) level via a smartphone-assisted analysis system (RGB analysis). Moreover, Cas12a increases the specificity by intrinsic sequence-specific template recognition. Overall, this method is fast, sensitive, and accurate, needing minimal equipment, which holds great promise to meet the requirements of point-of-care molecular detection of SARS-CoV-2.

Comparison of Severe Viral Pneumonia Caused by SARS-CoV-2 and Other Respiratory Viruses Among Malaysian Children During the COVID-19 Pandemic.

Objectives: We described the etiology of severe pneumonia in children during the height of the COVID-19 pandemic in Malaysia and compared the clinical features of severe SARS-CoV-2 to other respiratory viruses. Methods: This retrospective study included all children aged 12 years and below hospitalized with severe pneumonia in Negeri Sembilan, Malaysia, between 1 April 2021 and 31 October 2021. We extracted demographic and clinical data and used logistic regression to examine risk factors associated with severe SARS-CoV-2 or other viral pneumonia. Results: A total of 111 children were included. The median age was 15 months. Human rhinovirus/enterovirus, SARS-CoV-2 and respiratory syncytial virus were the most common etiology of severe pneumonia. Codetection of >1 viral pathogen was present in 14 (12.6%) patients. Children with severe COVID-19 presented early in the course of illness and had lower rates of pediatric intensive care admission. The presence of sick contact with an adult was a predictor for SARS-CoV-2, whereas adventitious breath sounds were predictive of other respiratory viruses. Conclusions: The etiology of severe pneumonia in children evolved with the epidemic curve of COVID-19 and school closures. Children with severe pneumonia due to SARS-CoV-2 experienced a milder clinical course when compared to other respiratory viruses.

Comparison of Severe Viral Pneumonia Caused by SARS-CoV-2 and Other Respiratory Viruses Among Malaysian Children During the COVID-19 Pandemic

Objectives We described the etiology of severe pneumonia in children during the height of the COVID-19 pandemic in Malaysia and compared the clinical features of severe SARS-CoV-2 to other respiratory viruses. Methods This retrospective study included all children aged 12 years and below hospitalized with severe pneumonia in Negeri Sembilan, Malaysia, between 1 April 2021 and 31 October 2021. We extracted demographic and clinical data and used logistic regression to examine risk factors associated with severe SARS-CoV-2 or other viral pneumonia. Results A total of 111 children were included. The median age was 15 months. Human rhinovirus/enterovirus, SARS-CoV-2 and respiratory syncytial virus were the most common etiology of severe pneumonia. Codetection of >1 viral pathogen was present in 14 (12.6%) patients. Children with severe COVID-19 presented early in the course of illness and had lower rates of pediatric intensive care admission. The presence of sick contact with an adult was a predictor for SARS-CoV-2, whereas adventitious breath sounds were predictive of other respiratory viruses. Conclusions The etiology of severe pneumonia in children evolved with the epidemic curve of COVID-19 and school closures. Children with severe pneumonia due to SARS-CoV-2 experienced a milder clinical course when compared to other respiratory viruses.

Physiotherapy-assisted prone or modified prone positioning in ward-based patients with COVID-19: a retrospective cohort study.

OBJECTIVES: To evaluate short-term change in oxygenation and feasibility of physiotherapy-assisted prone or modified prone positioning in awake, ward-based patients with COVID-19. DESIGN: Retrospective observational cohort study. SETTING: General wards, single-centre tertiary hospital in Australia. PARTICIPANTS: Patients were included if ≥18 years, had COVID-19, required FiO2 ≥ 0.28 or oxygen flow rate ≥4 l/minute and consented to positioning. MAIN OUTCOME MEASURES: Feasibility measures included barriers to therapy, assistance required, and comfort. Short-term change in oxygenation (SpO2) and oxygen requirements before and 15 minutes after positioning. RESULTS: Thirteen patients, mean age 75 (SD 14) years; median Clinical Frailty Scale score 6 (IQR 4 to 7) participated in 32 sessions of prone or modified prone positioning from a total of 125 ward-based patients admitted with COVID-19 who received physiotherapy intervention. Nine of thirteen patients (69%) required physiotherapy assistance and modified positions were utilised in 8/13 (62%). SpO2 increased in 27/32 sessions, with a mean increase from 90% (SD 5) pre-positioning to 94% (SD 4) (mean difference 4%; 95%CI 3 to 5%) after 15 minutes. Oxygen requirement decreased in 14/32 sessions, with a mean pre-positioning requirement of 8 l/minute (SD 4) to 7 l/minute (SD 4) (mean difference 2 l/minute; 95%CI 1 to 3 l/minute) after 15 minutes. In three sessions oxygen desaturation and discomfort occurred but resolved immediately by returning supine. CONCLUSION: Physiotherapy-assisted prone or modified prone positioning may be a feasible option leading to short-term improvements in oxygenation in awake, ward-based patients with hypoxemia due to COVID-19. Further research exploring longerterm health outcomes and safety is required.

Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.

The Impact of COVID-19 on Risky Behaviors and Health Changes in African-American Smokers Who Are Eligible for LDCT Screening.

The COVID-19 pandemic has disrupted much of day-to-day life in the US and around the world. Smokers have a higher risk of adverse outcomes due to COVID-19. This study investigated the impact of COVID-19 on risky behaviors and health changes in lower income African-American smokers eligible for Low dose computed tomography (LDCT) screening, who may be more adversely impacted by the COVID-19 pandemic. A total of 22 African-American daily smokers who were eligible for LDCT screening participated in this study. The mean age of participants was 61.2 years old (SD = 4.7), 77.3% of the smokers were female, all participants had an income below $20,000, and 63.6% were on Medicaid. Descriptive statistics were used to provide summary information on demographics, COVID-19, and health status. Results showed that participants increased cigarette smoking, spent more time on screens, increased sugary drink consumption, consumed more vegetables and fruits, and engaged in more gardening activities during the COVID-19 pandemic. However, participants also decreased physical activity time and slept less during the pandemic. In general, more than one-third of participants gained more body weight and reported increased stress and anxiety. Our results suggest that African-American smokers who qualify for LDCT screening should be encouraged to consider strategies not only for smoking cessation, but also risky behavior control and management.

Plastic waste associated with the COVID-19 pandemic: Crisis or opportunity?

Coronavirus Diseases 2019 (COVID-19) pandemic has a huge impact on the plastic waste management in many countries due to the sudden surge of medical waste which has led to a global waste management crisis. Improper management of plastic waste may lead to various negative impacts on the environment, animals, and human health. However, adopting proper waste management and the right technologies, looking in a different perception of the current crisis would be an opportunity. About 40% of the plastic waste ended up in landfill, 25% incinerated, 16% recycled and the remaining 19% are leaked into the environment. The increase of plastic wastes and demand of plastic markets serve as a good economic indicator for investor and government initiative to invest in technologies that converts plastic waste into value-added product such as fuel and construction materials. This will close the loop of the life cycle of plastic waste by achieving a sustainable circular economy. This review paper will provide insight of the state of plastic waste before and during the COVID-19 pandemic. The treatment pathway of plastic waste such as sterilisation technology, incineration, and alternative technologies available in converting plastic waste into value-added product were reviewed.

Practical Considerations for Converting Operating Rooms and Post-anaesthesia Care Units into Intensive Care Units in the COVID-19 Pandemic - Experience from a Large Singapore Tertiary Hospital.

COVID-19 has spread globally, infecting and killing millions of people worldwide. The use of operating rooms (ORs) and the post-anaesthesia care unit (PACU) for intensive care is part of surge response planning. We aim to describe and discuss some of the practical considerations involved in a large tertiary hospital in Singapore. Firstly, considerations for setting up a level III intensive care unit (ICU) include that of space, staff, supplies and standards. Secondly, oxygen supply of the entire hospital is a major determinant of the number of ventilators it can support, including those on non-invasive forms of oxygen therapy. Thirdly, air flows due to positive pressure systems within the OR complex need to be addressed. In addition, due to the worldwide shortage of ICU ventilators, the US Food and Drug Administration has granted temporary approval for the use of anaesthesia gas machines for patients requiring mechanical ventilation. Lastly, planning of logistics and staff deployment needs to be carefully considered during a crisis. Although OR and PACU are not designed for long-term care of critically ill patients, they may be adapted for ICU use with careful planning in the current pandemic.

Development a Nomogram to Predict Prognosis in Severe and Critically Ill Patients with COVID-19 (preprint)

Background: The number of deaths caused by COVID-19 are on the rising worldwide. This study focused on severe and critically ill COVID-19, aim to explore independent risk factors associated with disease severity and to build a nomogram to predict patients’ prognosis.Methods: Patients with laboratory-confirmed COVID-19 admitted to the Union Hospital, Tongji Medical College and Hankou Hospital of Wuhan, China, from February 8th to April 6th, 2020. LASSO Regression and Multivariate Analysis were applied to screen independent factors. COX Nomogram was built to predict the 7-day, 14-day and 1-month survival probability.Results: A total of 115 severe [73 (63.5%)] and critically ill [42 (36.5%)] patients were included in this study, containing 93 (80.9%) survivors and 22 (19.1%) non-survivors. For disease severity, D-dimer [OR 6.33 (95%CI, 1.27-45.57], eosinophil percentage [OR 8.02 (95%CI, 1.82-45.04)], total bilirubin [OR 12.38 (95%CI, 1.24-223.65)] and lung involvement score [OR 1.22 (95%CI, 1.08-1.40)] were the independent factors associated with critical illness. Troponin [HR 9.02 (95%CI, 3.02, 26.97)] and total bilirubin [HR 3.16 (95%CI, 1.13, 8.85)] were the independent predictors for patients’ prognosis. Troponin≥26.2 ng/L and total bilirubin＞20 μmol/L were associated with poor prognosis. The nomogram based on the independent risk factors had a C-index of 0.92 (95%CI, 0.87, 0.98) for predicting survival probability. The survival nomogram validated in the critically ill patients had a C-index of 0.83 (95%CI: 0.75, 0.94).Conclusions: In conclusion, in severe and critically ill patients with COVID-19, D-dimer, eosinophil percentage, total bilirubin and lung involvement score were the independent risk factors associated with disease severity. The proposed survival nomogram accurately predicted prognosis. The survival analysis may suggest that early incidence of multiple organ dysfunction may be an important predictor of poor prognosis.

Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study (preprint)

Background: Systemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. Methods: From December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. Results: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p< 0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. Conclusions: Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.

Response and Operating Room Preparation for the COVID-19 Outbreak: A Perspective From the National Heart Centre in Singapore.

The outbreak of coronavirus disease 2019 (COVID-19), a respiratory disease from a novel coronavirus that was first detected in Wuhan City, Hubei Province, China, is now a public health emergency and pandemic. Singapore, as a major international transportation hub in Asia, has been one of the worst hit countries by the disease. With the advent of local transmission, the authors share their preparation and response planning for the operating room of the National Heart Centre Singapore, the largest cardiothoracic tertiary center in Singapore. Protection of staff and patients, environmental concerns, and other logistic and equipment issues are considered.